Alcohol-associated liver disease (ALD) often gives few clues as it progresses, and most patients are asymptomatic. When symptoms do appear they are non-specific: anorexia, nausea and vomiting, weakness, jaundice, weight loss, abdominal pain, fever and diarrhea. In severe disease, portal hypertension (raised pressure in the portal venous system) and its complications can develop even before cirrhosis is established.
Since symptoms are often absent or non-specific, the physical examination and laboratory tests are where the disease shows itself.
Physical examination
The most frequent finding is hepatomegaly (an enlarged liver), present in more than 75% of patients regardless of disease severity. Jaundice and ascites (fluid in the abdominal cavity) are each found in 60% of patients. Other findings are hepatic tenderness, spider angioma, splenomegaly, edema and palmar erythema.
Laboratory findings
Serum aminotransferases. Even in patients with severe ALD the rise in serum aminotransferase levels, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), is only modest, and the AST level is almost always below 400 U/L. Patients with ALD are deficient in vitamin B6, a cofactor for the activity of the ALT enzyme, so laboratory measurement of ALT underestimates it unless the sample is supplemented with vitamin B6. The AST:ALT ratio is greater than 2, a pattern that points to ALD.
Serum alkaline phosphatase can range from normal to values above 1000 U/L.
Serum bilirubin can range from normal to 20–40 mg/dL.
Serum albumin can range from normal to as low as 1–1.5 g/dL.
Other findings include anemia and prolongation of prothrombin time (PT), mostly in severely ill patients.
Histopathology
In most cases the clinical and laboratory findings are quite sensitive and specific for the diagnosis of ALD, but the definitive diagnosis always rests on histopathological study. The features on liver biopsy are:
- ballooning degeneration of hepatocytes
- Mallory bodies within damaged hepatocytes, surrounded by neutrophil infiltrates — Mallory bodies are the most specific histological alteration in ALD
- perivenular and centrilobular steatosis
- megamitochondria
In cirrhotic patients who have ALD, the cirrhosis nodules are mostly micronodular at diagnosis, but over time the micronodules convert to macronodules, which makes the cirrhosis indistinguishable from other causes of cirrhosis.
Hepatocellular carcinoma
Patients with ALD have a higher risk of progression to hepatocellular carcinoma (HCC), and the relative risk rises with the quantity of alcohol consumed daily. After abstinence, the relative risk of HCC falls by 6% each year, and after about 20 years it becomes similar to the control group.