Incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among HIV-infected patients with chronic hepatitis C.

OBJECTIVES: To determine the incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients with known stage of liver fibrosis. METHODS: All HIV/HCV-coinfected patients were monitored for a period of 12 months after starting nelfinavir-containing regimens and, with an available liver biopsy, were included in a retrospective study. RESULTS: A total of 82 patients were included in the study. Nine (10.9%) HIV/HCV-coinfected patients showed an episode of severe hepatotoxicity during the study period. Eight (9.8%) individuals showed grade 3 or 4 change in levels of serum alanine aminotransferase and one subject presented with an event of decompensated liver cirrhosis. Six (18.2%) of 33 patients with advanced liver fibrosis and three (6%) of 49 individuals without advanced liver fibrosis showed an episode of severe hepatotoxicity (P = 0.1). In the multivariate analysis, only nevirapine use during nelfinavir therapy [adjusted odds ratio (AOR) 8.9; 95% confidence interval (CI), 1.4-54.1; P = 0.01] was independently associated with risk of development of severe liver toxicity. CONCLUSIONS: The incidence of severe hepatotoxicity of nelfinavir-containing regimens is low among HIV/HCV-coinfected patients with known stage of liver fibrosis. In addition, our findings show that concomitant nevirapine use is associated with an increased risk of severe hepatotoxicity in these subjects. Likewise, the proportion of severe liver toxicity tended to be higher in individuals with advanced liver fibrosis.

Incidence of and factors associated with hepatocellular carcinoma among hepatitis C virus and human immunodeficiency virus coinfected patients with decompensated cirrhosis.

We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.

HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.