Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance (10-year single clinic experience)

Background:Hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Persistent viral replication in chronic HBV infection promotes hepatocyte injury and fibrosis, predisposing patients to HCC. Loss of hepatitis B surface antigen (HBsAg), defined as a "functional cure," represents a desirable end-point in the management of chronic hepatitis B. However, the risk of HCC is not completely abolished after HBsAgseroclearance, particularly in older patients and those with cirrhosis. This study aimed to evaluate the impact of HBsAg seroclearance on HCC development and to identify risk factors for HCC during post-seroclearance follow-up. Methods:In this retrospective study, medical records of 6836 chronic hepatitis B patients followed at Cukurova University Faculty of Medicine Balcalı Hospital between 2013 and 2023 were reviewed. HBsAg seroclearance, defined as persistent loss of HBsAg for at least six months with or without anti-HBs positivity, occurred in 259 patients. Twenty-two patients developed HCC after seroclearance and were defined as cases; there maining 237 patients served as controls. Demographic data, HBV infection duration, cirrhosis status, REACH-B score, and laboratory parameters were recorded. Group comparisons were performed using Student's t-test, Mann–Whitney U test, and chi-square test, and risk factors for post-seroclearance HCC were analyzed using univariate and multivariate logistic regression. Results:Of the 259 patients with HBsAg seroclearance, 65.3% were male and the meanage at seroclearance was 60.7 ± 12.1 years. During follow-up, 22 patients (8.49%) developed HCC. The meanage at seroclearance was higher in patients who developed HCC, but it did not remain an independent predictor in multivariate analysis. Cirrhosis, a high REACH-B score, and shorter HBV infection duration were identified as independent predictors for HCC development (p < 0.05 for each). Although male sex and advanced age were associated with HCC in univariate analysis, they did not remain significant in the multivariate model. There was no significant difference in HCC incidence between spontaneous and therapy-induced seroclearance. Conclusion:Achieving HBsAg seroclearance favorably alters the course of chronic HBV infection but does not eliminate the risk of HCC. Cirrhosis, elevated REACH-B score, and shorter duration of HBV infection are the strongest predictors of post-seroclearance HCC. These findings under score the need for individualized long-term HCC surveillance in patients with HBsAg seroclearance, particularly among cirrhotic patients and those with high REACH-B scores. Keywords:HBsAg seroclearance, hepatocellular carcinoma, chronic hepatitis B, risk factors,cirrhosis.