ALT to qHBsAg ratio predicts long-term HBsAg seroclearance after entecavir cessation in Chinese patients with chronic hepatitis B

Background Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term HBsAg seroclearance after entecavir cessation. Methods This study followed up Chinese chronic hepatitis B patients from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They had close monitoring for 48 weeks with regular HBV DNA, qHBsAg and ALT measurements. Entecavir was resumed at HBV DNA >2000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every six months, regardless of entecavir resumption, to monitor for HBsAg seroclearance. Results 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited. 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1000 IU/ml respectively. 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p<0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (HR ranging from 1.003-1.028, all p<0.01) with excellent diagnostic performance (Area-under-receiver-operating-characteristics 0.799-0.933, negative-predictive-value >90% at different time points), regardless of whether entecavir was resumed. Conclusions The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption.