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

Abstract

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.

[Retracted] Finite versus Indefinite Nucleos(t)ide Analogue Therapy of Patients with Chronic Hepatitis B Exhibiting Negative HBsAg Levels after Treatment

“…The duration of any NUC consolidation therapy after achieving the criterion for cessation of treatment is another issue that must be addressed when optimizing the finite therapy approach [6,7]. Previous guidelines have suggested the use of 6-12 months of NUC consolidation therapy after HBeAg seroconversion [1][2][3], but there is no evidence-based suggestion for discontinuation of finite therapy after the loss of HBsAg. In the present study, long-term consolidation with NUCs (>1 year) did not improve patient outcomes compared with short-term consolidation (<1 year).…”

“…Clinical decision-making regarding the discontinuation of nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB) has recently become a subject of heated debate [1][2][3]. Conflicting factors that complicate whether to discontinue NUC therapy include the risks of viral breakthrough and relapse, hepatocellular carcinoma (HCC), liver cirrhosis, and patient preference [4,5].…”

“…Finite therapy with NUCs is an attractive strategy because indefinite use of NUCs is limited by several factors such as the economic burden of a long treatment course, risk of nonadherence to treatment, incidence of viral breakthrough, and increasing risk of adverse effects with increasing treatment time [1][2][3]. Nevertheless, viral relapse and consequent exacerbation of hepatitis after cessation of NUCs are nonnegligible risks of the finite approach to treatment [9,10].…”

“…The key requirement for finite therapy is the identification of an evidence-based marker for discontinuation. For hepatitis B e antigen-(HBeAg-) positive patients, HBeAg seroconversion was considered a potential marker for NUC discontinuation [1]. Unfortunately, several studies have demonstrated that a large proportion of patients experience viral relapse and elevations of ALT upon discontinuation of NUC treatment following HBeAg seroconversion [1,7,8,11].…”

“…For hepatitis B e antigen-(HBeAg-) positive patients, HBeAg seroconversion was considered a potential marker for NUC discontinuation [1]. Unfortunately, several studies have demonstrated that a large proportion of patients experience viral relapse and elevations of ALT upon discontinuation of NUC treatment following HBeAg seroconversion [1,7,8,11]. As an alternative criterion, loss of hepatitis B surface antigen (HBsAg) was found to be a much safer potential endpoint since NUC discontinuation after loss of HBsAg did not result in adverse events in most cases [5].…”