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A 64-year-old woman presents with complaints of itchy skin and fatigue. She is noted on physical examination to have scleral icterus and jaundice (Figure 63-1). Laboratory testing revealed elevated liver enzymes, particularly the serum alkaline phosphatase and γ-glutamyltranspeptidase, and positive antinuclear and anti-mitochondrial antibodies. A liver biopsy confirmed primary biliary cirrhosis. Two months later, she vomited up some blood and on endoscopy was found to have esophageal varices from her portal hypertension (Figure 63-2).


Scleral icterus in a 64-year-old Hispanic woman with primary biliary cirrhosis. (Reproduced with permission from Javid Ghandehari, MD.)


Esophageal varices in the patient in Figure 63-1 secondary to her cirrhosis and portal hypertension. (Reproduced with permission from Javid Ghandehari, MD.)


Liver disease can be caused by any number of metabolic, toxic, microbial, circulatory, or neoplastic insults resulting in direct liver injury or from obstruction of bile flow or both. Liver injury falls anywhere on the spectrum from transient abnormalities in biomarkers to life-threatening multiorgan failure. Cirrhosis refers to the development of liver fibrosis with resulting architectural distortion and the formation of regenerative nodules.


The following terms refer to various types of liver diseases: hepatic failure, hepatic dysfunction, alcoholic hepatitis, viral hepatitis, cirrhosis, hepatocellular disease, cholestatic disease, liver fibrosis.


Common causes of liver disease include:

  • Nonalcoholic fatty liver disease (NAFLD)—Present in about 30% of adults in the United States; now the most common cause of liver disease worldwide.1 NAFLD is believed responsible for 90% of cases of elevated liver enzymes without an identifiable cause (e.g., viral hepatitis, alcohol, genetic, medications).2

  • Alcohol, excessive use—Approximately 5% of the population are at risk; this includes women who drink more than two drinks per day and men who drink more than three drinks per day.3

  • Drug-induced liver disease4:

    • Drugs causing hepatitis include phenytoin, captopril, enalapril, isoniazid, amitriptyline, and ibuprofen.

    • Drugs causing cholestasis include oral contraceptives, erythromycin, and nitrofurantoin.

    • Drugs causing hepatitis and cholestasis include azathioprine, carbamazepine, statins, nifedipine, verapamil, amoxicillin/clavulanic acid, and trimethoprim-sulfamethoxazole.

  • Infectious disease—Viral hepatitis, infectious mononucleosis, Cytomegalovirus, and coxsackievirus are most common. Viral hepatitis infections include:

    • Hepatitis A—Anti–hepatitis A virus prevalence in the U.S. population is 35%, a stable frequency of infection over the past decade, representing both natural and vaccine-induced immunity; there are no chronic infections.5 Universal infant vaccination has occurred since 2006. Incidence rates continue to decline with 1239 cases reported in 2014 (0.4 per 100,000).6

    • Hepatitis B—Five percent to 10% of volunteer blood donors in the United States have evidence of prior infection, with 1% to 10% of those infected ...

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