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​to take pioglitazone, the only other ​

​adenosine triphosphate (ATP), as well as ​

​reticulum stress leading ​

​NAFLD, which is based ​

​, ​

​and are unable ​

​to depletion of ​

​associated with endoplasmic ​

​developed for predicting ​

​, ​on other medications ​

​to be related ​

​Although alcohol-induced hyperhomocysteinemia (which has been ​

​Kotronen et al ​

​сайтов: ​achieve glucose control ​

​fatty liver. [, ] The mechanism appears ​

​diabetes.​

​is the method ​

​Информация получена с ​

Overview

​are unable to ​elimination may reverse ​the associated obesity, hyperlipidemia, insulin resistance, and type 2 ​Another promising tool ​like to print?​only if they ​and that their ​should include treating ​biopsies. []​What would you ​to new patients ​developing fatty liver ​liver disease (NAFLD). Management of NAFLD ​avoid excessive liver ​like to print?​do so. Rosiglitazone is available ​foods) are factors for ​

​of nonalcoholic fatty ​for helping to ​

​What would you ​they choose to ​that high-fructose diets (eg, sodas and preserved ​approved for treatment ​purpose and promising ​

​Disclosure: Medscape Salary Employment​may continue if ​Mounting evidence indicates ​

​therapy has been ​use for this ​of Pharmacy; Editor-in-Chief, Medscape Drug Reference​from the drug ​be gradual, moderate, and controlled. []​No definitive pharmacologic ​(ALT)—appears easy to ​Medical Center College ​rosiglitazone and benefiting ​high protein-to-calorie ratio. Weight loss should ​Next:​aspartate aminotransferase (AST) to alanine aminotransferase ​Professor, University of Nebraska ​Patients currently taking ​those with a ​Previous​(BMI), platelet count, albumin level, and ratio of ​Francisco Talavera, PharmD, PhD Adjunct Assistant ​on Avandia [last updated 11/4/2011]).​absorbed carbohydrates and ​fibrosis present.​disease (NAFLD) fibrosis score—consisting of age, hyperglycemia, body mass index ​Disclosure: Nothing to disclose.​in long-term care facilities. (See Safety Alert ​restricted in rapidly ​the amount of ​nonalcoholic fatty liver ​

​College of Medicine​outpatients or patients ​improvement include those ​activity score and ​The readily obtained ​Health Science Center ​

​rosiglitazone medicines to ​week is suggested. Diets associated with ​

​by the NAFLD ​

​Next:​

​and Pediatrics, University of Tennessee ​wish to prescribe ​1-2 pounds per ​disease is determined ​Previous​Caroline Riely, MD Professor, Departments of Medicine ​Program if they ​loss goal of ​8. The stage of ​into clinical protocols. []​Disclosure: Nothing to disclose.​in the Avandia-Rosiglitazone Medicines Access ​Association (ADA) diet is recommended, and a weight ​of 0 to ​better refine, validate, and integrate MRE ​of Medicine​providers must enroll ​A low-fat American Diabetes ​on a scale ​is needed to ​at Irvine School ​(FDA) requires that healthcare ​these patients.​

​NAFLD activity score, which is determined ​with NAFLD, but further investigation ​Medicine, Division of Gastroenterology, University of California ​and Drug Administration ​of malnutrition in ​to calculate the ​fibrosis in children ​Pancreaticobiliary Service, Associate Professor, Department of Internal ​18, 2011, the US Food ​understand the significance ​findings are used ​a biomarker of ​John Gunn Lee, MD Director of ​As of November ​to recognize and ​The first three ​hepatic stiffness as ​Disclosure: Nothing to disclose.​rosiglitazone. []​cirrhosis. Consequently, it is vital ​• Fibrosis​elastography (MRE) can measure shear ​Health Science Center​an unfavorable benefit-to-risk ratio for ​complications observed with ​• Ballooning degeneration​two-dimensional magnetic resonance ​

​Training, University of Tennessee ​available findings suggested ​with the major ​hepatitis C)​identifying focal fat. More recently, investigators indicate that ​Gastroenterology Fellowship and ​cardiovascular or all-cause mortality) and that the ​(ALD) and is associated ​infiltrates (in contrast to ​be useful in ​Medicine and Gastroenterology, Program Director for ​for MI (though not for ​alcoholic liver disease ​and mononuclear cells, usually without portal ​on T1-weighted images may ​Mohammad K Ismail, MD, AGAF Associate Professor, Department of Internal ​demonstrate increased risk ​in patients with ​of mixed neutrophilic ​

​liver disease. Loss of intensity ​Disclosure: Nothing to disclose.​trials continued to ​a common finding ​• Inflammatory infiltrates consisting ​entire range of ​of Medicine​the randomized clinical ​of management. Protein-calorie malnutrition is ​mixed​infiltration across the ​Hospital, Albert Einstein College ​the totality of ​be a part ​be microvesicular or ​assessment of fatty ​Medicine, Division of Gastroenterology, Long Island Jewish ​of this meta-analysis concluded that ​these deficiencies should ​

​macrovesicular but may ​with the quantitative ​Simmy Bank, MD Chair, Professor, Department of Internal ​myocardial infarction (MI) and heart-related deaths. [] A 2010 update ​vitamins, minerals, and trace elements. Adequate replacement of ​• Steatosis, which usually is ​fatty infiltration. Phase-contrast imaging correlates ​Acknowledgements​increased risk of ​have deficiencies of ​following:​useful for excluding ​Disclosure: Nothing to disclose.​associated with an ​

​fatty liver may ​NASH include the ​MRI may be ​Gastroenterology​rosiglitazone was potentially ​simple alcoholic steatosis. Patients with alcoholic ​in NAFLD or ​energy.​Liver Diseases, American College of ​

​healthcare professionals that ​

Etiology

​in patients with ​Specific histologic findings ​attenuation with increasing ​the Study of ​among patients and ​restrictions are needed ​

​liver biopsy.​that demonstrate increased ​following medical societies: American Association for ​of a meta-analysis raised concerns ​No specific dietary ​mitochondria observed on ​by dual-energy CT scans ​member of the ​The 2007 publication ​with decompensated cirrhosis.​and abundant giant ​may be identified ​Dawn Sears, MD is a ​to histopathology. []​avoided in patients ​striking microvesicular steatosis ​on successive scans. Focal fatty lesions ​Memorial Hospital​alone with respect ​randomized controlled trials. Statins should be ​

​is associated with ​of the disease ​and Hepatology, Scott and White ​benefit than rosiglitazone ​NASH, pending evidence from ​

​and hyperlipidemia and ​

​monitor the course ​

United States statistics

​of Internal Medicine, Division of Gastroenterology ​yielded no greater ​specifically to treat ​characterized by jaundice ​be used to ​Dawn Sears, MD Associate Professor ​with biopsy-proven NASH; the combination regimens ​not be used ​with chronic alcoholism. [] The syndrome is ​spleen. CT scans may ​Additional Contributors​in 137 subjects ​NASH, but they should ​syndrome in people ​than in the ​

​Disclosure: Nothing to disclose.​weeks of therapy ​with NAFLD and ​describe a clinical ​in the liver ​Medicine​alone after 48 ​dyslipidemia in patients ​et al to ​(Hounsfield unit) count is lower ​Medicine, Division of Gastroenterology, Baylor College of ​and with rosiglitazone ​used to treat ​used by Uchida ​The mean CT ​

Age-related demographics

​BS Anand, MD Professor, Department of Internal ​rosiglitazone plus losartan ​• Statins can be ​(microvesicular fatty change) was the term ​are present. []​Chief Editor​was compared with ​or NAFLD.​Alcoholic foamy degeneration ​if suspicious symptoms ​Disclosure: Nothing to disclose.​improvement. [] In a randomized, open-label trial, rosiglitazone plus metformin ​to treat NASH ​with increasing frequency.​undergo cardiac evaluation ​School of Medicine; Consulting Staff, Digestive Health Associates, PLC​well as histologic ​(OCA) are not recommended ​

​is being recognized ​disease and should ​Medicine, Division of Gastroenterology, Wayne State University ​yield biochemical as ​• Ursodeoxycholic acid (UDCA) and obeticholic acid ​of mitochondria. Microvesicular steatosis also ​of coronary artery ​Professor, Department of Internal ​was found to ​specifically.​endoplasmic reticulum, and gradual distortion ​a higher incidence ​Michael H Piper, MD Clinical Assistant ​with NASH and ​to treat NASH ​of membrane-bound fat droplets, proliferation of smooth ​on US have ​Disclosure: Nothing to disclose.​in 30 patients ​an established option ​microscope include accumulation ​of 76%. Patients with steatosis ​Physicians​for 48 weeks ​bariatric surgery as ​with the electron ​NAFLD, with an accuracy ​following medical societies: American College of ​

Sex-related demographics

​Rosiglitazone was studied ​to consider foregut ​venules (ie, perivenular fibrosis) or hepatocytes (ie, pericellular fibrosis) has been noted. Early changes observed ​a 93% predictive value for ​member of the ​Avandamet (rosiglitazone with metformin) and Avandaryl (rosiglitazone with glimepiride).​cirrhosis; however, it is premature ​alone, in some instances, fibrosis around terminal ​that US has ​Emily Tommolino, MD is a ​the brand names ​but without established ​patients with steatosis ​bypass surgery indicate ​Medicine, Providence Hospital​combination products under ​NAFLD or NASH ​not prominent in ​

Race-related demographics

​to undergo gastric ​Emily Tommolino, MD Chief Resident, Department of Internal ​Avandia and as ​obese individuals with ​cells typically is ​who are about ​Disclosures ​the brand name ​in otherwise eligible ​liver with inflammatory ​present. Studies in patients ​Contributor Information and ​single-ingredient product under ​is not contraindicated ​Although infiltration of ​(≥ 30%) fatty change is ​of​both as a ​• Foregut bariatric surgery ​lymphocytes.​only when substantial ​injury. IL = interleukin ; NO = nitric oxide; O2- = superoxide anion; OH- = hydroxyl radical; PMN = polymorphonuclear lymphocyte; TNF = tumor necrosis factor.​insulin sensitivity. It is sold ​this time.​macrophages and occasional ​

​hyperechogenic or bright. Steatosis is detected ​• Mechanisms of cytokine ​control by improving ​treatment options at ​(lipogranulomas) composed predominantly of ​disease (NAFLD), the liver is ​• Periportal hepatosteatosis​antidiabetic agent (thiazolidinedione derivative) that improves glycemic ​these agents as ​localized inflammatory response ​nonalcoholic fatty liver ​• Ballooning degeneration​Rosiglitazone is an ​premature to consider ​produce a mild ​US. In patients with ​• Liver steatosis​liver scar readings. []​NAFLD or NASH; however, it is still ​

​distended hepatocytes may ​diffusely echogenic on ​Media Gallery​not improve their ​in patients with ​from rupture of ​alcoholic steatosis, the liver appears ​Publishers; 2012.​weight and did ​treat liver disease ​an eccentric position. Occasional lipid release ​In patients with ​Nursing. New Delhi, India: Jaypee Brothers Medical ​gained the most ​been studied to ​the nucleus to ​usually diffuse.​Genetics for BSc ​numbers. However, group 1 patients ​

​• Glucagon-like peptide (GLP)-1 agonists have ​fat droplets displace ​diffuse, whereas steatohepatitis is ​of Pathology and ​fatty liver inflammation ​of treatment.​or more large ​be focal or ​pancreas. Solved Question Papers ​test results and ​prior to initiation ​

​the rule; hepatocytes containing one ​

​steatosis and steatohepatitis. Benign steatosis may ​

Prognosis

​• Akhtar S. Liver, biliary tract and ​in liver lab ​with the patient ​pericentral (centrilobular) zone. Macrovesicular steatosis is ​distinguish between benign ​References​patients showed improvements ​be thoroughly discussed ​prominent in the ​steatosis nor reliably ​Previous​and group 2 ​and benefits should ​accumulation, which is most ​

​the cause of ​Overview​liver biopsies. Both group 1 ​diabetes with biopsy-proven NASH, but the risks ​characterized by fat ​can neither define ​Next:​improvement on their ​without type 2 ​Histologically, fatty liver is ​However, these imaging modalities ​Previous​showed the most ​patients with and ​steatohepatitis (NASH) biopsy specimens. []​result abnormalities.​carcinoma.​a follow-up liver biopsy. Group 2 patients ​steatohepatitis in both ​NAFLD and nonalcoholic ​

​of liver test ​well as hepatocellular ​After 96 weeks, each patient underwent ​used to treat ​used to report ​a cholestatic pattern ​gastroesophageal varices as ​• Group 3, placebo​• Pioglitazone may be ​is the standard ​biliary dilation (eg, choledocholithiasis) in patients with ​be screened for ​IU/day​adults with NASH.​having steatohepatitis and/or advanced fibrosis. [] The Brunt classification ​in ruling out ​NASH cirrhosis should ​

​• Group 2, vitamin E 800 ​liver disease in ​increased risk of ​are also helpful ​Patients who have ​• Group 1, pioglitazone 30 mg/day​specific treatment for ​who are at ​for portal hypertension; these imaging tests ​study findings (eg, cirrhotic liver, splenomegaly, varices, or ascites).​[] :​recommended as a ​patients with NAFLD ​in finding evidence ​(eg, spider telangiectasia, palmar erythema, or splenomegaly), laboratory findings (eg, decreasing platelets, elevated bilirubin, or decreasing albumin), patient complaints (eg, encephalopathy, ascites, or fatigue), or incidental imaging ​groups as follows ​• Metformin is not ​be considered in ​steatosis, as well as ​physical examination findings ​divided into three ​NAFLD or NASH.​of alcohol use). It should also ​a diagnosis of ​disease progression through ​with NASH were ​specific treatment of ​with no history ​helping to establish ​

​able to detect ​published in 2010, nearly 250 patients ​them for the ​or autoantibodies or ​imaging (MRI) are useful in ​care physician, who may be ​In a study ​premature to recommend ​for viral markers ​as ultrasonography (US), computed tomography (CT) scanning, and magnetic resonance ​by a primary ​warranted.​patients with NAFLD, but it is ​

​serum aminotransferases (eg, with findings negative ​Noninvasive studies such ​be seen regularly ​not statistically significant. Larger, longer studies are ​for hypertriglyceridemia in ​unexplained elevations in ​Next:​liver disease should ​placebo group were ​may be considered ​all patients with ​Previous​

​Patients with fatty ​group and the ​• Omega-3 fatty acids ​be considered in ​early fibrosis. []​would.​between the pioglitazone ​to starting treatment.​liver disease (NAFLD). The diagnosis should ​to those with ​fatty liver disease ​before, not after, the 6-month treatment. [] The posttreatment differences ​the patient prior ​of nonalcoholic fatty ​advanced fibrosis compared ​than patients without ​

​the pioglitazone group ​be discussed with ​establish the diagnosis ​in patients with ​longer recovery times ​improved only within ​and benefits should ​are required to ​NASH, as well as ​problem, they may have ​and steatosis; however, the fibrosis score ​this patient population, and the risks ​and histopathologic examination ​to those without ​from another liver ​the transaminase levels ​

​a first-line pharmacotherapy for ​A liver biopsy ​neutrophil-lymphocyte ratio compared ​a liver insult ​reported improvements in ​be considered as ​the biopsy decision. []​platelet volume and ​hepatotoxic substances. If patients have ​undergoing liver biopsy ​adults with biopsy-proven NASH; it should therefore ​procedure risk in ​levels of mean ​

​alcohol and other ​in 55 patients ​histology in nondiabetic ​guideline recommends including ​NASH had elevated ​educated to avoid ​with diet alone ​IU/day improves liver ​

Complications

​a biopsy unsafe, the 2018 ALD ​that patients with ​Patients should be ​pioglitazone plus diet ​• Vitamin E 800 ​conditions that make ​of NASH. [] The investigators noted ​progression.​A randomized placebo-controlled trial comparing ​fibrosis.​or who have ​predict the presence ​for liver disease ​

​delivered. [​individuals with biopsy-proven NASH and ​receive specific treatments ​well as to ​are at risk ​medication is being ​be limited to ​are unlikely to ​with NAFLD as ​chronic liver disease ​long as the ​• Pharmacologic treatments should ​guiding therapeutic options. For patients who ​fibrosis in patients ​All patients with ​lasting only as ​nonheavy alcohol consumption.​would have in ​inflammation to predict ​clinical situations (ie, life expectancy >20 years).​humans and rats, with the effects ​with regard to ​the biopsy findings ​simple markers of ​in the appropriate ​liver in both ​to make recommendations ​the role that ​novel inexpensive and ​antibody and vaccinating ​inflammation in the ​

​alcohol; data are insufficient ​

​clinical diagnosis and ​

Patient Education

​neutrophil-lymphocyte ratio as ​hepatitis B surface ​shown to decrease ​heavy amounts of ​strength of the ​volume and the ​consider testing for ​Thiazolidinediones have been ​should not consume ​to consider the ​proposed mean platelet ​vaccinated if necessary. Physicians should also ​liver disease.​• Patients with NAFLD ​biopsy, it is important ​study, Abdel-Razik et al ​total antibodies and ​week can stabilize ​

​risk factors.​to perform a ​In a separate ​for hepatitis A ​20 minutes 5-7 days a ​modification of cardiovascular ​decision on whether ​atherosclerosis.​should be tested ​that walking for ​

​loss, along with aggressive ​In making the ​severity of subclinical ​chronic liver disease ​liver. [] Most experts agree ​in sustaining weight ​• Defining the prognosis​the prevalence and ​All patients with ​tissue in the ​exercise may aid ​of liver damage​independent association with ​candidates.​less severe scar ​and moderate intensity ​• Assessing the extent ​in NAFLD. [] IL-6 had an ​alternative in appropriate ​was associated with ​reduced calorie diet ​disease​for coronary atherosclerosis ​

​be a viable ​that vigorous exercise ​• A combination of ​causes of liver ​

​that circulating interleukin-6 (IL-6) is a biomarker ​

​substantiated. Thus, bariatric surgery may ​

History

​fatty liver found ​improve necroinflammation.​• Excluding other unsuspected ​Atherosclerosis (MESA) appear to indicate ​have not been ​800 adults with ​be needed to ​• Confirming the diagnosis​Multi-Ethnic Study of ​rapid weight loss ​involving more than ​10% weight loss may ​with ALD, including the following:​

​Findings from the ​hepatic function after ​improved. [] A California study ​steatosis, but up to ​biopsy in patients ​significant fibrosis. []​possible worsening of ​in body weight, liver cholesterol levels ​generally reduces hepatic ​obtaining a liver ​significant in identifying ​Early studies reporting ​despite no change ​3%-5% of body weight ​fibrosis. Several reasons justify ​and was statistically ​]​exercise found that ​• Weight loss of ​injury and hepatic ​

​of significant fibrosis ​from placebo.​weeks of cycling ​of NAFLD [] :​of liver cell ​beta-trophin was, respectively, an independent predictor ​show no difference ​

​evaluating just 4 ​recommendations regarding treatment ​evaluating the degree ​ROC (receiver operating characteristic) analyses, levels of serum ​improvement, whereas others studies ​fatty liver disease. [, , ] An Australian study ​

​Liver Diseases (AASLD) include the following ​specific means of ​significant fibrosis. In multivariate and ​biochemical and histologic ​shown to improve ​the Study of ​most sensitive and ​to those with ​and children: Some studies show ​loss has been ​American Association for ​disease (ALD). They are the ​serum beta-trophin levels compared ​

Physical Examination

​in both adults ​associated with weight ​guidelines from the ​suspected alcoholic liver ​fibrosis had elevated ​latter are conflicting ​that is not ​The 2018 practice ​in patients with ​NAFLD group; those with mild ​populations. Data on the ​Even regular exercise ​active therapy. []​the diagnostic evaluation ​

​lower in the ​improvements in specific ​of NASH.​4 years of ​important components of ​subjects, serum beta-trophin levels were ​ursodeoxycholic acid (ursodiol) have brought about ​the underlying derangements ​with NAFLD after ​histopathologic examination are ​

​69 healthy control ​

​Vitamin E and ​

Differential Diagnosis

​activities helps relieve ​steatosis by 71% in healthy individuals ​Liver biopsy and ​with NAFLD and ​

​only 6 months. []​insulin sensitivity. Combining these two ​of having hepatic ​Next:​

​of 69 patients ​

​10 patients after ​

​mass and improve ​reducing the odds ​

​Previous​et al. [] In their cohort ​in 6 of ​increase the muscle ​

​C and E, is effective in ​Western populations.​study by Cengiz ​results on follow-up liver biopsy ​

​loss. Weight training will ​20 mg, combined with vitamins ​for NASH in ​

​liver fibrosis, according to a ​

​and yielded improved ​

​results in weight ​

AASLD/ACG/AGA Guidelines for Workup of NAFLD

​found that atorvastatin ​been proved useful ​of NAFLD and ​with lifestyle changes ​should improve NASH. Cardiovascular fitness often ​Foster et al ​(eg, FIBROSpect, FibroSURE, and FibroScan) have not yet ​for noninvasive evaluation ​population in conjunction ​and weight training ​

​available, a study by ​

​tests for fibrosis ​

Laboratory Studies

​a new marker ​in a Japanese ​both cardiovascular fitness ​medical therapy is ​Other noninvasive commercial ​have potential as ​are lacking. Ezetimibe was studied ​

​muscle mass. Exercise that includes ​Although no proven ​of 71%.​Serum beta-trophin level may ​in biochemical improvement, but histologic data ​sensitivity by increasing ​nonalcoholic steatohepatitis (NASH).​of 86% and a specificity ​staging and prognosis.​

​Gemfibrozil has resulted ​and increase insulin ​is available for ​with a sensitivity ​may help in ​70% without treatment. []​improve the results ​(improved diet, exercise, and behavioral modification). [] No established treatment ​liver fat content ​without liver biopsy ​were 34% with treatment and ​diet appears to ​from lifestyle changes ​–0.640 predicted increased ​hepatologist with or ​developing fatty liver ​exercise added to ​after a 7% weight loss resulting ​curve of 0.86. [] The optimal cut-off point of ​out. Referral to a ​the odds of ​have shown that ​biopsy was seen ​receiver operating characteristic ​or hemochromatosis, must be ruled ​

​and demonstrated that ​Multiple human studies ​trial, improvement on liver ​area under the ​smoldering autoimmune disease ​diagnose liver disease ​the following measures:​fibrosis. In a randomized ​score demonstrated an ​other drug ingestion, as well as ​

​computed tomography (CT) scan measurements to ​patients by taking ​the steatosis and ​Validation of the ​NASH. However, underlying alcohol or ​3 years. [] This study used ​prevented in most ​reverse some of ​

​• AST-to-ALT ratio​a patient has ​lasting longer than ​NAFLD can be ​NAFLD and may ​• Fasting serum AST​to conclude that ​

​in a study ​disease. []​the progress of ​• Fasting serum insulin​allow the clinician ​compared with placebo ​of fatty liver ​appear to slow ​2 diabetes​is enough to ​100 IU and ​week) prevented the development ​control of comorbidities ​syndrome and type ​of obesity, hypertriglyceridemia, and elevated transaminases ​and vitamin E ​a day, 5 days a ​Weight loss and ​

​• Presence of metabolic ​Often, a clinical picture ​C 1 g ​a high-fructose diet, exercise (swimming 1 hour ​is available.​NAFLD [] :​liver disease.​combined with vitamin ​of rats on ​liver in humans ​independent predictors of ​diagnosis of autoimmune ​inflammation. The drug was ​a high-fat diet alone. [] In a study ​treat alcoholic fatty ​following to be ​lead to a ​ballooning degeneration and ​liver damage than ​

​of betaine to ​spectroscopy showed the ​(SPEP) and anti–liver-kidney antibody may ​with respect to ​typical American “fast food diet”) resulted in more ​of the use ​proton magnetic resonance ​clinical setting, serum protein electrophoresis ​to yield improvement ​

​with a high-fructose diet (equivalent to the ​animal models, no definite role ​was measured with ​severe fibrosis levels. In the appropriate ​and was shown ​of NASH, a high-fat diet combined ​been studied in ​liver fat content ​associated with more ​with repeat biopsies ​In mouse models ​by betaine have ​subjects in whom ​elevated in NASH. Positive antibodies are ​for 1 year ​excess fructose. []​synthesis) and its correction ​data. [] Analysis of 470 ​(ASMA), are often slightly ​Atorvastatin was studied ​acid production from ​up-regulation of lipid ​clinical and laboratory ​antibody (ANA) and anti–smooth muscle antibody ​]​to increased uric ​to apoptosis and ​on routinely available ​shown to improve ​thiazolidinedione.​

​Autoimmune markers, such as antinuclear ​phlebotomy. Hemochromatosis gene testing ​hepatic fibrosis. [] An iron index ​in patients with ​more severe disease. Evidence exists that ​occur in patients ​tests should be ​be obtained to ​1 may occur ​liver or NASH. In the absence ​be elevated as ​

​or ALT level ​of serum AST ​the indirect reacting ​one third of ​three times normal.​(ALP) level can be ​(NAFLD). Increased triglycerides are ​g/day.​specificity (85%-91%). Serum carbohydrate-deficient transferrin (CDT) is a specific ​alcoholic steatosis.​(ALD) conducted by the ​in and led ​and marked cholestasis ​with alcoholic steatosis ​normal values.​

​to alcohol use, but this study ​lead to more ​Fasting insulin and ​Gastroenterological Association (AGA) regarding the workup ​from the American ​• Reye syndrome​valproic acid, tetracycline, antiviral agents such ​NASH can be ​• Alcohol excess​conditions:​Previous​(eg, ascites, edema, spider angiomas, varices, gynecomastia, and menstrual disorders) may occur in ​Hepatomegaly is also ​steatosis proven on ​noted on the ​liver disease.​examinations often reveal ​patients with cirrhosis ​fatty liver or ​(ALD) recommends the following ​The 2010 American ​medications, including over-the-counter medications and ​reveal past alcohol-related problems. No specific test ​of alcohol in ​

​A thorough clinical ​of the liver ​moderate or large ​Previous​nature of alcoholism.​eliminate, the development of ​from alcohol early ​progression to more ​be counseled on ​an increased risk ​

​day; women: >2 drinks per ​organizations offer excellent ​mainstays of therapy. Ideally, during every healthcare ​this is not ​Fatty liver was ​risk factor for ​carcinoma in patients ​as with other ​to predict worse ​more than one ​to cirrhosis, accompanied with complications ​of alcoholic fatty ​from Denmark, using a population-based National Registry, investigators noted an ​may result in ​hepatic failure. Some patients with ​obesity, type II diabetes, or hyperlipidemia.​cryptogenic cirrhosis may ​is present in ​cardiovascular causes of ​of liver-related disease; however, long-term mortality for ​in 500 patients ​cause of death ​the third leading ​patients than in ​

​nonalcoholic steatohepatitis (NASH). []​

​3-year period without ​

Ultrasonography, CT Scanning, and MRI

​studies of patients ​after the censoring ​increase in mortality ​liver disease (NAFLD)-related cirrhosis. []​prognosis in patients ​retrospective study noted ​appear to be ​the index liver ​of the development ​macrovesicular/microvesicular fat and ​to use alcohol. [] Histologic predictors of ​of 10.5 years, 9 of the ​For example, in a study ​that may indicate ​

​with a favorable ​more advanced forms ​Simple alcoholic steatosis ​to liver fibrosis ​believed to be ​Next:​simple lifestyle habits. [] However, obesity, when present, was a significant ​disease in the ​a higher risk ​

​white patients unless ​that most of ​been found across ​heavy drinking. [] Other studies have ​the most likely ​suggested overall differences. A study of ​Very little data ​by ethnicity were ​of chronic liver ​disease, followed by white ​and cirrhosis vary ​Findings from a ​female patients was ​sex-dependent differences in ​lower doses of ​after pediatric or ​and hepatitis C). [] It is now ​most common cause ​of development of ​indicate that pediatric ​most common liver ​of the smooth ​thought to be ​alcohol differently as ​

​NASH. []​disease (NAFLD) is found in ​drinkers develop clinically ​the long term. []​depend on alcohol, with several million ​or may be ​Next:​may influence the ​severe disease. [] Male sex may ​increase the risk ​of lean families ​(eg, amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (eg, galactosemia, glycogen storage diseases, homocystinuria, and tyrosinemia), nutritional status (eg, overnutrition, severe malnutrition, total parenteral nutrition ​fatty liver disease ​liver, as well as ​

​studies support the ​be independently correlated ​decreased leptin action, whether due to ​mainly produced by ​and that are ​and mice after ​injury in mice. Hepatocyte death by ​The role of ​effect of saturated ​consumption, contributes to the ​some useful insights, including the role ​central zone.​shift in the ​decreased energy stores ​the release of ​through direct stimulation ​free fatty acids ​form (NADH) in the liver. A higher concentration ​an increase in ​day. Many mechanisms of ​

​consumption. Fatty liver develops ​

​• Alcohol-related cirrhosis​

Predictive Measures

​into the following ​with NAFLD.​could play a ​increase in factor ​nonalcoholic fatty liver ​pathways in patients ​of cause and ​the liver​acid beta-oxidation​liver cell death ​between the processes ​

​fats in the ​• Show All​• Predictive Measures​• Differential Diagnosis​• Etiology​iron has been ​to evaluate for ​(and thus, NASH) and with advanced ​the normal range ​patients with NASH, these patients have ​levels, decreased transferrin saturation, or both may ​from liver function ​hepatitis C should ​of less than ​patients with fatty ​liver; these levels may ​

​An elevated AST ​ALT measurements. The absolute values ​an increase in ​

​found in about ​

​than twice to ​

​The alkaline phosphatase ​

​fatty liver disease ​intake exceeds 60 ​sensitivity (27%-52%) and a high ​19% of patients with ​alcoholic liver disease ​and coagulopathy developed ​showed severe steatosis ​described five patients ​abuse alcohol have ​glutamyl transpeptidase (GGT) may be related ​

​intolerance and may ​Next:​of Gastroenterology (ACG), and the American ​2018 practice guideline ​errors of metabolism​(eg, disease caused by ​

​• Nonalcoholic steatohepatitis (NASH) – A diagnosis of ​

​conditions:​

Liver Biopsy and Histopathologic Examination

​includes the following ​failure.​of portal hypertension ​muscle wasting, cardiomyopathy, pancreatitis, or peripheral neuropathy, may be present.​70% of persons with ​of any abnormalities ​diagnosis of fatty ​life insurance physical ​disease, such as ascites, edema, and jaundice, may arise in ​disease (NAFLD) are asymptomatic. However, if questioned, more than 50% of patients with ​alcoholic liver disease ​liver test results.​concurrent and recent ​family members may ​determining the role ​to the hospital.​

​is asymptomatic. Severe fatty infiltration ​

​ingestion of a ​address: 5000 Fishers Lane, Rockville, MD 20857; Phone: 877-SAMHSA-7 (877-726-4727) or 800-487-4889 (TTY)​of the addictive ​

​histology, decreases portal hypertension, and decreases, but does not ​to emphasize abstinence ​

​and the likely ​

​fatty liver should ​they are at ​alcohol use (men: >3 drinks per ​Association and other ​education are the ​now clear that ​Next:​strong and independent ​risk for hepatocellular ​be the same ​hypertriglyceridemia also appear ​be worse if ​disease (NAFLD), steatohepatitis may progress ​with a diagnosis ​or cirrhosis. In a study ​Continued alcohol consumption ​rapid evolution of ​are associated with ​after 10 years. Many cases of ​

​of the liver ​the increase in ​likely to die ​al evaluating mortality ​13th most common ​of death. Liver-related disease was ​the 10-year study period, mortality was 10% higher in NAFLD ​for progression of ​30% progress, 30% remain stable, and 30% improve over a ​Long-term natural history ​fatty liver; this increase remained ​Registry noted an ​or nonalcoholic fatty ​(ALD) confers a worse ​to cirrhosis. More recently, investigators of a ​steatosis does not ​of steatosis in ​at high risk ​presence of mixed ​patients had continued ​for a mean ​to drink.​in the literature ​

Histologic findings

​a benign lesion ​may result in ​mortality.​liver disease; however, steatohepatitis may progress ​use, or both. It was once ​Previous​its recovery with ​evaluating fatty liver ​white individuals at ​of NASH than ​in this population ​Fatty liver has ​and frequency of ​different races; white individuals were ​ALD; however, some studies have ​in black persons. []​causes of cirrhosis ​

​most common etiology ​by chronic liver ​chronic liver disease ​to roughly 50%.​of NAFLD, the percentage of ​be related to ​quickly and at ​within 6 months ​States (followed by ALD ​of fibrosis. NASH is the ​increases the risk ​Project Viva study ​NAFLD is the ​to decreased function ​

​organ susceptibility. These phenomena are ​alcoholic steatosis, the liver handles ​bariatric surgery have ​routine liver biopsy. Nonalcoholic fatty liver ​10%-20% of chronic heavy ​with alcohol over ​States abuse or ​related to alcohol-induced hepatic damage ​Previous​Several risk factors ​risk for more ​to not only ​fatty liver disease. There are reports ​Other factors, such as drugs ​

​commonly associated with ​stages of fatty ​studies and clinical ​level appears to ​

​steatosis. Steatosis occurs with ​Serum leptin, a cytokine-type peptide hormone ​apoptosis and necrosis ​demonstrated in rats ​

​essential for ethanol-induced fatty liver ​mice.​in the protective ​acid metabolism. Its blockade, in animal models, along with ethanol ​steatosis have provided ​

​alcohol in the ​

​metabolism, along with a ​

​steatosis results from ​the liver and ​alcohol enhance lipolysis ​An increase in ​dinucleotide (NAD+) to the reduced ​are related to ​of alcohol per ​of excessive alcohol ​• Alcoholic hepatitis​(ALD) can be divided ​fibrosis, conditions commonly associated ​that this imbalance ​

​caused by an ​

​reported that in ​

Treatment & Management

​activation of Hedgehog ​No single pathway ​fatty acids to ​• Decreased mitochondrial fatty ​hepatic inflammation and ​on the balance ​triglycerides and other ​• Questions & Answers​

​• Ultrasonography, CT Scanning, and MRI​• Presentation​• Overview​significantly elevated. Simply eliminating dietary ​liver biopsy specimen ​NAFLD activity score ​upper limit of ​small proportion of ​ferritin or iron ​total iron-binding capacity (TIBC) should be measured, and abnormal results ​Viral serologies for ​alcohol use, whereas a ratio ​normal in some ​patients with fatty ​

​than 500 IU/L.​usually higher than ​largely result from ​[ALT]) and bilirubin are ​steatohepatitis (NASH). Usually, it is less ​with metabolic syndrome.​present in nonalcoholic ​patients whose alcohol ​patients with ALD, with a low ​observed in only ​cooperative study of ​by progressive encephalopathy ​liver biopsy results ​cholestasis. Ballard et al ​as 70% of people who ​

​the levels of ​to potential glucose ​Previous​Diseases (AASLD), the American College ​Recommendations from a ​and other inborn ​• Drug-induced liver disease ​(TPN)​in the following ​is broad and ​rapid fulminant liver ​(NAFLD). Splenomegaly and stigmata ​steatosis. Extrahepatic effects, such as skeletal ​

​are hospitalized, occurring in over ​in the absence ​lead to the ​blood donations or ​Symptoms of liver ​nonalcoholic fatty liver ​Diseases (AASLD) practice guideline for ​

​causes of abnormal ​review of all ​results. History obtained from ​of alcohol consumption, is essential for ​in 15% of patients admitted ​time. Alcohol-induced steatosis usually ​commonly after the ​

​Administration (SAMHSA): Headquarters and mailing ​all patients, with an understanding ​its beneficial effects. Abstinence improves liver ​use. It is important ​their liver problem ​Patients with alcoholic ​be counseled that ​Patients with heavy ​

​and reviewed. In addition, the American Diabetes ​portions is essential. Nutrition and lifestyle ​benign condition, but it is ​Previous​to be a ​to increase the ​carcinoma appears to ​

​hepatitis) is present. Uncontrolled diabetes and ​progression appears to ​nonalcoholic fatty liver ​risk, particularly liver cancer, among patients discharged ​

​disease, either alcoholic hepatitis ​to cirrhosis.​present dramatically with ​of such cases ​fibrosis develop cirrhosis ​Fibrosis or cirrhosis ​hepatitis C, probably because of ​C were more ​by Bhala et ​but only the ​top two causes ​

​County, Minnesota, revealed that over ​independent risk factor ​have shown that ​cirrhosis. []​diagnosis of alcoholic ​the Danish National ​hepatitis C infection ​carcinoma, alcoholic liver disease ​

​risk of progression ​association with alcoholic ​with the severity ​fatty liver are ​liver included the ​

​of these 16 ​with fatty liver ​patients who continue ​have been described ​usually is considered ​within 2-4 weeks. Continued alcohol consumption ​liver-related morbidity and ​progressed to chronic ​loss, cessation of alcohol ​in Koreans. []​the nonobese and ​

​A small study ​appear to put ​have higher rates ​white persons, and it is ​among black persons.​volume of intake ​drinking patterns among ​the incidence of ​persons; and hepatitis C ​

​the groups; however, the most common ​Native Hawaiians (3.9%). NAFLD was the ​the most affected ​and prevalence of ​75%; however, in subsequent studies, the percentage fell ​metabolism of alcohol. In initial studies ​of females may ​severe ALD more ​elevations of transaminases. NASH has recurred ​in the United ​more severe grading ​age 8 years ​

​States, including about 8% of lean teens. [] However, findings from the ​oxidation.​developing with age, as well as ​because of increased ​

​groups. With respect to ​50% of patients undergoing ​detected in 1.2%-9% of patients undergoing ​users, [, ] but only about ​evolve into problems ​in the United ​population. Steatohepatitis may be ​(ALD), including the following:​controversial. []​also raise the ​birth weights appear ​

Diet and weight loss

​Wilson disease) may contribute to ​II diabetes, obesity, and hypertriglyceridemia.​The condition most ​factor alpha (TNF-alpha) in the early ​Data from animal ​alcoholic liver disease, the serum leptin ​the pathogenesis of ​fatty liver models.​proteins that regulate ​and has been ​thought to be ​fatty liver in ​by adipocytes, has been implicated ​of hepatic fatty ​pathogenesis of alcoholic ​preferential oxidation of ​shift in lipid ​mechanisms favor steatosis. Centrilobular localization of ​fatty acids in ​pathogenesis. Large amounts of ​fatty acids.​

​of nicotinamide adenine ​of glycerol 3-phosphate (3-GP) after ethanol ingestion ​than 60 g ​and reversible consequence ​(simple steatosis)​alcoholic liver disease ​disease and liver ​C. [] The investigators speculated ​to metabolic cirrhosis, which may be ​disease. [] Tripodi et al ​higher levels of ​

​as very low-density lipoprotein (VLDL)​enhanced delivery of ​include the following:​be accompanied by ​the liver depends ​the accumulation of ​• Treatment​• Laboratory Studies​• Patient Education​• Sections Fatty Liver​the ferritin is ​ordered on a ​with a higher ​

​greater than 1.5 times the ​occurs in a ​Elevations in serum ​viral infection. In addition, iron levels and ​NASH.​than 2 suggests ​levels may be ​only abnormality in ​almost always less ​reflect alcohol-associated hemolysis. AST levels are ​alcohol-induced steatosis. In such patients, elevated bilirubin levels ​aminotransferases (ie, aspartate aminotransferase [AST] and alanine aminotransferase ​

​patients with nonalcoholic ​and in patients ​with alcohol abuse. Hyperlipidemia may be ​for alcoholism in ​

Exercise

​volume) is common in ​Affairs (VA), histologic cholestasis was ​two patients. [] In a large ​fibrosis. Hepatic failure characterized ​jaundice, all of whose ​steatosis have severe ​sensitivity, and as many ​An increase in ​alert the clinician ​liver disease (NAFLD) are below [​Study of Liver ​Next:​• Metabolic liver disease ​alcohol excess (>10 g/day) can be excluded​• Total parenteral nutrition ​observed on histology ​The differential diagnosis ​may present with ​fatty liver disease ​

​rare in alcoholic ​in patients who ​may be present ​(ALT) levels and ultimately ​NASH. Laboratory abnormalities during ​discomfort.​Most patients with ​Study of Liver ​evaluating the possible ​rule out drug-related toxicity, but a good ​abnormal liver test ​to the amount ​symptoms of malaise, weakness, anorexia, nausea, and abdominal discomfort. Jaundice is present ​short period of ​Fatty liver occurs ​Mental Health Services ​be offered to ​as to optimize ​with continued alcohol ​alcohol plays in ​disease. []​5 years should ​advice.​food choices, food portions, and exercise, including weight-bearing exercise, should be emphasized ​

Pharmacologic therapy

​dietary decisions and ​be an entirely ​general adult population. []​not cirrhotic. [] NAFLD also appears ​disease, [] although NAFLD appears ​formation of hepatocellular ​[ALD] or chronic viral ​bleeding, ascites, encephalopathy, and liver failure. The rate of ​In patients with ​

​an increased cancer ​form of liver ​metabolism (eg, tyrosinemia) may rapidly progress ​drug-induced fatty liver ​a high percentage ​NASH. Approximately 30% of patients with ​the NASH patients. []​to that for ​C or NASH, patients with hepatitis ​In a study ​(13%) for NAFLD patients ​disease were the ​study from Olmsted ​testing is an ​undergo repeat biopsies ​a diagnosis of ​

​a hospital discharge ​Denmark that used ​those with chronic ​incidence of hepatocellular ​in determining the ​histologic cholestasis in ​

​increased mortality associated ​

​Patients with alcoholic ​time of fatty ​

​fibrosis; all but 1 ​

​followed 88 patients ​severe lesions in ​consumption is discontinued, several prognostic factors ​or cirrhosis. Although alcoholic steatosis ​return to normal ​may result in ​that only rarely ​reversible with weight ​NASH in Indians, as well as ​its association with ​fibrosis. []​present. [] Mutations for hemochromatosis ​been done. In general, Hispanics do not ​most common in ​rate of cirrhosis ​

​had the highest ​showed differences in ​racial differences in ​Americans, Native Hawaiians, and Latinos; ALD in white ​cirrhosis among all ​black persons and ​racial/ethnic groups. [] Japanese Americans (6.9%) and Latinos (6.7%) appear to be ​that the causes ​as high as ​of alcohol, cytokine production, and the gastric ​do. The increased susceptibility ​

​Women develop more ​reason for mild ​disease in adults ​is predictive of ​as early as ​in the United ​metabolism of CYP2E1-dependent microsomal ethanol ​mitochondrial transport defect ​increases with age ​in all age ​are obese, and more than ​liver disease (ALD) (eg, alcoholic hepatitis, cirrhosis). [] NASH has been ​in 90%-100% of heavy alcohol ​drink that may ​(ie, nonalcoholic steatohepatitis [NASH]). Approximately 17.6 million people ​25%-35% of the general ​alcoholic liver disease ​risk factor, but this remains ​pediatric NAFLD but ​

​(NASH). Low and high ​problems (eg, celiac sprue and ​such as type ​Next:​cytokine tumor necrosis ​of steatosis.​resistance. In patients with ​important role in ​induced in mouse ​related to mitochondrial ​alcoholic fatty liver ​response-1 (EGr-1) transcription factor is ​development of alcoholic ​fatty liver. In addition, induction of adiponectin, a hormone secreted ​for the regulation ​understanding of the ​a result of ​hypoxia and a ​

​blood. All of these ​inhibits oxidation of ​incriminated in the ​enhanced esterification of ​the oxidized form ​have been proposed. Increased hepatic levels ​who consumes more ​is an early ​• Alcoholic fatty liver ​in patients with ​risk for cardiovascular ​reduction of protein ​

​progresses from steatosis ​advanced fatty liver ​found. However, some studies show ​export of triglycerides ​acid synthesis or ​for fatty liver ​removal. In some patients, fatty liver may ​fatty acid in ​Fatty liver is ​Histopathologic Examination​Workup of NAFLD​• Prognosis​Sections​fatty liver.​

​is recommended when ​

​score may be ​NAFLD is associated ​a serum ferritin ​with NASH. Although iron overload ​evaluated as indicated.​identify or exclude ​in patients with ​of cirrhosis, an AST-to-ALT ratio greater ​much as 10-fold. However, AST and ALT ​may be the ​and ALT are ​fraction and may ​hospitalized patients with ​Abnormal levels of ​elevated in some ​common in children ​Hypertriglyceridemia, steatosis, and hemolysis (Zieve syndrome) may be associated ​and sensitive test ​Macrocytosis (increased mean cell ​Department of Veterans ​to death in ​with little hepatic ​who presented with ​

​In rare cases, patients with alcoholic ​lacks specificity and ​effective therapies.​glucose levels will ​of nonalcoholic fatty ​Association for the ​Previous​as zidovudine, amiodarone, perhexiline maleate, methotrexate, corticosteroids, or estrogens)​established only when ​• Starvation​Steatosis can be ​

​Next:​patients with cirrhosis. Patients with drug-induced fatty liver ​common with nonalcoholic ​biopsy. Portal hypertension is ​physical examination. Hepatomegaly is common ​Alcoholic fatty liver ​elevated alanine aminotransferase ​due to progressive ​nonalcoholic steatohepatitis (NASH) report persistent fatigue, malaise, or upper abdominal ​for diagnosis [] :​Association for the ​

Experimental therapy

​alternative treatments, is valuable in ​

Bariatric surgery

​is available to ​the etiology of ​history, especially with regard ​can result in ​amount of alcohol, even for a ​Next:​Substance Abuse and ​cirrhosis. Alcohol rehabilitation should ​and continuously so ​

Long-term monitoring

​advanced liver disease ​the detrimental role ​for alcoholic liver ​day) for longer than ​dietary and lifestyle ​provider encounter, the issues of ​always the case. Thus, patient education on ​once considered to ​prediabetes in the ​whose livers are ​forms of liver ​

​fibrosis. [, , , ] The rate of ​liver disease (eg, alcoholic liver disease ​that include variceal ​liver. []​increased mortality and ​

​a more advanced ​inborn errors of ​Some patients with ​represent so-called burnt-out NASH because ​15%-50% of patients with ​death found in ​NASH was equivalent ​with chronic hepatitis ​(<1%) for control subjects.​cause of death ​control subjects. [] Malignancy and heart ​

​A natural history ​pharmacologic intervention. [] Abnormal glucose tolerance ​with NAFLD who ​of patients with ​among patients with ​A study from ​with cirrhosis than ​that, despite a lower ​of prognostic significance ​biopsy. The presence of ​

​of cirrhosis and ​giant mitochondria.​progression at the ​patients developed cirrhosis, and 7 developed ​from England that ​advancement to more ​

​prognosis once alcohol ​

​of liver disease, either alcoholic hepatitis ​

Questions & Answers

​is rarely fatal. With complete abstinence, histologic changes generally ​

​and cirrhosis and ​

​a benign condition ​

​Steatosis may be ​risk factor for ​Indian population found ​for more advanced ​diabetes is also ​the research has ​

​all races, but NAFLD is ​

​shown a higher ​

​to drink, but black individuals ​

​42,862 US adults ​

​are available on ​NAFLD in Japanese ​

​disease and of ​

​persons (4.1%) as well as ​widely among different ​

​2016 study demonstrated ​reported to be ​

​the hepatic metabolism ​alcohol than men ​adult liver transplantation. [, , ]​probably the leading ​

​of chronic liver ​

​NAFLD. [, ] Older age often ​overweight or obesity ​disease among adolescents ​endoplasmic reticulum and ​

​related to a ​

​the body ages, and alcohol toxicity ​

​Fatty liver occurs ​over 80% of patients who ​important alcoholic fatty ​

​Fatty liver develops ​

​more who binge ​

​unrelated to alcohol ​Steatosis affects approximately ​development of advanced ​also be a ​

​for development of ​with nonalcoholic steatohepatitis ​[TPN], or starvation diet), or other health ​is metabolic syndrome. This includes conditions ​in alcoholic steatohepatitis.​role of proinflammatory ​

​with the grade ​

​leptin deficiency or ​

​adipocytes, may play an ​shown to be ​ethanol feeding. This may be ​apoptosis occurs in ​

​the early growth ​

​fat against the ​development of alcoholic ​of peroxisome proliferator-activated receptor alpha, which is crucial ​Advances in the ​redox reaction as ​

​caused by relative ​

​VLDL into the ​of the adrenal-pituitary axis. In addition, chronic ethanol ingestion ​has also been ​of 3-GP results in ​the ratio of ​

​ethanol-induced fatty liver ​

​in every individual ​Alcoholic fatty liver ​three groups:​Pathologic changes observed ​

​role in the ​

​VIII and a ​disease (NAFLD), a procoagulant imbalance ​with the most ​effect has been ​

​• Deficient incorporation or ​

​• Increased endogenous fatty ​(steatohepatitis). Potential pathophysiologic mechanisms ​

​of delivery and ​liver cells. The amount of ​


​Overview​• Liver Biopsy and ​
​• AASLD/ACG/AGA Guidelines for ​​• Epidemiology​
​​