Pre‐Treatment Liver Stiffness Is a Stronger Predictor of Hepatocellular Carcinoma Development Than Post‐Treatment Liver Stiffness After Hepatitis C Virus Eradication

ABSTRACT Introduction Liver stiffness measurement (LSM) values decrease after hepatitis C virus eradication. However, whether this reduction translates into a reduced risk of hepatocellular carcinoma (HCC) development in patients who achieve sustained virological response (SVR) remains unclear. Methods We retrospectively analyzed 501 patients with chronic hepatitis C who achieved SVR after direct‐acting antiviral (DAA) treatment. LSM and FIB‐4 levels were measured before DAA treatment and at multiple follow‐up points. Time‐dependent Cox proportional hazards models evaluated the association between these time‐dependent markers and HCC development. Results LSM and FIB‐4 significantly decreased after DAA treatment in 80.4% and 70.8% of patients, respectively. During a mean follow‐up of 5.7 years, 28 patients developed HCC, and in 57% of them, LSM was reduced to < 10 kPa and FIB‐4 to < 3.25 at HCC diagnosis. Multivariable analysis revealed higher pre‐treatment LSM (adjusted hazard ratio aHR, 8.10; 95% confidence interval CI, 1.82–35.95) and higher pre‐treatment FIB‐4 (aHR, 1.29; 95% CI, 1.11–1.51) as independent predictors of HCC, while post‐treatment values at any time point showed no significant association. Patients with LSM < 10 kPa at HCC diagnosis showed better liver function and less fibrosis, but more metabolic risk factors and excessive alcohol consumption than those with LSM ≥ 10 kPa. Conclusion Pre‐treatment LSM and FIB‐4 were stronger predictors of post‐SVR HCC risk than post‐treatment values. Patients with higher pre‐treatment values remained at an increased risk of HCC development even if these values decreased after DAA treatment, emphasizing the importance of continued HCC surveillance in this group.