Chapter 40 ALCOHOLIC LIVER DISEASE
Alcohol remains one of the most common causes of liver disease and contributes to 1000 deaths and 64,000 hospital admissions per year in Australia. National per capita alcohol consumption correlates with mortality from alcoholic liver disease (ALD), has fallen from a peak in 1985 but has been relatively static for the last decade.
Symptoms and signs are not reliable indicators of the presence or severity of ALD. There may be no symptoms even in the presence of cirrhosis. In other cases, clinical features do allow a confident diagnosis. The clinical and pathological spectrum of alcoholic liver disease includes fatty liver, hepatitis and cirrhosis, but these commonly coexist.
Alcoholic fatty liver results from accumulation of fat droplets within hepatocytes (steatosis) without inflammation or fibrosis. It may commence after a few days of heavy drinking and manifests as anorexia, nausea and right upper quadrant discomfort. The liver is enlarged, firm and may be tender. There are typically no other signs.
Alcoholic hepatitis is defined pathologically by polymorphonuclear infiltration with hepatocyte injury (ballooning necrosis and apoptosis), accumulation of Mallory’s hyaline (derived from intermediate filaments) and variable hepatic fibrosis. It presents with anorexia, nausea and abdominal pain, with jaundice, bruising and encephalopathy in association with alcohol abuse. Hepatomegaly may be marked and associated with tenderness, splenomegaly, signs of liver failure and ascites. Systemic disturbances include fever and neutrophilic leucocytosis. The gamma-glutamyltransferase (GGT) is the predominant abnormality. The AST generally exceeds the ALT, but both are only moderately raised. Values for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 500 U/L suggest another disorder that may coexist with ALD, most often viral hepatitis or paracetamol (acetaminophen) toxicity.
Mild cases are common and typically manifest with abnormal serum biochemistry, and hepatomegaly. Severe alcoholic hepatitis is relatively rare and carries a short-term mortality of approximately 50%. The severity of alcoholic hepatitis can be assessed using a number of simple quantitative indices (Maddrey score, MELD Score, Combined Clinical and Laboratory Index). Of these, the Maddrey Discriminant Function (MDF) is the simplest (Table 40.1).
Maddrey score = 4.6 × (prolongation of prothrombin time above control in seconds) + bilirubin (μmol/L)/17
Example: Patient prothrombin time 16 s, bilirubin 150 μmol/L, laboratory control prothrombin time 12 s
Alcoholic cirrhosis may present with fatigue, anorexia, nausea, malaise or weight loss but typically presents with complications such as portal hypertension leading to variceal bleeding and/or ascites, liver failure and hepatocellular carcinoma. Alcoholic cirrhosis is a recognised risk factor for hepatocellular carcinoma but it is not clear that there is an association between alcohol abuse and hepatocellular carcinoma in the absence of cirrhosis.
Physical examination may be normal in compensated cirrhosis. Peripheral signs include spider naevi, palmar erythema and Dupuytren’s contracture (a sign of alcohol use but not cirrhosis). Among hospitalised patients, hepatomegaly is the most common finding. Jaundice, ascites and encephalopathy are found in about half and alcohol withdrawal is evident in 29% of patients.
The risk of liver disease is related to the amount of alcohol consumed, but female gender, other undefined genetic factors, chronic viral hepatitis, hepatotoxins, obesity and other nutritional impairment all accelerate the disease process. Hepatitis C is more common in alcoholics than in the general community and when the two are combined, liver disease progresses more rapidly.
Excessive drinkers are at increased risk of some types of drug-induced liver injury. For example, paracetamol in apparently therapeutic doses has led to acute liver failure in alcoholics and methotrexate accelerates hepatic fibrosis in heavy drinkers.
A quantitative alcohol history should be recorded for all patients. Average daily consumption is expressed in grams of alcohol or standard drinks (each containing 10 g ethanol). Consumption is frequently underreported. In some cases, alcohol abuse may be recognised via other typical medical or psychosocial problems such as depression, neurological toxicity, abdominal pain, relationship difficulties, poor work performance, trauma and violence.
|A positive response on screening indicates the need for further assesssment|
a. AUDIT (original version has 10 questions, but question 3 on its own is very useful)
b. The CAGE screening questions: two or more positive responses suggest alcohol dependence
Laboratory markers such as gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) are only moderately sensitive and specific for drinking problems in general. In ALD, the GGT level is almost invariably elevated. However, elevated levels may also be seen in other liver diseases and with some drugs (notably anticonvulsants). The MCV is generally less sensitive and less specific than GGT. Combined assessment of MCV and GGT detects 70% of the alcohol-dependent population. The carbohydrate-deficient transferrin (CDT) test may be more specific than GGT, but the test is not widely available at present and there are false positives in any form of advanced liver disease. Several other laboratory parameters may be elevated, including uric acid, triglycerides and high-density lipoprotein cholesterol. These are not adequately sensitive or specific for use as a screening test.