Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B

TLDR

HBeAg seroconversion in chronic HBV often aligns with biochemical remission, yet long‑term outcomes remain poorly characterized and active hepatitis can still progress to cirrhosis and hepatocellular carcinoma. The study followed 283 chronic HBV patients for at least one year after spontaneous seroconversion, performing serial clinical, biochemical, virologic assessments and hepatocellular carcinoma screening with ultrasonography and α‑fetoprotein. Over a median 8.6‑year follow‑up, 66.8% of patients maintained remission while 33.2% experienced ALT elevations, and among those without cirrhosis at seroconversion, 7.8% progressed to cirrhosis and 2.2% developed hepatocellular carcinoma—both complications occurring more frequently in patients with active hepatitis, underscoring that spontaneous seroconversion generally confers favorable long‑term outcomes.

Abstract

During the course of chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) seroconversion to its antibody (anti-HBe) often coincides with normalization of liver biochemical test and clinical remission, but data regarding long-term outcome after spontaneous seroconversion are still scarce. Excluding patients with other virus(es) concurrent infection, 283 patients with chronic HBV infection were followed up for at least 1 year after spontaneous HBeAg seroconversion to anti-HBe. Follow-up studies included clinical, biochemical, and virologic evaluation and hepatocellular carcinoma (HCC) screening with ultrasonography and α-fetoprotein assay. During a median follow-up period of 8.6 years (range, 1 to 18.4 years) after HBeAg seroconversion in 283 patients, 189 (66.8%) showed sustained remission, whereas the remaining 94 (33.2%) experienced alanine aminotransferase (ALT) elevation over twice the upper limit of normal: 12 (4.2%) associated with HBeAg reversion, 68 (24%) with detectable serum HBV DNA but HBeAg negative, and 14 (4.9%) of undetermined causes. Of the 269 patients without evidence of cirrhosis at the time of HBeAg seroconversion, 21 (7.8%) developed cirrhosis with a cumulative incidence and relative risk significantly higher in patients developing active hepatitis than in patients with sustained remission ( P < .05). HCC developed in 6 (2.2%) of the 283 patients, also with a significantly higher cumulative incidence in patients developing active hepatitis after HBeAg seroconversion ( P < .005). In conclusion, the results suggest that spontaneous HBeAg seroconversion confers favorable long-term outcomes. However, active hepatitis still may develop and lead to cirrhosis and HCC.