Risk of Hepatocellular Carcinoma After Direct-Acting Antiviral Treatment for Hepatitis C Virus Infection in People With HIV

Background: To inform hepatocellular carcinoma (HCC) surveillance after hepatitis C virus (HCV) cure with direct-acting antivirals (DAA), we estimated HCC risk post-DAA in people with human immunodeficiency virus (HIV) with advanced liver fibrosis or cirrhosis under universal DAA. Methods: We used data from HepCAUSAL, a collaboration of cohorts of HIV–HCV coinfection from Europe and North America. Eligibility criteria were HIV–HCV coinfection, advanced liver fibrosis or cirrhosis, DAA naïve, HIV-RNA < 50 copies/mL, on antiretroviral therapy, no HBV coinfection, and no prior HCC diagnosis or liver transplant. Follow-up started when eligibility was met and ended at HCC diagnosis, death, loss to follow-up, 6 years, or database closure, whichever came first. We estimated the 6-year risk and annual probability of HCC if all eligible individuals had initiated DAA at baseline using a weighted pooled logistic model for the monthly HCC risk among DAA initiators. Results: Of 3824 eligible individuals (92% males, median age 60 years [IQR: 54, 64]), 2373 (62%) who initiated DAA, 43 had an HCC diagnosis during follow-up. The estimated 6-year HCC risk (95% CI) under universal DAA was 2.5% (1.6, 3.9). Annual HCC probability was 0.81% (0.34, 1.54) between baseline and month 12 after DAA initiation, 0.64% (0.28, 1.19) between years 1 and 2, 0.50% (0.27, 0.84) between years 2 and 3, 0.34% (0.13, 0.63) between years 3 and 4, 0.19% (0.07, 0.33) between years 4 and 5, and 0.10% (0.01, 0.24) between years 5 and 6. Conclusions: An estimated 2.5% of people with HIV and advanced liver fibrosis or cirrhosis are diagnosed with HCC by 6 years post-DAA. Annual probability of HCC declines over time and falls below 0.4% after 3 years.