The term cirrhosis refers to the histological findings of regenerative hepatic nodules surrounded by fibrous bands (collagenous scars) in the liver.1 These abnormal findings are caused by chronic liver injury and can lead to portal hypertension, esophageal varices, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, hepatocellular carcinoma, thrombocytopenia, and coagulopathies. While the exact prevalence of cirrhosis worldwide is difficult to determine for a number of reasons, a reasonable estimate is that up to 1% of populations are afflicted with the histological abnormalities that define cirrhosis. In the United States, liver disease is currently ranked 12th among the leading causes of death.2 Alcoholism and hepatitis C are the most common causes of cirrhosis in the western world.1 Other causes include hepatitis B, nonalcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson disease, and alpha-1-antitrypsin deficiency. Liver injury has been linked to nearly 1000 drugs.3 Examples of common drugs which may cause liver injury include amiodarone, HMG-CoA reductase inhibitors, highly active antiretroviral therapy, ketoconazole, nicotinic acid, acetaminophen, retinol, rifampin, isoniazid, phenytoin, valproic acid, azathioprine, estrogens, and oral contraceptives. Usually, drug-induced liver disease resembles acute hepatitis, cholestatic liver disease or mixed hepatitis/cholestasis, but may also resemble fibrosis and cirrhosis (eg, methotrexate).
Cirrhosis is an advanced state of liver fibrosis.1 Fibrosis is, in essence, the encapsulation or replacement of injured tissue by scar tissue. In cirrhosis, fibrosis is accompanied by a distortion of the hepatic vasculature. It leads to shunting of the hepatic blood supply from the portal vein and hepatic artery directly to hepatic outflow the central vein. This shunting compromises exchange between hepatic sinusoids and hepatocytes, which normally execute the expected functions of the liver (Figure 37-1). The major consequences of cirrhosis include impaired hepatocyte function, portal hypertension, and hepatocellular carcinoma. Portal hypertension can manifest as ascites, gastric or esophageal varices, and hepatic encephalopathy. Cirrhosis may be clinically silent or may include a variety of symptoms. Some of the possible symptoms of uncompensated cirrhosis include jaundice, spider angiomata, splenomegaly, ascites, palmar erythema, gynecomastia, hypogonadism, anorexia, fatigue, weight loss, muscle wasting, and type 2 diabetes.
The hepatic lobule. The numbers 1, 2, and 3 indicate the three functional zones based on relative oxygen supply, 1 being the highest.
Reproduced with permission from Sease JM, Timm EG, Stragand JJ. Portal hypertension and cirrhosis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY: McGraw-Hill; 2008:633-649.
Abnormal liver enzyme levels may signal liver damage.4 Both acute and chronic liver injury lead to increases in serum concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). ALT elevation is more specific for liver damage than AST elevation as AST is also present in the heart, skeletal muscle, kidneys, brain, and red blood cells. Marked elevations ...