Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome.
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.
Puoti
Massimo
M
Istituto di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Italy. puoti_brambilla@iol.it
Torti
Carlo
C
Ripamonti
Diego
D
Castelli
Francesco
F
Zaltron
Serena
S
Zanini
Barbara
B
Spinetti
Angiola
A
Putzolu
Valeria
V
Casari
Salvatore
S
Tomasoni
Lina
L
Quiros-Roldan
Eugenia
E
Favret
Maurizio
M
Berchich
Luisa
L
Grigolato
Piergiovanni
P
Callea
Francesco
F
Carosi
Giampiero
G
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
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D007372:Interferons; D000410:Alanine Transaminase