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ART & Hepatotoxicity: Alanine aminotransferase (ALT) decrease in HIV-hepatitis C virus co-infected patients responding to antiretroviral therapy
  AIDS 2003; 17(14):2141-2142 CORRESPONDENCE
Antonio Aceti; Caterina Pasquazzi; Barbara Zechini
Department of Infectious Diseases, II Faculty of Medicine, University of Rome 'La Sapienza', Rome, Italy.
Diaz et al. [1] recently reported a case of the normalization of liver enzymes in an HIV-hepatitis C virus (HCV) co-infected patient after potent antiretroviral therapy (ART). The authors suggested that ART may diminish the risk of hepatitis C progression to cirrhosis. We previously found alanine aminotransferase (ALT) levels to be decreased in HIV-HCV co-infected patients responding to ART.
The aim of this study was to evaluate the occurrence of hepatotoxicity in patients during ART containing protease inhibitors (PI) and the role of hepatitis viruses in its development. A total of 1325 HIV patients treated with ART for at least 6 months were enrolled. The presence or absence of hepatitis viruses, ALT, CD4 cell count, and plasma HIV-RNA levels were retrospectively evaluated. The occurrence of hepatotoxicity was defined by a serum ALT increase relative to the upper limit of normal values.
For patients with elevated pretreatment serum ALT, liver toxicity was classified by considering the increase relative to baseline values. A total of 616 out of 1325 patients (46.5%) were anti-HCV positive (384 men, 232 women, mean age 35 ± 8.6 years). Of these patients, 453 individuals (73.5%) were intravenous drug users, 77 patients (12.5%) were heterosexual, 41 patients (6.7%) were homosexual and 45 patients (7.3%) showed other HIV transmission routes. One hundred and four HCV-co-infected patients (16.9%) were chronic alcohol abusers. Hepatotoxicity was found in 92 out of 616 HCV-co-infected patients after 6 months, in 71 out of 474 HCV-co-infected patients after 12 months, and in 42 out of 227 HCV-co-infected patients after 24 months of treatment.
Univariate logistic regression analysis showed that HCV co-infection is an independent risk factor for the development of hepatotoxicity after 6 [odds ratio (OR) 6.79, 95% confidence interval (CI) 4.57-10.09; P < 0.0001], 12 (OR 5.76, 95% CI 3.66-9.16; P < 0.0001) and 24 months of treatment (OR 12.14, 95% CI 5.28-27.91; P < 0.0001). In HCV-co-infected patients, after 12 months of treatment, the incidence of hepatotoxicity was higher in patients with no CD4 cell increase when compared with patients with a CD4 cell count increase (20.9 versus 10.2%; P = 0.017, OR 2.3, 95% CI 1.15-4.7). Moreover, after 12 months of treatment, the incidence of liver toxicity was significantly greater in HCV-co-infected patients with an increase in HIV viral load compared with patients with stable or decreased HIV-RNA levels (34 versus 13%; P = 0.018). Conversely, after 12 and 24 months of therapy, in HCV-co-infected patients, the ALT decrease was found to be higher in patients with a CD4 cell count increase compared with patients without a CD4 cell increase (12 months: 25.5 versus 15.8%; P = 0.03; OR 1.8, 95% CI 1.03-3.23; 24 months: 30.9 versus 13.9%; P = 0.006; OR 3.22, 95% CI 1.4-7.9). Moreover, after 12 months of treatment, ALT levels were significantly correlated with the HIV viral load (P = 0.018; OR 0.627, 95% CI 0.425-0.924).
Our data seem to indicate that chronic hepatotoxicity during long-term treatment mainly occurs in patients not responding to ART. These findings do not support the pathogenic role of immune recovery in the development of chronic liver toxicity in patients with viral hepatitis treated with ART. After 12 and 24 months of treatment, the increase in CD4 cells in patients responding to ART seems to be related to an improvement in the chronic liver disease, as suggested by the ALT decrease. In this way, the immune restoration occurring after antiretroviral therapy with PI might be related to a reduction in HCV replication, as confirmed by recent studies. Moreover, the chronic use of ART containing PI together with the maintenance of a high CD4 cell count seemsems to be associated with a low liver fibrosis progression rate in HIV-HCV-co-infected patients.
The present data would be another reason not to withhold ART from HIV-HCV-infected individuals.
1.Diaz B, Martìn-Carbonero L, Pèrez-Olmeda M, Soriano V. Normalization of liver enzymes in an HIV-hepatitis C virus co-infected patient after potent antiretroviral therapy. AIDS 2002, 16:1193.1193.
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