Host and viral predictive factors of spontaneous hepatitis B surface antigen seroclearance in chronic hepatitis B patients

Abstract

Spontaneous seroclearance of hepatitis B surface antigen (HBsAg) is a rare event that occurs in patients that are chronically infected with the hepatitis B virus. Due to the favourable prognosis and the substantially reduced hepatocellular carcinoma risk that accompany HBsAg seroclearance, it is seen as the functional cure and ultimate treatment endpoint of chronic hepatitis B (CHB) and has therefore attracted great research interest. This is a retrospective study that aims to identify host and viral factors that are associated with HBsAg seroclearance. It utilized plasmas from 120 CHB patients who cleared HBsAg (S-losers) and 120 age- and sex-matched CHB patients who remained HBsAg-positive (controls) collected from 2015 – 2021 in the Queen Mary Hospital, Hong Kong. The levels of several biomarkers were compared between the s-loser and control groups cross-sectionally at the time of HBsAg seroclearance (Year 0). Retrospective samples collected at up to 10 years before HBsAg seroclearance were also analysed and compared. Lower levels of anti-HBc and IP-10 are found respectively to be associated with HBsAg seroclearance since 8 – 10 and 3 – 5 years ago (p<0.05). A significant trend of declining plasma anti-HBc begins 8 – 5 years prior to HBsAg seroclearance (p<0.01). Higher levels of HBV spliced variants Sp1 and Sp3 are associated with HBsAg seroclearance since 8 – 10 years ago (p<0.05). ROC curve analysis reveals that plasma anti-HBc and IP-10 levels at multiple time points before HBsAg seroclearance return AUC greater than 0.7 – plasma anti-HBc levels, at the cut-off value of 82.50 COI, can effectively predict HBsAg seroclearance within 1 year with 68.3 sensitivity and 90.0 specificity, whereas plasma IP-10 levels, at the cut-off value of 29.452pg/ml, can predict HBsAg seroclearance within 1 – 3 years with 52.0 sensitivity and 83.7 specificity, suggesting potential clinical utilities of anti-HBc and IP-10 in predicting HBsAg seroclearance.