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--A chronic degenerative disease of the liver characterized by destruction of the hepatic parenchymal cells, which are replaced by regenerative nodules surrounded by fibrotic tissue.

Causes and Incidence The etiology is not fully understood, but several factors play important roles, including alcohol abuse; malnutrition; infectious processes (e.g., hepatitis, schistosomiasis, syphilis); toxins (e.g., arsenic, carbon tetrachloride, phosphorus); drugs (e.g., chlorpromazine, methyldopa, methotrexate, tolbutamide, isoniazid, amitrip-tyline); genetic disorders (e.g., galactosemia, Wilson's disease, alpha-antitrypsin deficiency); congenital malformations (e.g., biliary atresia); and vascular disorders (e.g., portal vein thrombosis, Budd-Chiari syndrome, chronic heart failure). Other factors remain unknown.

In the United States, most cirrhosis develops secondary to alcohol abuse. It is the ninth leading cause of death across all age groups, and the third leading cause of death in the 45 to 65 age group. In Africa and Asia, cirrhosis secondary to chronic viral hepatitis B is a major cause of death.

Disease Process Cirrhosis is the end-stage disease that begins with one of the many etiologic factors. The development and progression of cirrhosis are tied to the severity of the injury and the liver's response. A severe, acute injury may be involved, as in hepatitis, or a moderate chronic injury may be the cause, as in alcohol abuse. When an injury causes destruction of parenchymal cells, the initial response is fibrosis, as the liver attempts to repair itself. Fat-storing cells proliferate and are transformed into myofibroblasts, which alter the secretion, synthesis, and degradation of collagen. This results in deposition of excessive connective tissue, which alters normal lobular structures, interferes with cellular nutrition, obstructs hepatic blood flow, and forms anastomotic channels that shunt arterial blood away to efferent hepatic veins. The regenerative attempts continue as long as an injury is present. The resulting changes in the intrahepatic circulatory pathways make the system less efficient and eventually lead to an increase in portal vein pressure. The change in or destruction of lobular architecture interferes with various liver functions, such as metabolism, detoxification, storage, and blood and bile formation.

Symptoms

Early

Often asymptomatic; otherwise, abdominal pain, diarrhea, nausea, vomiting, fatigue, fever

Mid-course

Chronic dyspepsia, constipation, anorexia, weight loss, pruritus, easy bruising, bleeding gums, nose bleeds, upper gastrointestinal bleeding, enlarged liver

Late

Telangiectasis, spider angiomas, enlarged breasts, testicular atrophy, jaundice, impotence, enlarged spleen, depression, abdominal vein distention, ascites, encephalopathy, peripheral neuropathy

Potential Complications Complications include bleeding esophageal varices, which can lead to massive hemorrhage; hepatorenal syndrome, which leads to renal failure; and hepatic encephalopathy, which leads to coma and death.

Diagnostic Tests

Liver biopsy

Definitive histologic changes

Serum albumin

Decreased

Prothrombin time

Prolonged

Complete blood count

Evidence of anemia, leukopenia, thrombocytopenia

Blood glucose

Decreased

Ultrasonography

Hepatosplenomegaly, enlarged portal veins

Liver scans

Reduced liver uptake

Treatments

Surgery

Liver transplantation for advanced disease; portal systemic shunt to treat resistant esophageal varices; peritoneovenous shunt for ascites

Drugs

Diuretics to reduce edema; digestants to promote fat digestion; supplemental vitamins; stool softeners

General

Elimination of toxic agents such as alcohol or drugs; diet high in protein, carbohydrates, and calories and low in sodium; blood and blood products, gastric lavage, esophageal balloon for bleeding varices; abdominal paracentesis for ascites; renal dialysis for renal failure