SPECIFIC CAUSES OF CIRRHOSIS



Alcohol. Alcoholic cirrhosis may coexist with alcoholic hepatitis. Features of hepatocellular dysfunction are thus often marked and may im­prove with abstinence. Micronodular cirrhosis is the rule but is not specific for alcohol. Evidence of malnutrition and vitamin deficiency is fre­quently found, particularly in the severely alco­holic patient. Anemia of mixed etiology is com­mon, often with macrocytic indices.

Chronic Active Hepatitis. Chronic active hep­atitis from any cause may progress to cirrhosis. The liver is typically small with a macronodular pattern. Evidence of continued inflammatory activity is often present, including moderate elevation of transaminase levels and hypergam­maglobulinemia. HBsAg is usually persistently positive in cirrhosis due to hepatitis B virus.

Primary Biliary Cirrhosis. Almost exclusively a disease affecting women, primary biliary cir­rhosis manifests mainly between the ages of 30 and 65 and results from a progressive, probably immune-mediated, destruction of the intralobular bile ductules. Cholestatic features predominate with high serum levels of alkaline phosphatase and cholesterol. Pruritus is a major early symp­tom, followed later in the course of the disease by xanthomas, pigmentation, and bone pain. Com­monly associated conditions include Sjogren’s syndrome, scleroderma, and the CREST syndrome (calcinosis, Raynaud’s syndrome, esophageal dys­function, sclerodactyly, telangiectasia). Antimi-tochondrial antibodies are present in high titer, and serum IgM levels are elevated. Liver biopsy may show characteristic destructive lesions of the bile ductules and is of value in confirming the diagnosis. Jaundice is a prominent feature late in the course of the disease.

Hemochromatosis. Hemochromatosis is a ge­netically determined disorder of inappropriate iron absorption. Hepatic iron overload eventually leads to fibrosis and cirrhosis. Iron deposition oc­curs in other tissues as well, leading to skin pig­mentation, diabetes, cardiac failure, hypogonad­ism, and arthropathy. Hepatomegaly is usually found, and the risk of developing hepatocellular carcinoma is high. The diagnosis is supported by findings of high serum iron and ferritin levels with increased transferrin saturation. Liver biopsy shows increased iron in hepatocytes, and direct estimation of liver iron in biopsy specimens is of value in making the diagnosis. Treatment consists of removal of excess body iron stores through phlebotomy at weekly intervals, or more rarely through the use of chelating agents.
Wilson’s Disease. Wilson’s disease is an au­tosomal recessive abnormality in hepatic copper excretion. Copper accumulates in the liver, cen­tral nervous system, and othertissues. Wilson’s dis­ease may eventualy lead to cirrhosis or may pre­sent as acute, fulminant hepatic failure or chronic active hepatitis. Deposition of copper in the cen­tral nervous system leads to a predominantly ex­trapyramidal form of motor disorder (basal gan­glia damage) with rigidity, tremor, chorea, and dysarthria. Psychiatric disorders are also com­mon. Copper deposited in Descemet’s membrane of the cornea manifests as the characteristic KayserFleischer rings, which are best seen on slit-lamp examination. Typical laboratory findings are low serum levels of ceruloplasmin and in­creased urinary copper excretion. Direct mea­surement of copper in liver biopsy specimens may be of great value in diagnosing Wilson’s disease and monitoring its response to therapy. Copper chelation therapy with Dpenicillamine arrests progression of the disease and may prevent its manifestations if instituted early enough.