Alcoholic Liver Disease

Alcoholic liver disease is a spectrum of liver injury caused by heavy and prolonged alcohol use, ranging from simple fatty liver to frank cirrhosis.

The burden of alcohol-related disease is highest in the developed world.

Alcoholic liver disease may be classified as:

Alcoholic fatty liver
Alcoholic hepatitis
Alcoholic cirrhosis of liver

Multiple stages that may be present simultaneously in a given individual.

Fatty liver develops in about 90% of individuals who drink more than 60 g/day of alcohol but may also occur in individuals who drink less.

There is no specific determined amount of alcohol consumption associated with liver injury, though a daily high intake for 10 to 20 years duration or longer is associated with higher risk.

If alcoholic liver disease develops, continued alcohol intake worsens the prognosis.

Only 10% of alcoholics develop end-stage liver disease. What separates those who develop advanced liver disease from those who do not is not clear.

The risk of developing cirrhosis is increased by coexisting hepatitis C virus infection

Pathogenesis of Alcoholic Liver Disease

The mechanism whereby alcohol produces different liver lesions is poorly understood. Fatty change may be due to increased production and decreased use of fatty acids in the liver cells

For the development of alcoholic hepatitis, fibrosis and cirrhosis, the production of toxic metabolites c during the conversion of acetaldehyde to acetate may be responsible. In addition, the immune reaction to liver cells altered by alcohol may also be involved.

Ethanol is principally metabolized by hepatocyte alcohol dehydrogenase to acetaldehyde, which is further metabolized by aldehyde dehydrogenase to acetate. Faster formation of acetaldehyde by alcohol dehydrogenase or decrease in clearance of acetaldehyde by variants of aldehyde dehydrogenase could increase the exposure of hepatocytes to highly reactive acetaldehyde.

Determinants of Liver Injury

Amount and duration of alcohol ingestion
Malnutrition
Female Sex
Obesity
Hepatic iron overload
Genetic predisposition may play a role in alcohol dependence.
Blacks and Hispanics race

Alcoholic Fatty Liver

Fatty liver is the most common hepatic manifestation of chronic alcohol intake.

The fatty change in the liver begins as early as two days of alcohol intake and resolves within two weeks of discontinuation of alcohol.

Pathology

The liver is enlarged, greasy, yellow and firm. Hepatocytes are distended with fatty vacuoles which pushes the nucleus to the periphery.

This occurs because the fatty acid oxidation is impaired and they are taken up by the cells and esterified to form triglycerides.

Presentation

The clinical features are minimum or absent.

Patients may have mild right upper quadrant pain and hepatomegaly.

Aminotransferases can be elevated and gamma-glutamyl transpeptidase levels are often increased as a result of ethanol-induced microsomal enzyme activity.

Alcoholic fatty liver can be difficult to differentiate from non-alcoholic fatty liver disease.

Following features suggest alcoholic cause

History of alcohol consumption
Aspartate transaminase (AST)/ alanine transaminase (ALT) ratio > 2,
Markedly elevated GGT suggest alcoholic fatty liver
Changes consistent with fatty liver on ultrasound

Liver Biopsy is not required for diagnosis but if done, would reveal

Macrovesicular fat of perivenular hepatocytes.
Microvesicular fatty change (alcoholic foamy degeneration) – This develops due to mitochondrial dysfunction associated with severe hepatic encephalopathy and hyperbilirubinemia.

Treatment

Abstinence from alcohol
Nutritional support

Prognosis

Alcoholic fatty liver has a good prognosis. Complete resolution occurs after cessation of alcohol intake.

Alcoholic Hepatitis

Alcoholic is an inflammatory lesion characterized by infiltration of the liver with leucocytes, liver cell necrosis, and alcoholic hyaline deposition. Alcoholic hepatitis develops in approximately 10% of those with long-term daily ethanol consumption.

Clinical Features

This varies from asymptomatic patient to mild illness to fatal liver cell failure.

Anorexia, nausea, vomiting, abdominal pain, malaise, weight loss, and jaundice.
Fever as high as 39 to 40 degree Celsius may be seen in 50 percent of cases
Tender hepatomegaly is usually present. Splenomegaly occurs in 33 percent of cases
Signs of liver cell failure like spider angioma, jaundice, ascites, edema, GI bleeding, and encephalopathy may be present
Cholestatic jaundice may occur in some

Anemia due to
- Gastrointestinal bleed
- Nutritional deficiency (folate and B12 deficiency)
- Hypersplenism
- Direct bone marrow suppression
- Hemolysis

Arterial bruit will be heard over the liver.

Laboratory studies in Alcoholic Hepatitis

Mild leukocytosis
In hypersplenism, leucopenia and thrombocytopenia can be present
AST/ALT > 2
Elevated alkaline phosphatase and GGT
Hypothrombinemia
Hyperbilirubinemia
Cholestasis
Hypoalbuminemia
Prolonged prothrombin time [reflects reduced synthesis of vitamin K]
Hypomagnesemia and hypophosphatemia [ dietary deficiency]
Hypokalemia may occur due to hyperaldosteronism (aldosterone is normally destroyed in liver).

Histological changes in alcoholic hepatitis.

Hepatocellular necrosis
Ballooning degeneration of hepatocytes
Macro- and microvesicular steatosis/fatty metamorphosis of hepatocytes
Polymorphonuclear leukocyte inflammation
Cholestasis
Mallory’s hyaline
Pericellular fibrosis

Note: Mallory bodies are also seen with morbid obesity, jejuno-ileal shunt, uncontrolled diabetes mellitus, Wilson disease, Indian childhood cirrhosis, etc.

Treatment of Alcoholic Hepatitis

Maddrey’s Discriminating Factor Score is calculated for all patients with alcoholic hepatitis. It can predict outcome and treatment could be tailored to it.

Maddrey’s DF score = Bilirubin (mg/dL) + 4.6 times (prothrombin time in seconds minus control).

> 32 is associated with 50% mortality within 2 months of the onset of alcoholic hepatitis.

The treatment of alcoholic hepatitis is

Abstinence – Mild alcoholic hepatitis may resolve with abstinence alone. Patients might require rehabilitation for the same
Nutrition – All patients should consume a minimum of 2000 dietary kcal daily. Enteral feeding may be instituted. Nutrition improves liver function tests and intestinal function^] reducing systemic

Corticosteroids if DF > 32
Pentoxifylline if DF < 32.

Prognosis

In milder cases, clinical recovery can occur completely. However, repeated bouts of alcoholic hepatitis may lead to irreversible progressive liver injury, abstinence from alcohol can reduce long term morbidity and mortality.

Marked hyperbilirubinemia, elevated creatinine, elevated prothrombin time, ascites and encephalopathy are associated with poor short term prognosis.

Overall, alcoholic hepatitis carries 35%-45% mortality.

Alcoholic Cirrhosis

These patients may not have any symptoms or may present with end-stage liver disease and portal hypertension including ascites, encephalopathy, or variceal bleeding.

Laboratory findings are deranged as in other liver diseases- elevated prothrombin time, abnormal liver function tests and hypoalbuminemia.

Prognosis

The prognosis of cirrhosis depends whether it is compensated or decompensated

In compensated alcoholic cirrhosis

90% 5- year survival who stop alcohol consumption
70% 5-year survival if they continue alcohol consumption.

Patients with decompensated cirrhosis who continue alcohol consumption have a 5-year survival rate of only 30%.

Overall outcomes for liver transplantation for alcoholic cirrhosis are excellent. Twenty percent of transplanted patients return to excessive alcohol consumption.

Summary of Treatment of Alcoholic Liver Disease through Different Stages

All Alcoholics

Total Abstinence
Rehabilitation for alcoholism
Nutritional supplementation.

Alcoholic Hepatitis

Corticosteroids if DF > 32; and
Pentoxifylline if DF < 32.

Alcoholic Cirrhosis

Liver transplantation for decompensation.

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