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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Histology
Liver
Incidence
Liver Failure
Therapeutics
CD4 Lymphocyte Count
Hepatitis
T-Lymphocytes
Biopsy
Recurrence
Premedication
Liver Function Tests
Chronic Hepatitis
Alanine Transaminase
Coinfection
Hepacivirus
Interferons
HIV
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

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

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 32, No. 3, 03.2003, p. 259-267.

Research output: Contribution to journalArticle

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, vol. 32, no. 3, pp. 259-267. https://doi.org/10.1097/00126334-200303010-00004
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. / Severe hepatotoxicity during combination antiretroviral treatment : Incidence, liver histology, and outcome. In: Journal of Acquired Immune Deficiency Syndromes. 2003 ; Vol. 32, No. 3. pp. 259-267.
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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.",
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AU - Puoti, Massimo

AU - Torti, Carlo

AU - Ripamonti, Diego

AU - Castelli, Francesco

AU - Zaltron, Serena

AU - Zanini, Barbara

AU - Spinetti, Angiola

AU - Putzolu, Valeria

AU - Casari, Salvatore

AU - Tomasoni, Lina

AU - Quiros-Roldan, Eugenia

AU - Favret, Maurizio

AU - Berchich, Luisa

AU - Grigolato, Piergiovanni

AU - Callea, Francesco

AU - Carosi, Giampiero

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N2 - 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.

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KW - Antiretroviral treatment

KW - Histology

KW - Immune reconstitution

KW - Interferon

KW - Liver damage

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