Development and validation of a model for hepatitis B e antigen seroconversion in entecavir‐treated patients with chronic hepatitis B

Achieving hepatitis B e antigen (HBeAg) seroconversion is a satisfactory endpoint during antiviral treatment for chronic hepatitis B (CHB). This study aimed to develop and validate a novel scoring system to predict HBeAg seroconversion during entecavir (ETV) treatment. A total of 526 patients with HBeAg‐positive CHB treated with ETV for at least 1 year were randomly assigned to the training and validation cohorts. Baseline parameters including hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and alanine aminotransferase level were quantified. Patients who achieved HBeAg seroconversion were compared with those without HBeAg seroconversion. A prediction model was established to predict HBeAg seroconversion during ETV treatment. After a median follow up of 2.67 years, 93 (36.0%) and 87 (32.5%) patients in the training and validation cohorts developed HBeAg seroconversion. A prediction score composed of age, HBsAg and HBcAb quantification was derived. Areas under receiver operating characteristic curve at 5 years of this prediction score were 0.70 and 0.72 in the training and validation cohorts. By using the dual cutoff values of 0.28 and 0.58, the model was endowed with high sensitivity and specificity to exclude or identify patients developing HBeAg seroconversion (90.3% sensitivity and 90.2% specificity in the training cohort as well as 92.8% sensitivity and 84.4% specificity in the validation cohort, respectively). A novel prediction score that uses baseline clinical variables was developed and validated. The score accurately estimates the probabilities of developing HBeAg seroconversion at 5‐years ETV therapy in patients with CHB. Highlights HBeAg seroconversion is a satisfactory endpoint for the treatment ofHBeAg‐positive CHB patients. In the study, we established a novel score model which was composed ofHBcAb and two routinely available clinical and laboratory parameters (age andHBsAg). Our results demonstrated the model was not only good in terms ofaccuracy and sensitivity to predict 5‐year probability of HBeAg seroconversion,but also simpler. Importantly, this model performed equally well in cirrhotic andnon‐cirrhotic patients. The probability of HBeAg seroconversion in individual patients treated withETV could be accurately calculated by this novel model.