Serum Agalactosyl IgG Predicts Hepatocellular Carcinoma and All-Cause Mortality After SVR in Advanced Chronic
Daisuke Sakon1, Jumpei Kondo1, Yuki Tahata2
1Department of Molecular Biochemistry and Clinical Investigation, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan.
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.