A randomized clinical trial of peginterferon alpha‐2b with or without entecavir in patients with HBeAg‐negative chronic hepatitis B: Role of host and viral factors associated with treatment response

Abstract

Combining peginterferon (PEG-IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG-IFN alpha-2b with or without entecavir in HBeAg-negative CHB and to investigate predictors of response. A total of 126 treatment-naïve patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level <2000 IU/mL at week 96. Baseline factors including polymorphisms in the IFNL3 (rs12979860) and HLA-DPA1 (rs3077) genes and on-treatment viral kinetics were determined. At week 48, rates of undetectable HBV DNA were lower in the monotherapy than combination groups, but rates of HBsAg clearance and decline were comparable. At week 96, there was no difference between the corresponding groups regarding virological response (41.3% vs 38.1%, P = 0.856), HBsAg clearance (9.5% vs 4.8%, P = 0.491) and HBsAg decline. Baseline HBsAg level [odds ratio (OR): 3.14 (1.34-7.69), P = 0.012] and rs3077 polymorphism [OR: 2.78 (1.27-6.11), P = 0.011] were independent predictors of response. Patients carried GG genotype of rs3077 with low baseline HBV (<1000 IU/mL) had high probability of achieving VR (76.5%) and HBsAg clearance (29.4%). None of the patients without decrease in HBsAg combined with <2 log10 HBV DNA decline at week 12 achieved a virological response. In conclusion, the combination therapy lead to greater on-treatment HBV DNA suppression but did not improve virological response and HBsAg clearance/decline over monotherapy. Host and viral factors could help optimize decision-making at baseline and during PEG-IFN-based therapy.

Systematic review with meta‐analysis: combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance

“…As illustrated in Figure , a total of 24 trials were selected from 2632 potentially eligible studies, all of which were published in English . After removal of duplicates and initial screening, 87 studies were further evaluated for eligibility.…”

“…Sixty-three studies were then excluded, for 45 of which did not involve available data, 13 had too small sample sizes, five were focused on occult CHB patients co-infected with HIV. Combination therapies were used in all 24 trials, including IFN combined with LAM in three trials, 37-39 IFN combined with ADV in seven trials, 14,[25][26][27][28][29][30] IFN combined with ETV in six trials, [31][32][33][34][35][36] IFN combined with TDF in two trial 46,47 and IFN combined with at least 2 NAs in seven trials. [40][41][42][43][44][45] Study characteristics are shown in Table 1.…”

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

“…Out of the 43 studies included, 11‐39 7 were abstracts presented as posters 40‐46 in congresses and 7 full articles were published in Chinese 47‐53 . In 15 studies, patients received antivirals up till enrolment date while in 14 other studies, patients went through 3‐12 months of a washout period before being enrolled.…”

Genome Wide Association Study Identifies Genetic Variants Associated with Early and Sustained Response to (Peg)Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

“…In this investigator-initiated multicentre global GWA study, CHB patients treated with PegIFN alpha or conventional interferon α (IFN α) within randomized controlled trials, prospective cohort studies, or as part of standard of care at 21 tertiary care centers from Europe, Asia, and North America were initially eligible for inclusion. The inclusion and exclusion criteria for the trials are described elsewhere [7,8,10,[12][13][14][15][16][17][18][19][20][21][22]. For the current study, the minimal duration of therapy was 12 weeks.…”