Cirrhosis is an advanced state of liver fibrosis and fibrosis is the replacement of injured tissue by scar tissue. Fibrosis is accompanied by a distortion of the hepatic vasculature leading to shunting of hepatic blood supply. The shunting compromises exchange between hepatic sinusoids and hepatocytes altering the functions of the liver. The consequences of cirrhosis include impaired hepatocyte function, portal hypertension, hepatocellular carcinoma, hepatorenal and hepatopulmonary syndrome, thrombocytopenia, and coagulopathies. Cirrhosis may be asymptomatic or encompass a variety of symptoms. Symptoms of cirrhosis include jaundice, spider angiomata, splenomegaly, ascites, palmar erythema, gynecomastia, hypogonadism, anorexia, fatigue, weight loss, muscle wasting, and type 2 diabetes.
Alcoholism and hepatitis C are the most common causes of cirrhosis. Examples of medications that cause liver injury are listed in Table 42-1. Drug-induced liver disease resembles acute hepatitis, cholestatic liver disease, or mixed hepatitis/cholestasis. Additionally, drug-induced liver disease may also resemble cirrhosis and fibrosis (eg, methotrexate).
TABLE 42-1Medications Associated With Liver Damage |Favorite Table|Download (.pdf) TABLE 42-1Medications Associated With Liver Damage
HMG-CoA reductase inhibitors
Highly active antiretroviral therapy
Acute and chronic liver injuries increase serum concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Abnormal AST and ALT liver enzymes may signal liver damage. ALT elevation is more specific for liver damage because AST is present in the heart, skeletal muscle, kidneys, brain, and red blood cells. AST and ALT elevations greater than 10 times the normal limit are associated with acute hepatic injury (eg, toxic liver injury or acute viral hepatitis). Cirrhosis and chronic hepatitis also increase AST and ALT, but not to the same degree as acute injury. AST and ALT levels may be within the normal range in patients with cirrhosis or chronic liver disease. Elevations in alkaline phosphatase (alk phos) and γ-Glutamyl transpeptidase (GGT) may accompany cholestatic liver disease (eg, drug-induced cholestasis, cholangitis). Alk phos and GGT are present in other tissues; therefore, they lack specificity for liver disease. Though also nonspecific for liver disease, decreased serum albumin, increased conjugated bilirubin, and increased prothrombin time are potential findings in end-stage liver disease.
QUANTIFICATION OF LIVER DYSFUNCTION AND DRUG DOSE ADJUSTMENT
The Child-Pugh classification system quantifies cirrhosis by evaluation of laboratory and clinical manifestations (Table 42-2). Drug dosing recommendations and adjustments for hepatically metabolized medications are based on the Child-Pugh score. However, the model for end-stage liver disease (MELD) scoring system is the classification used by the United Network for Organ Sharing in the allocation of livers for transplantation.
TABLE 42-2Criteria and Scoring for the Child-Pugh Grading of Chronic Liver Disease