--- title: "Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Nucleos(t)ide analogues" description: "Formulary evidence on Hibsago (bepirovirsen, GSK3228836) in Chronic hepatitis B virus infection in adults without cirrhosis: Nucleos(t)ide analogues. Topics: Preferred agents and selection criteria: AASLD/IDSA 2025 guideline, Treatment goals and indications: AASLD/IDSA 2025 guideline, Preferred initial therapy: AASLD 2018 guidance, First-line nucleos(t)ide analogue therapy: EASL 2025 guideline, and 6 further topics. 10 evidence topics quoted from 7 sources." canonical: "https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description/nucleos-t-ide-analogues" 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: Nucleos(t)ide analogues ## 2.2.2.1.1 Nucleos(t)ide Analogues ### Preferred agents and selection criteria: AASLD/IDSA 2025 guideline > “Two classes of drugs are approved for the treatment of CHB: peginterferon and nucleos(t)ide analogues (NAs).” > “There are three NAs that are preferred for treatment of CHB: entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). All 3 drugs provide high efficacy in achieving HBV DNA suppression, have low rates of antiviral resistance, and are well tolerated and broadly applicable (including for persons with decompensated cirrhosis and immunocompromised states).” > “Selecting among these drugs is based upon availability/cost, age, presence of renal or bone disease (avoid TDF), pregnancy (avoid ETV), HIV coinfection (avoid ETV unless HIV RNA suppressed on antiretroviral regimen), and prior treatment history (avoid ETV if prior lamivudine exposure).” > “TAF is not recommended if creatinine clearance is less than 15mL/min and not yet on dialysis.” Source: [Ghany et al. (2026)](https://doi.org/10.1097/HEP.0000000000001549) ### Treatment goals and indications: AASLD/IDSA 2025 guideline > “The goals of antiviral treatment are prevention of progression to cirrhosis, development of hepatocellular carcinoma (HCC) and liver-related death.” > “If cirrhosis is present, persons should initiate antiviral therapy regardless of HBV DNA or ALT level.” > “For HBeAg positive persons without cirrhosis, antiviral treatment is indicated for an ALT level ≥2 X ULN and HBV DNA ≥20,000 IU/mL.” > “For HBeAg negative persons without cirrhosis, treatment is indicated for an ALT level ≥2 X ULN and HBV DNA ≥2,000 IU/mL.” > “Treatment of these individuals has been shown to reduce the incidence of progression to cirrhosis, development of HCC, need for liver transplantation and HBV-related liver mortality.” Source: [Ghany et al. (2026)](https://doi.org/10.1097/HEP.0000000000001549) ### Preferred initial therapy: AASLD 2018 guidance > “The AASLD recommends antiviral therapy for adults with immune-active CHB (HBeAg negative or HBeAg positive) to decrease the risk of liver-related complications” > “The AASLD recommends peg-IFN, entecavir, or tenofovir (TDF) as preferred initial therapy for adults with immune-active CHB” > “TAF is also a preferred initial therapy for adults with immune-active CHB.” > “Consider TAF or entecavir in patients with or at risk for renal dysfunction or bone disease.” > “However, in recommending peg-IFN, tenofovir, and entecavir as preferred therapies, the most important factor considered was the lack resistance with long-term use.” Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) ### First-line nucleos(t)ide analogue therapy: EASL 2025 guideline > “ETV, TDF, or TAF should be used as first-line NA therapy. When selecting between ETV, TDF and TAF, comorbidities (especially renal insufficiency and reduction in bone density) and concomitant circumstances (e.g. women of childbearing age, pregnancy, age) as well as previous therapies should be taken into account (LoE 1, strong recommendation, strong consensus).” > “The virological response (HBV DNA “Patients with HBeAg-positive or HBeAg-negative chronic hepatitis B, HBV DNA level ≥2,000 IU/ml and elevated ALT (>ULN) and/or significant fibrosis should receive antiviral therapy (LoE 1, strong recommendation, strong consensus).” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### Preferred regimens: WHO 2024 guideline > “For all adults, adolescents and children (two years or older) for whom antiviral therapy is indicated, the nucleos(t)ide analogues that have a high genetic barrier to drug resistance – tenofovir disoproxil fumarate (TDF) or entecavir (ETV) are recommended as preferred regimens.” > “Nucleos(t)ide analogues with a low genetic barrier to resistance (lamivudine, adefovir or telbivudine) can lead to drug resistance and are not recommended.” Source: [WHO hepatitis B guidelines (2024)](https://iris.who.int/server/api/core/bitstreams/34470cc8-af90-4d7b-a949-ef27e5d0726f/content) ### Efficacy in HBeAg-negative immune-active chronic hepatitis B: pivotal trial summary | Outcome (HBeAg-negative, treatment-naive adults) | Peginterferon | Entecavir | Tenofovir disoproxil fumarate | Tenofovir alafenamide | | --- | --- | --- | --- | --- | | % HBV DNA suppression | “19 (<80 IU/mL)” | “90–91 (<50–60 IU/mL)” | “93 (<60 U/mL)” | “90 (<29 IU/mL)” | | % Normalization ALT | “59” | “78–88” | “76” | “81” | | % HBsAg loss | “4” | “0–1” | “0” | “<1” | Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) ### HBsAg seroclearance rate in untreated and treated cohorts: meta-analysis > “We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24).” > “HBsAg seroclearance was not associated with HBV genotype or treatment history.” > “Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.” Source: [Yeo et al. (2019)](https://pubmed.ncbi.nlm.nih.gov/30342034/) ### Long-term tenofovir alafenamide: 8-year suppression and HBsAg loss > “By year 8, 2%–3% of patients had achieved HBsAg loss with or without seroconversion (Table 2; Tables S1 and S2).” > “Conversely, rates of HBsAg loss and seroconversion were low at 2%–3%, and quantitative HBsAg titres declined minimally over 8 years.” > “No patients developed resistance to TAF.” Source: [Buti et al. (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11599788/) ### Long-term outcomes on entecavir or tenofovir: PAGE-B cohort beyond 10 years > “The long-term PAGE-B cohort included 1,644 Caucasian patients with CHB treated with entecavir or tenofovir.” > “The 10- and 15-year cumulative incidences of HBsAg loss on NA(s) were 8.3% and 14.3%, respectively; the IR of HBsAg loss increased from 0.94 before year 10 to 1.42/100 PYs after year 10 (p = 0.025).” > “NA therapy was discontinued in 125 (7.6%) patients who remained HBsAg positive.” Source: [Papatheodoridis et al. (2026)](https://pubmed.ncbi.nlm.nih.gov/42409322/) ### Clinical benefits of long-term viral suppression: EASL 2025 guideline > “Sustained suppression of HBV DNA is associated with an improvement in liver histology. After 5 years of treatment with ETV or tenofovir, improvement in liver fibrosis was observed in most patients and there was even reversal of Ishak F5/6 fibrosis/cirrhosis in some patients.” > “many studies with follow-up periods of around 5 years likely had insufficient duration and sample sizes to demonstrate a significant effect on preventing HCC and death.” > “However, one retrospective study with a follow-up of 8 years showed that TDF was associated with an HCC risk reduction of 73% in patients without cirrhosis.” > “Improvement of survival: multiple studies, as summarised in a meta-analysis, have demonstrated a 50% reduction in mortality in patients with cirrhosis achieving viral suppression on NA therapy.” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ## 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)