title: Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome.
abstract: OBJECTIVE
  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/mm(3) (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 population-based 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/mm(3). Antihepatitis pre- or comedication could be an effective preventive or curative measure.
authors.affiliation: Istituto di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Italy. puoti_brambilla@iol.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Diego
authors.initials: D
authors.lastname: Ripamonti
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.forename: Serena
authors.initials: S
authors.lastname: Zaltron
authors.forename: Barbara
authors.initials: B
authors.lastname: Zanini
authors.forename: Angiola
authors.initials: A
authors.lastname: Spinetti
authors.forename: Valeria
authors.initials: V
authors.lastname: Putzolu
authors.forename: Salvatore
authors.initials: S
authors.lastname: Casari
authors.forename: Lina
authors.initials: L
authors.lastname: Tomasoni
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros-Roldan
authors.forename: Maurizio
authors.initials: M
authors.lastname: Favret
authors.forename: Luisa
authors.initials: L
authors.lastname: Berchich
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Francesco
authors.initials: F
authors.lastname: Callea
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D019380:Anti-HIV Agents / Q000009:adverse effects*; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006679:HIV Seropositivity / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1 / Q000472:pathogenicity; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007372:Interferons / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000821:virology; D017093:Liver Failure / Q000209:etiology / Q000473:pathology / Q000628:therapy; D008297:Male; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D007372:Interferons; D000410:Alanine Transaminase