Hepatotoxicity and liver disease in the context of HIV therapy.

PURPOSE OF REVIEW

Elevated liver transaminases are frequently observed under highly active antiretroviral therapy in HIV-positive individuals. We review current data on the epidemiology, pathophysiology and associated risk factors of hepatotoxicity and liver disease under highly active antiretroviral therapy, and make suggestions for the management of antiretroviral drug-related liver injury.

RECENT FINDINGS

Severe hepatotoxicity in HIV-infected patients receiving highly active antiretroviral therapy occurs in 5-10% of cases. The main risk factors are hepatitis co-infection, advanced liver disease, and elevated liver transaminases at the start of therapy. Antiretroviral drugs associated with an increased risk of severe hepatotoxicity are stavudine, didanosine, nevirapine, full-dose ritonavir and tipranavir.

SUMMARY

Liver transaminases should be closely monitored after the start of highly active antiretroviral therapy, and if elevated, differential diagnoses including immune reconstitution syndrome and infectious hepatitis must be ruled out. Light to moderate transaminase elevations may improve under continued therapy, but life-threatening liver injury associated with jaundice or transaminase elevations above 10 times the upper limit of normal mandate the discontinuation of antiretroviral therapy. Hypersensitivity reactions may take a rapid and fulminant course, and thorough information for the patient is vital in the early detection of symptoms and prevention of life-threatening complications.