The influence of HIV infection on the natural history of hepatocellular carcinoma: results from a global multi-cohort study
Purpose. Conflicting evidence indicates HIV-seropositivity to influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify whether HIV affected the overall survival (OS) of patients with HCC independent of treatment and geographic origin. Patients and Methods: We designed an international multi-cohort study of HCC patients who did not receive any anticancer treatment accrued from four continents. We estimated the effect of HIV-seropositivity on patients’ OS while accounting for common prognostic factors and demographic characteristics in uni- and multi-variable models. Results: A total of 1588 patients were recruited, 132 of whom were HIV-positive. Most patients clustered within Barcelona Clinic Liver Cancer (BCLC) C/D criteria (n=1168, 74%), Child-Turcotte-Pugh (CTP) Class B (median score 7, IQR 3). At HCC diagnosis the majority of HIV-positive patients (n=65, 64%) had been on anti-retrovirals for a median duration of 8.3 years (IQR 8.59) and had median CD4+ cell counts of 256 (IQR 284) with undetectable HIV RNA (n=68, 52%). OS significantly reduced throughout BCLC stages 0-D (16, 12, 7.5, 3.1 and 3 months, p<0.001). Median OS of HIV-positive patients was half that of HIV-uninfected counterparts: 2.2 months, (bootstrap 95%CI 1.2-3.1) versus 4.1 months (95%CI 3.6-4.4). In adjusted analyses HIV-seropositivity increased the hazard of death by 24% (p=0.0333) independent of BCLC (p<0.0001), CTP (p<0.0001), alpha-fetoprotein (AFP) (p<0.0001), geographical origin (p<0.0001) and male gender (p=0.0016). Predictors of worse OS in HIV-positive patients included CTP (p=0.0071) and AFP (p<0.0001). Conclusions. Despite adequate antiretroviral treatment, HIV-seropositivity is associated with decreased survival in HCC independent of stage, anti-cancer treatment and geographical origin. Mechanistic studies investigating the immuno-biology of HIV-associated HCC are urgently required.