Cirrhosis (or end-stage liver disease) is an advanced state of liver fibrosis. Fibrosis, the replacement of injured tissue by scar tissue, 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 complications of cirrhosis include impaired hepatocyte function, portal hypertension, esophageal varices, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, thrombocytopenia, coagulopathies, hepatocellular carcinoma, hepatorenal syndrome, and hepatopulmonary syndrome. Cirrhosis may be asymptomatic or encompass a variety of symptoms. Symptoms of cirrhosis include jaundice, spider angiomas 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 40-1. 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 40-1Medications Associated with Liver Damage (list not all inclusive) ||Download (.pdf) TABLE 40-1Medications Associated with Liver Damage (list not all inclusive)
HMG-CoA reductase inhibitors (eg, [statins])
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 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 to a lower degree than acute injury. AST and ALT levels may be within the normal range in patients with cirrhosis or chronic liver disease. Elevations in alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) may accompany cholestatic liver disease (eg, drug-induced cholestatis, cholangitis). ALP 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 parameters and clinical manifestations (Table 40-2). Drug dosing recommendations and adjustments for hepatically metabolized medications are based upon 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 and determines mortality risk.
TABLE 40-2Criteria and Scoringa for the Child-Pugh Grading of Chronic Liver Disease