Common causes are (1) ethanol, (2) chronic hepatitis C virus infection, and (3) chronic hepatitis B virus infection with or without hepatitis D virus infection.

Infrequent causes are (1) primary biliary cirrhosis, (2) primary sclerosing cholangitis, (3) secondary biliary cirrhosis, (4) autoimmune hepatitis, (5) hemochromatosis, and (6) cryptogenic cirrhosis.

Rare causes are (1) Wilson disease, (2) α ₁-antitrypsin deficiency, (3) small bowel bypass, (4) methotrexate, (5) amiodarone, (6) methyldopa, (7) cystic fibrosis, (8) sarcoidosis, (9) glycogen storage disease, and (10) hypervitaminosis A.

Malignancy can be a cause of end-stage hepatic disease and is often potentiated by the risk factors associated with hepatitis B, hepatitis C, chronic hepatitis B infection, cirrhosis, hemochromatosis, and ingestion of estrogens and androgens. The progression of disease occurs via direct extension within or from around the liver. Tumors typically alter blood flow within the liver, resulting in the rapid spread of tumor. In patients with advanced disease, pneumonia, hepatic failure, and hemorrhage are frequently the cause of death. Tamponade can occur within the liver and lead to necrosis and rupture, and ultimately hemorrhage. If left untreated, death can occur in approximately 6 to 8 weeks.

Hepatic failure can also take the form of a rejected liver transplant. Obviously, these patients and families come to palliative care with unique issues. While the end-stage symptoms of cirrhosis and liver failure are the same, the meaning of the illness for the patient and family is important to recognize, explore, and incorporate into the individual plan of care.

The majority of medications used in the palliative care setting are metabolized through the liver (Bernard & Bruera, 2000; Kuebler et al., 2003). If used inappropriately, many of these medications can cause liver injury; acetaminophen poisoning is the most common medication cause of liver failure in the United States (Litovitz, Watson, & Klein-Schwartz, 2000). Acetaminophen ( N-acetyl- p-aminophenol, paracetamol, or APAP) is the most popular over-the-counter (OTC) analgesic used in the United States and is reported as one of the most common toxic exposures reported to poison control centers nationwide (Hung & Nelson, 2000). Acetaminophen has been available since 1950 and is widely used in its single and compound formulas in both OTC and prescription medications. This drug is used for a variety of pain syndromes in both long-term care and palliative care settings, which can attribute to chronic use.

Acetaminophen use was identified by the American College of Rheumatology (2000) and the American Geriatrics Society (1998) as the analgesic of choice for the treatment and management of osteoarthritis. Numerous studies have identified that the U.S. population is living longer and often experiencing chronic pain syndromes that potentiate an increased vulnerability to drug-induced hepatic injury, while at the same time necessitating medical treatment for pain conditions that warrant aggressive symptom control. Hepatic injury with acetaminophen can occur with chronic use over time at lower doses (<4 g/day), particularly in the presence of other predisposing factors (McClain, Price, Barve et al., 1999). Therefore, the influence of advanced age in conjunction with the management of treating symptoms can pose an increased risk for liver toxicity. Age-related hepatic and renal dysfunction can lead to higher drug concentrations—a result of reduced drug metabolism and excretion capacities (Jakobsson, Klevsgard, & Westergen, 2003).

Liver damage from excessive acetaminophen ingestion can occur in four circumstances (Lee, 2003):

A number of other factors can influence the propensity of acetaminophen to cause hepatotoxicity, including comorbid diseases and the patient’s age, genetic background, and/or nutritional status. Food and dietary regimens high in protein can enhance the activity of the cytochrome P450 system as it relates to pharmaceutical utilization. Protein can increase the potential for converting a specific drug to its toxic metabolite (Lee, 2003). These metabolites can mediate toxicity close to or within the tissue where they are generated—creating additional tissue injury (Meyer, 2001). Numerous studies have also correlated a strong association between the age of the patient and the number of medications prescribed, all adding to the complexity of pharmaceutical biotransformation (see Chapter 7