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Latest revision as of 18:05, 27 July 2020

Main article: COVID-19

For COVID-19 frequently asked inpatient questions, click here

For COVID-19 frequently asked outpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2] Javaria Anwer M.D.[3]

Overview

According to 12 clinical studies, 14.8%-53% of COVID-19 patients have liver impairment, evidence of a COVID-19-associated hepatic injury, which has been a common complication observed among COVID-19 patients. With the number of COVID-19 cases increasing, abnormal liver function test results have been observed in some patients with COVID-19, making this organ the second most frequently damaged, next to the respiratory system. According to one study, serum ALT and AST levels increased up to 7590 U/L and 1445 U/L, respectively, in a severe COVID-19 patient. The diagnosis of COVID-19-associated hepatic injury is based on abnormal liver biochemical and function tests such as LDH, albumin, ALT, AST, total bilirubin, and INR. The mainstay of medical therapy is to target the viral infection using antivirals such as remdesivir, lopinavir/ritonavir, and darunavir/cobicistat, control and prevent inflammation, and symptomatic treatment. For severe hepatic injury, The Chinese Pharmaceutical Association recommends the use of jaundice-reducing, hepatoprotective and anti-inflammatory agents such as phosphatidylcholine, glycyrrhizin, bicyclol, and vitamin E. Maximum of one to two hepatoprotective or anti-viral drugs should be used to minimize drug interactions and possible liver damage. At this time, the only effective measures for the primary prevention of COVID-19 related liver damage include prevention of COVID-19 infection. Drug-induced liver injury can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with antiviral drugs.

To browse the complete page of COVID-19, click here.

Historical Perspective

Severe acute respiratory syndrome (SARS) has shown manifestations of liver impairment in up to 60% of patients.^[1]
Liver impairment has also been reported in patients infected with MERS-CoV.^[2]
Holshue et al.12 reported the first Chinese case of COVID-19 confirmed in the USA with detailed information of liver function tests.^[3]
According to 12 clinical studies, 14.8%-53% of COVID-19 patients have liver impairment, suggesting COVID-19-associated hepatic injury, which has been a common complication observed among COVID-19 patients. COVID-19-associated hepatic injury is mainly indicated by abnormal ALT/AST levels accompanied by slightly elevated bilirubin levels. ^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]^[13]^[14]^[15]^[16]^[17]^[18]
In severe cases, albumin is seen to be diminished and the level of albumin is around 26.3-30.9 g/l.^[5]
Patients with severe COVID-19 symptoms showed a high percentage of liver injury than that of mild patients.^[19]^[20]^[21]
According to one study, serum ALT and AST levels increased up to 7590 U/L and 1445 U/L, respectively, in a severe COVID-19 patient.^[5]

To browse the historical perspectives of COVID-19, click here.

Classification

There is no formal classification of liver damage associated with COVID-19 but, we attempt to divide the disease classification based on the etiology and mechanism of liver damage:^[22]^[23]^[9]^[24]^[25]^[26]^[27]^[28]

Direct viral damage to hepatocytes
Drug induced liver injury
Overactive immune response
Ischemia and reperfusion injury
Aggravation/ Recurrence of existing liver disease- According to the data available, 2% to 11% of COVID-19 patients had pre-existing chronic liver disease.

To browse the classification of COVID-19, click here.

Pathophysiology

The exact mechanism of liver injury is still unclear. There are several proposed mechanisms in an effort to understand the pathogenesis of hepatic injury but the hepatic complications in COVID-19 patients are described as multifactorial and heterogeneous. A few of the proposed mechanisms include:

Hepatic Injury through ACE2 receptors

S protein facilitates SARS-CoV-2 to enter host cells through binding to ACE2 receptors. ACE2 is the primary receptors that enable the entry of SARS-CoV into different target tissues, including hepatic cells.^[29]^[30]
According to a biopsy performed in a COVID-19 patient following death, moderate microvascular steatosis, and mild portal and lobular activity in liver tissue were observed.^[31]
Another study included four autopsies performed on COVID-19 patients. In 2 cases, mild zone 3 sinusoidal dilatation, patchy hepatic necrosis, and minimal increase in sinusoidal lymphocytes were observed in hepatocytes. In one case, RT-PCR showed direct evidence of the SARS-CoV-2 RNA sequence in the liver cells.^[32]
The expression of ACE2 receptors in liver tissue is only 0.31%. The expression of ACE2 receptors is 20 times higher in bile duct epithelial cells as compared to hepatocytes.^[33] Because of the low number of ACE2 expression in the liver, further research is needed to investigate direct damage of liver tissue by SARS-CoV-2.

Antibody-mediated Hepatic Injury

Antibody-mediated liver injury may occur in patients with SARS.^[34] It involves the binding of a virus-specific antibody to Fc receptors (FcR) and complement receptor (CR) that enables the virus to enter immune cells such as granulocytes, monocytes, and macrophages. The virus can damage the liver by constant replication in these immune cells.^[35] Further investigation is required to understand whether SARS-CoV-2 causes liver injury through this pathway.

Cytokine-mediated Hepatic Injury

Historical data on SARS-CoV and MERS-CoV suggest that cytokine storm including interleukin (IL), tumor necrosis factor (TNF), and endotoxin and systemic inflammatory response syndrome played a major role in liver impairment among infected patients.^[36]^[37]^[38]
A high serum levels of interleukin-2, interleukin-6, interleukin-7, interleukin-10, tumor necrosis factor-α, granulocyte-colony stimulating factor, interferon-inducible protein-10, monocyte chemotactic protein 1, macrophage inflammatory protein 1 alpha, Th17, and CD8 T cells are observed in severe cases of COVID-19.^[19]^[21]^[39]^[40]^[41]

COVID-19 medical therapy-induced Hepatic Injury

COVID-19 medical therapy includes antibiotics, antivirals, and steroids similar to the treatment for SARS infection. These medications are on the whole likely reasons for liver injury during COVID‐19, however not yet being obvious.^[4]
Most antipyretic medications contain paracetamol, which is commonly perceived as a typical explanation behind liver injury.^[42]
According to a study by Fan et al., the liver injury observed in COVID‐19 patients might be caused by lopinavir/ritonavir, which is used as antivirals for the treatment of COVID-19.^[43]
In this way, if variation from the norm of liver enzymes happens in the wake of utilizing a hepatotoxic medication, the drug-induced hepatic injury should initially be affirmed or precluded. China has a high prevalence of chronic liver diseases such as nonalcoholic fatty liver disease, chronic hepatitis B, and liver cirrhosis. Immune reactions as a result of COVID-19 infection may be viewed as a "second hit" to already existing liver disease and can actuate liver injury and steatohepatitis.^[44]

Sepsis-induced COVID-19-associated Hepatic Injury

Sepsis can also be considered as a contributing factor to COVID-19-associated hepatic injury and can impair the prognosis of COVID-19. Sepsis is a dysregulated immune response to an infection that leads to psychological stress and multiple organ dysfunction.^[45]
The pathophysiology of sepsis-related liver injury is likely multifactorial and may include hypoxic liver injury due of ischemia and shock, cholestasis due to an altered bile metabolism, hepatocellular injury due to drug toxicity, or overwhelming inflammation.^[46]

Ischemia-reperfusion-induced Hepatic Injury

Ischemia and hypoxia as a result of COVID-19 infection can result in metabolic acidosis, calcium overloading, and changes in mitochondrial membrane permeability. These factors have impacted hepatic injury manifested as very high aminotransferase concentrations in serum.^[47]

To browse the pathophysiology of COVID-19, click here.

Differentiating COVID-19-associated hepatic injury from other causes of hepatic injury

For further information about the differential diagnosis, click here.

To browse the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

In a cohort of 41 COVID-19 patients, levels of aspartate aminotransferase increased by 15 (37%) patients. Among these 15 patients, eight (62%) of 13 ICU patients and seven (25%) of 28 non-ICU patients.^[19]
According to a single-center study of 99 COVID-19 patients, a wide range of liver function abnormality was observed among 43 patients, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the normal range. A severe liver function abnormality was observed in one patient (ALT 7590 U/L, AST 1445 U/L).^[5]

Liver test abnormalities from various COVID-19 studies^[10]
Author	Group	Number of patients	Alanine aminotransferase (IU)	Aspartate aminotransferase (IU)	Prothrombin time (s)	Bilirubin (μmol/L)	Elevated lactate dehydrogenase, creatinine kinase, or myoglobin	Mortality (%)
Guan et al (2020)^[20]	ICU or death	67	Not known	Not known	Not known	Not known	Yes	22% (day 51)
Huang et al (2020)^[19]	ICU	13	49 (29–115)	44 (32–70)	12·2 (11·2–13·4)	14·0 (11·9–32·9)	Yes	38% (day 37)
Chen et al (2020)^[5]	Hospitalised	99	39 (22–53)	34 (26–48)	11·3 (1·9)	15·1 (7·3)	Yes	11% (day 24)
Wang et al (2020)^[48]	ICU	36	35 (19–57)	52 (30–70)	13·2 (12·3–14·5)	11·5 (9·6–18·6)	Yes	17% (day 34)
Shi et al (2020)^[49]	Hospitalised	81	46 (30)	41 (18)	10·7 (0·9)	11·9 (3·6)	Unclear	5% (day 50)
Xu et al (2020)^[50]	Hospitalised	62	22 (14–34)	26 (20–32)	Not known	Not known	Unclear	0% (day 34)
Yang et al (2020)^[4]	ICU	52	Not known	Not known	12·9 (2·9)*	19·5 (11·6)*	Not described	62% (day 28)
Extracted from all studies above	Chronic liver disease	42	Not known	Not known	Not known	Not known	Not known	0–2%†

In addition, abnormal liver function test in cases of COVID-19 is often transient and often simultaneously combined with increased enzymes from the cardiac muscle; these laboratory changes can return to normal without liver-related morbidity and mortality.

Gender

Although very limited data is available, the incidence of liver injury associated with COVID-19 is reported to be higher in males.^[43]

To browse the epidemiology and demographics of COVID-19, click here.

Risk Factors

Common risk factors in the development of COVID-19 associated hepatic injury complications include:
- Critical/ severe COVID-19 infection, especially ICU admissions.^[51]^[52]
- Pre-existing Chronic liver disease.^[51] Also patients with decompensated liver cirrhosis have higher mortality due to COVID-19.^[53]
- Old age^[51]
- Severe hypoxemia^[24]^[52]
- Hyper‐inflammatory reactions during COVID-19 infection^[24]^[52]
- Drugs causing hepatotoxicity. This may include drugs used for the treatment of COVID-19 itself such as interferon beta , lopinavir, ritonavir and imatinib.^[54]

To browse the risk factors of COVID-19 clicking here.

Natural History, Complications and Prognosis

Out of 148 COVID-19 patients, ninety-two (62.2%) patients were released from the hospital as of February 19, 2020, that includes 34 cases with abnormal liver function before admission, 24 cases with abnormal liver function during hospitalization, and 34 cases with normal liver function during the stay in hospital. Of note, we found that baseline abnormal liver function was associated with a prolonged hospital stay. Whereas, abnormal liver function observed during admission had little impact on the length of hospital stay.
According to the data available to date, mild liver injury can occur in patients with moderate-severe illness but the incidence of hepatic dysfunction higher among patients with severe or critical COVID-19 illness. ^[9]^[55]^[25]
The association of acute liver injury with higher mortality has been reported.^[55] Research is underway and few studies describe the correlation of liver biochemical indicators and severity of COVID-19. The impairment of hepatic function (guaged via biochemical markers of hepatic function) may become a predictor of the exacerbation and deterioration in patients with COVID‐19.^[25]

To browse the natural history, complications, and prognosis of COVID-19, click here.

Diagnosis

Diagnostic Study of Choice

The diagnosis of COVID-19-associated hepatic injury is based on the abnormal liver biochemical and function tests. The key lies in suspecting liver damage among COVID-19 patients and testing liver biochemical and function tests such as LDH, albumin, ALT, AST, total bilirubin, and INR. A COVID-19 patient with acute liver failure should be investigated and effort has to be made to find the cause liver injury.

History and Symptoms

The majority of patients (14.5%) with COVID-19 associated hepatic injury have a fever, which may be related to the immune response following viral infection.^[19]^[48]^[43]
The symptoms mentioned below may be due to hepatic injury itself, or commonly associated abdominal sequels. In order of prevalence, other COVID-19 associated symptoms reported among patients with COVID-19 include:^[28]^[43]^[56]
- Diarrhea, nausea and vomiting, abdominal pain, anorexia (Loss of appetite), and pruritis (due to bilirubin accumulation).
The involvement of the respiratory system by COVID-19 manifests as the following symptoms:
- Cough (dry or productive), pharyngitis, anosmia (partial or complete loss of smell), and ageusia (Loss of smell).
In general due to infection:
- Fatigue, chills, skin rash
The patient history and symptom associated with COVID-19 can be viewed by clicking here.

Physical Examination

Patients with COVID-19 associated hepatic injury may appear lethargic or confused due to hepatic encephalopathy. Jaundice, rash and bruises (signs of liver's deranged synthetic function) are more common among patients with chronic liver disease.^[56] Jaundice is reported among the cases of drug-induced liver injury. This may include drugs used for the treatment of COVID-19 itself such as interferon beta , lopinavir, ritonavir and imatinib.^[54]^[57]
Vital signs:^[56]
- The most common physical examination finding reported among patients with COVID-19 associated hepatic injury includes fever (however, normal temperature is not uncommon).^[43]
- Tachycardia
- Hypotension is common among patients with chronic liver disease
- Tachypnea maybe due to fever, respiratory involvement due to COVID-19 infection or massive ascites.
On Abdominal exam:^[54]^[56]^[58]
- Inspection: Jaundice, Ascites, abdominal distension or bulging flanks.
- Auscultation: Accompanying gastrointestinal infection may present as Increased bowel sounds due to enteritis.
- Palpation: Tenderness on superficial palpation. The presence of hepatomegaly on deep palpation among patients with COVID-19-associated hepatic injury is a forethought of organomegaly.
- Percussion: Shifting dullness
The physical exam findings associated with COVID-19 can be viewed by clicking here.

Laboratory Findings

Laboratory findings consistent with the diagnosis of COVID-19-associated hepatic injury include abnormal Liver function tests, especially raised AST.^[51] The arrangement is based upon the commonality of the presentation of the mentioned lab abnormality. CBC findings can vary depending on the infection status.
ALT and AST: The level of both enzymes is elevated in the blood of patients (reported among one-third of patients in a few studies) with liver injury on admission. AST elevation is more common than ALT, reflecting a possible source outside of liver. The enzyme levels may rise above three times the normal level. ICU patients have higher levels of ALT and AST and reduced levels of serum albumin indicating severe liver damage affecting the liver's synthetic ability.^[27]^[51] The AST/ALT ratio has been found to be 1.64 in a retrospective study.^[59]
LDH: Following AST and ALT, LDH rise has the highest incidence. Some studies suggest that LDH can be used as an early alarm to prompt further analysis for COVID-19 but the data is insufficient to be conclusive.^[59]^[43]
Alkaline phosphatase (ALP): The test is a good marker of cholestasis. The levels are raised.^[60]^[28]
Serum albumin: The test measures the synthetic function of the liver. The levels are found to decrease during the course of hospitalization. Marked hypoalbuminemia among critically-ill patients makes it a maker of poor prognosis of COVID-19 (retrospective study).^[61]
Total bilirubin and direct bilirubin: The data from limited studies show a higher incidence of hyperbilirubinemia among patients who required aggressive management during the course of their disease and patients that died.^[25]
C-reactive protein, ESR and Procalcitonin (CRP): 80% rise has been reported in a study.^[59], ESR and especially procalcitonin levels are found to be higher among patients and can indicate infection.^[19]^[48]^[43]
Glycoprotein gamma-glutamyltransferase (GGT): A rise in the level of GGT points towards cholestasis and thus hepatobiliary involvement. Three-fold rise from the upper normal limit has been reported among patients in ICU with COVID-19 associated hepatic injury.^[60]
PT/APTT: Provides a good estimate of liver synthetic function. Prolonged APTT was found among critically-ill patients in a retrospective study. It reflects coagulopathy.^[61]
Serum cholesterol: Serum LDL and HDL have been found to be remarkably low among critically-ill patients with COVID-19.^[61]
Interleukins: Levels of IL‐2‐receptor (IL‐2R), IL‐4, IL‐6, IL‐18, IL‐10, TNF‐α are significantly increased. In particular, IL‐6 in the serum of COVID‐19 patients are significantly increased and correlates with disease severity.^[62]
CBC: Leukocytosis indicates infection and lymphocytosis indicating possible viral infection.^[43]
Serum electrolytes: Retrospective studies from Italy and China demonstrated an assocition between hypokalemia, hypomagnesemia and COVID-19 due to degradation of ACE 2 loss, diuretic and corticosteroid use. Hypokalemia may lead to life-threatening arrhythmias. Close monitoring of serum electrolyte levels is essential especially in ICU patients.^[63]^[64]
Abnormal liver biochemistries are uncommon in children.^[28]

Electrocardiogram

There are no ECG findings associated with COVID-19-associated hepatic injury.
ECG shows significant findings in other manifestations or complications of COVID-19 infection such as COVID-19-associated myocardial injury, COVID-19-associated myocardial infarction, COVID-19-associated arrhythmia and conduction system disease, or COVID-19-associated pericarditis.
The electrocardiogram findings on COVID-19 can be viewed by clicking here.

X-ray

There are no x-ray findings associated with COVID-19-associated hepatic injury.
However, an x-ray may be helpful in the diagnosis of complications of COVID-19 such as COVID-19-associated pneumonia, which is the most common finding associated with COVID-19 infection.
The x-ray findings on COVID-19 can be viewed by clicking here.

Echocardiography or Ultrasound

The most common ultrasound findings associated with COVID-19-associated hepatic injury was fatty liver on the right upper quadrant abdominal ultrasound. Abnormal liver laboratory findings as indicated in Lab finding sections served as an indication to perform the abdominal ultrasound. Distended sludge-filled gallbladder suggestive of cholestasis has been reported in half of the patients studied (fig 1). Portal venous gas has also been identified in a few patients. ^[65]
However, echocardiography may be helpful in the diagnosis of cardiac complications of COVID-19 which include COVID-19-associated heart failure, or COVID-19-associated pericarditis. An abdominal ultrasound may be helpful in the case of COVID-19-associated abdominal pain.
The echocardiographic findings on COVID-19 can be viewed by clicking here.
Fig 1 Upper abdominal ultrasound in an 83-year-old patient with raised enzymes on liver function tests and sepsis is suggestive of cholestasis. A distended gallbladder is marked by arrows and sludge by a (*) - ^[65]

CT scan

Portal venous gas on abdominal CT has been reported.^[65]
Fig 2: A non-peer-reviewed retrospective cohort study mentions upper abdominal CT findings in 115 COVID-19 patients in China. The study reports homogeneous or heterogeneous hepatic hypodensity as the most common CT finding (26% patients) and pericholecystic fat stranding (21.3% cases). The study claims the correlation between CT signs and disease severity grading.^[66]
Chest CT scan is helpful in suggesting lung involvement in patients with COVID-19 which is a multi-organ disease.
The CT scan findings in COVID-19 can be viewed by clicking here.
Fig 2 Transverse upper abdomen non-contrast CT scan film showing:
A and B: Lung consolidation with air bronchograms, ground-glass opacity, interlobular septal thickening, Crazy paving sign, and pleura effusion are visible in both lungs
C: Liver hypodensity
D: Pericholecystic fat stranding marked by yellow arrows - ^[66]

MRI

There is one liver MRI with gadolinium on a 3T MRI reported to have been performed in a patient with COVID-19-associated hepatic injury and abnormal liver biochemical tests.No specific findings have been reported.^[65]
The MRI findings in COVID-19 can be viewed by clicking here.

Other Imaging Findings

There are no other imaging findings associated with COVID-19-associated hepatic injury.

Other Diagnostic Studies

There are no other diagnostic studies associated with COVID-19-associated hepatic injury.

Treatment

Medical Therapy

Currently there is no specific treatment for patients with COVID-19 associated liver injury. The mainstay of medical therapy is to target the viral infection using antivirals such as remdesivir, lopinavir/ritonavir and darunavir/cobicistat, control and prevent inflammation and symptomatic treatment. The recommended medical therapy is based upon expert opinion rather than randomized control trials and is as follows: ^[25]^[28]^[67]^[68]

Mild hepatic injury

In a COVID-19 patient with mild hepatic biochemical abnormalities, the mainstay of treatment is actively managing the primary infection. The administration of hepatoprotective and enzyme‐lowering therapy is not recommended but supportive as well as specific antiviral therapy to halt viral replication and to reduce inflammation.

Severe hepatic injury

In patients with severe COVID-19 infection and liver injury, hyperinflammatory responses such as cytokine storms and tissue ischemia are usual causal factors. Treatment should focus on maintaining optimal blood oxygen saturation. This can be achieved either by oxygen therapy or administering extracorporeal membrane oxygenation. The patient should be monitored closely with ongoing supportive and symptomatic treatment and correction of hypoproteinemia if required. The Chinese Pharmaceutical Association recommends administering jaundice-reducing, hepatoprotective and anti-inflammatory agents such as phosphatidylcholine, glycyrrhizin, bicyclol, and vitamin E. Maximum of one to two hepatoprotective or anti-viral drugs should be adminstered to minimize drug interactions and possible liver damage.^[69]

Acute liver failure

In the case of acute liver failure in a COVID-19 patient, after the cause of liver failure has been established, hepatoprotective and enzyme‐lowering drugs are administered. It is important to choose lower doses and fewer types of drugs (not more than 2, in general) with known mechanism of action and composition as the hepatic drug metabolism may pose a potential risk of harming the organ. The patient should be closely monitored with frequent hepatic biochemical tests such as (AST, ALT, albumin, total bilirubin and INR). Acute liver injury should be managed with close monitoring, supportive and symptomatic treatment, and correction of hypoproteinemia.

Drug induced liver injury

It is important to assess the degree of liver damage and identify the drug responsible and then adjust the treatment accordingly. If possible completely stop the drug, reduce the amount, or administering an alternative drug. Anti‐inflammatory and hepatoprotective treatment should be provided.

Underlying chronic liver disease

Target the coronavirus infection and maintain the original therapy for chronic liver diseases.The American Association for the Study of Liver Diseases (AASLD) does not recommend to discontinue Hepatitis B and Hepatitis C antiviral treatments but recommends that large doses of hormones are not to be administered simultaneously. However, direct-acting antiviral therapy initiation for Hepatitis C patients may be delayed.

Liver transplant patients

Specific COVID-19 therapy administered in patients includes steroids (the study does not specify the type), hydroxychloroquine, antivirals (such as lopinavir/ritonavir, darunavir/cobicistat, and remdesivir). Some patients were administered antibiotics such as azithromycin and immunomodulatory therapies such as rituximab and tocilizumab. Immunosuppression has been reduced in the majority of patients and discontinued in some. It is also advised at some places to keep the immunosuppression to the minimal possible dosage.

Monitoring

There are no clear guidelines on the evaluation of response to COVID-19 associated hepatic injury. A review article on evidence-based management guidelines for the COVID-19 reports a raised CRP and low albumin to be associated with deterioration in patients' condition. Demonstration of viral clearance in two respiratory tract specimens (at least 24 hours apart) may also serve as a monitoring tool.^[70]
Liver function tests can serve as indicators of disease progression. Treatment and prevention of inflammation in the early stages of the disease prevent severe disease.

To view medical treatment for COVID-19, click here.

Surgery

Surgical intervention is not recommended for the management of COVID-19-associated hepatic injury.

Primary Prevention

The disease itself is associated with COVID-19 infection so prevention of the infection is a promising primary prevention strategy at the moment.
There are no available vaccines against COVID-19 at the moment. There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.^[71]
At this time, the only effective measures for the primary prevention of COVID-19 related liver damage include prevention of itself COVID-19. Drug induced liver injury can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with antiviral drugs.
The only prevention for COVID-19 associated hepatic injury is the prevention and early diagnosis of the coronavirus-19 infection itself. According to the CDC, the measures include:^[72]
- Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% ethyl alcohol. It is essential to be sure that the hand sanitizer is free of methanol (wood alcohol) as FDA recently warns that methanol is harmful to human skin.^[73]
- Staying at least 6 feet (approximately 2 arms’ length) from other individuals who do not live with you.
- Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs.
- Cleaning and disinfecting.

Secondary prevention

Effective measures for the secondary prevention of contact tracing as it helps reduce the spread of the disease.^[74]
In unexplained abnormal hepatic biochemical tests, CXR, Chest CT scan or nasopharyngeal swab RT-PCR should be performed to diagnose the infection and treat it timely.

References

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[pmid32266987-69] Zha L, Li S, Pan L, Tefsen B, Li Y, French N, Chen L, Yang G, Villanueva EV (May 2020). "Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19)". Med. J. Aust. 212 (9): 416–420. doi:10.5694/mja2.50577. PMC 7262211 Check |pmc= value (help). PMID 32266987 Check |pmid= value (help).

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[urlNIH_clinical_trial_of_investigational_vaccine_for_COVID-19_begins_|_National_Institutes_of_Health_(NIH)-71] "NIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)".

[urlHow_to_Protect_Yourself_&_Others_|_CDC-72] "How to Protect Yourself & Others | CDC".

[urlFDA_Updates_on_Hand_Sanitizers_with_Methanol_|_FDA-73] "FDA Updates on Hand Sanitizers with Methanol | FDA".

[urlContact_Tracing_for_COVID-19_|_CDC-74] "Contact Tracing for COVID-19 | CDC".

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@@ Line 1: / Line 1: @@
-__NOTOC__
+<br />__NOTOC__
-'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''<br>'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br>
+{{SI}}
-{{COVID-19}}
+''Main article:'' [[COVID-19]]
+'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''
+'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br>
 {{CMG}} ; {{AE}} {{TAM}} [[User:Javaria Anwer|Javaria Anwer M.D.]][mailto:javaria.anwer@gmail.com]
 ==Overview==
-According to 12 clinical studies, 14.8%-53% of [[COVID-19]] patients have [[Hepatic failure|liver impairment]], suggesting COVID-19-associated hepatic injury, a common [[Complications|complication]] observed among [[COVID-19]] patients. With the number of cases increasing, [[Liver function tests|abnormal liver function test]] results have been observed in some patients with [[COVID-19]], making this organ the most frequently damaged outside of the [[respiratory system]].
+According to 12 clinical studies, 14.8%-53% of [[COVID-19]] patients have [[Hepatic failure|liver impairment]], evidence of a COVID-19-associated hepatic injury, which has been a common [[Complications|complication]] observed among [[COVID-19]] patients. With the number of COVID-19 cases increasing, [[Liver function tests|abnormal liver function test]] results have been observed in some patients with [[COVID-19]], making this organ the second most frequently damaged, next to the [[respiratory system]]. According to one study, serum [[Alanine transaminase|ALT]] and [[Aspartate transaminase|AST]] levels increased up to 7590 U/L and 1445 U/L, respectively, in a severe [[COVID-19]] patient. The diagnosis of [[COVID-19]]-associated hepatic injury is based on [[Liver function tests|abnormal liver biochemical and function tests]] such as [[Lactate dehydrogenase|LDH]], [[albumin]], [[Alanine transaminase|ALT]], [[Aspartate transaminase|AST]], [[Bilirubin|total bilirubin]], and [[International normalized ratio|INR]]. The mainstay of medical therapy is to target the viral infection using antivirals such as [[remdesivir]], [[lopinavir]]/[[Ritonavir|ritonavir,]] and [[darunavir]]/[[cobicistat]], control and prevent inflammation, and symptomatic treatment. For severe hepatic injury, The Chinese Pharmaceutical Association recommends the use of jaundice-reducing, hepatoprotective and [[Anti inflammatory medications|anti-inflammatory agents]] such as [[phosphatidylcholine]], [[glycyrrhizin]], bicyclol, and [[Tocopherol|vitamin E]]. Maximum of one to two hepatoprotective or anti-viral drugs should be used to minimize drug interactions and possible liver damage. At this time, the only effective measures for the primary prevention of [[COVID-19]] related liver damage include prevention of [[COVID-19]] infection. [[Drug induced liver injury|Drug-induced liver injury]] can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with [[Antiviral drug (patient information)|antiviral drugs]].
-To browse the complete page of COVID-19, [[COVID-19|Click here]].
+To browse the complete page of [[COVID-19]], [[COVID-19|click here]].
 ==Historical Perspective==
 *[[Severe acute respiratory syndrome|Severe acute respiratory syndrome (SARS)]] has shown manifestations of [[Liver Failure|liver impairment]] in up to 60% of patients.<ref name="ChauLee2004">{{cite journal|last1=Chau|first1=Tai-Nin|last2=Lee|first2=Kam-Cheong|last3=Yao|first3=Hung|last4=Tsang|first4=Tak-Yin|last5=Chow|first5=Tat-Chong|last6=Yeung|first6=Yiu-Cheong|last7=Choi|first7=Kin-Wing|last8=Tso|first8=Yuk-Keung|last9=Lau|first9=Terence|last10=Lai|first10=Sik-To|last11=Lai|first11=Ching-Lung|title=SARS-associated viral hepatitis caused by a novel coronavirus: Report of three cases|journal=Hepatology|volume=39|issue=2|year=2004|pages=302–310|issn=0270-9139|doi=10.1002/hep.20111}}</ref>
 *[[Hepatic failure|Liver impairment]] has also been reported in patients infected with [[Middle East respiratory syndrome coronavirus infection causes|MERS-CoV]].<ref name="AlsaadHajeer2018">{{cite journal|last1=Alsaad|first1=Khaled O|last2=Hajeer|first2=Ali H|last3=Al Balwi|first3=Mohammed|last4=Al Moaiqel|first4=Mohammed|last5=Al Oudah|first5=Nourah|last6=Al Ajlan|first6=Abdulaziz|last7=AlJohani|first7=Sameera|last8=Alsolamy|first8=Sami|last9=Gmati|first9=Giamal E|last10=Balkhy|first10=Hanan|last11=Al-Jahdali|first11=Hamdan H|last12=Baharoon|first12=Salim A|last13=Arabi|first13=Yaseen M|title=Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study|journal=Histopathology|volume=72|issue=3|year=2018|pages=516–524|issn=03090167|doi=10.1111/his.13379}}</ref>
-* According to 12 clinical studies, 14.8%-53% of [[COVID-19]] patients have [[Hepatic failure|liver impairment]], suggesting COVID-19-associated hepatic injury, a common [[complication]] observed among [[COVID-19]] patients. COVID-19-associated hepatic injury is mainly indicated by [[Liver function tests|abnormal ALT/AST levels]] accompanied by slightly [[Bilirubin|elevated bilirubin levels]]. <ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref><ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref><ref name="pmid32077660">{{cite journal| author=Liu C, Jiang ZC, Shao CX, Zhang HG, Yue HM, Chen ZH | display-authors=etal| title=[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study]. | journal=Zhonghua Gan Zang Bing Za Zhi | year= 2020 | volume= 28 | issue= 2 | pages= 107-111 | pmid=32077660 | doi=10.3760/cma.j.issn.1007-3418.2020.02.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32077660  }} </ref><ref name="pmid32026671">{{cite journal| author=Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J | display-authors=etal| title=[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. | journal=Zhonghua Jie He He Hu Xi Za Zhi | year= 2020 | volume= 43 | issue= 0 | pages= E005 | pmid=32026671 | doi=10.3760/cma.j.issn.1001-0939.2020.0005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32026671  }} </ref><ref name="pmid32031570">{{cite journal| author=Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J | display-authors=etal| title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. | journal=JAMA | year= 2020 | volume=  | issue=  | pages=  | pmid=32031570 | doi=10.1001/jama.2020.1585 | pmc=7042881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32031570  }} </ref><ref name="pmid32145190">{{cite journal| author=Zhang C, Shi L, Wang FS| title=Liver injury in COVID-19: management and challenges. | journal=Lancet Gastroenterol Hepatol | year= 2020 | volume= 5 | issue= 5 | pages= 428-430 | pmid=32145190 | doi=10.1016/S2468-1253(20)30057-1 | pmc=7129165 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32145190  }} </ref><ref name="pmid32203680">{{cite journal| author=Bangash MN, Patel J, Parekh D| title=COVID-19 and the liver: little cause for concern. | journal=Lancet Gastroenterol Hepatol | year= 2020 | volume= 5 | issue= 6 | pages= 529-530 | pmid=32203680 | doi=10.1016/S2468-1253(20)30084-4 | pmc=7270582 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32203680  }} </ref><ref name="pmid32171057">{{cite journal| author=Mao R, Liang J, Shen J, Ghosh S, Zhu LR, Yang H | display-authors=etal| title=Implications of COVID-19 for patients with pre-existing digestive diseases. | journal=Lancet Gastroenterol Hepatol | year= 2020 | volume= 5 | issue= 5 | pages= 425-427 | pmid=32171057 | doi=10.1016/S2468-1253(20)30076-5 | pmc=7103943 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171057  }} </ref><ref name="pmid32075364">{{cite journal| author=Hu LL, Wang WJ, Zhu QJ, Yang L| title=[Novel coronavirus pneumonia-related liver injury: etiological analysis and treatment strategy]. | journal=Zhonghua Gan Zang Bing Za Zhi | year= 2020 | volume= 28 | issue= 2 | pages= 97-99 | pmid=32075364 | doi=10.3760/cma.j.issn.1007-3418.2020.02.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32075364  }} </ref><ref name="pmid32004165">{{cite journal| author=Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T | display-authors=etal| title=Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. | journal=Chin Med J (Engl) | year= 2020 | volume= 133 | issue= 9 | pages= 1015-1024 | pmid=32004165 | doi=10.1097/CM9.0000000000000722 | pmc=7147275 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32004165  }} </ref><ref name="pmid32105637">{{cite journal| author=Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J | display-authors=etal| title=Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. | journal=Lancet Infect Dis | year= 2020 | volume= 20 | issue= 4 | pages= 425-434 | pmid=32105637 | doi=10.1016/S1473-3099(20)30086-4 | pmc=7159053 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32105637  }} </ref><ref name="pmid32075786">{{cite journal| author=Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL | display-authors=etal| title=Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. | journal=BMJ | year= 2020 | volume= 368 | issue=  | pages= m606 | pmid=32075786 | doi=10.1136/bmj.m606 | pmc=7224340 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32075786  }} </ref><ref name="pmid31986264">{{cite journal| author=Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y | display-authors=etal| title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 497-506 | pmid=31986264 | doi=10.1016/S0140-6736(20)30183-5 | pmc=7159299 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31986264  }} </ref><ref name="pmid32153170">{{cite journal| author=Yao N, Wang SN, Lian JQ, Sun YT, Zhang GF, Kang WZ | display-authors=etal| title=[Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region]. | journal=Zhonghua Gan Zang Bing Za Zhi | year= 2020 | volume= 28 | issue= 3 | pages= 234-239 | pmid=32153170 | doi=10.3760/cma.j.cn501113-20200226-00070 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32153170  }} </ref><ref name="pmid32220206">{{cite journal| author=Guan WJ, Zhong NS| title=Clinical Characteristics of Covid-19 in China. Reply. | journal=N Engl J Med | year= 2020 | volume= 382 | issue= 19 | pages= 1861-1862 | pmid=32220206 | doi=10.1056/NEJMc2005203 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32220206  }} </ref>
+*Holshue et al.12 reported the first Chinese case of COVID-19 confirmed in the USA with detailed information of liver function tests.<ref name="pmid32004427">{{cite journal| author=Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H | display-authors=etal| title=First Case of 2019 Novel Coronavirus in the United States. | journal=N Engl J Med | year= 2020 | volume= 382 | issue= 10 | pages= 929-936 | pmid=32004427 | doi=10.1056/NEJMoa2001191 | pmc=7092802 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32004427  }} </ref>
+*According to 12 clinical studies, 14.8%-53% of [[COVID-19]] patients have [[Hepatic failure|liver impairment]], suggesting COVID-19-associated hepatic injury, which has been a common [[complication]] observed among [[COVID-19]] patients. COVID-19-associated hepatic injury is mainly indicated by [[Liver function tests|abnormal ALT/AST levels]] accompanied by slightly [[Bilirubin|elevated bilirubin levels]]. <ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref><ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref><ref name="pmid32077660">{{cite journal| author=Liu C, Jiang ZC, Shao CX, Zhang HG, Yue HM, Chen ZH | display-authors=etal| title=[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study]. | journal=Zhonghua Gan Zang Bing Za Zhi | year= 2020 | volume= 28 | issue= 2 | pages= 107-111 | pmid=32077660 | doi=10.3760/cma.j.issn.1007-3418.2020.02.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32077660  }} </ref><ref name="pmid32026671">{{cite journal| author=Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J | display-authors=etal| title=[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. | journal=Zhonghua Jie He He Hu Xi Za Zhi | year= 2020 | volume= 43 | issue= 0 | pages= E005 | pmid=32026671 | doi=10.3760/cma.j.issn.1001-0939.2020.0005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32026671  }} </ref><ref name="pmid32031570">{{cite journal| author=Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J | display-authors=etal| title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. | journal=JAMA | year= 2020 | volume=  | issue=  | pages=  | pmid=32031570 | doi=10.1001/jama.2020.1585 | pmc=7042881 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32031570  }} </ref><ref name="pmid32145190">{{cite journal| author=Zhang C, Shi L, Wang FS| title=Liver injury in COVID-19: management and challenges. | journal=Lancet Gastroenterol Hepatol | year= 2020 | volume= 5 | issue= 5 | pages= 428-430 | pmid=32145190 | doi=10.1016/S2468-1253(20)30057-1 | pmc=7129165 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32145190  }} </ref><ref name="pmid32203680">{{cite journal| author=Bangash MN, Patel J, Parekh D| title=COVID-19 and the liver: little cause for concern. | journal=Lancet Gastroenterol Hepatol | year= 2020 | volume= 5 | issue= 6 | pages= 529-530 | pmid=32203680 | doi=10.1016/S2468-1253(20)30084-4 | pmc=7270582 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32203680  }} </ref><ref name="pmid32171057">{{cite journal| author=Mao R, Liang J, Shen J, Ghosh S, Zhu LR, Yang H | display-authors=etal| title=Implications of COVID-19 for patients with pre-existing digestive diseases. | journal=Lancet Gastroenterol Hepatol | year= 2020 | volume= 5 | issue= 5 | pages= 425-427 | pmid=32171057 | doi=10.1016/S2468-1253(20)30076-5 | pmc=7103943 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171057  }} </ref><ref name="pmid32075364">{{cite journal| author=Hu LL, Wang WJ, Zhu QJ, Yang L| title=[Novel coronavirus pneumonia-related liver injury: etiological analysis and treatment strategy]. | journal=Zhonghua Gan Zang Bing Za Zhi | year= 2020 | volume= 28 | issue= 2 | pages= 97-99 | pmid=32075364 | doi=10.3760/cma.j.issn.1007-3418.2020.02.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32075364  }} </ref><ref name="pmid32004165">{{cite journal| author=Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T | display-authors=etal| title=Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. | journal=Chin Med J (Engl) | year= 2020 | volume= 133 | issue= 9 | pages= 1015-1024 | pmid=32004165 | doi=10.1097/CM9.0000000000000722 | pmc=7147275 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32004165  }} </ref><ref name="pmid32105637">{{cite journal| author=Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J | display-authors=etal| title=Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. | journal=Lancet Infect Dis | year= 2020 | volume= 20 | issue= 4 | pages= 425-434 | pmid=32105637 | doi=10.1016/S1473-3099(20)30086-4 | pmc=7159053 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32105637  }} </ref><ref name="pmid32075786">{{cite journal| author=Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL | display-authors=etal| title=Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. | journal=BMJ | year= 2020 | volume= 368 | issue=  | pages= m606 | pmid=32075786 | doi=10.1136/bmj.m606 | pmc=7224340 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32075786  }} </ref><ref name="pmid31986264">{{cite journal| author=Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y | display-authors=etal| title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 497-506 | pmid=31986264 | doi=10.1016/S0140-6736(20)30183-5 | pmc=7159299 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31986264  }} </ref><ref name="pmid32153170">{{cite journal| author=Yao N, Wang SN, Lian JQ, Sun YT, Zhang GF, Kang WZ | display-authors=etal| title=[Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region]. | journal=Zhonghua Gan Zang Bing Za Zhi | year= 2020 | volume= 28 | issue= 3 | pages= 234-239 | pmid=32153170 | doi=10.3760/cma.j.cn501113-20200226-00070 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32153170  }} </ref><ref name="pmid32220206">{{cite journal| author=Guan WJ, Zhong NS| title=Clinical Characteristics of Covid-19 in China. Reply. | journal=N Engl J Med | year= 2020 | volume= 382 | issue= 19 | pages= 1861-1862 | pmid=32220206 | doi=10.1056/NEJMc2005203 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32220206  }} </ref>
 *In severe cases, [[albumin]] is seen to be diminished and the [[Albumin|level of albumin i]]<nowiki/>s around 26.3-30.9 g/l.<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>
 *Patients with [[COVID-19 history and symptoms|severe COVID-19 symptoms]] showed a high percentage of liver injury than that of mild patients.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="GuanNi2020">{{cite journal|last1=Guan|first1=Wei-jie|last2=Ni|first2=Zheng-yi|last3=Hu|first3=Yu|last4=Liang|first4=Wen-hua|last5=Ou|first5=Chun-quan|last6=He|first6=Jian-xing|last7=Liu|first7=Lei|last8=Shan|first8=Hong|last9=Lei|first9=Chun-liang|last10=Hui|first10=David SC|last11=Du|first11=Bin|last12=Li|first12=Lan-juan|last13=Zeng|first13=Guang|last14=Yuen|first14=Kowk-Yung|last15=Chen|first15=Ru-chong|last16=Tang|first16=Chun-li|last17=Wang|first17=Tao|last18=Chen|first18=Ping-yan|last19=Xiang|first19=Jie|last20=Li|first20=Shi-yue|last21=Wang|first21=Jin-lin|last22=Liang|first22=Zi-jing|last23=Peng|first23=Yi-xiang|last24=Wei|first24=Li|last25=Liu|first25=Yong|last26=Hu|first26=Ya-hua|last27=Peng|first27=Peng|last28=Wang|first28=Jian-ming|last29=Liu|first29=Ji-yang|last30=Chen|first30=Zhong|last31=Li|first31=Gang|last32=Zheng|first32=Zhi-jian|last33=Qiu|first33=Shao-qin|last34=Luo|first34=Jie|last35=Ye|first35=Chang-jiang|last36=Zhu|first36=Shao-yong|last37=Zhong|first37=Nan-shan|year=2020|doi=10.1101/2020.02.06.20020974}}</ref><ref name="CaiHuang2020">{{cite journal|last1=Cai|first1=Qingxian|last2=Huang|first2=Deliang|last3=Ou|first3=Pengcheng|last4=Yu|first4=Hong|last5=Zhu|first5=Zhibin|last6=Xia|first6=Zhang|last7=Su|first7=Yinan|last8=Ma|first8=Zhenghua|last9=Zhang|first9=Yiming|last10=Li|first10=Zhiwei|last11=He|first11=Qing|last12=Fu|first12=Yang|last13=Liu|first13=Lei|last14=Chen|first14=Jun|year=2020|doi=10.1101/2020.02.17.20024018}}</ref>
 *According to one study, serum [[Alanine transaminase|ALT]] and [[Aspartate transaminase|AST]] levels increased up to 7590 U/L and 1445 U/L, respectively, in a severe [[COVID-19]] patient.<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>
-To browse the historical perspectives of COVID-19, [[COVID-19 historical perspective|Click here]].
+To browse the historical perspectives of COVID-19, [[COVID-19 historical perspective|click here]].
 == Classification ==
-There is no formal classification of [[liver damage]] associated with [[COVID-19]] but, we attempt to divide the entity based on the [[etiology]] and mechanism of [[liver damage]]:<ref name="pmid32243269">{{cite journal |vauthors=Lee IC, Huo TI, Huang YH |title=Gastrointestinal and liver manifestations in patients with COVID-19 |journal=J Chin Med Assoc |volume=83 |issue=6 |pages=521–523 |date=June 2020 |pmid=32243269 |pmc=7176263 |doi=10.1097/JCMA.0000000000000319 |url=}}</ref><ref name="KumarSharma2020">{{cite journal|last1=Kumar|first1=Pramod|last2=Sharma|first2=Mithun|last3=Kulkarni|first3=Anand|last4=Rao|first4=Padaki N.|title=Pathogenesis of Liver Injury in Coronavirus Disease 2019|journal=Journal of Clinical and Experimental Hepatology|year=2020|issn=09736883|doi=10.1016/j.jceh.2020.05.006}}</ref><ref name="pmid32145190">{{cite journal |vauthors=Zhang C, Shi L, Wang FS |title=Liver injury in COVID-19: management and challenges |journal=Lancet Gastroenterol Hepatol |volume=5 |issue=5 |pages=428–430 |date=May 2020 |pmid=32145190 |pmc=7129165 |doi=10.1016/S2468-1253(20)30057-1 |url=}}</ref><ref name="LiXiao2020">{{cite journal|last1=Li|first1=Yueying|last2=Xiao|first2=Shu‐Yuan|title=Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.25973}}</ref><ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref><ref name="ShehuLu2019">{{cite journal|last1=Shehu|first1=Amina I.|last2=Lu|first2=Jie|last3=Wang|first3=Pengcheng|last4=Zhu|first4=Junjie|last5=Wang|first5=Yue|last6=Yang|first6=Da|last7=McMahon|first7=Deborah|last8=Xie|first8=Wen|last9=Gonzalez|first9=Frank J.|last10=Ma|first10=Xiaochao|title=Pregnane X receptor activation potentiates ritonavir hepatotoxicity|journal=Journal of Clinical Investigation|volume=129|issue=7|year=2019|pages=2898–2903|issn=0021-9738|doi=10.1172/JCI128274}}</ref><ref name="pmid32298767">{{cite journal |vauthors=Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y, Liu Y, He Q, Chen J, Liu L, Xu L |title=COVID-19: Abnormal liver function tests |journal=J. Hepatol. |volume= |issue= |pages= |date=April 2020 |pmid=32298767 |pmc=7194951 |doi=10.1016/j.jhep.2020.04.006 |url=}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}
+There is no formal classification of [[liver damage]] associated with [[COVID-19]] but, we attempt to divide the disease classification based on the [[etiology]] and mechanism of [[liver damage]]:<ref name="pmid32243269">{{cite journal |vauthors=Lee IC, Huo TI, Huang YH |title=Gastrointestinal and liver manifestations in patients with COVID-19 |journal=J Chin Med Assoc |volume=83 |issue=6 |pages=521–523 |date=June 2020 |pmid=32243269 |pmc=7176263 |doi=10.1097/JCMA.0000000000000319 |url=}}</ref><ref name="KumarSharma2020">{{cite journal|last1=Kumar|first1=Pramod|last2=Sharma|first2=Mithun|last3=Kulkarni|first3=Anand|last4=Rao|first4=Padaki N.|title=Pathogenesis of Liver Injury in Coronavirus Disease 2019|journal=Journal of Clinical and Experimental Hepatology|year=2020|issn=09736883|doi=10.1016/j.jceh.2020.05.006}}</ref><ref name="pmid32145190">{{cite journal |vauthors=Zhang C, Shi L, Wang FS |title=Liver injury in COVID-19: management and challenges |journal=Lancet Gastroenterol Hepatol |volume=5 |issue=5 |pages=428–430 |date=May 2020 |pmid=32145190 |pmc=7129165 |doi=10.1016/S2468-1253(20)30057-1 |url=}}</ref><ref name="LiXiao2020">{{cite journal|last1=Li|first1=Yueying|last2=Xiao|first2=Shu‐Yuan|title=Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.25973}}</ref><ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref><ref name="ShehuLu2019">{{cite journal|last1=Shehu|first1=Amina I.|last2=Lu|first2=Jie|last3=Wang|first3=Pengcheng|last4=Zhu|first4=Junjie|last5=Wang|first5=Yue|last6=Yang|first6=Da|last7=McMahon|first7=Deborah|last8=Xie|first8=Wen|last9=Gonzalez|first9=Frank J.|last10=Ma|first10=Xiaochao|title=Pregnane X receptor activation potentiates ritonavir hepatotoxicity|journal=Journal of Clinical Investigation|volume=129|issue=7|year=2019|pages=2898–2903|issn=0021-9738|doi=10.1172/JCI128274}}</ref><ref name="pmid32298767">{{cite journal |vauthors=Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y, Liu Y, He Q, Chen J, Liu L, Xu L |title=COVID-19: Abnormal liver function tests |journal=J. Hepatol. |volume= |issue= |pages= |date=April 2020 |pmid=32298767 |pmc=7194951 |doi=10.1016/j.jhep.2020.04.006 |url=}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}
 </ref>
 *Direct [[viral]] damage to [[hepatocytes]]
@@ Line 28: / Line 33: @@
 *Aggravation/ Recurrence of existing [[liver disease]]- According to the data available, 2% to 11% of [[COVID-19]] patients had pre-existing [[chronic liver disease]].
-To browse the classification of COVID-19, [[COVID-19 classification|Click here]].
+To browse the classification of COVID-19, [[COVID-19 classification|click here]].
 ==Pathophysiology==
@@ Line 35: / Line 40: @@
 :* S protein facilitates [[SARS-CoV-2]] to enter host cells through binding to [[ACER2|ACE2 receptors]]. [[ACER2|ACE2]] is the primary receptors that enable the entry of [[SARS-CoV]] into different target tissues, including [[Hepatocyte|hepatic cells]].<ref name="pmid32009228">{{cite journal| author=Xu X, Chen P, Wang J, Feng J, Zhou H, Li X | display-authors=etal| title=Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. | journal=Sci China Life Sci | year= 2020 | volume= 63 | issue= 3 | pages= 457-460 | pmid=32009228 | doi=10.1007/s11427-020-1637-5 | pmc=7089049 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32009228  }} </ref><ref name="pmid32094589">{{cite journal| author=Letko M, Marzi A, Munster V| title=Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. | journal=Nat Microbiol | year= 2020 | volume= 5 | issue= 4 | pages= 562-569 | pmid=32094589 | doi=10.1038/s41564-020-0688-y | pmc=7095430 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32094589  }} </ref>
-:* According to a [[biopsy]] performed in a  [[COVID-19]] patient after death, moderate [[Steatosis|microvascular steatosis]], and mild portal and lobular activity in liver tissue were observed.<ref name="pmid32085846">{{cite journal| author=Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C | display-authors=etal| title=Pathological findings of COVID-19 associated with acute respiratory distress syndrome. | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= 420-422 | pmid=32085846 | doi=10.1016/S2213-2600(20)30076-X | pmc=7164771 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32085846  }} </ref>
+:* According to a [[biopsy]] performed in a  [[COVID-19]] patient following death, moderate [[Steatosis|microvascular steatosis]], and mild portal and lobular activity in liver tissue were observed.<ref name="pmid32085846">{{cite journal| author=Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C | display-authors=etal| title=Pathological findings of COVID-19 associated with acute respiratory distress syndrome. | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= 420-422 | pmid=32085846 | doi=10.1016/S2213-2600(20)30076-X | pmc=7164771 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32085846  }} </ref>
-:* Another four autopsies were performed on [[COVID-19]] patients. In 2 cases, mild zone 3 [[sinusoidal]] dilatation, patchy [[Necrosis|hepatic necrosis]], minimal increase in sinusoidal [[Lymphocyte|lymphocytes]] were observed in [[Hepatocyte|hepatocytes]]. In one case, [[Reverse transcription polymerase chain reaction|RT-PCR]] showed direct evidence of the [[SARS-CoV-2]] RNA sequence in the [[Hepatocyte|liver cells]].<ref name="pmid32291399">{{cite journal| author=Tian S, Xiong Y, Liu H, Niu L, Guo J, Liao M | display-authors=etal| title=Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. | journal=Mod Pathol | year= 2020 | volume= 33 | issue= 6 | pages= 1007-1014 | pmid=32291399 | doi=10.1038/s41379-020-0536-x | pmc=7156231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32291399  }} </ref>
+:* Another study included four autopsies performed on [[COVID-19]] patients. In 2 cases, mild zone 3 [[sinusoidal]] dilatation, patchy [[Necrosis|hepatic necrosis]], and minimal increase in sinusoidal [[Lymphocyte|lymphocytes]] were observed in [[Hepatocyte|hepatocytes]]. In one case, [[Reverse transcription polymerase chain reaction|RT-PCR]] showed direct evidence of the [[SARS-CoV-2]] RNA sequence in the [[Hepatocyte|liver cells]].<ref name="pmid32291399">{{cite journal| author=Tian S, Xiong Y, Liu H, Niu L, Guo J, Liao M | display-authors=etal| title=Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. | journal=Mod Pathol | year= 2020 | volume= 33 | issue= 6 | pages= 1007-1014 | pmid=32291399 | doi=10.1038/s41379-020-0536-x | pmc=7156231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32291399  }} </ref>
 :* The expression of [[ACER2|ACE2 receptors]] in liver tissue is only 0.31%. The expression of [[ACER2|ACE2 receptors]] is 20 times higher in [[Bile duct|bile duct epithelial cells]] as compared to [[Hepatocyte|hepatocytes]].<ref name="ChaiHu2020">{{cite journal|last1=Chai|first1=Xiaoqiang|last2=Hu|first2=Longfei|last3=Zhang|first3=Yan|last4=Han|first4=Weiyu|last5=Lu|first5=Zhou|last6=Ke|first6=Aiwu|last7=Zhou|first7=Jian|last8=Shi|first8=Guoming|last9=Fang|first9=Nan|last10=Fan|first10=Jia|last11=Cai|first11=Jiabin|last12=Fan|first12=Jue|last13=Lan|first13=Fei|year=2020|doi=10.1101/2020.02.03.931766}}</ref> Because of the low number of [[ACER2|ACE2]] expression in the liver, further research is needed to investigate direct damage of liver tissue by [[SARS-CoV-2]].
@@ Line 58: / Line 63: @@
 :*[[Sepsis]] can also be considered as a contributing factor to COVID-19-associated hepatic injury and can impair the prognosis of [[COVID-19]]. [[Sepsis]] is a dysregulated immune response to an infection that leads to [[psychological stress]] and [[Multiple organ dysfunction syndrome|multiple organ dysfunction]].<ref name="LelubreVincent2018">{{cite journal|last1=Lelubre|first1=Christophe|last2=Vincent|first2=Jean-Louis|title=Mechanisms and treatment of organ failure in sepsis|journal=Nature Reviews Nephrology|volume=14|issue=7|year=2018|pages=417–427|issn=1759-5061|doi=10.1038/s41581-018-0005-7}}</ref>
-:*The pathophysiology of sepsis-related liver injury incorporates [[Hypoxemia|hypoxic liver injury]] because of [[ischemia]] and [[shock]], [[cholestasis]] because of altered [[Bile acid malabsorption|bile metabolism]], hepatocellular injury because of [[drug toxicity]], or overwhelming [[inflammation]].<ref name="StrnadTacke2016">{{cite journal|last1=Strnad|first1=Pavel|last2=Tacke|first2=Frank|last3=Koch|first3=Alexander|last4=Trautwein|first4=Christian|title=Liver — guardian, modifier and target of sepsis|journal=Nature Reviews Gastroenterology & Hepatology|volume=14|issue=1|year=2016|pages=55–66|issn=1759-5045|doi=10.1038/nrgastro.2016.168}}</ref>
+:*The pathophysiology of sepsis-related liver injury is likely multifactorial and may include [[Hypoxemia|hypoxic liver injury]] due of [[ischemia]] and [[shock]], [[cholestasis]] due to an altered [[Bile acid malabsorption|bile metabolism]], hepatocellular injury due to [[drug toxicity]], or overwhelming [[inflammation]].<ref name="StrnadTacke2016">{{cite journal|last1=Strnad|first1=Pavel|last2=Tacke|first2=Frank|last3=Koch|first3=Alexander|last4=Trautwein|first4=Christian|title=Liver — guardian, modifier and target of sepsis|journal=Nature Reviews Gastroenterology & Hepatology|volume=14|issue=1|year=2016|pages=55–66|issn=1759-5045|doi=10.1038/nrgastro.2016.168}}</ref>
 ===Ischemia-reperfusion-induced Hepatic Injury===
@@ Line 64: / Line 69: @@
 :*[[Ischemia]] and [[Hypoxia (medical)|hypoxia]] as a result of [[COVID-19]] infection can result in [[metabolic acidosis]], [[Calcium|calcium overloading]], and changes in [[Mitochondrial membrane|mitochondrial membrane permeability]]. These factors have impacted [[Hepatic failure|hepatic injury]] manifested as very high [[Transaminase|aminotransferase]] concentrations in serum.<ref name="pmid26125267">{{cite journal| author=Li J, Li RJ, Lv GY, Liu HQ| title=The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. | journal=Eur Rev Med Pharmacol Sci | year= 2015 | volume= 19 | issue= 11 | pages= 2036-47 | pmid=26125267 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26125267  }} </ref>
-To browse the pathophysiology of COVID-19, [[COVID-19 pathophysiology|Click here]].
+To browse the pathophysiology of COVID-19, [[COVID-19 pathophysiology|click here]].
 ==Differentiating COVID-19-associated hepatic injury from other causes of hepatic injury==
-*For further information about the differential diagnosis, [[click here]].
+*For further information about the differential diagnosis, [[COVID-19-associated hepatic injury differential diagnosis|click here]].
-To browse the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|Click here]].
+To browse the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|click here]].
 ==Epidemiology and Demographics==
 * In a cohort of 41 [[COVID-19]] patients, levels of [[Aspartate transaminase|aspartate aminotransferase]] increased by 15 (37%) patients. Among these 15 patients, eight (62%) of 13 [[ICU]] patients and seven (25%) of 28 non-ICU patients.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref>
-* According to a single-center study of 99 [[COVID-19]] patients. A wide range of [[Liver function tests|liver function abnormality]] was observed among 43 patients, with [[Alanine transaminase|alanine aminotransferase]] (ALT) or [[Aspartate transaminase|aspartate aminotransferase]] (AST) above the normal range. A severe [[Liver function tests|liver function abnormality]] was observed in one patient (ALT 7590 U/L, AST 1445 U/L).<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>
+* According to a single-center study of 99 [[COVID-19]] patients, a wide range of [[Liver function tests|liver function abnormality]] was observed among 43 patients, with [[Alanine transaminase|alanine aminotransferase]] (ALT) or [[Aspartate transaminase|aspartate aminotransferase]] (AST) above the normal range. A severe [[Liver function tests|liver function abnormality]] was observed in one patient (ALT 7590 U/L, AST 1445 U/L).<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>
 {| class="wikitable"
@@ Line 177: / Line 182: @@
 |0–2%†
 |}<br />
-In addition, abnormal [[liver function test]] in cases of [[COVID-19]] is often transient and often simultaneously combined with increased enzymes from muscle and heart; these laboratory changes can return to normal without liver-related [[morbidity]] and [[mortality]].
+In addition, abnormal [[liver function test]] in cases of [[COVID-19]] is often transient and often simultaneously combined with increased enzymes from the cardiac muscle; these laboratory changes can return to normal without liver-related [[morbidity]] and [[mortality]].
 ===Gender===
-Although  is very limited data available, the [[incidence]] of liver injury associated with [[COVID-19]] is reported to be higher in males.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
+Although very limited data is available, the [[incidence]] of liver injury associated with [[COVID-19]] is reported to be higher in males.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
-To browse the epidemiology and demographics of COVID-19, [[COVID-19 epidemiology and demographics|Click here]].
+To browse the epidemiology and demographics of COVID-19, [[COVID-19 epidemiology and demographics|click here]].
 ==Risk Factors==
 *Common risk factors in the development of [[COVID-19]] associated hepatic injury [[complications]] include:
 **Critical/ severe [[COVID-19]] infection, especially [[ICU]] admissions.<ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref><ref name="pmid32274341">{{cite journal |vauthors=Li J, Fan JG |title=Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease |journal=J Clin Transl Hepatol |volume=8 |issue=1 |pages=13–17 |date=March 2020 |pmid=32274341 |pmc=7132021 |doi=10.14218/JCTH.2020.00019 |url=}}</ref>
-**Prexisting [[Chronic liver disease]].<ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref> Also patients with decompensated [[liver cirrhosis]] have higher mortality due to [[COVID-19]].<ref name="SuKao2020">{{cite journal|last1=Su|first1=Tung-Hung|last2=Kao|first2=Jia-Horng|title=The clinical manifestations and management of COVID-19-related liver injury|journal=Journal of the Formosan Medical Association|volume=119|issue=6|year=2020|pages=1016–1018|issn=09296646|doi=10.1016/j.jfma.2020.04.020}}</ref>
+**Pre-existing [[Chronic liver disease]].<ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref> Also patients with decompensated [[liver cirrhosis]] have higher mortality due to [[COVID-19]].<ref name="SuKao2020">{{cite journal|last1=Su|first1=Tung-Hung|last2=Kao|first2=Jia-Horng|title=The clinical manifestations and management of COVID-19-related liver injury|journal=Journal of the Formosan Medical Association|volume=119|issue=6|year=2020|pages=1016–1018|issn=09296646|doi=10.1016/j.jfma.2020.04.020}}</ref>
 **Old age<ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref>
 **Severe [[hypoxemia]]<ref name="LiXiao2020">{{cite journal|last1=Li|first1=Yueying|last2=Xiao|first2=Shu‐Yuan|title=Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.25973}}</ref><ref name="pmid32274341">{{cite journal |vauthors=Li J, Fan JG |title=Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease |journal=J Clin Transl Hepatol |volume=8 |issue=1 |pages=13–17 |date=March 2020 |pmid=32274341 |pmc=7132021 |doi=10.14218/JCTH.2020.00019 |url=}}</ref>
@@ Line 198: / Line 203: @@
 *Out of 148 [[COVID-19]] patients, ninety-two (62.2%) patients were released from the hospital as of February 19, 2020, that includes 34 cases with [[Liver function tests|abnormal liver function]] before admission, 24 cases with [[Liver function tests|abnormal liver function]] during hospitalization, and 34 cases with normal [[Liver function tests|liver function]] during the stay in hospital. Of note, we found that baseline abnormal [[liver function]] was associated with a prolonged hospital stay. Whereas, [[Liver function tests|abnormal liver function]] observed during admission had little impact on the length of hospital stay.
 *According to the data available to date, mild liver injury can occur in patients with moderate-severe illness but the incidence of [[Hepatic failure|hepatic dysfunction]] higher among patients with severe or critical [[COVID-19]] illness. <ref name="pmid32145190">{{cite journal |vauthors=Zhang C, Shi L, Wang FS |title=Liver injury in COVID-19: management and challenges |journal=Lancet Gastroenterol Hepatol |volume=5 |issue=5 |pages=428–430 |date=May 2020 |pmid=32145190 |pmc=7129165 |doi=10.1016/S2468-1253(20)30057-1 |url=}}</ref><ref name="pmid32553666">{{cite journal |vauthors=Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M |title=COVID-19 and Liver |journal=J. Hepatol. |volume= |issue= |pages= |date=June 2020 |pmid=32553666 |pmc=7295524 |doi=10.1016/j.jhep.2020.06.006 |url=}}</ref><ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
-* The association of [[acute liver injury]] with higher [[mortality]] has also been reported.<ref name="pmid32553666">{{cite journal |vauthors=Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M |title=COVID-19 and Liver |journal=J. Hepatol. |volume= |issue= |pages= |date=June 2020 |pmid=32553666 |pmc=7295524 |doi=10.1016/j.jhep.2020.06.006 |url=}}</ref> Research is underway and few studies describe the correlation of [[Liver function tests|liver biochemical indicators]] and severity of [[COVID-19]]. The impairment of hepatic function (guaged via [[Liver function tests|biochemical markers of hepatic function]]) may become a predictor of the exacerbation and deterioration in patients with [[COVID-19|COVID‐19]].<ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
+* The association of [[acute liver injury]] with higher [[mortality]] has been reported.<ref name="pmid32553666">{{cite journal |vauthors=Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M |title=COVID-19 and Liver |journal=J. Hepatol. |volume= |issue= |pages= |date=June 2020 |pmid=32553666 |pmc=7295524 |doi=10.1016/j.jhep.2020.06.006 |url=}}</ref> Research is underway and few studies describe the correlation of [[Liver function tests|liver biochemical indicators]] and severity of [[COVID-19]]. The impairment of hepatic function (guaged via [[Liver function tests|biochemical markers of hepatic function]]) may become a predictor of the exacerbation and deterioration in patients with [[COVID-19|COVID‐19]].<ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
-To browse the natural history, complications, and prognosis of COVID-19, [[COVID-19 natural history, complications and prognosis|Click here]].
+To browse the natural history, complications, and prognosis of COVID-19, [[COVID-19 natural history, complications and prognosis|click here]].
 == Diagnosis ==
 ===Diagnostic Study of Choice===
-*The diagnosis of [[COVID-19]]-associated hepatic injury is based on the abnormal [[Liver function tests|liver biochemical]] and function tests. The key lies in suspecting liver damage in a [[COVID-19|SARS-CoV2]] patient and testing [[Liver function tests|liver biochemical]] and function tests such as [[LDH]], [[albumin]], [[ALT]], [[AST]], [[Bilirubin#Bilirubin blood tests|total bilirubin]], and [[INR]]. A [[COVID-19]] patient with [[acute liver failure]] should be investigated and effort has to be made to find the cause liver injury.
+*The diagnosis of [[COVID-19]]-associated hepatic injury is based on the abnormal [[Liver function tests|liver biochemical]] and function tests. The key lies in suspecting liver damage among [[COVID-19]] patients and testing [[Liver function tests|liver biochemical]] and function tests such as [[LDH]], [[albumin]], [[ALT]], [[AST]], [[Bilirubin#Bilirubin blood tests|total bilirubin]], and [[INR]]. A [[COVID-19]] patient with [[acute liver failure]] should be investigated and effort has to be made to find the cause liver injury.
 ===History and Symptoms===
-*The majority of patients (14.5%) with [[COVID-19]] associated hepatic injury have a [[fever]], which may be related to the [[immune response]] after viral infection.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
+*The majority of patients (14.5%) with [[COVID-19]] associated hepatic injury have a [[fever]], which may be related to the [[immune response]] following viral infection.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
-*Other [[COVID-19]] associated symptoms reported in patients with [[COVID-19]] include:<ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref><ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref>
+*The symptoms mentioned below may be due to [[hepatic injury]] itself, or commonly associated abdominal sequels. In order of prevalence, other [[COVID-19]] associated symptoms reported among patients with [[COVID-19]] include:<ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref><ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref>
-**[[Cough]] (dry or productive)
+**[[COVID-19-associated diarrhea|Diarrhea]], [[COVID-19-associated nausea and vomiting|nausea and vomiting]], [[COVID-19-associated abdominal pain|abdominal pain]], [[COVID-19-associated anorexia|anorexia]] (Loss of appetite), and [[pruritis]] (due to bilirubin accumulation).
-**[[COVID-19-associated diarrhea|Diarrhea]]
+*The involvement of the respiratory system by [[COVID-19]] manifests as the following symptoms:
-**[[COVID-19-associated nausea and vomiting|Nausea and vomiting]]
+**[[Cough]] (dry or productive), [[pharyngitis]], [[COVID-19-associated anosmia|anosmia]] (partial or complete loss of smell), and [[ageusia]] (Loss of smell).
-**[[Pharyngitis]]
+*In general due to [[infection]]:
-**[[COVID-19-associated abdominal pain|Abdominal pain]]
+**[[Fatigue]], [[chills]], [[skin rash]]
-**[[COVID-19-associated anosmia|Anosmia]] (partial or complete loss of smell)
-**[[COVID-19-associated anorexia|Anorexia]] (Loss of appetite)
-**[[Ageusia]] (Loss of smell)
-**[[Fatigue]]
-**[[Pruritis]]
-**[[Chills]]
-**[[Skin rash]]
 *The patient history and symptom associated with [[COVID-19]] can be viewed by [[COVID-19 physical examination|clicking here]].
 ===Physical Examination===
-*Patients with [[COVID-19]] associated hepatic injury may appear [[lethargic]] or [[confusion|confused]] due to [[hepatic encephalopathy]]. [[Jaundice physical examination|Jaundice]], [[rash]] and [[bruises]] (signs of liver's deranged synthetic function) are more common in patients with [[chronic liver disease]].<ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref>
+*Patients with [[COVID-19]] associated hepatic injury may appear [[lethargic]] or [[confusion|confused]] due to [[hepatic encephalopathy]]. [[Jaundice physical examination|Jaundice]], [[rash]] and [[bruises]] (signs of liver's deranged synthetic function) are more common among patients with [[chronic liver disease]].<ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref> [[Jaundice physical examination|Jaundice]] is reported among the cases of drug-induced liver injury. This may include drugs used for the treatment of [[COVID-19]] itself such as [[Interferon type I|interferon beta]] , [[lopinavir]], [[ritonavir]] and [[imatinib]].<ref name="pmid32514859">{{cite journal |vauthors=Olry A, Meunier L, Délire B, Larrey D, Horsmans Y, Le Louët H |title=Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same |journal=Drug Saf |volume=43 |issue=7 |pages=615–617 |date=July 2020 |pmid=32514859 |pmc=7279629 |doi=10.1007/s40264-020-00954-z |url=}}</ref><ref name="AndradeAithal2019">{{cite journal|last1=Andrade|first1=Raúl J.|last2=Aithal|first2=Guruprasad P.|last3=Björnsson|first3=Einar S.|last4=Kaplowitz|first4=Neil|last5=Kullak-Ublick|first5=Gerd A.|last6=Larrey|first6=Dominique|last7=Karlsen|first7=Tom H.|title=EASL Clinical Practice Guidelines: Drug-induced liver injury|journal=Journal of Hepatology|volume=70|issue=6|year=2019|pages=1222–1261|issn=01688278|doi=10.1016/j.jhep.2019.02.014}}</ref>
 *[[Vital signs]]:<ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref>
-**The most common physical examination finding reported in patients with [[COVID-19]] associated hepatic injury includes [[fever]] (normal temperature is not uncommon).<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
+**The most common physical examination finding reported among patients with [[COVID-19]] associated hepatic injury includes [[fever]] (however, normal temperature is not uncommon).<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
 **[[Tachycardia]]
-**[[Hypotension]] is common in patients with [[chronic liver disease]]
+**[[Hypotension]] is common among patients with [[chronic liver disease]]
 **[[Tachypnea]] maybe due to fever, respiratory involvement due to [[COVID-19]] infection or massive [[ascites]].
-*On [[Abdominal exam]]:<ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref><ref name="LiFan2020">{{cite journal|last1=Li|first1=Jie|last2=Fan|first2=Jian-Gao|title=Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease|journal=Journal of Clinical and Translational Hepatology|volume=8|issue=1|year=2020|pages=1–5|issn=2225-0719|doi=10.14218/JCTH.2020.00019}}</ref><ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref>
+*On [[Abdominal exam]]:<ref name="pmid32514859">{{cite journal |vauthors=Olry A, Meunier L, Délire B, Larrey D, Horsmans Y, Le Louët H |title=Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same |journal=Drug Saf |volume=43 |issue=7 |pages=615–617 |date=July 2020 |pmid=32514859 |pmc=7279629 |doi=10.1007/s40264-020-00954-z |url=}}</ref><ref name="pmid32289115">{{cite journal |vauthors=Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T |title=Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper |journal=JHEP Rep |volume=2 |issue=3 |pages=100113 |date=June 2020 |pmid=32289115 |pmc=7128473 |doi=10.1016/j.jhepr.2020.100113 |url=}}</ref><ref name="LiFan2020">{{cite journal|last1=Li|first1=Jie|last2=Fan|first2=Jian-Gao|title=Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease|journal=Journal of Clinical and Translational Hepatology|volume=8|issue=1|year=2020|pages=1–5|issn=2225-0719|doi=10.14218/JCTH.2020.00019}}</ref>
 **Inspection: [[Jaundice]], [[Ascites]], [[abdominal distension]] or [[bulging flanks]].
 **Auscultation: Accompanying [[gastrointestinal]] infection may present as [[Increased bowel sounds]] due to [[enteritis]].
-**Palpation: Tenderness on superficial palpation. The presence of [[hepatomegaly]] on deep [[palpation]] in patients with COVID-19-associated hepatic injury is a forethought of [[organomegaly]].
+**Palpation: Tenderness on superficial palpation. The presence of [[hepatomegaly]] on deep [[palpation]] among patients with COVID-19-associated hepatic injury is a forethought of [[organomegaly]].
 **Percussion: [[Shifting dullness]]
 * The physical exam findings associated with [[COVID-19]] can be viewed by [[COVID-19 history and symptoms|clicking here]].
 ===Laboratory Findings===
-*Laboratory findings consistent with the diagnosis of [[COVID-19]]-associated hepatic injury include abnormal [[Liver function tests]] specially raised [[AST]].<ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref>
+*Laboratory findings consistent with the diagnosis of [[COVID-19]]-associated hepatic injury include abnormal [[Liver function tests]], especially raised [[AST]].<ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref> The arrangement is based upon the commonality of the presentation of the mentioned lab abnormality. [[CBC]] findings can vary depending on the [[infection]] status.
-*''[[ALT]] and [[AST]]'': The level of both enzymes is elevated in the blood of patients (reported in one-third of patients in a few studies) with liver injury on admission. [[AST]] elevation is more common than [[ALT]], reflecting a possible source outside of liver. The enzyme levels may rise above three times the normal level. [[ICU]] patients have higher levels of [[ALT]] and [[AST]] and reduced levels of [[serum albumin]] indicating severe liver damage affecting the liver's synthetic ability.<ref name="pmid32298767">{{cite journal |vauthors=Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y, Liu Y, He Q, Chen J, Liu L, Xu L |title=COVID-19: Abnormal liver function tests |journal=J. Hepatol. |volume= |issue= |pages= |date=April 2020 |pmid=32298767 |pmc=7194951 |doi=10.1016/j.jhep.2020.04.006 |url=}}</ref><ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref>
+*'''[[ALT]] and [[AST]]''': The level of both enzymes is elevated in the blood of patients (reported among one-third of patients in a few studies) with liver injury on admission. [[AST]] elevation is more common than [[ALT]], reflecting a possible source outside of liver. The enzyme levels may rise above three times the normal level. [[ICU]] patients have higher levels of [[ALT]] and [[AST]] and reduced levels of [[serum albumin]] indicating severe liver damage affecting the liver's synthetic ability.<ref name="pmid32298767">{{cite journal |vauthors=Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y, Liu Y, He Q, Chen J, Liu L, Xu L |title=COVID-19: Abnormal liver function tests |journal=J. Hepatol. |volume= |issue= |pages= |date=April 2020 |pmid=32298767 |pmc=7194951 |doi=10.1016/j.jhep.2020.04.006 |url=}}</ref><ref name="AlqahtaniSchattenberg2020">{{cite journal|last1=Alqahtani|first1=Saleh A|last2=Schattenberg|first2=Jörn M|title=Liver injury in COVID-19:  The current evidence|journal=United European Gastroenterology Journal|volume=8|issue=5|year=2020|pages=509–519|issn=2050-6406|doi=10.1177/2050640620924157}}</ref> The AST/ALT ratio has been found to be 1.64 in a retrospective study.<ref name="pmid32669866">{{cite journal |vauthors=Gholizadeh P, Safari R, Marofi P, Zeinalzadeh E, Pagliano P, Ganbarov K, Esposito S, Khodadadi E, Yousefi M, Samadi Kafil H |title=Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19) |journal=J Inflamm Res |volume=13 |issue= |pages=285–292 |date=2020 |pmid=32669866 |pmc=7335895 |doi=10.2147/JIR.S257078 |url=}}</ref>
-*''[[LDH]]'': Following [[AST]] and [[ALT]], [[LDH]]] rise has the highest [[incidence]]. Some studies suggest that LDH can be used as an early alarm to prompt further analysis for [[COVID-19]] but the data is insufficient to be conclusive.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
+*'''[[LDH]]''': Following [[AST]] and [[ALT]], [[LDH]] rise has the highest [[incidence]]. Some studies suggest that [[LDH]] can be used as an early alarm to prompt further analysis for [[COVID-19]] but the data is insufficient to be conclusive.<ref name="pmid32669866">{{cite journal |vauthors=Gholizadeh P, Safari R, Marofi P, Zeinalzadeh E, Pagliano P, Ganbarov K, Esposito S, Khodadadi E, Yousefi M, Samadi Kafil H |title=Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19) |journal=J Inflamm Res |volume=13 |issue= |pages=285–292 |date=2020 |pmid=32669866 |pmc=7335895 |doi=10.2147/JIR.S257078 |url=}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
-*''[[Alkaline phosphatase]] (ALP)'': The levels are raised.<ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref>
+*'''[[Alkaline phosphatase]]''' (ALP): The test is a good marker of [[cholestasis]]. The levels are raised.<ref name="pmid32366282">{{cite journal |vauthors=Cardoso FS, Pereira R, Germano N |title=Liver injury in critically ill patients with COVID-19: a case series |journal=Crit Care |volume=24 |issue=1 |pages=190 |date=May 2020 |pmid=32366282 |pmc=7198236 |doi=10.1186/s13054-020-02924-4 |url=}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref>
-*''[[Serum albumin]]'': The levels are found to decrease during the course of hospitalization. The tests are a measure of the synthetic function of the liver.
+*'''[[Serum albumin]]''': The test measures the synthetic function of the liver. The levels are found to decrease during the course of hospitalization. Marked [[hypoalbuminemia]] among critically-ill patients makes it a maker of poor [[prognosis]] of [[COVID-19]] (retrospective study).<ref name="HuangLi2020">{{cite journal|last1=Huang|first1=Wei|last2=Li|first2=Chenze|last3=Wang|first3=Zhiquan|last4=Wang|first4=Hong|last5=Zhou|first5=Ning|last6=Jiang|first6=Jiangang|last7=Ni|first7=Li|last8=Zhang|first8=Xin A.|last9=Wang|first9=Dao-Wen|title=Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases|journal=Science China Life Sciences|year=2020|issn=1674-7305|doi=10.1007/s11427-020-1733-4}}</ref>
-*''Total [[bilirubin]] and [[direct bilirubin]]'': The data from limited studies show a higher incidence of [[hyperbilirubinemia]] in patients who required aggressive management during the course of their disease or died.<ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
+*'''Total [[bilirubin]] and [[direct bilirubin]]''': The data from limited studies show a higher incidence of [[hyperbilirubinemia]] among patients who required aggressive management during the course of their disease and patients that died.<ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
-*''[[C-reactive protein]] (CRP), [[ESR]] and specially [[procalcitonin]]'' levels are found to be higher in patients and can give a fair idea of [[infection]].<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
+*'''[[C-reactive protein]], [[ESR]] and [[Procalcitonin]]''' (CRP): 80% rise has been reported in a study.<ref name="pmid32669866">{{cite journal |vauthors=Gholizadeh P, Safari R, Marofi P, Zeinalzadeh E, Pagliano P, Ganbarov K, Esposito S, Khodadadi E, Yousefi M, Samadi Kafil H |title=Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19) |journal=J Inflamm Res |volume=13 |issue= |pages=285–292 |date=2020 |pmid=32669866 |pmc=7335895 |doi=10.2147/JIR.S257078 |url=}}</ref>, [[ESR]] and especially [[procalcitonin]] levels are found to be higher among patients and can indicate [[infection]].<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref><ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
-* ''Glycoprotein [[gamma-glutamyltransferase]] (GGT)'': A rise in the level of GGT points towards [[cholestasis]] and thus [[Biliary|hepatobiliary]] involvement.
+* '''Glycoprotein [[gamma-glutamyltransferase]]''' (GGT): A rise in the level of GGT points towards [[cholestasis]] and thus [[Biliary|hepatobiliary]] involvement. Three-fold rise from the upper normal limit has been reported among [[patients]] in [[ICU]] with [[COVID-19]] associated hepatic injury.<ref name="pmid32366282">{{cite journal |vauthors=Cardoso FS, Pereira R, Germano N |title=Liver injury in critically ill patients with COVID-19: a case series |journal=Crit Care |volume=24 |issue=1 |pages=190 |date=May 2020 |pmid=32366282 |pmc=7198236 |doi=10.1186/s13054-020-02924-4 |url=}}</ref>
-*''[[PTA]] (INR)'': It provides a good estimate of liver synthetic function.
+*'''[[PT]]/[[APTT]]''': Provides a good estimate of liver synthetic function. Prolonged [[APTT]] was found among critically-ill patients in a retrospective study. It reflects [[coagulopathy]].<ref name="HuangLi2020">{{cite journal|last1=Huang|first1=Wei|last2=Li|first2=Chenze|last3=Wang|first3=Zhiquan|last4=Wang|first4=Hong|last5=Zhou|first5=Ning|last6=Jiang|first6=Jiangang|last7=Ni|first7=Li|last8=Zhang|first8=Xin A.|last9=Wang|first9=Dao-Wen|title=Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases|journal=Science China Life Sciences|year=2020|issn=1674-7305|doi=10.1007/s11427-020-1733-4}}</ref>
-*''[[Interleukins]]'': Levels of [[Interleukin|IL]]‐2‐receptor (IL‐2R), IL‐4, IL‐6, IL‐18, IL‐10, [[Tumour necrosis factor|TNF‐α]] are significantly increased. Specially IL‐6 in the serum of [[COVID‐19]] patients are significantly increased and correlates with disease severity.<ref name="AliHossain2020">{{cite journal|last1=Ali|first1=Nurshad|last2=Hossain|first2=Khaled|title=Liver injury in severe COVID-19 infection: current insights and challenges|journal=Expert Review of Gastroenterology & Hepatology|year=2020|issn=1747-4124|doi=10.1080/17474124.2020.1794812}}</ref>
+*'''[[Cholesterol|Serum cholesterol]]''': Serum [[LDL]] and [[HDL]] have been found to be remarkably low among critically-ill patients with [[COVID-19]].<ref name="HuangLi2020">{{cite journal|last1=Huang|first1=Wei|last2=Li|first2=Chenze|last3=Wang|first3=Zhiquan|last4=Wang|first4=Hong|last5=Zhou|first5=Ning|last6=Jiang|first6=Jiangang|last7=Ni|first7=Li|last8=Zhang|first8=Xin A.|last9=Wang|first9=Dao-Wen|title=Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases|journal=Science China Life Sciences|year=2020|issn=1674-7305|doi=10.1007/s11427-020-1733-4}}</ref>
+*'''[[Interleukins]]''': Levels of [[Interleukin|IL]]‐2‐receptor (IL‐2R), IL‐4, IL‐6, IL‐18, IL‐10, [[Tumour necrosis factor|TNF‐α]] are significantly increased. In particular, IL‐6 in the serum of [[COVID‐19]] patients are significantly increased and correlates with disease severity.<ref name="AliHossain2020">{{cite journal|last1=Ali|first1=Nurshad|last2=Hossain|first2=Khaled|title=Liver injury in severe COVID-19 infection: current insights and challenges|journal=Expert Review of Gastroenterology & Hepatology|year=2020|issn=1747-4124|doi=10.1080/17474124.2020.1794812}}</ref>
+*'''[[CBC]]''': [[Leukocytosis]] indicates infection and [[lymphocytosis]] indicating possible viral infection.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
+*'''[[Serum electrolytes]]''': Retrospective studies from Italy and China demonstrated an assocition between [[hypokalemia]], [[hypomagnesemia]] and [[COVID-19]] due to degradation of [[angiotensin-converting enzyme|ACE 2]] loss, [[diuretic]] and [[corticosteroid]] use. [[Hypokalemia]] may lead to life-threatening [[arrhythmias]]. Close monitoring of serum electrolyte levels is essential especially in [[ICU]] patients.<ref name="pmid32525548">{{cite journal |vauthors=Chen D, Li X, Song Q, Hu C, Su F, Dai J, Ye Y, Huang J, Zhang X |title=Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China |journal=JAMA Netw Open |volume=3 |issue=6 |pages=e2011122 |date=June 2020 |pmid=32525548 |pmc=7290402 |doi=10.1001/jamanetworkopen.2020.11122 |url=}}</ref><ref name="AlfanoFerrari2020">{{cite journal|last1=Alfano|first1=Gaetano|last2=Ferrari|first2=Annachiara|last3=Fontana|first3=Francesco|last4=Perrone|first4=Rossella|last5=Mori|first5=Giacomo|last6=Ascione|first6=Elisabetta|last7=Riccardo|first7=Magistroni|last8=Venturi|first8=Giulia|last9=Pederzoli|first9=Simone|last10=Margiotta|first10=Gianluca|last11=Romeo|first11=Marilina|last12=Piccinini|first12=Francesca|last13=Franceschi|first13=Giacomo|last14=Volpi|first14=Sara|last15=Faltoni|first15=Matteo|last16=Ciusa|first16=Giacomo|last17=Bacca|first17=Erica|last18=Tutone|first18=Marco|last19=Raimondi|first19=Alessandro|last20=menozzi|first20=marianna|last21=Franceschini|first21=Erica|last22=Cuomo|first22=Gianluca|last23=Orlando|first23=Gabriella|last24=Santoro|first24=Antonella|last25=Di Gaetano|first25=Margherita|last26=Puzzolante|first26=Cinzia|last27=Carli|first27=Federica|last28=Bedini|first28=Andrea|last29=Milic|first29=Jovana|last30=Meschiari|first30=Marianna|last31=Mussini|first31=Cristina|last32=Cappelli|first32=Gianni|last33=Guaraldi|first33=Giovanni|year=2020|doi=10.1101/2020.06.14.20131169}}</ref>
 *Abnormal [[Liver function tests|liver biochemistries]] are uncommon in children.<ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref>
-*''[[CBC]]'': [[Leukocytosis]] indicates infection and [[lymphocytosis]] indicating possible viral infection.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
 ===Electrocardiogram===
@@ Line 258: / Line 258: @@
 ===X-ray===
 *There are no x-ray findings associated with [[COVID-19]]-associated hepatic injury.
-*However, an x-ray may be helpful in the diagnosis of complications of [[COVID-19]] such as [[COVID-19-associated pneumonia]] which is the most common finding associated with [[COVID-19]] infection.
+*However, an x-ray may be helpful in the diagnosis of complications of [[COVID-19]] such as [[COVID-19-associated pneumonia]], which is the most common finding associated with [[COVID-19]] infection.
-*The x-ray finidings on [[COVID-19]] can be viewed by [[COVID-19 x ray|clicking here]].
+*The x-ray findings on [[COVID-19]] can be viewed by [[COVID-19 x ray|clicking here]].
 ===Echocardiography or Ultrasound===
@@ Line 268: / Line 268: @@
 ===CT scan===
 *Portal venous gas on abdominal CT has been reported.<ref name="BhayanaSom2020">{{cite journal|last1=Bhayana|first1=Rajesh|last2=Som|first2=Avik|last3=Li|first3=Matthew D|last4=Carey|first4=Denston E|last5=Anderson|first5=Mark A|last6=Blake|first6=Michael A|last7=Catalano|first7=Onofrio|last8=Gee|first8=Michael S|last9=Hahn|first9=Peter F|last10=Harisinghani|first10=Mukesh|last11=Kilcoyne|first11=Aoife|last12=Lee|first12=Susanna I|last13=Mojtahed|first13=Amirkasra|last14=Pandharipande|first14=Pari V|last15=Pierce|first15=Theodore T|last16=Rosman|first16=David A|last17=Saini|first17=Sanjay|last18=Samir|first18=Anthony E|last19=Simeone|first19=Joseph F|last20=Gervais|first20=Debra A|last21=Velmahos|first21=George|last22=Misdraji|first22=Joseph|last23=Kambadakone|first23=Avinash|title=Abdominal Imaging Findings in COVID-19: Preliminary                     Observations|journal=Radiology|year=2020|pages=201908|issn=0033-8419|doi=10.1148/radiol.2020201908}}</ref>
-*'''Fig 2''': A non-peer-reviewed retrospective cohort study mentions upper abdominal CT findings in 115 [[COVID-19]] patients in China. The study reports homogeneous or heterogeneous hepatic hypodensity as the most common CT finding (26% patients) and pericholecystic fat stranding (21.3% cases). The study claims the correlation betwen CT signs and disease severity grading.<ref name="LeiZhang2020">{{cite journal|last1=Lei|first1=Ping|last2=Zhang|first2=Lan|last3=Han|first3=Ping|last4=Zheng|first4=Chuansheng|last5=Tong|first5=Qiaoxia|last6=Shang|first6=Haitao|last7=Yang|first7=Fan|last8=Hu|first8=Yu|last9=Li|first9=Xin|last10=Song|first10=Yuhu|year=2020|doi=10.21203/rs.3.rs-28692/v1}}</ref>
+*'''Fig 2''': A non-peer-reviewed retrospective cohort study mentions upper abdominal CT findings in 115 [[COVID-19]] patients in China. The study reports homogeneous or heterogeneous hepatic hypodensity as the most common CT finding (26% patients) and pericholecystic fat stranding (21.3% cases). The study claims the correlation between CT signs and disease severity grading.<ref name="LeiZhang2020">{{cite journal|last1=Lei|first1=Ping|last2=Zhang|first2=Lan|last3=Han|first3=Ping|last4=Zheng|first4=Chuansheng|last5=Tong|first5=Qiaoxia|last6=Shang|first6=Haitao|last7=Yang|first7=Fan|last8=Hu|first8=Yu|last9=Li|first9=Xin|last10=Song|first10=Yuhu|year=2020|doi=10.21203/rs.3.rs-28692/v1}}</ref>
-*Chest CT scan is helpful in suggesting lung involvement in the [[COVID-19]] which is a multi-organ [[disease]].
+*Chest CT scan is helpful in suggesting lung involvement in patients with [[COVID-19]] which is a multi-organ [[disease]].
 *The CT scan findings in [[COVID-19]] can be viewed by [[COVID-19 CT scan|clicking here]].[[Image:Ping Le et al.Hypodence liver COVID-19.jpg|thumb|center|600x600px| '''Fig 2''' Transverse upper abdomen non-contrast CT scan film showing: <br>A and B: [[Pulmonary consolidation|Lung consolidation]] with air bronchograms, [[Ground glass opacification on CT|ground-glass opacity]], interlobular septal thickening, [[Crazy paving sign]], and [[pleura effusion]] are visible in both lungs <br> C: Liver hypodensity<br> D: Pericholecystic fat stranding marked by yellow arrows - <ref name="LeiZhang2020">{{cite journal|last1=Lei|first1=Ping|last2=Zhang|first2=Lan|last3=Han|first3=Ping|last4=Zheng|first4=Chuansheng|last5=Tong|first5=Qiaoxia|last6=Shang|first6=Haitao|last7=Yang|first7=Fan|last8=Hu|first8=Yu|last9=Li|first9=Xin|last10=Song|first10=Yuhu|year=2020|doi=10.21203/rs.3.rs-28692/v1}}</ref>]]
@@ Line 285: / Line 285: @@
 === Medical Therapy ===
-Currently there is no specific [[treatment]] for patient with [[COVID-19]] associated liver injury. The mainstay of medical therapy is to target the viral infection using antivirals such as [[Remdesivir|remdesivir]], [[lopinavir]]/[[ritonavir]] and [[darunavir]]/[[cobicistat]], control and prevent [[inflammation]] and symptomatic treatment. The recommended medical therapy is based upon expert opinion rather than randomized control trials is as follows: <ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref><ref name="BecchettiZambelli2020">{{cite journal|last1=Becchetti|first1=Chiara|last2=Zambelli|first2=Marco Fabrizio|last3=Pasulo|first3=Luisa|last4=Donato|first4=Maria Francesca|last5=Invernizzi|first5=Federica|last6=Detry|first6=Olivier|last7=Dahlqvist|first7=Géraldine|last8=Ciccarelli|first8=Olga|last9=Morelli|first9=Maria Cristina|last10=Fraga|first10=Montserrat|last11=Svegliati-Baroni|first11=Gianluca|last12=van Vlierberghe|first12=Hans|last13=Coenraad|first13=Minneke J|last14=Romero|first14=Mario Cristobal|last15=de Gottardi|first15=Andrea|last16=Toniutto|first16=Pierluigi|last17=Del Prete|first17=Luca|last18=Abbati|first18=Claudia|last19=Samuel|first19=Didier|last20=Pirenne|first20=Jacques|last21=Nevens|first21=Frederik|last22=Dufour|first22=Jean-François|title=COVID-19 in an international European liver transplant recipient cohort|journal=Gut|year=2020|pages=gutjnl-2020-321923|issn=0017-5749|doi=10.1136/gutjnl-2020-321923}}</ref><ref name="pmid32476793">{{cite journal |vauthors=Wu J, Song S, Cao HC, Li LJ |title=Liver diseases in COVID-19: Etiology, treatment and prognosis |journal=World J. Gastroenterol. |volume=26 |issue=19 |pages=2286–2293 |date=May 2020 |pmid=32476793 |pmc=7243650 |doi=10.3748/wjg.v26.i19.2286 |url=}}</ref>
+Currently there is no specific [[treatment]] for patients with [[COVID-19]] associated liver injury. The mainstay of medical therapy is to target the viral infection using antivirals such as [[Remdesivir|remdesivir]], [[lopinavir]]/[[ritonavir]] and [[darunavir]]/[[cobicistat]], control and prevent [[inflammation]] and symptomatic treatment. The recommended medical therapy is based upon expert opinion rather than randomized control trials and is as follows: <ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref><ref name="BecchettiZambelli2020">{{cite journal|last1=Becchetti|first1=Chiara|last2=Zambelli|first2=Marco Fabrizio|last3=Pasulo|first3=Luisa|last4=Donato|first4=Maria Francesca|last5=Invernizzi|first5=Federica|last6=Detry|first6=Olivier|last7=Dahlqvist|first7=Géraldine|last8=Ciccarelli|first8=Olga|last9=Morelli|first9=Maria Cristina|last10=Fraga|first10=Montserrat|last11=Svegliati-Baroni|first11=Gianluca|last12=van Vlierberghe|first12=Hans|last13=Coenraad|first13=Minneke J|last14=Romero|first14=Mario Cristobal|last15=de Gottardi|first15=Andrea|last16=Toniutto|first16=Pierluigi|last17=Del Prete|first17=Luca|last18=Abbati|first18=Claudia|last19=Samuel|first19=Didier|last20=Pirenne|first20=Jacques|last21=Nevens|first21=Frederik|last22=Dufour|first22=Jean-François|title=COVID-19 in an international European liver transplant recipient cohort|journal=Gut|year=2020|pages=gutjnl-2020-321923|issn=0017-5749|doi=10.1136/gutjnl-2020-321923}}</ref><ref name="pmid32476793">{{cite journal |vauthors=Wu J, Song S, Cao HC, Li LJ |title=Liver diseases in COVID-19: Etiology, treatment and prognosis |journal=World J. Gastroenterol. |volume=26 |issue=19 |pages=2286–2293 |date=May 2020 |pmid=32476793 |pmc=7243650 |doi=10.3748/wjg.v26.i19.2286 |url=}}</ref>
 <br>
 ====Mild hepatic injury====
-In a [[SARS-Cov2]] patient with ''mild'' hepatic biochemical abnormalities, the mainstay of treatment is actively managing the primary infection. The use of hepatoprotective and [[enzyme]]‐lowering therapy is not recommended but supportive as well as specific antiviral therapy has to be given to halt [[viral replication]] and to reduce [[inflammation]].
+In a [[COVID-19]] patient with ''mild'' hepatic biochemical abnormalities, the mainstay of treatment is actively managing the primary infection. The administration of hepatoprotective and [[enzyme]]‐lowering therapy is not recommended but supportive as well as specific antiviral therapy to halt [[viral replication]] and to reduce [[inflammation]].
 ====Severe hepatic injury====
-In patients with ''severe'' [[COVID-19]] infection and liver injury, hyperinflammatory responses such as [[Cytokine storm|cytokine storms]] and tissue [[ischemia]] are usual causal factors. Treatment should focus on maintaining optimal blood [[oxygen saturation]]. This can be achieved either by [[oxygen therapy]] or the use of [[extracorporeal membrane oxygenation]]. The patient should be monitored closely with ongoing supportive and symptomatic treatment and correction of [[hypoproteinemia]] if required. The Chinese Pharmaceutical Association recommends the use of jaundice-reducing, hepatoprotective and anti-inflammatory agents such as [[phosphatidylcholine]], [[glycyrrhizin]], bicyclol, and [[Tocopherol|vitamin E]]. Maximum of one to two hepatoprotective or anti-viral drugs should be used to minimize drug interactions and possible liver damage.<ref name="pmid32266987">{{cite journal |vauthors=Zha L, Li S, Pan L, Tefsen B, Li Y, French N, Chen L, Yang G, Villanueva EV |title=Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19) |journal=Med. J. Aust. |volume=212 |issue=9 |pages=416–420 |date=May 2020 |pmid=32266987 |pmc=7262211 |doi=10.5694/mja2.50577 |url=}}</ref>
+In patients with ''severe'' [[COVID-19]] infection and liver injury, hyperinflammatory responses such as [[Cytokine storm|cytokine storms]] and tissue [[ischemia]] are usual causal factors. Treatment should focus on maintaining optimal blood [[oxygen saturation]]. This can be achieved either by [[oxygen therapy]] or administering [[extracorporeal membrane oxygenation]]. The patient should be monitored closely with ongoing supportive and symptomatic treatment and correction of [[hypoproteinemia]] if required. The Chinese Pharmaceutical Association recommends administering jaundice-reducing, hepatoprotective and anti-inflammatory agents such as [[phosphatidylcholine]], [[glycyrrhizin]], bicyclol, and [[Tocopherol|vitamin E]]. Maximum of one to two hepatoprotective or anti-viral drugs should be adminstered to minimize drug interactions and possible liver damage.<ref name="pmid32266987">{{cite journal |vauthors=Zha L, Li S, Pan L, Tefsen B, Li Y, French N, Chen L, Yang G, Villanueva EV |title=Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19) |journal=Med. J. Aust. |volume=212 |issue=9 |pages=416–420 |date=May 2020 |pmid=32266987 |pmc=7262211 |doi=10.5694/mja2.50577 |url=}}</ref>
 ====[[Acute liver failure]]====
 In the case of [[acute liver failure]] in a [[COVID-19]] patient, after the cause of liver failure has been established, hepatoprotective and [[enzyme]]‐lowering drugs are administered. It is important to choose lower doses and fewer types of drugs (not more than 2, in general) with known [[mechanism of action]] and composition as the hepatic [[drug metabolism]] may pose a potential risk of harming the organ. The patient should be closely monitored with frequent [[Liver function tests|hepatic biochemical tests]] such as ([[AST]], [[ALT]], [[albumin]], [[total bilirubin]] and [[INR]]). [[acute liver failure|Acute liver injury]] should be managed with close monitoring, supportive and symptomatic treatment, and correction of [[hypoproteinemia]].
 ====[[Drug induced liver injury]]====
-It is important to assess the degree of liver damage and identify the drug responsible and then adjust the treatment accordingly. If possible completely stop the drug, reduce the amount, or use an alternative drug. Anti‐inflammatory and hepatoprotective treatment should be provided.
+It is important to assess the degree of liver damage and identify the drug responsible and then adjust the treatment accordingly. If possible completely stop the drug, reduce the amount, or administering an alternative drug. Anti‐inflammatory and hepatoprotective treatment should be provided.
 ====Underlying [[chronic liver disease]]====
-Target the [[SARS CoV2|coronavirus]] infection and maintain the [[Chronic liver disease medical therapy|original therapy for chronic liver diseases]].The American Association for the Study of Liver Diseases (AASLD) does not recommend to discontinue [[Hepatitis B]] and [[Hepatitis C]] antiviral treatments but recommends that large doses of [[hormones]] are not to be used simultaneously. However, direct-acting antiviral therapy initiation for [[Hepatitis C]] [[patients]] may be delayed.
+Target the [[SARS CoV2|coronavirus]] infection and maintain the [[Chronic liver disease medical therapy|original therapy for chronic liver diseases]].The American Association for the Study of Liver Diseases (AASLD) does not recommend to discontinue [[Hepatitis B]] and [[Hepatitis C]] antiviral treatments but recommends that large doses of [[hormones]] are not to be administered simultaneously. However, direct-acting antiviral therapy initiation for [[Hepatitis C]] [[patients]] may be delayed.
 ====[[Liver transplantation|Liver transplant]] patients====
-Specific [[COVID-19]] therapy used in patients includes [[steroids]] (the study does not specify the type), [[hydroxychloroquine]], [[antiviral]]s (such as [[lopinavir]]/[[ritonavir]], [[darunavir]]/[[cobicistat]], and [[Remdesivir|remdesivir]]). Some patients were administered [[antibiotic]]s such as [[azithromycin]] and immunomodulatory therapies such as [[rituximab]] and [[tocilizumab]]. [[Immunosuppression]] has been reduced in most patients and discontinued in some. It is also advised at some places to keep the [[immunosuppression]] to the minimal possible dosage.
+Specific [[COVID-19]] therapy administered in patients includes [[steroids]] (the study does not specify the type), [[hydroxychloroquine]], [[antiviral]]s (such as [[lopinavir]]/[[ritonavir]], [[darunavir]]/[[cobicistat]], and [[Remdesivir|remdesivir]]). Some patients were administered [[antibiotic]]s such as [[azithromycin]] and immunomodulatory therapies such as [[rituximab]] and [[tocilizumab]]. [[Immunosuppression]] has been reduced in the majority of patients and discontinued in some. It is also advised at some places to keep the [[immunosuppression]] to the minimal possible dosage.
 ====Monitoring====
-[[Liver function tests]] can serve as indicators of disease progression. [[Treatment]] and prevention of [[inflammation]] in the early stages of the disease prevent severe [[disease]].
+*There are no clear guidelines on the evaluation of response to [[COVID-19]] associated hepatic injury. A review article on evidence-based management guidelines for the [[COVID-19]] reports a raised [[CRP]] and low [[albumin]] to be associated with deterioration in [[patient]]s' condition. Demonstration of viral clearance in two respiratory tract specimens (at least 24 hours apart) may also serve as a monitoring tool.<ref name="pmid32289472">{{cite journal |vauthors=Nicola M, O'Neill N, Sohrabi C, Khan M, Agha M, Agha R |title=Evidence based management guideline for the COVID-19 pandemic - Review article |journal=Int J Surg |volume=77 |issue= |pages=206–216 |date=May 2020 |pmid=32289472 |pmc=7151371 |doi=10.1016/j.ijsu.2020.04.001 |url=}}</ref>
+*[[Liver function tests]] can serve as indicators of disease progression. [[Treatment]] and prevention of [[inflammation]] in the early stages of the disease prevent severe [[disease]].
 <br>
 To view medical treatment for [[COVID-19]], [[COVID-19 medical therapy|click here]].
@@ Line 308: / Line 310: @@
 ===Primary Prevention===
-*The disease itself is associated with [[COVID-19]] infection so prevention of the [[infection]] itself is the most promising [[primary prevention]] strategy at the moment.
+*The disease itself is associated with [[COVID-19]] infection so prevention of the [[infection]] is a promising [[primary prevention]] strategy at the moment.
 *There are no available vaccines against [[COVID-19]] at the moment. There have been rigorous efforts in order to develop a [[vaccine]] for [[COVID-10|novel coronavirus]] and several vaccines are in the later phases of trials.<ref name="urlNIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)">{{cite web |url=https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins |title=NIH clinical trial of investigational vaccine for COVID-19 begins &#124; National Institutes of Health (NIH) |format= |work= |accessdate=}}</ref>
 *At this time, the only effective measures for the [[primary prevention]] of COVID-19 related liver damage include prevention of itself [[COVID-19]]. [[Drug induced liver injury]] can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of [[hormones]] along with [[antiviral drugs]].
 *The only prevention for [[COVID-19]] associated hepatic injury is the prevention and early [[diagnosis]] of the [[coronavirus-19]] infection itself. According to the [[CDC]], the measures include:<ref name="urlHow to Protect Yourself & Others | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html |title=How to Protect Yourself & Others &#124; CDC |format= |work= |accessdate=}}</ref>
-**Frequent handwashing with soap and water for at least 20 seconds or using a [[alcohol rub|alcohol based hand sanitizer]] with at least 60% ethyl alcohol. It is essential to be sure that the hand sanitizer is free of methanol (wood alcohol) as [[FDA]] recently warns that ma=ethanol is harmful to human skin.<ref name="urlFDA Updates on Hand Sanitizers with Methanol | FDA">{{cite web |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-methanol |title=FDA Updates on Hand Sanitizers with Methanol &#124; FDA |format= |work= |accessdate=}}</ref>
+**Frequent handwashing with soap and water for at least 20 seconds or using a [[alcohol rub|alcohol based hand sanitizer]] with at least 60% [[ethyl alcohol]]. It is essential to be sure that the hand sanitizer is free of [[methanol]] (wood alcohol) as [[FDA]] recently warns that [[methanol]] is harmful to human skin.<ref name="urlFDA Updates on Hand Sanitizers with Methanol | FDA">{{cite web |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-methanol |title=FDA Updates on Hand Sanitizers with Methanol &#124; FDA |format= |work= |accessdate=}}</ref>
-**Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you.
+**Staying at least 6 feet (approximately 2 arms’ length) from other individuals who do not live with you.
 **Covering your mouth and nose with a cloth face cover when around others and covering [[sneeze]]s and [[cough]]s.
 **Cleaning and [[Disinfectant|disinfecting]].