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Puoti Massimo; Torti, Carlo; Ripamonti, Diego; Castelli, Francesco; Zaltron, Serena; Zanini, Barbara; Spinetti, Angiola; Putzolu, Valeria; Casari, Salvatore; Tomasoni, Lina; Quiros-Roldan, Eugenia; Favret, Maurizio; Berchich, Luisa; Grigolato, Piergiovanni; Callea, Francesco; Carosi, Giampiero; for the HIV-HCV Co-Infection Study Group
JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2003

Objectives:To assess incidence, risk factors, histology, and outcome of severe hepatotoxicity (SH) during antiretroviral treatment (ART).

Methods:Seven hundred fifty-five HIV-seropositive patients consecutively prescribed new ART were selected. Liver function tests were assessed at baseline, after 1 month, and every 4 months thereafter. Liver biopsy was recommended in case of SH (i.e., increase in liver enzymes ≥10 times the upper limit of normal or 5 times baseline if markedly abnormal).

Results:Twenty-six cases of SH were observed with an incidence of 4.2% personyears. Liver failure (LF) was rarely seen (1.1 per 100 person-years). 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. A direct correlation was found between alanine aminotransferase increase and increase in CD4+ T-cell count in patients with SH (r = 0.53, p < .001). Death occurred during follow-up in 7 of 26 (27%) patients, all of whom showed LF and baseline CD4+ count less than 200 cells/mm3 (7/7 patients = 100% vs. 8/19 patients without LF; p < .01). Relapse of SH was observed after ART was recommenced in 7 of 17 (41%) patients. Five of these 7 patients did not show further SH relapse after treatment with interferon.

Conclusions:This study provides estimates of SH and LF in a large populationbased setting 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.

Manuscript received July 31, 2002; accepted December 17, 2002.

Address correspondence and reprint requests to Massimo Puoti, Istituto di Malattie Infettive Spedali Civili. Piazza Spedali Civili. 1 25123 Brescia, Italy; e-mail:

© 2003 Lippincott Williams & Wilkins, Inc.