Non-liver Malignancies as Main Cause of Mortality After HCV Eradication Among People Living With HIV

In people living with HIV (PLWH) with hepatitis C virus (HCV) infection, liver and nonliver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virologic response induced by DAAs.

Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved sustained virologic response after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95% CI); baseline variables included in the model were age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), and albumin-bilirubin (ALBI) grade.

Among 663 people included with a median follow-up of 4.4 years (interquartile range = 3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95% CI: 5.5% to 0.4%); 63.2% (n = 31/49) died from nonliver-related events [mainly nonliver malignancies (18/49) and cardiovascular events (7/49)]. At multivariate analysis, death was more likely in older people [aHR (5-year older) = 1.46, 95% CI: 1.16 to 1.83, P = 0.0009], and in people with diabetes (aHR = 2.98, 95% CI: 1.55 to 5.71, P = 0.001), ALBI grade ≥2 (aHR = 2.13, 95% CI: 1.17 to 3.90, P = 0.014), and AFP ≥3.4 ng/mL (aHR = 1.96, 95% CI: 1.01; 3.84, P = 0.049).

In our cohort, nonliver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2, and AFP ≥3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of nonliver events, particularly malignancies, should be recommended.