Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance.

Objective: Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies.

Methods: We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years.

Results: Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04).

Conclusions: The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.