HCC Risk Post-SVR with DAAS in East Asians: Findings from the Real-C Cohort

Abstract

Background: Despite HCV cure, patients remain at risk for HCC. Current evidence has provided some data on risk factors; however, due to a paucity of data from Asia, the generalizability of these findings has not been established. To address this gap, we determined HCC incidence post-SVR and risk factors in a large cohort from East Asia. Methods: Data were obtained from the Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C) registry to determine incidence of HCC. Eligible patients (no HCC within 6 months from DAA initiation, n=5814) were divided into SVR12 (n=5,646) and non-SVR12 groups (n=168). We used 1:4 propensity score matching [(PSM), age, sex, baseline cirrhosis, and AFP] to balance the two groups, Kaplan-Meier methods to estimate cumulative incidence rates, and Cox proportional hazards regression modeling to identify predictors for HCC incidence. Results: Initial analysis of the overall cohort revealed significant differences between the two groups in certain characteristics. After the PSM, the two groups were well matched. In both the overall (168 non-SVR, 5,646 SVR) and PSM cohorts (160 non-SVR and 612 SVR), the incidence rate per 1000 person years was higher in the non-SVR (49.54 and 52.64) compared to the SVR group (16.62 and 19.4, respectively, P<0.001 for both). Achieving SVR was independently associated with decreased HCC risk (adjusted HR [aHR]: 0.46 and 0.41, P=0.001 and 0.002, respectively). However, among SVR patients (Table), the 5-year cumulative HCC incidence were still very high among cirrhotic patients (>10% in those ≥ 60 years of age, higher ALBI grades, highest in those with elevated [≥ 10 ng /mL] pretreatment AFP [22.4%, 95% CI: 16.7-29.7]) and among noncirrhotic patients with elevated AFP levels (4.33%, 95% CI: 1.8-10.1). On multivariable regression analysis adjusted for the following factors, age ≥60, having an albumin bilirubin (ALBI) grade of 2 or 3 (aHR: 2.5, P<0.001), and AFP ≥ 10 ng /mL (aHR: 1.6, P=0.001) were independently associated with higher HCC risk among cirrhotic SVR patients, while only AFP ≥ 10 ng /mL was significant among non-cirrhotic SVR patients (aHR: 4.26, P=0.005). Conclusion: Achieving SVR decreases HCC risk; however, among East Asians, patients with elevated pretreatment AFP remained at risk. Baseline AFP, an easily obtained serum marker, may provide both prognostic and surveillance value for HCC in East Asian patients who obtained SVR.