Influence of liver fibrosis on highly active antiretroviral therapy-associated hepatotoxicity in patients with HIV and hepatitis C virus coinfection.
BACKGROUND
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is a known risk factor for hepatotoxicity in patients receiving highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the role of HCV-related liver fibrosis in HAART-associated hepatotoxicity.


METHODS
In a prospective study involving 107 patients who underwent liver biopsy, fibrosis was graded according 5 stages, from F0 (no fibrosis) to F4 (cirrhosis). Hepatotoxicity was defined as an increase in levels of aspartate aminotransferase and alanine aminotransferase to >5 times the upper limit of normal, or a >3.5-fold increase if baseline levels were abnormal. The incidence of hepatotoxicity was compared with liver fibrosis stage and with time and composition of HAART.


RESULTS
Overall, 27 patients (25%) had hepatotoxic events (5.1 events/100 person-years of therapy). The incidence was greater for patients with stage F3 or F4 fibrosis (38%) than for those with stage F1 or F2 fibrosis (15%; 7.6 vs. 3 events/100 person-years; relative risk, 2.75; 95% confidence interval, 1.08-6.97; P=.013). Duration of HCV infection, duration of HAART, diagnosis of acquired immunodeficiency syndrome, HCV load, HCV genotype, and nadir CD4(+) cell count did not affect the risk of hepatotoxicity. Of the 86 patients who received nonnucleoside reverse-transcriptase inhibitors (NNRTIs), 11 (13%) developed liver toxicity. In these patients, fibrosis stages F1 and F2 were associated with similar rates of toxicity (3 events/100 person-years for patients who received nevirapine, 3.3 events/100 person-years for those who received efavirenz, and 3.4 events/100 person-years for those who received non-NNRTIs). There was a greater incidence among patients with F3 or F4 fibrosis who received NNRTIs (11.7 events/100 person-years for patients who received nevirapine, and 8.6 events/100 person-years for those who received efavirenz), compared with those who received non-NNRTIs (4 events/100 person-years).


CONCLUSIONS
HAART-associated hepatotoxicity correlates with liver histological stage in patients coinfected with HIV and HCV. There was no difference in hepatotoxicity risk for different antiretroviral therapies in patients with mild-to-moderate fibrosis.
Aranzabal
Lidia
L
Department of Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain. laranzabal.hrc@salud.madrid.org
Casado
José L
JL
Moya
Javier
J
Quereda
Carmen
C
Diz
Sergio
S
Moreno
Ana
A
Moreno
Leonor
L
Antela
Antonio
A
Perez-Elias
Maria J
MJ
Dronda
Fernando
F
Marín
Ana
A
Hernandez-Ranz
Felix
F
Moreno
Alberto
A
Moreno
Santiago
S
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D048588:Benzoxazines; D056486:Chemical and Drug Induced Liver Injury; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology*; D008107:Liver Diseases / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects; D010078:Oxazines / Q000009:adverse effects; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012720:Severity of Illness Index
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz