--- title: "Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Pegylated interferon alfa" description: "Formulary evidence on Hibsago (bepirovirsen, GSK3228836) in Chronic hepatitis B virus infection in adults without cirrhosis: Pegylated interferon alfa. Topics: Current role: AASLD/IDSA 2025 guideline; Recommendations on administration, stopping rules, and add-on therapy: EASL 2025 guideline; Patient selection and duration: AASLD 2018 guidance; Differences between peginterferon and nucleos(t)ide analogue therapy; 7 further topics. 11 evidence topics quoted from 8 sources." canonical: "https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description/pegylated-interferon-alfa" published: "2026-10-21T22:39:04-04:00" modified: "2026-10-22T19:07:03-04:00" --- # Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Pegylated interferon alfa ## 2.2.2.1.2 Pegylated Interferon Alfa ### Current role: AASLD/IDSA 2025 guideline > “Peginterferon is rarely used, given its limitations of applicability, safety and tolerability, compared with NA therapy.” > “Role of peginterferon add-on or switch therapy to NA as strategy to achieve functional cure” Source: [Ghany et al. (2026)](https://doi.org/10.1097/HEP.0000000000001549) ### Recommendations on administration, stopping rules, and add-on therapy: EASL 2025 guideline > “Predictive factors should be used to guide the decision to initiate PEG-IFNα treatment. In addition, PEG-IFNα-associated side effects should be considered, and the patient's treatment preferences should be taken into account to support the decision-making process (LoE 2, strong recommendation, strong consensus).” > “PEG-IFNα should be administered once a week, typically for a duration of 48 weeks. The dose of PEG-IFNα-2a should be 180 μg weekly (s.c.) (LoE 1, strong recommendation, strong consensus).” > “Stopping rules should be considered based on the quantitative determinations of HBV DNA and HBsAg at treatment week 12 and 24 (LoE 2, strong recommendation, strong consensus).” > “De novo combination therapy with PEG-IFNα and NAs cannot be generally recommended. PEG-IFNα as an add-on therapy can be considered in selected HBeAg-negative patients undergoing NA therapy with low HBsAg levels (LoE 2, weak recommendation, consensus).” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### Patient selection and duration: AASLD 2018 guidance > “Comorbidities: peg-IFN is contraindicated in persons with autoimmune disease, uncontrolled psychiatric disease, cytopenia, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis.” > “For patients treated with peg-IFN, 48 weeks’ duration is used in most studies and is preferred. This treatment duration yields HBeAg seroconversion rates of 20% to 31% and sustained off-treatment HBV DNA suppression of <2,000 IU/mL in 65% of persons who achieve HBeAg to anti-HBe seroconversion. The combination of peg-IFN and NAs has not yielded higher rates of off-treatment serological or virological responses and is not recommended.” Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) ### Differences between peginterferon and nucleos(t)ide analogue therapy | Feature | ETV, tenofovir (TDF, TAF) | PEG-IFNα | | --- | --- | --- | | Strategy | “Preventing disease progression through persistent HBV suppression” | “Induction of an off-treatment response through finite treatment” | | Administration | “Oral, once daily” | “Subcutaneous, once weekly” | | Treatment duration | “Long-term” | “Finite (48 weeks)” | | Side effects | “Very low” | “Moderate to high” | | Contraindications | “Very few (e.g. ETV in pregnancy)” | “Numerous” | | HBsAg loss | “Very low” | “Low, higher compared to NAs” | | Risk of viral resistance | “Very low” | “Absent” | Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### HBsAg loss with peginterferon monotherapy: HBeAg-negative pivotal trial > “We compared the efficacy and safety of peginterferon alfa-2a (180 microg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAg-negative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks.” > “Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone.” Source: [Marcellin et al. (2004)](https://pubmed.ncbi.nlm.nih.gov/15371578/) ### HBsAg seroconversion with peginterferon: HBeAg-positive pivotal trial > “Sixteen patients receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001).” > “In this study, HBsAg seroconversion was identified in 8 of 473 Asian patients (2 percent) and 8 of 47 white patients (17 percent) receiving peginterferon alfa-2a alone or in combination with lamivudine, as compared with none receiving lamivudine alone.” Source: [Lau et al. (2005)](https://doi.org/10.1056/NEJMoa043470) ### Durable HBsAg loss after finite peginterferon: 2022 AASLD-EASL endpoints conference > “Historically, a finite course of pegIFNa monotherapy (48 weeks) can result in durable off-treatment HBsAg loss in up to approximately 11% of patients (mostly HBeAg positive) although these results vary by genotype and baseline serum ALT.” Source: [Ghany et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12373085/) ### Peginterferon added to or switched from nucleos(t)ide analogues: EASL 2025 evidence review > “HBsAg loss rates can be improved by PEG-IFNα therapy. However, overall HBsAg loss rates were only 8% for the "add-on" therapy and 14% for the "switch" therapy.” > “Tolerance and acceptance of add-on PEG-IFNα may be a concern as a recent multicentre, open-label, randomised-controlled trial in France found this regimen to be poorly tolerated, leading to early discontinuation of PEG-IFNα in 20% of patients but no significant increase in HBsAg clearance.” > “Notably, a randomised-controlled trial demonstrated that in HBeAg-negative patients with HBV DNA <60 IU/ml for ≥2.5 years, switching from NAs to PEG-IFNα for 48 weeks significantly reduced virological relapse rates (7.8% vs. 20.9%) and increased HBsAg loss (21.5% vs. 9.0%) compared to NA cessation alone,” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### Peginterferon add-on to nucleos(t)ide analogues: individual participant data meta-analysis > “581 patients were included. At the start of peg-IFN therapy (SOT), 44% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12%; 100–1000: 28%; ≥1000: 60%), and planned duration of peg-IFN was 48 weeks in 496 patients (85%).” > “At EOF, 50 (8.6%) patients achieved HBsAg loss (HBsAg<100/100–1000/≥1000: 37.7/9.8/2.3%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6%; Asian: 39.3/9.2/2.2%).” > “Peg-IFN add-on results in HBsAg loss in 18% of patients with SOT HBsAg<1000 IU/mL, and in 38% if SOT HBsAg<100 IU/mL.” > “57 (10%) patients discontinued peg-IFN prior to the planned end-date, and these rates varied between 0% and 21% in the included studies (online supplemental table S1).” Source: [Dongelmans et al. (2026)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13638273/) ### Adverse effects and safety monitoring > “Flu-like symptoms, fatigue, mood disturbances, cytopenia, autoimmune disorders in adults, anorexia and weight loss in children” Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) > “A decline in leukocytes and platelets is common during PEG-IFNα-based therapy.” > “ALT flares can also occur during treatment despite suppression of HBV DNA, particularly in the early treatment phase” > “Psychiatric side effects, including depression, are significant concerns with PEG-IFNα treatment and should be carefully considered both during patient selection and throughout therapy to ensure proper management.” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) > “Thirty-three patients had serious adverse events during treatment and up to eight weeks after therapy: 12 patients (4 percent) receiving peginterferon alfa-2a monotherapy, 16 patients (6 percent) receiving peginterferon alfa-2a plus lamivudine, and 5 patients (2 percent) receiving lamivudine monotherapy (Table 4).” > “However, the rate of withdrawal from peginterferon alfa-2a therapy was less than 5 percent.” Source: [Lau et al. (2005)](https://doi.org/10.1056/NEJMoa043470) ### Concomitant use with bepirovirsen > “Concomitant administration of HIBSAGO and peginterferon alfa-2a is not recommended.” Source: [Hibsago prescribing information (2026)](https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Hibsago/pdf/HIBSAGO-PI-MG-IFU.PDF) ## Related pages - [Hibsago (bepirovirsen): Chronic hepatitis B virus infection in adults without cirrhosis](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Terms and abbreviations](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/terms-and-abbreviations) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/terms-and-abbreviations.md) - [Hibsago (bepirovirsen): Chronic hepatitis B virus infection in adults without cirrhosis](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/executive-summary) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/executive-summary.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Product information and disease description](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Clinical evidence](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/clinical-evidence) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/clinical-evidence.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Economic information and modeling report](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/economics) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/economics.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: References](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/references) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/references.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: new drug review](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/monograph/review) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/monograph/review.md) - [Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: cost-effectiveness analyses and utility weights](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/cost-effectiveness-analyses) · [Markdown](https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/cost-effectiveness-analyses.md)