eMedicine Specialties > Gastroenterology > Liver

Alcoholic Fatty Liver

Author: Mohammad K Ismail, MD, Assistant Professor, Department of Internal Medicine and Gastroenterology, University of Tennessee at Memphis
Coauthor(s): Caroline Riely, MD, Professor, Departments of Medicine and Pediatrics, University of Tennessee Health Science Center
Contributor Information and Disclosures

Updated: Sep 15, 2008

Introduction

Background

Pathologic changes observed in patients with alcohol-induced liver disease can be divided into the following 3 groups: alcoholic fatty liver (simple steatosis), alcoholic hepatitis, and alcohol-related cirrhosis. Alcoholic fatty liver is an early and reversible consequence of excessive alcohol consumption.

See related CME at Advances in Alcoholic Liver Disease and NAFLD.

Pathophysiology

The amount of fatty acid in the liver depends on the balance between the processes of delivery and removal. Fatty liver develops in every individual who consumes more than 60 g/d of alcohol. Many mechanisms of ethanol-induced fatty liver have been proposed. Increased hepatic levels of glycerol 3-phosphate (3-GP) following ethanol ingestion are related to an increase in the ratio of nicotinamide adenine dinucleotide, reduced form, (NADH) to nicotinamide adenine dinucleotide (NAD) in the liver. Increasing concentration of 3-GP results in enhanced esterification of fatty acids.

An increased level of free fatty acids also has been incriminated in the pathogenesis of fatty liver. Large amounts of alcohol enhance lipolysis because of the direct stimulatory effect on the adrenal and pituitary axis. In addition, chronic ingestion of ethanol inhibits the oxidation of fatty acids in the liver and the release of very low-density lipoprotein (VLDL) into the blood. All of these mechanisms favor steatosis. Centrilobular localization of steatosis results from decreased energy stores from relative hypoxia and a shift in lipid metabolism, along with a shift in the redox reaction caused by the preferential oxidation of alcohol in the central zone.

Advancement in the understanding of the pathogenesis of alcoholic steatosis provided some novel insights, including the role of peroxisome proliferator-activated receptor alpha, which is crucial for the regulation of hepatic fatty acid metabolism. Its blockade, in animal models, along with ethanol consumption, contributes to the development of alcoholic fatty liver. In addition, induction of adiponectin, a hormone secreted by adipocytes, has been implicated in the protective action of saturated fat against the development of alcoholic fatty liver in mice.

Recent developments in the understanding of the pathogenesis of fatty liver provided the findings described below.

The role of the early growth response-1 (EGr-1) transcription factor is thought to be essential for ethanol-induced fatty liver injury in mice. Hepatocyte death by apoptosis occurs in alcoholic fatty liver and has been demonstrated in rats and mice after ethanol feeding. This may be related to mitochondrial proteins that regulate apoptosis and necrosis and that are shown to be induced in mouse fatty liver models.

Serum leptin, a cytokine-type peptide hormone mainly produced by adipocytes, may play an important role in the pathogenesis of steatosis. Steatosis occurs with decreased leptin action, whether due to leptin deficiency or resistance. In a recent study in patients with alcoholic liver disease, serum leptin was noted to be independently correlated with the grade of steatosis.

Recent data from both animal studies and clinical studies support the role of proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in the early stage of fatty liver as well as alcoholic steatohepatitis.

Frequency

United States

Approximately 15.3 million people in United States abuse or depend on alcohol. Fatty liver develops in 90-100% of patients with heavy alcohol use.

International

One observational study from northern Italy demonstrated prevalence rates of steatosis in 46.4% of heavy drinkers (>60 g/d of alcohol) and in 94.5% of obese heavy drinkers.

Mortality/Morbidity

  • Simple steatosis rarely is fatal. With complete abstinence, histologic changes can return to normal within 2-4 weeks.
  • Continued alcohol consumption may result in more advanced forms of liver disease, either alcoholic hepatitis or cirrhosis.
  • A study from Denmark, which used the Danish National Registry, noted an increase in mortality among patients with a hospital discharge diagnosis of alcoholic fatty liver, which remained increased after censoring patients upon a diagnosis of cirrhosis.

Race

Very little data are available on racial differences in the incidence of alcoholic fatty liver. However, overall differences in alcoholic liver disease have been noted in various studies.

  • One study of 42,862 US adults showed differences in drinking patterns among different races. Whites were the most likely to drink, but blacks had the highest volume of intake and frequency of heavy drinking.
  • Another study showed a higher rate of cirrhosis among blacks.

Sex

  • Women develop more severe alcoholic liver disease (ALD) more quickly and at lower doses of alcohol than men.
  • Increased susceptibility of females possibly is related to sex-dependent differences in the hepatic metabolism of alcohol, cytokine production, and the gastric metabolism of alcohol.

Age

  • The liver handles alcohol differently with age, and alcohol toxicity increases with age because of increased organ susceptibility. This is thought to be related to a mitochondrial transport defect with age as well as decreased function of the smooth endoplasmic reticulum and metabolism of CYP2E1-dependent microsomal ethanol oxidation.

Clinical

History

Alcohol-induced steatosis usually is asymptomatic in ambulatory patients.

  • Fatty liver occurs commonly after the ingestion of a moderate or large amount of alcohol, even for a short period of time.
  • A thorough clinical history, especially with regard to the amount of alcohol consumption, is essential to determining the role of alcohol in the etiology of the abnormal liver test results. History obtained from the family members may reveal past alcohol-related problems.
  • No specific test is available to rule out drug-related toxicity, but a good review of all concurrent and recent medications, including over-the-counter medications and alternative treatments, is essential in evaluating the possible causes of abnormal liver test results.
  • Severe fatty infiltration of the liver can result in symptoms of malaise, weakness, anorexia, nausea, and abdominal discomfort.
  • Jaundice is present in 15% of patients admitted to the hospital because of these symptoms of fatty infiltration of the liver.

Physical

Fatty liver may be present in the absence of any abnormalities noted on the physical examination.

  • Hepatomegaly is common in patients who are hospitalized, occurring in over 70% of persons with steatosis proven on biopsy.
  • Portal hypertension is rare in alcoholic steatosis.

Causes

  • Several risk factors may be cofactors required for the development of advanced ALD.
  • Minimum amounts of alcohol intake associated with an increased risk for developing ALD range from 40-80 g/d for 10-12 years.
  • Genetics play a role in alcohol consumption and alcoholism. In addition, early data suggested a genetic predisposition to the development of ALD mostly related to differences in major hepatic enzymes involved in the metabolism of alcohol—alcohol dehydrogenase (ADH), acetaldehyde dehydrogenase (ALDH), and cytochrome P-450 system (CYP4502E1).
  • Several studies demonstrate a high prevalence of hepatitis C virus (HCV) antibody in patients with ALD, as well as iron overload.
  • Obesity and dietary habits have been implicated in individual susceptibility to ALD.

More on Alcoholic Fatty Liver

Overview: Alcoholic Fatty Liver
Differential Diagnoses & Workup: Alcoholic Fatty Liver
Treatment & Medication: Alcoholic Fatty Liver
Follow-up: Alcoholic Fatty Liver
References
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Further Reading

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Keywords

alcoholic fatty liver, alcoholic steatosis, alcoholism, fatty liver, alcohol-related fatty liver, alcoholic liver disease, alcohol-related liver disease, simple steatosis, alcohol-related steatosis, fatty acids, alcoholic complications, alcohol-induced steatosis, alcohol-induced fatty liver

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Contributor Information and Disclosures

Author

Mohammad K Ismail, MD, Assistant Professor, Department of Internal Medicine and Gastroenterology, University of Tennessee at Memphis
Mohammad K Ismail, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Caroline Riely, MD, Professor, Departments of Medicine and Pediatrics, University of Tennessee Health Science Center
Caroline Riely, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Federation for Medical Research, American Gastroenterological Association, North American Society for Pediatric Gastroenterology and Nutrition, and Society of Obstetric Medicine
Disclosure: Nothing to disclose.

Medical Editor

Ann Ouyang, MBBS, Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Attending Physician, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine
James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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