Alcoholic Liver Disease : Pretransplant Evaluation

by National Institute of Health

(Page 3 of 7)

Skeletal Myopathy. Muscle damage occurs in up to 42 percent of alcoholic patients with ALD; 46 percent of actively alcoholic men show changes in muscle cell structure indicative of skeletal myopathy. This condition is manifested as muscle weakness, muscle pain, and abnormal tests for muscle enzymes; the disorder results from a combination of alcohol's direct effects on the muscles, malnutrition, and alcohol-related inflammation or degeneration of nerves. The presence of skeletal myopathy appears to depend on how much alcohol the person has consumed over his or her lifetime. In general, skeletal myopathy is not a contraindication for OLT, and severe myopathy is unusual in potential alcoholic OLT candidates.

Pancreatitis. Chronic inflammation of the pancreas is five times less common in people with ALD than in alcoholics without liver disease; the reasons for this difference are not known. In general, pancreatitis is not considered a contraindication for liver transplantation; however, severe chronic pancreatitis can adversely affect the absorption of medications that prevent the immune system from rejecting the transplanted liver. Therefore, patients with pancreatitis may require closer monitoring for rejection of the transplanted organ as well as administration of higher doses of antirejection medications to achieve effective concentrations.

Malnutrition. Malnutrition occurs in many, if not all, patients with ALD. Causes of malnutrition include a poor diet; increased breakdown (catabolism) of carbohydrates, proteins, and lipids in the body; as well as impaired absorption of nutrients, interruption of the bile flow (cholestasis), reduced pancreatic function, bacterial overgrowth, and/or alcohol-induced injury to the intestinal mucosa. In particular, alcoholics commonly show deficiencies in various vitamins, including thiamine, which is essential for normal brain functioning. Therefore, alcoholics with ALD routinely should be prescribed thiamine and multivitamins. Severe malnutrition is associated with a poorer prognosis after OLT and may require postponement of the procedure until the patient has achieved a better state of nutrition. The nutritional status of OLT candidates can be improved by providing additional nutrition directly into the gastrointestinal tract (by enteral feeding). Moreover, nutritional support before and after the transplant can improve the clinical outcome after OLT.

Neurological Deficits. Chronic alcoholism may lead to neurological deficits through alcohol's direct actions on the brain and nerve fibers, which can result in structural damage. In patients with ALD, however, neurological deficits also can result from a condition called hepatic encephalopathy, which is caused by the damaged liver's inability to remove substances from the blood that can interrupt brain function. In these patients, it is difficult to distinguish deficits resulting from alcohol's direct effects on the brain from those resulting from hepatic encephalopathy. Severe neurological deficits may contraindicate liver transplantation because the patient may not be able to comply with post-transplant medication regimens and because OLT may not improve the patient's quality of life significantly. Therefore, most transplant centers routinely perform brain-imaging analysis of OLT candidates to identify any structural damage that may exist before the transplant and which could affect the patient's outcome after the transplant.

Abnormal Bone Structure. Patients with ALD are prone to bone loss because of impaired activity of the bone-producing cells; reduced activity of the ovaries or testes, which produce hormones regulating bone formation; reduced body mass index; and limited physical activity. Between 10 and 42 percent of patients with ALD have a reduced bone density, which can lead to a condition called osteopenia (or, in severe cases, osteoporosis), which is characterized by bone softening, accompanied by weakness and susceptibility to fractures. Therefore, routine bone mineral density measurements and, in appropriate cases, blood tests assessing calcium metabolism and ovarian or testicular function are recommended in patients with ALD. Treatment with calcium and vitamin D (which regulates calcium metabolism) can improve bone mineral density in patients with ALD. Other approaches used to improve bone mineral density in patients with non-ALD include administration of hormones to compensate for reduced ovarian or testicular activity as well as treatment with other compounds that influence calcium metabolism (calcitonin and biphosphonates). The effectiveness of these approaches in alcoholics, however, has not been studied specifically.

HCV Infection. About 20 to 30 percent of patients with ALD are infected with HCV, and the rate of progression of liver disease and the long-term outcome are worse for these patients than for alcoholics not infected with HCV. In addition, the most commonly used treatment for HCV infection - an agent called interferon - is less effective in active alcoholics, probably because the antiviral activity of interferon is decreased in these patients. HCV infection in alcoholic patients also influences the outcome after liver transplantation; in fact, the transplanted liver is much more likely to be damaged by renewed HCV infection in these patients than by a relapse to alcohol abuse.

Patients with ALD who also are infected with the hepatitis B virus face challenges similar to those experienced by ALD patients with HCV infection.

In general, patients with liver disease resulting from alcohol abuse and coexisting viral infection appear to have a worse prognosis than patients with liver disease resulting from only one of these factors.

Liver Cancer. Patients with alcoholic cirrhosis have an increased prevalence of liver cancer (hepatocellular carcinoma, or HCC). These tumors can substantially influence the patient's outcome after OLT because of the risk that they will recur. The presence of HCC itself is not a contraindication for OLT, because patients can have a reasonably good prognosis after OLT if they have only small tumors and/or fewer than four tumors of 3 cm or less each that have not spread to major blood vessels or outside the liver. Studies have found that cancers other than HCC (cancers of the airways and digestive tract or lymph node tumors) occur significantly more commonly in patients undergoing OLT for ALD than for non-ALD and are a major cause of illness and death late after OLT for ALD. To rule out the presence of a coexisting liver cancer, routine hepatic imaging studies are recommended as part of a pretransplant workup for all OLT candidates. Similarly, it is imperative that patients being considered for OLT undergo a thorough pretransplant screening for tumors outside the liver as well as a regular evaluation after the transplantation.

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