The efficacy of addition of Tenofovir Disoproxil Fumarate to Peg-IFNα-2b is superior to the addition of Entecavir in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone

Abstract

Background: There are limited data regarding the efficacy of addition of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to Peg-IFNα-2b in HBeAg positive chronic hepatitis B (CHB) patients without early response to Peg-IFNα-2b. In this study, we aimed to evaluate the efficacy of ETV and TDF in HBeAg positive CHB patients who had a poor response to Peg-INFα-2b at the end of 12 weeks of monotherapy. Methods: A total of 40 HBeAg-positive CHB patients who were naive to antiviral therapy were recruited. The patients received a subcutaneous injection of Peg-IFNα-2b (180 µg) once a week for 12 weeks. However, the patients had a poor response to Peg-INFα-2b at the end of the 12-week-period monotherapy. The patients were then divided into two therapeutic protocol groups: (1) Group A: Patients received Peg-IFNα-2b (180 µg) subcutaneously weekly and ETV (0.5 mg) orally once daily for 48 weeks; (2) Group B: Patients received Peg-IFNα-2b (180 µg) subcutaneously weekly and TDF (300 mg) orally once daily for 48 weeks. The therapeutic efficacy was evaluated. Blood samples were collected at baseline and every 12 weeks. Routine biochemical tests including ALT, AST, etc. were measured by automated biochemical technique. HBV DNA was quantified using the TaqMan PCR assay. The levels of HBsAg, HBsAb, HBeAg, HBeAb and HBcAb were measured using a commercial chemiluminescent microparticle immunoassay. Results: The HBsAg level declined rapidly in both two treatment groups during the first 12 weeks and declined gradually in the next 36 weeks. At week 48, the mean ΔHBsAg level in Peg-IFNα-2b+TDF group was significantly higher than that in Peg-IFNα-2b +ETV group (-1.799 ± 0.3063 vs. -1.078 ± 0.2028, P=0.0491). The HBeAg loss rate was significantly higher in TDF add-on group than that in ETV add-on group at week 48 (40% vs. 10%, P=0.028). At week 48, the proportions of patients with undetectable HBV DNA (<500 IU/mL) were 80% (16 out of 20) and 95% (19 out of 20) in Peg-IFNα-2b+ETV group and Peg-IFNα-2b+TDF group, respectively. Conclusions:This real world study demonstrated that the efficacy of addition of TDF to Peg-IFNα-2b is superior to the efficacy of addition of ETV to Peg-IFNα-2b in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b treatment alone. However, this present study also requires a larger sample size study to verify in the future.

[Retracted] Efficacy and Safety of Peginterferon α‐2a and Entecavir Tenofovir in the Treatment of Chronic Hepatitis B Genotype C

“…is was consistent with the study conclusions of Hagiwara et al [11] and Lin et al [12]. In addition, the ALT normalization rate, NCR of HBV-DNA, and seroconversion rate of HBeAg were higher in the tenofovir group than in the entecavir group, which suggested that tenofovir was superior to entecavir in the intensity of hepatitis B surface antigen clearance in patients with CHB genotype C. In agreement with the conclusion proposed by Lin et al [13], the addition of tenofovir was more effective than the addition of entecavir to peginterferon α-2a in HBeAg-positive CHB patients who had a poor response after 12 weeks of peginterferon α-2a treatment.…”

Reduction of Hepatitis B Surface Antigen May Be More Significant in PEGylated Interferon-Alpha Therapy Combined with Nucleotide Analogues than Combined with Nucleoside Analogues in Chronic Hepatitis B Patients: A Propensity Score Matching Study

“…After PSM, the results showed that the HBsAg levels of the PegIFNα + NSs group decreased by an average of −2.33 log 10 IU/mL from baseline at 48 weeks, while it decreased signifcantly more in the PegIFNα + NTs group, by an average of −3.52 log 10 IU/ mL (P � 0.032). Te reductions of HBsAg in both groups were more than those in Lin et al' study [31]. Tis could be because our study had a longer combination course and some patients had previously received NA treatment.…”

Reduction of Hepatitis B Surface Antigen More Pronounced In Pegylated Interferon Alpha Therapy Combined With Nucleotide Analogues Than Nucleoside Analogues In Chronic Hepatitis B Patients

“…After PSM, the results showed that the HBsAg of the PegIFNα + NSs group decreased by an average of −2.33 log 10 IU/mL from baseline at 48 weeks, while it decreased signi cantly more in the PegIFNα + NTs group, by an average of −3.52 log 10 IU/mL (P = 0.032). The reductions of HBsAg in both groups were more than the reductions in Lin's study (Lin et al 2020). This might be because our study had a longer combination course and some patients had a prior treatment of NAs.…”

“…On the contrary, there are meta-analyses showing that the differences in HBsAg loss rates at the end of the combination therapy are not statistically signi cant among different NAs (ETV 11% vs ADV 12% vs LAM 9% vs TDF 6%, P > 0.05), and have found similar results for the HBsAg seroconversion rate (5% vs 5% vs 9% vs 4%, P > 0.05) [29]. Lin et al recently found that addition of TDF to Peg-IFNα-2b in HBeAg positive CHB patients with a poor response after 12 weeks of Peg-IFNα-2b monotherapy reduced HBsAg signi cantly more than addition of ETV to Peg-IFNα-2b (−1.799 log 10 IU/mL vs −1.078 log 10 IU/mL, P = 0.0491) [30]. It was an important result as it compared the addition of TDF or ETV to Peg-IFNα-2b directly.…”

“…No advantages were found when PegIFNα was combined with LAM or ETV [32]. But Lin et al showed than the HBeAg loss rate was signi cantly higher in TDF add-on group than that in ETV add-on group at week 48 (40% vs 10%, P = 0.028) [30]. Interestingly, these studies suggested a possibility that PegIFNα combined with different NAs could have different e cacies, but direct evidence was demanded and mechanism behind the differences need to be discussed.…”