Serum growth differentiation factor 15 predicts hepatocellular carcinoma occurrence after hepatitis C virus elimination

Summary Background After hepatitis C virus (HCV) elimination, patients should be followed up due to risk of hepatocellular carcinoma (HCC). Growth differentiation factor 15 (GDF15) is a cytokine induced by mitochondrial dysfunction or oxidative stress. Aim To evaluate the prognostic value of GDF15 for HCC occurrence after HCV elimination. Methods We measured GDF15 levels in stored serum from patients with chronic HCV infection without a history of HCC who had achieved sustained virological response with direct‐acting antiviral agents (DAAs). The patients were randomly divided into derivation (n = 964) and validation (n = 642) cohorts. Results In the derivation cohort, serum GDF15 levels were higher in those with HCC occurrence after DAA treatment than in those without. Multivariate Cox proportional hazards analysis revealed baseline GDF15 (>1350 pg/mL, HR 2.54), AFP (>5 ng/mL, HR 2.00), and the FIB‐4 index (>3.25, HR 2.69) to be independent risk factors for HCC. Scoring based on GDF15, AFP and the FIB‐4 index stratified HCC occurrence risk. In the validation cohort, the cumulative HCC occurrence rate at 3 years was 0.64%, 3.27% and 15.3% in low‐score (N = 171), medium‐score (N = 300) and high‐score (N = 166) groups, respectively. In the total cohort, scoring divided patients with a FIB‐4 index ≤3.25, whose HCC occurrence rate was 2.0% at 3 years, into medium‐score and low‐score groups with HCC occurrence rates at 3 years of 3.76% and 0.24%, respectively. Conclusions Serum GDF15 predicts de novo HCC occurrence. Scoring using GDF15, AFP, and the FIB‐4 index can predict de novo HCC occurrence risk after HCV elimination.