Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B

Abstract

Early declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6–12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of <100 IU/mL in the HBeAg-negative patients, and HBsAg loss in all the patients during treatment. HBsAg levels of <3,000 IU/mL at baseline combined with an HBsAg decline of ≥75% from baseline provided a predictive algorithm for HBsAg loss (positive and negative predictive values: 70% and 100%, respectively) during 5 years of treatment. The proposed cutoffs for defining an HBsAg decline may assist clinicians in early assessments of treatment responses in genotype B-infected or C-infected CHB patients receiving entecavir therapy.

Re‐treatment for severe hepatitis flare in HBeAg‐negative chronic hepatitis B: An appraisal with combined HBsAg/ALT kinetics

“…The results of the current study have shown that timely re‐treatment in all 16 patients with increasing/increased qHBsAg prior to re‐treatment (Pattern I) not only improved hepatitis and rescued the impending/ensuring hepatic decompensation but also led to ‘rapid HBsAg decline’, a reported predictor for achieving qHBsAg <100 IU/mL (5.8‐fold) and HBsAg loss (8.2‐fold) during 5‐year ETV therapy . The four patients with further increase of ALT 1‐2 weeks after starting re‐treatment might develop hepatic decompensation if re‐treatment were delayed, as observed in patient 12 (Figure B).…”

Usefulness of a Hepatitis B Surface Antigen-Based Model for the Prediction of Functional Cure in Patients with Chronic Hepatitis B Virus Infection Treated with Nucleos(t)ide Analogues: A Real-World Study

“…Low pre-treatment HBsAg levels were significantly associated with HBsAg loss, particularly in hepatitis B e antigen (HBeAg)-positive patients [ 16 ]. Furthermore, several pieces of evidence suggest that on-treatment HBsAg decline was able to predict HBsAg seroclearance, both in HBeAg–positive and –negative patients [ 17 , 18 , 19 ]. However, these results predominantly derive from studies involving Asian patients infected with genotypes B and C. To date, in HBeAg–negative Caucasian patients under long-term treatment with NAs, the predictive value of HBsAg kinetic is less clear [ 20 , 21 ].…”

Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy

“…For patients receiving NA treatment, HBsAg quantification may help to predict clinical outcomes. HBsAg levels of < 3000 IU/mL at the baseline combined with HBsAg declines of ≥ 75% from the baseline could predict the eventual loss of HBsAg[ 14 ]. An HBsAg reduction of > 1 log IU/mL could reflect improved immune control[ 12 , 15 ], and a reduction of ≥ 0.5 log IU/mL after 6 mo of treatment had a high negative predictive value for HBsAg seroclearance[ 16 ].…”