Background: Hepatitis C virus (HCV) eradication is associated with a reduction in the risk of hepatocellular carcinoma (HCC). It is unclear how the risk of HCC changes as more time accrues since HCV eradication, especially during long-term follow-up. We aimed to determine if the time accrued since sustained virologic response (SVR) is independently associated with HCC risk.

Methods: We identified 75,965 HCV-infected patients within the Veterans Affairs (VA) healthcare system who achieved SVR and had not died, underwent liver transplant, or developed HCC prior to 1/1/2018. We ascertained baseline characteristics between 1/1/2018 and 12/31/2018 and followed these patients from 1/1/2019 to 1/1/2020 for incident HCC. We used multivariate Cox proportional hazards regression to adjust for baseline characteristics (age, diabetes, alcohol use disorder, hypertension, body mass index, Charlson comorbidity index, race/ethnicity, gender, HCV genotype, Fibrosis-4 score, hepatitis B virus co-infection/exposure, and HIV co-infection) and assessed the association between time since SVR (1-2, 2-4, and >4 years) and HCC risk. Analyses were stratified by baseline cirrhosis status.

Results: Among these 75,965 patients with cured-HCV, 96.0% were male, 54.7% non-Hispanic White, 34.2% non-Hispanic Black, and the mean age was 64.6 ± 7 years. Approximately a quarter (n=19,678, 25.9%) had cirrhosis and 547 (0.72%) developed HCC during follow-up. Among those with cirrhosis, HCC incidence was highest for those who accrued 1-2 years (2.68 per 100 Person-Years[P-Ys]), lower for those who accrued 2 to 4 years (2.11 per 100 P-Ys), and lowest for those who accrued >4 years since SVR (1.67 per 100 P-Ys) (Table). After adjusting for baseline characteristics, compared to patients who had accrued 1-2 years since SVR, those who had accrued 2-4 years (aHR 0.80, 95% CI 0.63-1.01) and >4 years (aHR 0.65, 95% CI 0.47 – 0.9) had lower risks of developing HCC. Among the patients without baseline cirrhosis, there was no significant association between time since SVR and risk of HCC (Table).

Conclusion: In patients with cirrhosis, increasing time accrued since SVR is associated with a decreased risk of HCC even after adjusting for non-HCV related factors. However, the risk of HCC remains substantial (i.e. > 1% per year) even for after the accrual of more than 4 years since SVR (1.67 per 100 P-Ys). For those without cirrhosis, increasing time accrued since SVR is not associated with reduced risk of HCC.