Managing antiretroviral-associated liver disease

The use of all potent drugs is associated with toxicities and antiretroviral (ARV) drugs are no exception. Antiretroviral therapy-associated hepatic toxicity is of increasing concern in the management of patients with HIV/AIDS. Liver toxicity has been reported in some HIV-infected patients being treated with drugs from all of these classes of ARV drugs: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although the majority of cases involve asymptomatic elevations of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), severe, and, in a minority of cases, life threatening, liver disease has been reported in patients treated with ARV drugs. The exact causes of elevated plasma levels of AST and ALT are complex and, in many cases, obscure. The combination of viral hepatic disease, drugs that act adversely directly on the liver and drugs that act on other systems of the body which in turn, adversely affect the liver, can result in hepatic toxicity. Such toxicity may be inappropriately attributed solely to the direct effect of a drug. Knowledge of the possible causes of liver toxicity, and ways to avoid it, should reduce the risk of developing hepatotoxicity. The physician's task is to prevent the development of liver toxicity, e.g., by choosing appropriate therapeutic regimens and by careful management of the patient. This involves frequent monitoring of the patient, both clinically and by utilizing liver function tests on a regular basis. If signs and symptoms of liver disease do develop, prompt and expert management is essential. This review discusses the influence of a number of factors on hepatic toxicity including viral hepatitis, insulin resistance and the specific ARV drugs used in the treatment of patients with HIV/AIDS.