Hepatology and ART

Hepatotoxicity has been associated with all drug classes, and is a common cause of adverse effects of antiretroviral drugs (ARVs), but a relatively rare cause of ARV discontinuation.

Liver disease has emerged as a leading cause of morbidity and mortality in HIV-infected persons. The aetiology is often multifactorial and influenced by host factors, pre-existing liver disease, alcohol consumption and concomitant use of other drugs. For these reasons, the exact contribution of ARVs can be difficult to assess.

Defining Hepatotoxicity
The definition differs among investigators. The AIDS Clinical Trial Group has developed a commonly used grading system (grade 1 to 4). Grades 3 and 4 are usually used to define hepatotoxicity and are respectively associated with a >5-fold and >10-fold elevation of ALT/AST above normal pre-therapy level or >3.5-fold and >5-fold elevation above normally high pre-therapy levels.

Comparisons across studies are difficult due to differences in definitons of hepatotoxicity, time of follow up and prevalence of other risk factors for liver disease.

Risk factors for hepatotoxicity

  • The incidence of hepatotoxicity in observational studies is 4.5 to 11.4%. Grade 4 events occur with a rate of 2.6 per 100 person-years.
  • Risk factors for hepatotoxicity, in most studies, are elevated baseline alanine amiontransferase (ALT) level and coinfection with HCV or HBV
  • Some studies have found increased age, female gender, ritonavir (full dose), nevirapine, stavudine, didanosine, renal insufficiency and thrombocytopenia to be associated with risk of hepatotoxicity

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Photo courtesy of Centers for Disease Control and Prevention (CDC).