Long-term risk of HCC in a DAA-treated national hepatitis C cohort, and a proposed risk score

Background: The risk of hepatocellular carcinoma (HCC) remains elevated in cirrhotic hepatitis C patients with sustained virological response (SVR) after DAA treatment. We assessed long-term HCC risk stratified by pretreatment liver stiffness measurement (LSM) and developed a risk score algorithm.

Methods: This register-based nationwide cohort study of 7,227 DAA-treated patients with SVR evaluated annual HCC incidence rates (IRs) and cumulative incidences stratified by pretreatment LSM. The association between LSM and HCC risk was analyzed using multivariate Cox regression. A risk score algorithm was developed and internally validated in 2,664 individuals with LSM >9.5 kPa, assigning each patient a score based on risk factors, proportionally weighted by the association with HCC risk.

Results: During a median follow-up of 1.8 years (3.2 years for LSM ≥12.5 kPa), 92 patients (1.3%) developed HCC. The IRs for LSM 9.5-12.4, 12.5-19.9 and ≥20 kPa were 0.21, 0.99 and 2.20 HCC/100 PY, respectively, with no significant risk reduction during follow-up. The HRs (and 95% CI) for LSM 9.5-12.5, 12.5-19.9 and ≥20 kPa are 1.19 (0.43-3.28), 4.66 (2.17-10.01) and 10.53 (5.26-21.08), respectively. Risk score models including FIB-4, alcohol, diabetes, age and LSM effectively stratified patients with LSM >9.5 kPa into low-, intermediate- and high-risk groups, with a Harrell's C of 0.799. Notably, 48% with LSM ≥9.5 kPa and 27% ≥12.5 kPa were classified as low-risk.

Conclusion: Pretreatment LSM is associated with HCC risk, which remains stable during the initial five years post-SVR. The HCC risk score algorithm effectively identifies low-risk patients, who may not require HCC surveillance.