Severe hepatotoxicity during combination antiretroviral treatment: Incidence, liver histology, and outcome

Massimo Puoti, Carlo Torti, Diego Ripamonti, Francesco Castelli, Serena Zaltron, Barbara Zanini, Angiola Spinetti, Valeria Putzolu, Salvatore Casari, Lina Tomasoni, Eugenia Quiros-Roldan, Maurizio Favret, Luisa Berchich, Piergiovanni Grigolato, Francesco Callea, Giampiero Carosi

Research output: Contribution to journalArticle

Abstract

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% person-years. 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 + T cells/mm3. Antihepatitis pre- or comedication could be an effective preventive or curative measure.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 2003

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Keywords

  • Antiretroviral treatment
  • Histology
  • Immune reconstitution
  • Interferon
  • Liver damage

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Puoti, M., Torti, C., Ripamonti, D., Castelli, F., Zaltron, S., Zanini, B., Spinetti, A., Putzolu, V., Casari, S., Tomasoni, L., Quiros-Roldan, E., Favret, M., Berchich, L., Grigolato, P., Callea, F., & Carosi, G. (2003). Severe hepatotoxicity during combination antiretroviral treatment: Incidence, liver histology, and outcome. Journal of Acquired Immune Deficiency Syndromes, 32(3), 259-267. https://doi.org/10.1097/00126334-200303010-00004