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Severe hepatotoxicity during combination antiretroviral treatment

Liver damage may be caused by immune reconstitution and related exacerbation of viral hepatitis during antiretroviral therapy, find researchers in the March issue of the Journal of Acquired Immune Deficiency Syndromes.

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In this study, researchers from Italy assessed incidence, risk factors, histology, and outcome of severe hepatotoxicity (SH) during antiretroviral treatment (ART).

The team included 755 HIV-seropositive patients prescribed new ART in the study.

Liver function tests were assessed at baseline, after 1 month, and every 4 months thereafter.

The team performed liver biopsies in the case of SH.

Liver damage was invariably observed in patients with chronic viral hepatitis.
Journal of Acquired Immune Deficiency Syndromes

The research team observed 26 cases of SH, with an incidence of 4% person-years. However, liver failure was rarely seen.

The team found that liver damage was invariably observed in patients with chronic viral hepatitis.

Liver histology showed exacerbation of viral hepatitis in all 16 patients for whom a liver biopsy was available at the time of SH.

They found a direct correlation between alanine aminotransferase increase and increase in CD4+ T-cell count in patients with SH.

Death occurred during follow-up in 7 of the 26 patients with SH. All showed liver failure and a baseline CD4+ count less than 200 cells/mm3.

In addition, the researchers observed relapse of SH following recommencement of ART, in 7 of 17 patients. However, 5 of these 7 patients did not show further SH relapse after treatment with interferon.

Dr Massimo Puoti’s team concluded, “This study provides estimates of SH and liver failure…where hepatitis C virus coinfection is highly prevalent and provides indications that liver damage may be caused by immune reconstitution and related exacerbation of viral hepatitis”.

“A strict follow-up for hepatotoxicity is mandatory when ART is initiated in patients with < 200 CD4+ T cells/mm3.”

“Antihepatitis pre- or comedication could be an effective preventive or curative measure.”

J Acquir Immune Defic Syndr 2003; 32(3): 259-67
12 March 2003

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