Non-alcoholic fatty liver disease overview: Difference between revisions

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Latest revision as of 02:36, 10 September 2023

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

A non-alcoholic fatty liver disease, aslo called metabolic dysfunction-associated steatotic liver disease (MASLD) in the new AASLD nomenclature, is a form of chronic hepatitis that shares the histologic features of alcohol-induced hepatitis but is found in patients without prior history of alcohol abuse. Based on the severity of the disease non-alcoholic fatty liver disease encompasses a range of disorders including mild steatosis, steatohepatitis, advanced fibrosis, cirrhosis, and less commonly fulminant hepatic failure. Risk factors for non alcoholic liver disease include obesity, diabetes mellitus type 2, hyperlipidemia, and sudden dramatic weight loss. The diagnosis of NAFLD should be considered in any patient presenting with elevated transaminases without any underlying condition or pathological process. NAFLD must be distinguished from steatosis and steatohepatitis due to secondary causes. These include various forms of malnutrition, drugs (eg, warfarin, methotrexate, amiodarone, glucocorticoids, synthetic estrogens, tamoxifen, and various antibiotic and antiviral agents), metabolic and genetic disorders (eg lipodystrophy, dysbetalipoproteinemia, and acute fatty liver of pregnancy), use of total parenteral nutrition, and gastric bypass and other weight loss surgeries. NAFLD is mostly seen in obese individuals but may be encountered in thin or normal weight patients. Insulin resistance is a core feature of NAFLD, diabetes, obesity, and dyslipidemia. NAFLD can therefore be considered part of the insulin resistance (or metabolic) syndrome. Insulin resistance leads to accumulation of fat within hepatocytesvialipogenesis (and inhibition of lipolysis) and hyperinsulinemia. The pathogenesis of NAFLD and its progression to NASH appears to result from a two-step process, whereby an initial insult in the form of insulin resistance due to genetic and acquired factors leads to hyperinsulinemia and accumulation of fat within hepatocytes (steatosis). The steatotic liver is then vulnerable to further insult; hepatocellular injury and fibrosis may develop in the presence of oxidative stress and the proinflammatory activity of cytokines and similar agents. This leads to exacerbation of insulin resistance; further oxidative stress; and acceleration of inflammatory, degenerative, and fibrotic processes. The natural history of NAFLD is dependent on the stage of the disease. The prognosis of simple steatosis seems to be relatively benign, with a 1% to 2% risk of developing cirrhosis over 15 to 20 years. Patients with NASH and fibrosis can progress to cirrhosis, which can lead to end-stage liver disease; hepatic decompensation; or hepatocellular carcinoma, a rare, end-stage outcome. Imaging techniques can be helpful by showing steatosis, but liver biopsy is the only way to assess the severity of inflammation and fibrosis. The mainstay of treatment for NAFLD is lifestyle modifications and treatment of underlying risk factors such as obesity, diabetes mellitus type 2, and hyperlipidemia.

Historical Perspective

Ludwig was the first physician to describe the non-alcoholic fatty liver disease as a separate medical entity from other fatty liver diseases.

Classification

Non-alcoholic fatty liver (NAFLD) disease may be classified into:

Non-alcoholic fatty liver or hepatic steatosis
Non-alcoholic steatohepatitis

Pathophysiology

The exact pathogenesis of NAFLD is not fully understood, but is believed due to interaction of multiple factors such as obesity, Insulin resistance, and metabolic syndrome. Pathogenesis of non-alcoholic liver disease can be best explained by 2 hit hypothesis. The first hit is steatosis. The second hit is controversial and is likely cause changes 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

Usually, NAFLD presents with no or few symptoms but if symptomatic NAFLD must be differentiated from other diseases that cause jaundice and abdominal pain which include Wilson's disease, hemochromatosis, alcoholic hepatitis and cholestatic jaundice.

Epidemiology and Demographics

The estimated annual incidence of non alcoholic liver disease with steatosis in the United States is approximately 9,255 per 100,000 individuals. The prevalence of non-alcoholic liver disease in the United States is estimated to be 10,000 to 24,000 cases per 100,000 individuals annually. Non-alcoholic fatty liver disease may occur at any age, but is diagnosed most commonly in patients aged 50 to 60 years. Hepatic steatosis is more prevalent in the hispanics.

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 NAFLD in general population. However, screening is recommended in high-risk population groups(obesity, insulin resistance and patients with metabolic syndrome) as more than 50 million Americans have been estimated to have metabolic syndrome and about 80% of them have NAFD.

Natural History, Complications and Prognosis

If left untreated non alcoholic fatty liver disease 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. Common complications of NAFLD include fibrosis, cirrhosis, internal bleeding, encephalopathy. The presence of fibrosis and cirrhosisassociated with a particularly poor prognosis among patients with NAFLD.

Diagnosis

History and Symptoms

The majority of patients with non-alcoholic fatty liver disease are asymptomatic. However, very rarely patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice can also be noticed. Often following an asymptomatic course, the disease may present first with cirrhosis and/or the complication of portal hypertension.

Physical Examination

Patients with non-alcoholic fatty liver disease usually appear normal. Physical examination of patients with non-alcoholic fatty liver disease is usually unremarkable.

Laboratory Findings

There are no specific diagnostic laboratory findings associated with non alcoholic fatty liver disease. Laboratory findings include abnormal liver function tests but are unspecific. Other laboratory tests are generally performed to rule out other diagnosis.

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 non-alcoholic fatty liver disease. Increased echogenicity and coarsened echotexture of the liver is the most prominent and diagnostic finding on an ultrasound in patients diagnosed non-alcoholic fatty liver disease.

CT scan

CT scan may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on a CT scan diagnostic for non-alcoholic liver disease include a diffuse, low-density hepatic parenchyma without mass effect.

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.

Treatment

Medical Therapy

Weight loss, withdrawal of hepatotoxic agents, and management of underlying insulin resistance/metabolic syndrome is the mainstay of treatment in non-alcoholic fatty liver disease (NAFLD).

Surgery

Surgery is not the first-line treatment option for patients with non- Alcoholic fatty liver disease (NAFLD). However, gastric bypass surgery is recommended in patients with non-alcoholic fatty liver disease whose BMI is greater than 40 who psychologically stable and failed medical therapy.

Primary Prevention

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

Secondary Prevention

There are no established measures for the secondary prevention of non-alcoholic fatty liver disease.

References

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@@ Line 7: / Line 7: @@
 __NOTOC__
 {{Non alcoholic fatty liver disease}}
-'''Editor in Chief''': Elliot Tapper, M.D., Beth Israel Deaconess Medical Center, [[User:C Michael Gibson |C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]; {{AE}}{{VKG}}
+{{CMG}} ; {{AE}} {{VKG}}
 ==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 is more than 5 -10 percent of the liver’s weight is fat, then it is called a fatty liver (steatosis).NAFLD is marked by inflammation that can progress to irreversible damage.NAFLD 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 NAFLD. NAFLD 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.
+A non-alcoholic fatty liver disease, aslo called metabolic dysfunction-associated steatotic liver disease (MASLD) in the new [https://www.aasld.org/new-nafld-nomenclature AASLD nomenclature], is a form of [[Hepatitis|chronic hepatitis]] that shares the histologic features of alcohol-induced [[hepatitis]] but is found in patients without prior history of alcohol abuse. Based on the severity of the disease non-alcoholic fatty liver disease encompasses a range of disorders including mild [[steatosis]], [[steatohepatitis]], advanced [[fibrosis]], [[cirrhosis]], and less commonly [[fulminant]] hepatic failure. Risk factors for non alcoholic liver disease include [[obesity]], [[diabetes mellitus type 2]], [[hyperlipidemia]], and sudden dramatic weight loss. The diagnosis of NAFLD should be considered in any patient presenting with elevated [[Transaminase|transaminases]] without any underlying condition or pathological process. NAFLD must be distinguished from steatosis and steatohepatitis due to secondary causes. These include various forms of [[malnutrition]], drugs (eg, [[warfarin]], [[methotrexate]], [[amiodarone]], [[glucocorticoids]], synthetic [[Estrogen|estrogens]], [[tamoxifen]], and various [[antibiotic]] and [[Antiviral|antivira]]<nowiki/>l agents), metabolic and genetic disorders (eg [[lipodystrophy]], [[dysbetalipoproteinemia]], and acute [[fatty liver]] of [[pregnancy]]), use of total [[Parenteral nutrition|parenteral]] nutrition, and [[gastric bypass]] and other weight loss surgeries. NAFLD is mostly seen in obese individuals but may be encountered in thin or normal weight patients. [[Insulin resistance]] is a core feature of NAFLD, diabetes, obesity, and dyslipidemia. NAFLD can therefore be considered part of the insulin resistance (or metabolic) syndrome. Insulin resistance leads to accumulation of fat within hepatocytesvialipogenesis (and inhibition of lipolysis) and [[Hyperinsulinism|hyperinsulinemia]]. The pathogenesis of NAFLD and its progression to NASH appears to result from a two-step process, whereby an initial insult in the form of insulin resistance due to genetic and acquired factors leads to hyperinsulinemia and accumulation of fat within hepatocytes (steatosis). The steatotic liver is then vulnerable to further insult; hepatocellular injury and fibrosis may develop in the presence of [[oxidative stress]] and the [[proinflammatory]] activity of cytokines and similar agents. This leads to exacerbation of insulin resistance; further [[oxidative stress]]; and acceleration of inflammatory, [[degenerative]], and fibrotic processes. The natural history of NAFLD is dependent on the stage of the disease. The prognosis of simple steatosis seems to be relatively benign, with a 1% to 2% risk of developing [[cirrhosis]] over 15 to 20 years. Patients with NASH and fibrosis can progress to [[cirrhosis]], which can lead to end-stage liver disease; hepatic [[decompensation]]; or [[hepatocellular carcinoma]], a rare, end-stage outcome. Imaging techniques can be helpful by showing steatosis, but liver biopsy is the only way to assess the severity of inflammation and fibrosis. The mainstay of treatment for NAFLD is lifestyle modifications and treatment of underlying risk factors such as obesity, diabetes mellitus type 2, and hyperlipidemia.
 ==Historical Perspective==
-*NAFLD is relatively new concept first introduced in 1980.
+Ludwig was the first physician to describe the non-alcoholic fatty liver disease as a separate medical entity from other fatty liver diseases.
 ==Classification==
+Non-alcoholic fatty liver (NAFLD) disease may be classified into:
-*Based on histology it is classified into the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH).NAFL mostly considered as a benign condition but recent studies show it can progress to NASH up to 44%. The more severe form of NAFLD is called non-alcoholic steatohepatitis (NASH).<ref name="urlAmerican Liver Foundation - Non-Alcoholic Fatty Liver Disease">{{cite web |url=http://www.liverfoundation.org/abouttheliver/info/nafld/ |title=American Liver Foundation - Non-Alcoholic Fatty Liver Disease |format= |work= |accessdate=}}</ref>
+* Non-alcoholic [[fatty liver]] or hepatic steatosis
-*One of the leading cause for cirrhosis in adults in united states is NASH. Almost 25 percent of adults with NASH may lead to cirrhosis.
+* Non-alcoholic steatohepatitis
-*On the other hand, NASH progress to fibrosis that can lead to cirrhosis and hepatocellular cancer (HCC).<ref name="urlEvidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. - PubMed - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmed/25477264 |title=Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. - PubMed - NCBI |format= |work= |accessdate=}}</ref>
-*Rate of progression does not correlate with body mass index (BMI) or hyperlipidemia
 ==Pathophysiology==
-* It is thought that pathophysiology of NAFLD  is multifactorial that includes numerous genetic, dietary, metabolic and hormonal factors.
+The exact pathogenesis of NAFLD is not fully understood, but is believed due to interaction of multiple factors such as [[obesity]], [[Insulin resistance]], and [[metabolic syndrome]]. Pathogenesis of non-alcoholic liver disease can be best explained by 2 hit hypothesis. The first hit is steatosis. The second hit is controversial and is likely cause changes that leads from hepatic steatosis to hepatic inflammation and fibrosis by way of lipid peroxidation.
-* Most experts believe that NAFLD is a 2 hit hypothesis.
-** The first hit resulting in increased fat accumulation especially triglycerides within the hepatocyte and increases the risk of liver injury.
-** On the second hit inflammatory cytokines causes mitochondrial dysfunction and oxidative stress which in turn lead to steatohepatitis and/or fibrosis.<ref name="pmid19914930">{{cite journal |vauthors=Dowman JK, Tomlinson JW, Newsome PN |title=Pathogenesis of non-alcoholic fatty liver disease |journal=QJM |volume=103 |issue=2 |pages=71–83 |year=2010 |pmid=19914930 |pmc=2810391 |doi=10.1093/qjmed/hcp158 |url=}}</ref>.
-* Free fatty acids (FFA) play very crucial role in damaging the liver indirectly by either undergoing β-oxidation or are esterified with glycerol to form triglycerides, leading to hepatic fat accumulation.
-* Now there is new evidence that FFA is directly causing the liver damage by increasing the oxidative stress by upregulation of TNF-alpha expression via a lysosomal pathway.
-<ref name="pmid15239102">{{cite journal |vauthors=Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, Burgart LJ, Gores GJ |title=Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway |journal=Hepatology |volume=40 |issue=1 |pages=185–94 |year=2004 |pmid=15239102 |doi=10.1002/hep.20283 |url=}}</ref>
-* Oxidative stress inhibits the replication process in the mature hepatocytes, Results in the proliferation of progenitor (oval ) cell population and later they differentiate into hepatocyte-like cells. Now both the oval and hepatocyte-like cells play a very important role in the process of fibrosis and hepatocellular carcinogenesis.<ref name="pmid19914930">{{cite journal |vauthors=Dowman JK, Tomlinson JW, Newsome PN |title=Pathogenesis of non-alcoholic fatty liver disease |journal=QJM |volume=103 |issue=2 |pages=71–83 |year=2010 |pmid=19914930 |pmc=2810391 |doi=10.1093/qjmed/hcp158 |url=}}</ref>
-* Alterations in MTP/apoB synthesis and secretion have been implicated as one of the  potential mechanisms in the pathogenesis of NAFLD which in turn leads to a decreased capacity for lipid export
-* Normally triglycerides are transported from the liver in the form of VLDL particles which are then formed by the incorporation of triglyceride into apolipoprotein B (apoB) by microsomal transfer protein (MTP).<ref name="urlApolipoprotein synthesis in nonalcoholic steatohepatitis - Charlton - 2002 - Hepatology - Wiley Online Library">{{cite web |url=http://onlinelibrary.wiley.com/doi/10.1053/jhep.2002.32527/abstract |title=Apolipoprotein synthesis in nonalcoholic steatohepatitis - Charlton - 2002 - Hepatology - Wiley Online Library |format= |work= |accessdate=}}</ref>
 ==Causes==
-* Common causes in the development of NAFLD is related to [[obesity]] which will result in [[insulin resistance]] and [[metabolic syndrome]].<ref>{{Cite web|url=https://www.medscape.com/viewarticle/757336_2|title=Nonalcoholic Fatty Liver Disease|last=|first=|date=|website=|publisher=|access-date=}}</ref><ref name="pmid22338098">{{cite journal |vauthors=Sung KC, Jeong WS, Wild SH, Byrne CD |title=Combined influence of insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes |journal=Diabetes Care |volume=35 |issue=4 |pages=717–22 |year=2012 |pmid=22338098 |pmc=3308286 |doi=10.2337/dc11-1853 |url=}}</ref>It is estimated that approximately 80% of the obese people suffer from NAFLD.<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567|title=Nonalcoholic fatty liver disease|last=|first=|date=|website=|publisher=|access-date=}}</ref>
+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&nbsp;[[hypertension]] and [[dyslipidemia]]&nbsp;are also associated with developing nonalcoholic fatty liver disease
-* Patients who are having [[type 2 diabetes mellitus]] are more prone to develop Nafld<ref>{{Cite web|url=https://www.medscape.com/viewarticle/757336_2|title=Nonalcoholic Fatty Liver Disease|last=|first=|date=|website=|publisher=|access-date=}}</ref><ref name="urlNonalcoholic Fatty Liver Disease & NASH | NIDDK">{{cite web |url=https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash |title=Nonalcoholic Fatty Liver Disease & NASH &#124; NIDDK |format= |work= |accessdate=}}</ref>
-*Less commonly Patients with [[hypertension]] and [[dyslipidemia]] are also associated with developing NAFLD
 ==Differentiating Non-alcoholic fatty liver disease from Other Diseas ==
+Usually, NAFLD presents with no or few symptoms&nbsp;but if symptomatic NAFLD must be differentiated from other diseases that cause [[jaundice]] and [[abdominal pain]] which include [[Wilson's disease]], [[hemochromatosis]], [[alcoholic hepatitis]] and [[cholestatic jaundice]].
 ==Epidemiology and Demographics==
-* Estimates are that between 30 - 90 million Americans have some degree of [[NAFLD]] and 5-6% have [[NASH]]. <ref name="McCullough">McCullough, AJ. Thiazolidinediones for NASH. NEJM 2006;355(22):2361-2363.</ref>
+The estimated annual incidence of non alcoholic liver disease with steatosis in the United States is approximately 9,255 per 100,000 individuals. The prevalence of non-alcoholic liver disease in the United States is estimated to be 10,000 to 24,000 cases per 100,000 individuals annually. Non-alcoholic fatty liver disease may occur at any age, but is diagnosed most commonly in patients aged 50 to 60 years.&nbsp;[[Hepatic]]&nbsp;[[steatosis]]&nbsp;is more prevalent in the hispanics.
-* 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.<ref>Ong JP et al. Epidemiology and Natural History of NAFLD and NASH. Clin Liver Dis 11 (2007) 1–16</ref><ref>Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the united states. Gastroenterology 2003;124(1):71–9.</ref>
 ==Risk Factors==
-*Medications like [[Tamoxifen]] ,[[corticosteriods]] , [[methotrexate]]
+The most potent risk factor in the development of NAFLD is [[obesity]]. Other risk factors include [[insulin resistance]] and [[metabolic syndrome]].
-*[[Viral Hepatitis]].
-*Rapid weight loss.
-*Malnutrition.
-*High levels of triglyceride in blood.
-*Sleep apnea.
-*Hypothyroid.
-*Hypopituitarism .
 ==Screening==
+There is insufficient evidence to recommend routine screening for NAFLD in general population. However, screening is recommended in high-risk population groups([[obesity]], [[insulin resistance]] and patients with [[metabolic syndrome]]) as more than 50 million Americans have been estimated to have metabolic syndrome and about 80% of them have NAFD.
 ==Natural History, Complications and Prognosis==
-* [[NASH]] may progress to [[fibrosis]] and, later, to [[cirrhosis]].
+If left untreated non alcoholic fatty liver disease may progress to&nbsp;[[fibrosis]]&nbsp;and, later&nbsp;[[cirrhosis]]. Studies of serial&nbsp;[[liver biopsies]]&nbsp;estimate a 26-37% rate of&nbsp;[[hepatic]]&nbsp;[[fibrosis]]&nbsp;and 2-15% rate of&nbsp;[[cirrhosis]]&nbsp;in less than 6 years. Common complications of NAFLD include [[fibrosis]], [[cirrhosis]], [[internal bleeding]], [[encephalopathy]]. The presence of&nbsp;[[fibrosis]]&nbsp;and&nbsp;[[cirrhosis]]<nowiki/>associated with a particularly poor prognosis among patients with NAFLD.
-* Studies of serial [[liver biopsy|liver biopsies]] estimate a 26-37% rate of hepatic fibrosis and 2-15% rate of [[cirrhosis]] in less than 6 years. <ref>Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42(1):132–8.</ref><ref>Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease:a clinical histopathological study. Am J Gastroenterol 2003;98(9):2042–7.</ref><ref>Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73.</ref>
-* In 2001, [[NASH]] represented 2.9% of the indications of [[liver transplantation]].<ref name="Charlton">Charlton M et al. Frequency of Nonalcoholic Steatohepatitis as a Cause of Advanced Liver Disease. Liver Transpl 2001;7:608-614</ref>
-* 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.<ref>Adams et al. The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study. GASTROENTEROLOGY 2005;129:113–121</ref><ref>Feldstein AE et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009;58:1538–1544</ref>
-* patients with NAFLD when high NAFLD fibrosis score (NFS) and a high fibrosis-4 (FIB-4) score have increased the risk of developing Hepatocellular cancer, colorectal cancer in males, and breast cancer in females.<ref name="pmid29150142">{{cite journal |vauthors=Kim GA, Lee HC, Choe J, Kim MJ, Lee MJ, Chang HS, Bae IY, Kim HK, An J, Shim JH, Kim KM, Lim YS |title=Association between non-alcoholic fatty liver disease and cancer incidence rate |journal=J. Hepatol. |volume= |issue= |pages= |year=2017 |pmid=29150142 |doi=10.1016/j.jhep.2017.09.012 |url=}}</ref>
-* Esophageal varices.
-* Hepatic failure leads to encephalopathy.
 ==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===
-Usually, NAFLD [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>
+The majority of patients with non-alcoholic fatty liver disease are asymptomatic. However, very rarely patients may complain of [[fatigue]], [[malaise]] and dull [[right upper quadrant]] [[Abdominal pain|abdominal discomfort]]. Mild [[jaundice]] can also be noticed. 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===
+Patients with non-alcoholic fatty liver disease usually appear normal. Physical examination of patients with non-alcoholic fatty liver disease is usually unremarkable.
 ===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>
+There are no specific diagnostic laboratory findings associated with non alcoholic fatty liver disease. Laboratory findings include [[Liver function tests abnormality|abnormal liver function tests]] but are unspecific. Other laboratory tests are generally performed to rule out other diagnosis.
-* Furthermore,high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/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 NAFLD, 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 non-alcoholic fatty liver disease. Increased [[echogenicity]] and coarsened echotexture of the [[liver]] is the most prominent and diagnostic finding on an ultrasound in patients diagnosed non-alcoholic fatty liver disease.
-===Imaging Findings===
+===CT scan===
-* Imaging is often ordered in the workup of suspected NAFLD.
+CT scan may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on a CT scan diagnostic for non-alcoholic liver disease include a diffuse, low-density hepatic [[parenchyma]] without mass effect.
-* '''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 NAFLD 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 (tests)|sensitivity]] of 96% and [[Specificity (tests)|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===
+Liver biopsy may be helpful in the diagnosis of non-alcoholic fatty liver disease. Findings on biopsy include [[Steatosis|macrovesicular steatosis]], [[inflammation]], ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal [[fibrosis]] and, finally, [[mallory bodies]].
-===Other Diagnostic Studies===
+== Treatment ==
-* A biopsy of the liver is still considered the gold standard in diagnosis.
-* 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===
-* Trials are presently being conducted to optimize treatment of NASH. No standard treatment has yet emerged as the gold standard.
+[[Weight loss]], withdrawal of&nbsp;[[Hepatotoxicity causes|hepatotoxic agents]], and management of underlying&nbsp;[[insulin resistance]]/[[metabolic syndrome]]&nbsp;is the mainstay of treatment in non-alcoholic fatty liver disease (NAFLD).
-* 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 NAFLD and in prevention and alleviation of NAFLD.<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>
 ===Surgery===
+Surgery is not the first-line treatment option for patients with non- Alcoholic fatty liver disease (NAFLD). However, [[gastric bypass surgery]] is recommended in patients with non-alcoholic fatty liver disease whose [[Body mass index|BMI]] is greater than 40 who psychologically stable and failed medical therapy.
 ===Primary Prevention===
-There are some ways to prevent NAFLD,
+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===
+There are no established measures for the secondary prevention of non-alcoholic fatty liver disease.
 ==References==