Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-co-infected patients: results from ANRS CO13 HEPAVIH.

Background & Aims: Compared to HCV-mono-infected patients, hepatocellular carcinoma (HCC) occurs at younger age in HIV/HCV-co-infected patients, is markedly more advanced at diagnosis, is less amenable to curative treatment, and has a more severe outcome. The aim of this study was to identify factors predictive of HCC occurrence in a large cohort of HIV/HCV-co-infected patients with cirrhosis.

Methods: This study involved 244 HIV/HCV-co-infected patients included in the ANRS CO13 HEPAVIH cohort, who had HCV-related cirrhosis (clinically or histologically proven cirrhosis, or liver stiffness ≥12.5 kPa) and no signs of HCC at baseline. Cox proportional hazards models were used to identify factors associated with HCC occurrence.

Results: During a median follow-up of 2.6 (IQR, 1.8-3.5) years, 21 patients (8.6%) developed HCC. Diagnosis of HCC was based on histology in 5 patients (24%) and non-invasive criteria in 16 patients (76%). In univariate analyses, the following factors were related to HCC occurrence: age, previous cirrhosis decompensation, a HOMA value >3.8 (patients with treated diabetes were excluded from the HOMA calculation), a lower platelet count, a lower prothrombin level, and higher alpha-fetoprotein levels. The HOMA value was >3.8 at baseline in 66.7% of patients who developed HCC and in 35.3% of the remaining patients (p=0.016). In multivariate analysis, age over 50 years (adjusted RR 3.2, 95% CI 1.2-9.0; p=0.02) and a HOMA value >3.8 (adjusted RR 3.4, 95% CI 1.1-10.3; p=0.03) remained significantly associated with HCC occurrence.

Conclusions: As in HCV-mono-infected patients with HCV-related cirrhosis, insulin resistance appears to play a key role in HCC occurrence in HCV/HIV-co-infected patients with cirrhosis. This finding calls for specific screening strategies for patients with a particularly high risk of developing HCC.