Serum Agalactosyl IgG Predicts Hepatocellular Carcinoma and All‐Cause Mortality After SVR in Advanced Chronic Hepatitis C

BACKGROUND AND AIMS: Patients with chronic hepatitis C and advanced fibrosis remain at substantial risk of hepatocellular carcinoma (HCC) and non-liver-related death even after sustained virological response (SVR) to direct-acting antivirals (DAA). Serum agalactosyl IgG (agal-IgG) reflects chronic inflammation and fibrogenic activity, but its prognostic value after SVR is unknown. We investigated whether serum agal-IgG at end of treatment (EOT) predicts HCC and all-cause mortality in DAA-treated patients with advanced fibrosis. METHODS: Among 3550 patients with chronic hepatitis C treated with DAAs at Osaka University Hospital and affiliated centers, the stored sera of 136 patients with biopsy-proven F3-F4 fibrosis before DAA treatment, who achieved SVR, and had no history of HCC were available at EOT. Serum agal-IgG at EOT was measured using a 42B1-based ELISA. RESULTS: During a median follow-up of 68.7 months (interquartile range, 36.8-84.9) for HCC surveillance, 15 patients developed HCC. Over a median overall follow-up of 73.7 months (54.5-86.7), 11 patients died. Higher EOT agal-IgG levels were significantly associated with both HCC occurrence and all-cause mortality, and these associations remained independent after adjustment for age, sex, and baseline fibrosis (FIB-4 index). The adjusted hazard ratios per 1-unit increase in agal-IgG were 1.050 (95% CI, 1.008-1.094) for HCC and 1.085 (95% CI, 1.035-1.137) for all-cause mortality. Patients with EOT agal-IgG levels above the cohort median also showed significantly higher cumulative incidences of HCC and all-cause death than those with lower levels. CONCLUSIONS: Serum agalactosyl IgG measured at the end of DAA therapy independently predicts HCC and all-cause mortality after SVR in patients with chronic hepatitis C and advanced fibrosis. EOT agal-IgG may offer additional prognostic information for post-SVR risk stratification and help identify patients at higher risk of HCC and all-cause mortality after SVR.