Non-alcoholic fatty liver disease overview: Difference between revisions

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==Diagnosis==
==Diagnosis==
===Diagnosis Criteria===
{{Family tree/start}}
{{Family tree ||| | A01 | | | |A01= Incidental finding of Fatty liver on ultrasound}}
{{Family tree | | | | |!| | | | | }}
{{Family tree ||| | A01 | | | |A01= Check for persistently raised LFTs}}
{{Family tree | | | | |!| | | | | }}
{{Family tree || | | B01 | | | |B01= Ask the patient for significant alcohol intake}}
{{Family tree | |,|-|-|^|-|-|.| | }}
{{Family tree | C01 | | | | C02| |C01= NO| C02= YES}}
{{familytree  | |!| | | | | |!| | | | | | | | | | }}
{{Family tree | D01 | | | | D02 |D01= Diagnose NAFLD| D02= Consider other<br> alcoholic related diseases}}
{{Family tree/end}}
'''Monitor severity of the disease'''
{{Family tree/start}}
{{Family tree | | | | | | A01 | | | |A01= Offer Enhanced Liver Fibrosis Test (ELF)}}
{{Family tree | | | | | | |!| | | | | }}
{{Family tree | | | |,|-|-|^|-|-|.| | }}
{{Family tree | | | C01 | | | | C02 |C01= (>10.51)  ELF  Positive| C02= (<10.51) ELF Negative}}
{{Family tree | | | |!| | | | | |!| | }}
{{Family tree | | | D01 | | | | D02 |D01= Indicating advanced fibrosis and risk of progression to cirrhosis| D02= Typically Benign -- Advanced fibrosis unlikely}}
{{Family tree | | | |!| | | | | | | | }}
{{Family tree | | | E01 | | | | |E01= Refer the patient to Heptologist}}
{{Family tree/end}}
* On negative ELF test offer retest for every 3 years for adults and 2 years for children.
===History and Symptoms===
===History and Symptoms===
Usually, Nonalcoholic fatty liver disease [Nonalcoholic fatty liver disease] presents with no or few symptoms and sighs but when it does it shows the following<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567|title=Nafld|last=|first=|date=|website=|publisher=|access-date=}}</ref>
Most patients with NAFLD have no or few symptoms. Infrequently patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice can rarely be noticed. More commonly it is diagnosed as a result of abnormal liver function tests during routine blood tests. Often following an asymptomatic course, the disease may present first with cirrhosis and/or the complication of portal hypertension.
*Hepatomegaly
*Patient presents with fatigue
*Abdominal swelling ([[ascites]])
*Enlarged breasts in men ( due to decreased estrogen clearance by liver damage )
*Pain in the upper right abdomen
*Yellowing of the skin and eyes (jaundice)
*Splenomegaly
*The disease may present first with [[cirrhosis]] and/or the complication of [[portal hypertension]].
 
===Physical Examination===
===Physical Examination===
Patients with NAFLD usually appear asymptomatic. Physical examination of patients with NAFLD is usually unremarkable.
Patients with NAFLD usually appear asymptomatic. Physical examination of patients with NAFLD is usually unremarkable.
===Laboratory Findings===
===Laboratory Findings===
* Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above normal limit and an ALT/AST ratio of greater than 1.<ref>Powell et al. The Natural History of Nonalcoholic Steatohepatitis: A Follow-up Study of Forty-two Patients for Up to 21 YearsHEPATOLOGY 1990; 11: 74-80</ref> This ratio is imperfect, as AST tends to rise with the degree of fibrosis.<ref>Sorbi et al. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver DiseaseAm J Gastroenterol 1999;94:1018–1022</ref>
Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above the normal limit and an ALT/AST ratio of greater than 1.This ratio is imperfect, as AST tends to rise with the degree of fibrosis. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver disease.Furthermore, high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease.Another blood test that can be elevated is the ferritin. Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.
* Furthermore,high ALT values within the reference range (less than 40 IU) are still predictive of Nonalcoholic fatty liver disease/NASH.<ref>Chang Y et al. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease. Clinical Chemistry 2007;53(4):686–692</ref>
===Electrocardiogram===
* Another blood test that can be elevated is the ferritin.  
There are no ECG findings associated with NAFLD.
* Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.  
===X-ray===
* When considering Nonalcoholic fatty liver disease, other tests are generally performed, including those for associated conditions (e.g. glucose, hemoglobin A1C) and those to distinguish this disease from viral [[hepatitis]]. Additionally, autoimmune causes are ruled out with serology.
There are no x-ray findings associated with NAFLD.
* [[Thyroid-stimulating hormone|TSH]] is warranted, as [[hypothyroidism]] is more prevalent in NASH patients.<ref>Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? ''J Clin Gastroenterol'' 2003;37:340-3. PMID 14506393</ref>
===Ultrasound===
 
Ultrasound may be helpful in the diagnosis of complications of NAFLD, which include detection of fat percentage in the liver. Ultrasound is a qualitative test and should be considered as the reliable imaging test to diagnose NAFLD. Ultrasound is non- invasive, Inexpensive and no threat of radiation exposure to the patient. However, the accuracy of ultrasound is limited if the patient has hepatic fibrosis which Ultrasound cannot differentiate between hepatic fibrosis and steatosis.
===Imaging Findings===
===CT scan===
* Imaging is often ordered in the workup of suspected Nonalcoholic fatty liver disease.  
CT scan may be helpful in the diagnosis of complications of NAFLD, which include the structure of the liver. But using CT is limited because of the exposure to ionizing radiation. Contrast-enhanced CT has a sensitivity up to 84-87% and specificity of 75-86%.
* '''Ultrasound''', and '''computed tomography''' have sensitivities between 93-100%, but 62-76% positive predictive values. Problematically, ultrasound of fatty liver reveals a hyperechoic echotexture - a so-called 'bright liver' - that can often be indistinguishable from [[fibrosis]] and generally cannot reliably delineate Nonalcoholic fatty liver disease from [[NASH]].<ref>MIshra P et al. Abdominal Ultrasound for Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD). Am J Gastroenterol 2007;102:2716–2717).</ref> 
===MRI===
* '''Computed tomography''', is less sensitive, rarely detecting steatosis when fatty infiltration is less than 33%, but is potentially more specific.<ref>Saadeh et al. The Utility of Radiological Imaging in Nonalcoholic Fatty Liver Disease. GASTROENTEROLOGY 2002;123:745–750</ref> Statistics are similar for MRI, however using advanced MR techniques, some groups have been able to both quantify steatosis and differentiate steatohepatitis from steatosis.<ref>Taouli B et al. Advanced MRI Methods for Assessment of Chronic Liver Disease. AJR 2009; 193:14–27.</ref><ref>McPherson S et al. Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered. J Hepatol. 2009;51(2):389-97</ref>
An MRI is one of the best tools in imaging modalities available to diagnose NAFLD. An MRI is simple to test which allows quantification of the hepatic steatosis. MRI has a sensitivity of 96% and specificity of 93% in diagnosing NAFLD. However, it uses is limited because of the cost.
* '''Transient elastography''', an enhanced form of ultrasound that measures the stiffness of your liver. Liver stiffness indicates fibrosis or scarring.
===Other Imaging Findings===
 
There are no other imaging findings associated with non-alcoholic fatty liver disease.
===Other Diagnostic Studies===
===Other Diagnostic Studies===
* A biopsy of the liver is still considered the gold standard in diagnosis.
Liver biopsy may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on biopsy include macrovesicular steatosis, inflammation, ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal fibrosis and, finally, mallory bodies.
* This is especially true for those patients with elevated liver enzymes for whom a non-invasive workup is inconclusive; 34% of these patients, in one series, were found to have NASH.<ref>Skelly et al. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001;35:195-9
</ref>
* Classically, biopsy reveals macrovesicular steatosis, inflammation, ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal fibrosis and, finally, mallory bodies.<ref>Angula P. Nonalcoholic Fatty Liver Disease. NEJM. 2002 346(16):1221-31</ref><ref>Brunt EM, Janney CG, Di Bisceglie AM et al. Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. Am. J. Gastroenterol. 1999; 94(9):2467-2474</ref>
 
===Medical Therapy===
===Medical Therapy===
* Trials are presently being conducted to optimize treatment of NASH. No standard treatment has yet emerged as the gold standard.
There is no standard treatment for the non-alcoholic fatty liver disease; the mainstay of therapy is dietary and life style modifications which include improving metabolic risk factors -[[weight loss]], treating [[diabetes]], managing [[lipids]] and reducing [[alcohol]] intake.
* General recommendations include improving metabolic risk factors - [[weight loss]], treating [[diabetes]], managing [[lipids]] - and reducing [[alcohol]] intake.
 
* ''Moringa Oleifera'' (''MO''), a plant from the family Moringacea is a major crop in Asia and Africa, the leaves of these plant have been studied extensively and it has shown to be beneficial in Nonalcoholic fatty liver disease and in prevention and alleviation of Nonalcoholic fatty liver disease.<ref name="pmid29144438">{{cite journal |vauthors=Vergara-Jimenez M, Almatrafi MM, Fernandez ML |title=Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease |journal=Antioxidants (Basel) |volume=6 |issue=4 |pages= |year=2017 |pmid=29144438 |doi=10.3390/antiox6040091 |url=}}</ref>
* Very recently treatment with probiotics shown very significant  decrease in the inflammation of the liver without any adverse side effects. <ref name="pmid29148175">{{cite journal |vauthors=Manzhalii E, Virchenko O, Falalyeyeva T, Beregova T, Stremmel W |title=Treatment efficacy of a probiotic preparation for non-alcoholic steatohepatitis: a pilot trial |journal=J Dig Dis |volume= |issue= |pages= |year=2017 |pmid=29148175 |doi=10.1111/1751-2980.12561 |url=}}</ref><ref name="pmid22734251">{{cite journal |vauthors=Das N, Sikder K, Ghosh S, Fromenty B, Dey S |title=Moringa oleifera Lam. leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet |journal=Indian J. Exp. Biol. |volume=50 |issue=6 |pages=404–12 |year=2012 |pmid=22734251 |doi= |url=}}</ref>


===Surgery===
===Surgery===
* meta-analyses display that various bariatric surgical modalities yielding loss of 20% to 40% of baseline BMI result in tremendous histologic development.
Surgery is not the first-line treatment option for patients with NAFLD.The mainstay of treatment for NAFLD is medical therapy and weight loss.
* A few sufferers revel in whole decision of NASH.Given the lack of randomized control trials, bariatric surgical procedure cannot yet be recommended as first-line remedy for the remedy of NASH.
 
===Primary Prevention===
===Primary Prevention===
There are some ways to prevent Nonalcoholic fatty liver disease,
Effective measures for the primary prevention of non-alcoholic fatty liver disease include eating a healthy diet and regular exercise.
* Eating a healthy diet is the first and very important step. Eat food that is rich in vegetables, fruits and healthy fats.
* Exercise on regular basis.
* Maintain a healthy weight.
* Alcohol cessation, If Patient drinks.
* Take medications under the guidance of physician when needed, don't take unnecessary medications
 
===Secondary Prevention===
===Secondary Prevention===



Revision as of 21:34, 19 December 2017

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Editor in Chief: Elliot Tapper, M.D., Beth Israel Deaconess Medical Center, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

Nonalcoholic fatty liver disease [NAFLD] is due to the deposition of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, when there fat amount exceeds more than 5 -10 percent of the liver’s weight then it is called a fatty liver (steatosis). Nonalcoholic fatty liver disease is marked by inflammation that can progress to irreversible damage. Nonalcoholic fatty liver disease is similar to the damage caused by alcohol consumption in most of the cases. It is estimated that in united states approximately 80 to 100 million people are affected with Nonalcoholic fatty liver disease. Reflecting the obesity worldwide now Nonalcoholic fatty liver disease has become one of the leading cause of chronic liver disease. Nonalcoholic fatty liver disease most commonly affects people in the age group 2-19 and 40-50 years.It is most commonly seen in Hispanic population when compared to Caucasian and African American populations.

Historical Perspective

NAFLD/NASH was first described as a medical entity in a 1980. Though its histological capabilities had lengthy been recognized , the time period non-alcoholic steatohepatitis (NASH) became first used by Ludwig et al. as recently as 1980 .Ludwig et al. described ‘‘the pathological and medical features of non-alcoholic disease of the liver related with the pathological features maximum generally seen inside the alcoholic liver disorder itself.

Classification

Non-alcoholic fatty liver disease may be classified into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathology.

Pathophysiology

The exact pathogenesis of NAFLD is not fully understood.It is thought that NAFLD is the caused by either obesity, Insulin resistance, and metabolic syndrome. The exact reasons and mechanisms by which this disease progresses from steatosis to steatohepatitis and fibrosis is a subject of much research and debate. The prevailing wisdom comes from the so-called ‘two-hit hypothesis.’ The first hit is steatosis. The second hit is controversial and is likely numerous; likely any injury which causes a change that leads from hepatic steatosis to hepatic inflammation and fibrosis by way of lipid peroxidation.

Causes

Common causes in the development of Nonalcoholic fatty liver disease is related to obesity which will result in insulin resistance and metabolic syndrome. Less commonly Patients with hypertension and dyslipidemia are also associated with developing Nonalcoholic fatty liver disease

Differentiating Non-alcoholic fatty liver disease from Other Diseas

Nonalcoholic fatty liver disease must be differentiated from Auto Immune Hepatitis,α1-antitrypsin deficiency,Wilson disease and Hereditary hemochromatosis.

Epidemiology and Demographics

In the third National Health and Nutrition Examination Survey (NHANES III), the peak prevalence of NAFLD in men occurred in the fourth decade and in the sixth decade for women.NAFLD is associated with visceral obesity and diabetes. It has mirrored the epidemiologic course of obesity in the US and is detected in 73–90% of obese individuals on biopsy. Approximately 1/3 of the usa population are estimated to have NAFL. Through most estimates, NASH accommodates approximately 15% of all NAFLD and 3–5% of the american populace.

Risk Factors

The most potent risk factor in the development of NAFLD is obesity. Other risk factors include insulin resistance and metabolic syndrome.

Screening

There is insufficient evidence to recommend routine screening for Nonalcoholic fatty liver disease.

Natural History, Complications and Prognosis

NASH may progress to fibrosis and, later, cirrhosis. Studies of serial liver biopsies estimate a 26-37% rate of hepatic fibrosis and 2-15% rate of cirrhosis in less than 6 years.The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies.The natural history of nonalcoholic fatty liver disease:a clinical histopathological study.Long-term follow-up of patients with NAFLD and elevated liver enzymes. In 2001, NASH represented 2.9% of the indications of liver transplantation.The frequency of Nonalcoholic Steatohepatitis as a Cause of Advanced Liver Disease. The impact of NAFLD is manifest at each step along the spectrum of the disease. Studies in the United States and Sweden have revealed that both simple steatosis as well as steatohepatitis significantly reduce life expectancy, even when the diagnosis is made in children.The natural history of the non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years.

Diagnosis

History and Symptoms

Most patients with NAFLD have no or few symptoms. Infrequently patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice can rarely be noticed. More commonly it is diagnosed as a result of abnormal liver function tests during routine blood tests. Often following an asymptomatic course, the disease may present first with cirrhosis and/or the complication of portal hypertension.

Physical Examination

Patients with NAFLD usually appear asymptomatic. Physical examination of patients with NAFLD is usually unremarkable.

Laboratory Findings

Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above the normal limit and an ALT/AST ratio of greater than 1.This ratio is imperfect, as AST tends to rise with the degree of fibrosis. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver disease.Furthermore, high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease.Another blood test that can be elevated is the ferritin. Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.

Electrocardiogram

There are no ECG findings associated with NAFLD.

X-ray

There are no x-ray findings associated with NAFLD.

Ultrasound

Ultrasound may be helpful in the diagnosis of complications of NAFLD, which include detection of fat percentage in the liver. Ultrasound is a qualitative test and should be considered as the reliable imaging test to diagnose NAFLD. Ultrasound is non- invasive, Inexpensive and no threat of radiation exposure to the patient. However, the accuracy of ultrasound is limited if the patient has hepatic fibrosis which Ultrasound cannot differentiate between hepatic fibrosis and steatosis.

CT scan

CT scan may be helpful in the diagnosis of complications of NAFLD, which include the structure of the liver. But using CT is limited because of the exposure to ionizing radiation. Contrast-enhanced CT has a sensitivity up to 84-87% and specificity of 75-86%.

MRI

An MRI is one of the best tools in imaging modalities available to diagnose NAFLD. An MRI is simple to test which allows quantification of the hepatic steatosis. MRI has a sensitivity of 96% and specificity of 93% in diagnosing NAFLD. However, it uses is limited because of the cost.

Other Imaging Findings

There are no other imaging findings associated with non-alcoholic fatty liver disease.

Other Diagnostic Studies

Liver biopsy may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on biopsy include macrovesicular steatosis, inflammation, ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal fibrosis and, finally, mallory bodies.

Medical Therapy

There is no standard treatment for the non-alcoholic fatty liver disease; the mainstay of therapy is dietary and life style modifications which include improving metabolic risk factors -weight loss, treating diabetes, managing lipids and reducing alcohol intake.

Surgery

Surgery is not the first-line treatment option for patients with NAFLD.The mainstay of treatment for NAFLD is medical therapy and weight loss.

Primary Prevention

Effective measures for the primary prevention of non-alcoholic fatty liver disease include eating a healthy diet and regular exercise.

Secondary Prevention

References

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