Serum Growth Differentiation Factor 15 Can Be a Novel Biomarker to Predict the Prognosis of Patients With Hepatitis C Virus Cirrhosis After Virus Elimination.

Abstract

Background and aims: Although direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) rates, the long-term outcomes of patients with hepatitis C virus (HCV)-related cirrhosis remain variable. Growth differentiation factor 15 (GDF15), a stress-induced cytokine, has emerged as a potential biomarker for liver disease progression. This study aimed to evaluate the prognostic value of serum GDF15 levels in predicting hepatocellular carcinoma (HCC), hepatic decompensation, and mortality in patients with HCV-related cirrhosis.

Methods: We retrospectively analyzed 196 patients with HCV-related cirrhosis who achieved SVR at 18 Japanese institutions. Serum GDF15 levels were measured at baseline (BL) and 24 weeks posttreatment (p24w). A previously validated cutoff of 1.75 ng/mL was applied. The clinical outcomes included HCC occurrence, hepatic decompensation, and all-cause mortality.

Results: During a median follow-up of 46.2 months, 75 patients developed HCC, 28 experienced hepatic decompensation, and 25 died. Hepatic decompensation occurred significantly less frequently in the BL GDF15-low group. Importantly, no deaths occurred in the GDF15-low group, whereas the 5-year survival rate in the GDF15-high group was 71.7%. Similar trends were observed for GDF15 levels at p24w. In the overall cohort, GDF15 was not significantly associated with incident HCC; among HCC-naïve patients, a nonsignificant trend toward lower 3-year HCC incidence was observed in the GDF15-low group.

Conclusions: Serum GDF15 is a promising prognostic biomarker for post-SVR outcomes in patients with HCV-related cirrhosis. Its ability to predict decompensation and mortality through a validated cutoff supports its use for risk stratification and long-term management in patients with chronic liver disease.