--- title: "Hibsago (bepirovirsen) in Chronic hepatitis B virus infection in adults without cirrhosis: Definition and etiology" description: "Formulary evidence on Hibsago (bepirovirsen, GSK3228836) in Chronic hepatitis B virus infection in adults without cirrhosis: Definition and etiology. Topics: Disease definition: hepatitis B surface antigen persisting for at least 6 months; Diagnostic criteria for chronic hepatitis B in the AASLD 2018 guidance; Causative agent: hepatitis B virus, a hepatotropic DNA virus of the Hepadnaviridae family; Transmission routes: blood, sexual, perinatal, and percutaneous exposure; 4 further topics. 8 evidence topics quoted from 6 sources." canonical: "https://www.evicenter.com/drugs/hibsago--chronic-hepatitis-b-virus-infection-in-adults-without-cirrhosis/product-information-and-disease-description/definition-and-etiology" 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: Definition and etiology ## 2.2.1.1 Definition and Etiology ### Disease definition: hepatitis B surface antigen persisting for at least 6 months > “The presence of HBsAg establishes the diagnosis of hepatitis B. Chronic vs acute infection is defined by the presence of HBsAg for at least 6 months.” > “The presence of HBsAg for at least 6 months establishes the chronicity of infection.” Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) ### Diagnostic criteria for chronic hepatitis B in the AASLD 2018 guidance | Criterion | Quoted definition | | --- | --- | | Surface antigen | “HBsAg present for ≥6 months” | | Viral load range | “Serum HBV DNA varies from undetectable to several billion IU/mL” | | HBeAg subgroups | “Subdivided into HBeAg positive and negative. HBV DNA levels are typically >20,000 IU/mL in HBeAg-positive CHB, and lower values (2000–20,000 IU/mL) are often seen in HBeAg-negative CHB” | | Aminotransferases | “Normal or elevated ALT and/or AST levels” | | Histology | “Liver biopsy results showing chronic hepatitis with variable necroinflammation and/or fibrosis” | Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) ### Causative agent: hepatitis B virus, a hepatotropic DNA virus of the Hepadnaviridae family > “Hepatitis B is caused by infection with HBV. HBV is a 40–42-nanometer enveloped virus classified in the Hepadnaviridae family. HBV contains a circular, partially double-stranded DNA genome that is 3.2 kb in length. After a susceptible person is exposed, the virus enters the liver via the bloodstream. The liver is the primary site of HBV replication.” > “Is classified by serologic subtype and genotype, which vary geographically.” > “Is infectious for at least 7 days on surfaces.” Source: [CDC Clinical Overview of Hepatitis B (2025)](https://www.cdc.gov/hepatitis-b/hcp/clinical-overview/index.html) ### Transmission routes: blood, sexual, perinatal, and percutaneous exposure > “HBV is highly infectious and transmitted when blood, semen or other body fluids from a person infected with the virus enters the body of someone who is uninfected.” Source: [CDC Clinical Overview of Hepatitis B (2025)](https://www.cdc.gov/hepatitis-b/hcp/clinical-overview/index.html) > “In highly endemic areas, hepatitis B is most commonly spread from mother to child at birth (perinatal transmission) or horizontal transmission through person-to-person contact in the presence of open cuts and sores, especially from an infected child to an uninfected child during the first 5 years of life.” > “Hepatitis B is also spread by needlestick injury, tattooing, piercing and exposure to infected blood and body fluids, such as saliva and menstrual, vaginal and seminal fluids. Transmission of the virus may also occur through the sharing or reuse of contaminated needles and syringes or sharp objects either in health care settings, in the community or among persons who inject drugs. Sexual transmission is more prevalent in unvaccinated persons with multiple sexual partners.” Source: [WHO hepatitis B fact sheet (2026)](https://www.who.int/news-room/fact-sheets/detail/hepatitis-b) > “In regions with high endemicity, vertical transmission from mother to child during childbirth or through close personal contact contributes significantly to the prevalence of HBV infection. However, HBV can be transmitted through various routes, including perinatal transmission, sexual contact, sharing of contaminated needles or other injection equipment, and exposure to infected blood.” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### Age at infection and risk of chronicity > “The risk for chronic infection varies according to the age at infection and is greatest among young children. Approximately 90% of infected infants and 30% of children infected between 1–5 years will remain chronically infected with HBV. By contrast, approximately 95% of infected adults recover completely from acute HBV infection and do not become chronically infected.” > “The average incubation period for HBV is 60 days (range: 40–90 days) from exposure to onset of abnormal serum alanine aminotransferase (ALT) levels and 90 days (range: 60–150 days) from exposure to onset of signs and symptoms.” Source: [CDC Clinical Overview of Hepatitis B (2025)](https://www.cdc.gov/hepatitis-b/hcp/clinical-overview/index.html) > “Hepatitis B infection acquired in adulthood leads to chronic hepatitis in less than 5% of cases, whereas infection in infancy and early childhood leads to chronic hepatitis in about 95% of cases.” Source: [WHO hepatitis B fact sheet (2026)](https://www.who.int/news-room/fact-sheets/detail/hepatitis-b) ### Genotypes: ten genotypes, with genotypes A, B, and C most prevalent in the United States > “Ten genotypes of HBV have been identified labeled A through J (103, 104). The prevalence of HBV genotypes varies geographically. HBV genotypes A through H have been found in the United States, with genotypes A, B, and C being most prevalent (26). HBV genotypes may play an important role in the progression of HBV-related liver disease as well as response to interferon (IFN) therapy (103, 105).” > “Studies from Asia found that HBV genotype B is associated with HBeAg seroconversion at an earlier age, more sustained remission after HBeAg seroconversion, less active hepatic necroinflammation, a slower rate of progression to cirrhosis, and a lower rate of HCC development compared with genotype C (103).” Source: [Terrault et al. (2018)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5975958/) > “In terms of genotype, genotype C has been associated with a higher risk of HCC than genotype B in individuals with chronic HBV infection in Asia.105,196 In individuals from Africa (e.g. The Gambia), HBV genotype A has been identified as a risk factor for liver fibrosis202 and HCC199 compared with genotype E. In Alaska, genotype F was associated with the highest HCC risk.197” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### Cirrhosis: liver stiffness thresholds used to stage HBV-related fibrosis > “In an optimal setting, liver fibrosis is assessed using LSM, with defined cut-off values for VCTE indicating significant fibrosis (7.2-7.9 kPa), advanced fibrosis (8.8-9.4 kPa) and cirrhosis (≥11.7-12.2 kPa), as shown in two systematic reviews and meta-analyses focused on individuals with HBV infection.” > “The most recent meta-analysis, focused exclusively on individuals with HBV infection, proposes thresholds of 6.0–8.0 kPa for significant fibrosis (with a cut-off of >7.0 kPa identifying most cases), >8.0–11.0 kPa for advanced fibrosis, and >11.0–14.0 kPa for cirrhosis.” > “The Baveno VI consensus introduced the term “compensated advanced chronic liver disease (cACLD)” to describe patients with advanced fibrosis or early cirrhosis who remain asymptomatic but are at risk of developing clinically significant portal hypertension (CSPH) and disease progression.80 Liver stiffness values <10 kPa were proposed as a safe cut-off for excluding cACLD and values >15 kPa as highly suggestive of cACLD.” Source: [EASL (2025)](https://doi.org/10.1016/j.jhep.2025.03.018) ### Resolution terms: functional cure and partial cure | Term | Quoted definition | | --- | --- | | Functional cure | “HBsAg-negative and HBV DNA undetectable off treatment for at least 6 mo (± anti-HBs)” | | Partial cure | “HBsAg <100 IU/mL with HBV DNA undetectable off treatment for at least 6 mo” | | HBsAg loss | “Loss of HBsAg on antiviral therapy or spontaneously in person who was previously HBsAg-positive” | Source: [Ghany et al. (2026)](https://doi.org/10.1097/HEP.0000000000001549) > “The recommended endpoint of novel therapy is functional cure defined as HBsAg loss using a conventional assay for detection of HBsAg (limit of detection 0.05 IU/mL) and HBV DNA below the lower limit of quantification (i.e. < 10 IU/ml) at 24 weeks off-therapy.” Source: [Ghany et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12373085/) > “Loss of HBsAg with acquisition of anti-HBs has been termed functional cure. This is distinguished from true cure, in which HBsAg and covalently closed circular DNA are eliminated.” Source: [Terrault et al. 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