Alcoholic Fatty Liver

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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.

Epidemiology

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

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.

Sex

Age

History

Alcohol-induced steatosis usually is asymptomatic in ambulatory patients.

The American Association for the Study of Liver Diseases 2010 practice guideline for ALD recommends the following for diagnosis:[1]

Physical

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

Causes

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Histologically, fatty liver is characterized by fat accumulation, which is most prominent in the pericentral (centrilobular) zone. Macrovesicular steatosis is the rule; hepatocytes containing one or more large fat droplets displace the nucleus to an eccentric position. Occasional lipid release from rupture of distended hepatocytes may produce a mild localized inflammatory response (lipogranulomas) composed predominantly of macrophages and occasional lymphocytes. Although infiltration of liver with inflammatory cells is not prominent in patients with steatosis alone, in some instances, fibrosis around terminal venules (ie, perivenular fibrosis) and/or hepatocytes (ie, pericellular fibrosis) has been noted. Early changes observed with the electron microscope include accumulation of membrane-bound fat droplets, proliferation of smooth endoplasmic reticulum, and gradual distortion of mitochondria. Microvesicular steatosis also is being recognized with increasing frequency.

Alcoholic foamy degeneration (microvesicular fatty change) was the term used by Uchida et al (1983) to describe a clinical syndrome in people with chronic alcoholism.[3] The syndrome is characterized by jaundice and hyperlipidemia and is associated with striking microvesicular steatosis and abundant giant mitochondria observed on liver biopsy.

Medical Care

Consultations

Diet

Medication Summary

No drug therapy is indicated for patients with alcoholic fatty liver unless the patient has alcoholic hepatitis.

Further Outpatient Care

Deterrence/Prevention

Complications

Prognosis

Author

Mohammad K Ismail, MD, AGAF, Associate Professor, Department of Internal Medicine and Gastroenterology, Program Director for Gastroenterology Fellowship and Training, University of Tennessee Health Science Center

Disclosure: Nothing to disclose.

Coauthor(s)

Caroline Riely, MD, Professor, Departments of Medicine and Pediatrics, University of Tennessee Health Science Center College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

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.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP, Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

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