Practical Strategies for Patient-Centered Care in Chronic Hepatitis B: Insights from a Session at The Liver Meeting® 2025
Hepatology
The publication of this article was sponsored by GSK.
This medical disease state educational session took place during The Liver Meeting® 2025, held in Washington, D.C., USA, from November 7–11, 2025
Meeting Summary
INTRODUCTION
Chronic hepatitis B (CHB) affects approximately 1.7 million people in the United States and represents a significant public health challenge because of its potential to cause severe liver disease, including cirrhosis and hepatocellular carcinoma (HCC).1,2 A medical disease state educational session sponsored by GSK at The Liver Meeting® 2025, held in Washington, D.C., USA, from November 7–11, 2025, brought together distinguished hepatology experts and guideline authors to discuss practical, patient-centered strategies for managing CHB. The session occurred shortly after the publication of updated AASLD/IDSA guidelines for CHB treatment.2 The updated guidelines were discussed extensively during the session.
The educational session was led by three panelists: Mandana Khalili, Paul Kwo, and Norah Terrault. Through an interactive format combining audience polling and case-based discussion, the session addressed barriers and unmet needs in CHB management, including the role of quantitative HBsAg testing, focusing on the clinically challenging indeterminate phase of CHB infection. The panelists also discussed updated evidence-based recommendations for the management of CHB.2 This article synthesizes the key discussions from that session, providing clinicians with actionable insights for optimizing CHB care in their practice.
THE BURDEN OF CHRONIC HEPATITIS B
Non-US-born persons have a higher prevalence of CHB when compared to US-born persons.3
In 2023, there were more than 17,000 new cases of chronic hepatitis B virus (HBV) infections in the United States, with approximately 46% of all newly reported chronic HBV cases occurring in persons aged 30–39 years and 40–49 years.5
1.7
million Americans
higher in foreign-born individuals
17,000
new cases in 2023
Prevalence of CHB
Clinical impact of CHB
PHASES OF CHRONIC HEPATITIS B
Through a patient case study, the panelists discussed the importance of accurately characterizing the phase of CHB infection, as this fundamentally guides management decisions. The presenters emphasized that CHB is a dynamic disease that evolves over a person’s lifetime, making regular monitoring essential.2
The guidelines specify that normal ALT is defined as <25 U/L for females and <35 U/L for males.2 These thresholds are lower than the upper limits used in many clinical laboratories.13
THE INDETERMINATE PHASE OF CHRONIC HEPATITIS B
A large portion of the session focused on what the guidelines referred to as the “indeterminate phase” or “grey zone” of CHB, a term used to describe the disease state in patients who do not fit into any of the defined phases.2
The indeterminate phase describes patients who do not clearly meet criteria for either immune‑active or inactive CHB. These individuals often fluctuate over time, either declaring immune‑active disease with rising ALT and HBV DNA, or transitioning to inactive disease with low levels of both.2
According to the updated AASLD/IDSA guidelines, indeterminate phase CHB can predominantly manifest as normal (ULN) with HBV DNA <2,000 IU/mL.2 However, the criteria for different disease phases, including the indeterminate phase, can vary depending on the guidelines being used.2,8,17
Some patients may be classified as being in an indeterminate phase on follow-up. The indeterminate phase is in between these phases, where we may have elevation of the viral load, but normal liver enzymes.2
THE ROLE OF IMAGING AND BIOMARKERS IN CHRONIC HEPATITIS B ASSESSMENT
According to the CDC screening guidelines, serological qualitative testing for HBsAg, hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc) is recommended to assess immunity and past infection.18,22,23 However, the panelists emphasized that establishing the phase of CHB infection and determining appropriate treatment strategies require assessment beyond
standard serologic testing.
Kwo noted that hepatitis B is not static. "One doesn't evaluate someone with hepatitis B just at one visit. It's a process as you get to know your patients.”
The latest AASLD/IDSA guidelines recommend non-invasive tests of fibrosis, such as hepatic transient elastography or serum markers such as FIB-4 for fibrosis assessment.2
For the patient in this case scenario, imaging assessments included VCTE, which showed liver stiffness of 6.8 kPa (suggesting no to minimal fibrosis) and controlled attenuation parameter (CAP) of 275 dB/m (indicating hepatic steatosis); and abdominal ultrasound, which revealed mildly echogenic liver consistent with fatty liver, with no evidence of cirrhosis or portal hypertension. Additional laboratory testing showed that the patient was negative for HIV RNA and for hepatitis C virus and hepatitis D virus antibodies with a quantitative HBsAg value of 1,200 IU/mL.
THE ROLE OF QUANTITATIVE HEPATITIS B SURFACE ANTIGEN
The panelists discussed the role of quantitative HBsAg in the evaluation and management of CHB.
Kwo interpreted that a quantitative HBsAg level of 1,200 IU/mL was consistent with an indeterminate profile, suggesting features overlapping inactive and more active disease.
Quantitative HBsAg levels below 1,000 IU/mL are generally associated with the inactive phase and a lower risk of HCC, whereas higher levels suggest more active infection.24-26
Quantitative HBsAg may be used as a biomarker in CHB to monitor natural history of HBV infection by distinguishing HBeAg-negative chronic HBV infection (or inactive CHB) from CHB (or immune-active CHB), or by helping clinicians predict spontaneous HBsAg seroclearance, with HBsAg levels <100 IU/mL being significantly associated with spontaneous HBsAg loss.17,27-29
Quantitative HBsAg
may also be helpful in predicting prognosis in individuals with CHB.30
In addition, quantitative HBsAg measurements may be useful for monitoring treatment response and predicting response to antiviral therapies.2,29,30 HBsAg titers may help clinicians identify patients with CHB who may be eligible for clinical trials or who may respond to investigational medicines.2,19,28
IMPORTANCE OF SHARED DECISION-MAKING
The speakers discussed the importance of shared decision-making in the management of CHB, particularly for patients in indeterminate phase disease.
The shared decision-making approach may also consider the risks, benefits, and costs of treatment.2
Terrault explained that the intent with shared decision‑making is to provide the information about the disease, the potential risks of untreated hepatitis B, what commitment is needed if you start treatment, what the side effects related to that treatment are, and most importantly, to hear the patient's preferences, concerns, and their desires.2
MANAGEMENT OF CHB IN INDIVIDUALS WITH CO-EXISTING CONDITIONS AND IN PREGNANCY
CESSATION AND REINITIATION OF ANTIVIRAL THERAPY
The speakers discussed factors to take into account when considering cessation of nucleos(t)ide analogue therapy in CHB. The new AASLD/IDSA guideline suggests not withdrawing nucleos(t)ide analogue therapy in HBeAg-negative adults without cirrhosis who have achieved sustained undetectable HBV DNA until HBsAg loss is achieved.2
For persons younger than 40 years, observation and monitoring may be preferred.2 Treatment may be considered for individuals aged younger than 40 years through shared decision-making by considering the family history of HCC, the patient's likelihood to adhere to treatment, and the risk of transmission to others.2
THE MANAGEMENT OF IMMUNE-TOLERANT PHASE CHRONIC HEPATITIS B
Patients who consistently meet all criteria for immune-tolerant disease (HBeAg-positive, ALT 107 IU/mL) have a low risk of HCC.2,35,36 However, older age (>40 years), lower HBV DNA, higher ALT, and lower platelet counts may indicate transition out of the immune-tolerant phase and higher HCC risk.2
For patients who strongly desire to stop therapy despite these risks, the guidelines outline criteria for discontinuing antiviral therapy.2 These criteria include:
No history of cirrhosis, any hepatic decompensation (variceal bleed, hepatic encephalopathy, hepatorenal syndrome), HCC, or extrahepatic complications of HBV
HBeAg-negative/anti-HBe positive for a minimum of 1 year (if HBeAg-positive at start of treatment)
HBV DNA undetectable for a minimum of 2 years
HBsAg level <100 IU/mL
No co-infection with HIV or hepatitis D virus
Agree to frequent monitoring
AASLD/IDSA 2025 guidelines recommend that patients who discontinue treatment be closely monitored, and ALT and HBV DNA checked every 1–3 months for the first 6 months, then every 3 months for up to a year, and subsequently at 3–6-month intervals depending on results.2
Prompt reinitiation of treatment is recommended if HBV DNA rises ≥10,000 IU/mL, ALT exceeds ≥5× ULN, bilirubin surpasses 2.5 mg/dL, or if there are any signs of hepatic decompensation.2 Treatment may also be restarted at the patient’s request, in the presence of extrahepatic complications, or if standard treatment criteria are again met (HBV DNA ≥2,000 IU/mL with ALT ≥2× ULN).2
The panelists emphasized that quantitative HBsAg measurement could help clinicians identify appropriate candidates for treatment cessation and potential outcomes after withdrawal.2
The GSK-sponsored medical disease state educational session on CHB at AASLD 2025 was part of the Industry Programming Guide Sponsored Theater and featured an expert panel discussion of a patient case in the indeterminate phase of CHB.
The updated AASLD/IDSA treatment guidelines for hepatitis B provide a more patient-centered approach that acknowledges the heterogeneous clinical presentation of CHB and the importance of shared decision-making.2
CONCLUSION
The session highlighted that up to 50% of patients with CHB may be in the indeterminate phase, and that patients in indeterminate phase CHB are at higher risk of fibrosis and HCC compared with those in the inactive or immune-tolerant phase.8,20,21 The expert panelists discussed that for patients in indeterminate phase CHB, clinicians engage in discussions about the potential risks and benefits of treatment, considering individual factors such as age, sex, fibrosis stage, and patient preferences.2
Serological tests, including quantitative HBsAg measurements, are becoming increasingly important in guiding clinical decisions for patients with CHB.2,17,37 Quantitative HBsAg testing may provide valuable information for disease phase determination, risk stratification, treatment response monitoring, and identification of candidates for treatment cessation.2,17,37 Similarly, recognition and management of concurrent metabolic dysfunction is increasingly important, given the growing overlap between CHB and MASLD.2,17
Khalili concluded the session by reminding attendees that achieving functional cure, characterized by sustained HBsAg loss with undetectable HBV DNA off treatment for at least 6 months, may be considered the ultimate goal of CHB management, as it may reduce the risk of liver-related complications.2,17,32
References
This medical disease state educational session on Chronic Hepatitis B took place during The Liver Meeting® 2025, held in Washington, D.C., USA, from November 7–11, 2025
Support: The publication of this article was sponsored by GSK.
Panelists: Mandana Khalili, MD, MAS,1 Paul Y. Kwo, MD, FAASLD, FACG, AGAF,2 Norah Terrault, MD, MPH, FAASLD3
University of California, San Francisco (UCSF), San Francisco, CA 94143, USA
Stanford University, Stanford, CA 94305, USA
Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Disclosure: Khalili reported financial relationships with GSK, Gilead Sciences Inc., Intercept Pharmaceuticals, and Resolution Therapeutics. Kwo reported financial relationships with Altimmune, AusperBio, Gilead, Novo Nordisk, Salix, Takeda, Madrigal, Akero, 89bio, Vir Biotechnology, Aligos, Amgen, Arbutus, DURECT, HepQuant, Inventiva, and GSK. Terrault reported financial relationships with GSK, Genentech, Helio Health, DURECT, Eiger BioPharmaceuticals, Immunocore, Aligos, Bluejay Therapeutics, Siemens Healthcare, Vir Biotechnology, and F. Hoffman-La Roche.
Acknowledgments: Writing assistance was provided by Christos Evangelou, San Diego, California, USA.
Disclaimer: This content is intended for US Healthcare Professionals only.
Keywords: American Association for the Study of Liver Diseases (AASLD) guidelines, antiviral therapy, hepatology, chronic hepatitis B (CHB), indeterminate phase, liver fibrosis, patient management, surface antigen, treatment guidelines.
Meeting Summary
At The Liver Meeting® 2025, organized by the American Association for the Study of Liver Diseases (AASLD) and held in Washington, D.C., USA, hepatology experts Mandana Khalili, Professor of Medicine and Hepatologist at the University of California, San Francisco, USA; Paul Kwo, Professor of Medicine and Director of Hepatology at Stanford University, California, USA; and Norah Terrault, Professor of Medicine and Chief of Gastroenterology and Liver Diseases at the University of Southern California, Los Angeles, USA, discussed practical strategies for managing chronic hepatitis B (CHB), with a focus on an indeterminate phase case study within the context of the updated 2025 AASLD/Infectious Diseases Society of America (IDSA) treatment guidelines, in a GSK-sponsored medical disease state educational session. The panelists discussed the treatment of patients who fall into the indeterminate phase, which is a challenging aspect of CHB care. The indeterminate phase includes persons who are HBsAg-positive, HBeAg-positive or negative and have ALT and HBV DNA levels that do not meet the thresholds for immune active phase and are outside the thresholds defining immune tolerant or inactive CHB. Through a hypothetical case-based discussion of a 38-year-old patient with borderline viral load and mildly elevated levels of transaminases, the panelists discussed how comprehensive phase characterization using biomarker tests such as quantitative hepatitis B surface antigen (HBsAg) measurement and non-invasive fibrosis assessment can guide treatment decisions. The panelists highlighted the importance of shared decision-making for the management of CHB and concurrent management of metabolic dysfunction. The panelists also emphasized that caution is needed when considering discontinuation of antiviral treatments, given the high relapse rates in individuals who discontinue treatment. The session underscored the dynamic nature of CHB that requires serial assessments and long-term monitoring, as well as individualized surveillance and treatment decisions based on age, sex, fibrosis stage, family history, and patient preferences. Panelists discussed laboratory assessments, imaging and serology, and noted that achieving functional cure may be considered the ultimate goal of CHB management.
Racial and Ethnic Disparities of CHB in the US
Patients with CHB in the US (2003–2021)*,4
47%
26%
11%
9%
7%
Asian
White
Black
Hispanic
Unknown
Newly reported cases of CHB in the US5†
17,650 newly reported cases in 20235
Approximately 46% of all newly reported chronic HBV cases occurred in persons aged 30–39 years and 40–49 years5
Non-US-born persons have a higher prevalence of CHB when compared to US-born persons3
*Data from a retrospective analysis of 42,140 adult patients with CHB using information recorded in the deidentified Optum Clinformatics Data Mart Database (Stanford Center for Population Health Sciences, Stanford, CA, USA) between January 2003–March 2021. †Data reported for 44 states and the District of Columbia.
THE BURDEN OF CHRONIC HEPATITIS B
In 2024, HBV infections accounted for approximately 1.1 million deaths globally.6
If left untreated, ≈15–40% of individuals with CHB may develop cirrhosis, liver failure, or HCC over their lifetime.8,9
CHB is the most common etiology for HCC worldwide, accounting for at least 50% of HCC cases globally.10
~1.1
million
deaths
globally
cirrhosis, liver failure, and HCC related
50%
of HCC cases globally
Prevalence of CHB
Clinical impact of CHB
Meeting Summary
Deaths, n
Global Impact of CHB on Morbidity and Mortality
*Global data for 2023.6 †Data for 2021; all ages.
1,200,000
800,000
400,000
300,000
0
1,109,660
Overall HBV infection (2023)*,7
≈7,547 US deaths in 20236
253,999
339,345
Liver cancer secondary to hepatitis B (2021)†,7
Cirrhosis due to hepatitis B (2021)†,8
If left untreated, liver cancer is the third most common cause of cancer mortality;1 CHB accounts for ≥50% of HCC11
If left untreated, ≈15–40% of people who are chronically infected may develop cirrhosis, liver failure, or HCC over their lifetime8,9
Mortality rates linked to CHB have been rising since 2019, suggesting an increase in hepatitis-associated cancers12
Medical history
CHB (initial HBV DNA of 1,500 IU/mL; diagnosed 4 months prior).
No other comorbidities
No smoking; stopped light alcohol use after diagnosis
Physical exam: unremarkable; no stigmata of chronic liver disease
Family history
Father died of alcohol‑related liver disease
Hepatitis B status of parents is unknown
Patient snapshot
Name: Anh
Age: 38 years
Sex: Female
BMI: 25.3 kg/m²
Country of birth: Vietnam (moved to the US at age of 15 years)
Occupation: Warehouse manager
Reason for referral: Further evaluation and management
Personal situation: Recently engaged, planning pregnancy, but concerned about impact of diagnosis. Wants more information.
MEET ANH
Laboratory assessments
HBV:
HBsAg: (+)
Anti-HBs: (–)
Anti-HBc total: (+)
Additional serology:
ALT: 31 U/L (ULN: 25 U/L in females)
AST: 30 U/L (ULN: 25 U/L in females)
Platelets: 160 × 108/L
HBeAg: (–)
Anti-HBe: (+)
HBV DNA: 2,500 IU/mL
Quiz
Which CHB phase best fits this patient at presentation?
A
Immune tolerant
B
Immune active
C
Inactive phase
D
Indeterminate (gray zone)
D
Indeterminate (gray zone)
C
Inactive phase
B
Immune active
A
Immune tolerant
Feedback: Anh is HBeAg‑negative with HBV DNA between 2,000–20,000 IU/mL and ALT just above the ULN for women (≥25 U/L). She does not meet the criteria for immune–tolerant, inactive, or immune–active disease, placing her in the indeterminate phase.
Immune-tolerant CHB2
HBeAg-positive and ALT ≥2xULN and HBV DNA ≥20,000 IU/mL
HBeAg-negative and ALT ≥2xULN and HBV DNA ≥2,000 IU/mL
HBeAg-negative
Normal ALT levels
Low HBV DNA (<2,000 IU/mL)
Indeterminate CHB2
Close
Studies suggest that up to 30–50% of individuals with CHB fall into indeterminate phases at some point during their disease course.8 Patients in the HBeAg-negative indeterminate phase may have a higher risk of HCC incidence and mortality compared to those in the inactive phase.14-16
Norah Terrault
Keck School of Medicine, University of Southern California,
Los Angeles, CA, USA
Mandana Khalili
University of California, San Francisco (UCSF),
San Francisco, CA, USA
Quiz
What additional tests should be performed to optimize Anh’s clinical care?
D
Metabolic assessment
C
HIV, HCV, and HDV testing
B
Abdominal ultrasound
A
Vibration-controlled transient elastography (VCTE)
D
Metabolic assessment
C
HIV, HCV, and HDV testing
B
Abdominal ultrasound
A
Vibration-controlled transient elastography (VCTE)
Feedback: AASLD guidelines recommend serial monitoring plus enhanced assessment in indeterminate CHB. Non‑invasive fibrosis testing and quantitative HBsAg can be used to assess disease severity and guide management in indeterminate CHB.2
RESULTS 4 MONTHS AFTER INITIAL ASSESSMENT
Laboratory data
HBV DNA: 2,500 IU/mL
ALT: 31 U/L (ULN: 25 U/L)
E
All of the above
E
All of the above
Paul Y. Kwo
Stanford University, California, USA
This includes VCTE, to assess for and stage fibrosis, offering better performance than serum markers; serum fibrosis markers (e.g., fibrosis-4 index) when elastography is unavailable; and liver biopsy, which is infrequently used but the most accurate for grading liver inflammation and fibrosis.2
According to European Association for the Study of the Liver (EASL) 2025 guidelines, quantitative HBsAg testing may be valuable for differentiating the phases of chronic HBV infections, with 85–94% accuracy for identifying inactive infection in individuals of Asian and European cohorts with HBV DNA <2,000 IU/mL + HBsAg <1,000 IU/mL, and highest specificity across HBV genotypes in those with HBsAg <100 IU/mL + HBV DNA <2,000 IU/mL.17 The EASL 2025 guidelines recommend determining HBsAg levels using quantitative HBsAg testing every 12 months.17
It may be used to inform follow-up and treatment decisions, especially in indeterminate CHB, and to assess the risk of HCC. In select patients, it may also help inform risk-based approaches to HCC surveillance.28,31,32
However, the guidelines emphasize that quantitative HBsAg is not intended to replace HBV DNA measurement; rather, HBsAg titers and HBV DNA levels may be used in combination to differentiate the phases of CHB and guide management decisions.2,17 The AASLD/IDSA 2025 guidelines also note a quantitative HBsAg level of <100 IU/mL may be considered among several factors for stopping treatment; however, it does not guarantee the absence of risk of progression, and ongoing monitoring is required after withdrawal of treatment.2
Factors to consider in shared decision-making regarding antiviral treatment initiation include:2
Age (risk increases with age >40 years)
Requirements for regular monitoring
Sex
(males at higher risk)
Fibrosis stage (advanced fibrosis warrants treatment)
Pill burden
Preferences and concerns
Cost of therapy
Implications of long-term treatment commitment
The case scenario also prompted discussion around the management of CHB in individuals with concurrent metabolic dysfunction-associated steatotic liver disease (MASLD) and the importance of assessing metabolic health in all patients with liver disease.33 Metabolic assessment of the patient case indicated elevated levels of triglycerides (340 mg/dL) and normal comprehensive metabolic panel, including glucose. Kwo noted that the finding of hepatic steatosis adds complexity to the management of CHB, and that 35–42% of patients with CHB have concurrent MASLD.33,34
While the AASLD/IDSA guidelines do not provide recommendations for the management of CHB specifically in patients with metabolic dysfunction, the EASL guidelines emphasize the importance of managing both conditions.17 Although indications for antiviral therapy remain the same as for patients without metabolic disease (based on HBV DNA, ALT, fibrosis stage), metabolic disease modifies prognosis, and even patients in indeterminate CHB may progress faster if metabolic risk factors are present.17 Therefore, in addition to treating HBV with nucleos(t)ide analogues, the EASL guidelines also recommend addressing metabolic disease through lifestyle modification, weight reduction, and diabetes control.17
The case scenario prompted discussion about the management of CHB during pregnancy. The updated AASLD/IDSA guidelines provide recommendations for the prevention of mother-to-child transmission of HBV.2 For pregnant individuals with HBV DNA >200,000 IU/mL, the guidelines recommend initiating nucleos(t)ide analogues at gestational Week 28 to prevent transmission.2
Quiz
Would you initiate antiviral therapy now?
B
No, continue observation and monitoring, using shared decision-making to consider Ahn’s preferences, risk factors, and the benefits and risks of treatment.
A
Yes, start treatment immediately
Feedback: For persons in the immune-tolerant phase (defined as HBeAg-positive, HBV DNA >107 IU/mL, and normal ALT levels), AASLD suggests consideration of antiviral therapy for those over age 40 years or with significant liver inflammation (Grade 2 or higher) or fibrosis (F2 or greater) on liver biopsy or non-invasive tests. For persons under age 40 years who are interested in starting treatment earlier, AASLD suggests shared decision-making with consideration of risk factors as well as the benefits and risks of treatment.2
PATIENT: ANH
Virology
HBsAg: Positive
HBeAg: Positive
Anti‑HBe: Negative
HBV DNA: 45,000,000 IU/mL
Biochemistry
ALT: 22 U/L
AST: 20 U/L
Platelets: 185 × 109/L
Imaging
VCTE: Liver stiffness 5.2 kPa
CAO: 240 dB/m
Ultrasound: Normal liver echotexture
Symptoms
Asymptomatic
B
No, continue observation and monitoring, using shared decision-making to consider Ahn’s preferences, risk factors, and the benefits and risks of treatment.
A
Yes, start treatment immediately
Quiz
When is stopping therapy considered safe?
B
If HBeAg-positive at start of antiviral therapy, have seroconverted to HBeAg-negative and anti-HBe-positive for ≥1 year and have undetectable HBV DNA maintained for at least 2 years
A
No history of advanced cirrhosis, hepatic decompensation, HCC, or extrahepatic complications of HBV
For patients who strongly desire to stop therapy despite these risks, the guidelines outline the following criteria:2
PATIENT: ANH
Years later, Anh has NO cirrhosis, has been on nucleos(t)ide analogue therapy for >3 years, is HBeAg-negative with undetectable DNA, and wants to stop therapy.
F
All of the above must be true
C
Quantitative HBsAg <100 IU/mL
D
Willingness to adhere to frequent monitoring
E
No HIV or hepatitis D virus coinfection
F
All of the above must be true
E
No HIV or hepatitis D virus coinfection
D
Willingness to adhere to frequent monitoring
C
Quantitative HBsAg <100 IU/mL
B
If HBeAg-positive at start of antiviral therapy, have seroconverted to HBeAg-negative and anti-HBe-positive for ≥1 year and have undetectable HBV DNA maintained for at least 2 years
A
No history of advanced cirrhosis, hepatic decompensation, HCC, or extrahepatic complications of HBV
No history of cirrhosis, any hepatic decompensation (variceal bleed, hepatic encephalopathy, or hepatorenal syndrome), HCC, or extrahepatic complications of HBV
HBeAg-negative/anti-HBe positive for a minimum of 1 year (if HBeAg-positive at start of treatment), and HBV DNA undetectable for a minimum of 2 years
Quantitative HBsAg <100 IU/mL
No HIV or hepatitis D virus coinfection
Willingness to adhere to frequent monitoring
The 2025 AASLD/IDSA guidelines specify that quantitative HBsAg <100 IU/mL is a key criteria to meet before considering cessation, as this threshold is associated with a higher likelihood of sustained off-treatment response and lower risk of virological relapse.2 However, even with quantitative HBsAg <100 IU/mL, close monitoring remains essential as this does not guarantee absence of relapse risk.2
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8. Mak LY et al. Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase. J Viral Hepat. 2024;31 Suppl 2(Suppl 2):27-35.
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20. Li Y et al. HBeAg-positive CHB patients with indeterminate phase associated with a high risk of significant fibrosis. Virol J. 2024;21(1):287.
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30. Vachon A, Osiowy C. Novel biomarkers of hepatitis B virus and their use in chronic hepatitis B patient management. Viruses. 2021;13(6):951.
31. Tseng TC et al. Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers. J Infect Dis. 2013;208(4):584-93. 32. Yip TCF et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70(3):361-70.
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36. Jeon MY et al. Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B. Clin Mol Hepatol. 2021;27(2):295-304. 37. Leowattana W et al. Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: novel viral biomarkers for chronic hepatitis B management. World J Hepatol. 2024;16(4):550-65.
For patients who strongly desire to stop therapy despite these risks, the guidelines outline the following criteria:2
For patients who strongly desire to stop therapy despite these risks, the guidelines outline the following criteria:2
For patients who strongly desire to stop therapy despite these risks, the guidelines outline the following criteria:2
For patients who strongly desire to stop therapy despite these risks, the guidelines outline the following criteria:2
1.7 MILLION
PERSONS WITH CHB IN THE US1
Approximately 1.7 million Americans live with CHB, although published estimates range as high as 2.5 million.2-4
HBeAg-positive
HBV DNA levels: ≥10,000,000 IU/mL
Persistently normal alanine aminotransferase (ALT) levels (<25 U/L in women; <35 U/L in men)
Immune-active CHB2
Inactive CHB2
HBeAg-positive or negative with HBV DNA level and/or ALT level that do not meet criteria for immune-tolerant, immune active, or inactive CHB. An alternative term used to refer to this group is “grey zone”
