INDUSTRY ESSENTIAL
Optimizing treatment decisions in CHB: Insights from the 2025 AASLD/IDSA practice guideline
Chronic hepatitis B (CHB) remains a major global health burden, affecting approximately 258 million individuals worldwide in 2022 and causing an estimated 1.1 million deaths annually from cirrhosis and hepatocellular carcinoma (HCC).1 With half of those infected unaware of their diagnosis, continued efforts are needed to identify cases, prevent new infections through vaccination, initiate timely antiviral therapy, and monitor for complications to reduce CHB-related morbidity and mortality.¹ In late 2025, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA) published evidence-based practice recommendations, drawing on growing evidence of CHB prevention, surveillance, and treatment, to provide clear, practical guidance for health care professionals in optimizing care for individuals with CHB.1
This guideline was developed in accordance with National Academy of Medicine standards and employs the Grading of Recommendations A ssessment, Development and Evaluation (GRADE) framework.1 Multiple systematic reviews informed the recommendations, which were graded according to the strength of recommendation and certainty of evidence.1 The guideline is structured around six Population, Intervention, Comparison, Outcomes (PICO) questions: four focus on treatment initiation, continuation, or discontinuation; one addresses perinatal prevention of hepatitis B virus (HBV) transmission; and one centers on HCC surveillance in specific clinical contexts.1
Central to the guideline is a risk-stratified approach to treatment initiation based on HBV deoxyribonucleic acid (DNA) levels, alanine aminotransferase (ALT), and stage of liver disease.1 Antiviral therapy is recommended for all HBsAg-positive patients with cirrhosis, regardless of ALT and HBV DNA levels, as well as for non-cirrhotic patients with evidence of immune-active disease.¹ In contrast, routine treatment is generally not recommended for patients in the immune-tolerant or inactive CHB phases, underscoring the importance of regular monitoring to detect disease phase transition.1 The guideline emphasizes the use of high-barrier-to-resistance nucleos(t)ide analogues as the preferred therapy, reflecting their durable viral suppression and favorable safety profiles, including in patients with decompensated cirrhosis or immunocompromised states.1 Special clinical scenarios, such as pregnancy, renal impairment, and prior antiviral exposure, are addressed with tailored recommendations to guide individualized management.1
Importantly, the AASLD/IDSA highlight ongoing monitoring as a cornerstone of CHB management, regardless of treatment status, including regular assessment of virologic activity, liver biochemistry, and HCC risk.1 Collectively, these recommendations reinforce a structured, evidence-based framework for the long-term management of CHB, balancing timely antiviral intervention with appropriate surveillance.¹ The new guideline recommendations are summarized in table 1.1
|
Recommendation |
SOR |
COE |
|
PICO Q1: What is the optimal antiviral strategy for HBsAg-positive pregnant individuals with HBV DNA >200,000IU/ml to prevent mother-to-child transmission of HBV |
||
|
For pregnant persons with HBV DNA levels greater than 200,000IU/mL at any time point during pregnancy, regardless of HBeAg status, AASLD recommends initiating tenofovir disoproxil fumarate or tenofovir alafenamide at gestational week 28 to prevent mother-to-child transmission. Tenofovir disoproxil fumarate has a more extensive safety record in pregnancy than tenofovir alafenamide |
Strong |
Moderate |
|
PICO Q2: Should antiviral therapy be provided to persons who are HBsAg-positive with viremia that do not meet disease-specific treatment indications to reduce transmission in high-risk scenarios? |
||
|
For persons who are HBsAg-positive with viremia not meeting disease-specific treatment indications and who are in high-risk scenarios for transmission to others, AASLD suggests a shared decision-making approach regarding antiviral treatment |
Conditional |
Very low |
|
PICO Q3: Should individuals in the immune-tolerant phase start antiviral therapy vs. observation |
||
|
For persons in the immune-tolerant phase (defined as HBeAg-positive, HBV DNA >107IU/mL, and normal ALT levels), the AASLD suggests 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 noninvasive tests. For persons under age 40 years who are interested in starting treatment earlier, the AASLD suggests shared decision-making with consideration of risk factors as well as the benefits and risks of treatment |
Conditional |
Very low |
|
PICO Q4: Should HBsAg-positive, HBeAg-negative individuals without cirrhosis and in the indeterminate phase start antiviral therapy vs. observation |
||
|
In adults with HBsAg-positive, HBeAg-negative chronic HBV infection without cirrhosis and in the indeterminate phase, AASLD suggests antiviral therapy using a shared decision-making approach by assessing risks and benefits and to reevaluate that decision at each follow-up visit if treatment has not been initiated |
Conditional |
Very low |
|
PICO Q5: Should HBsAg-positive individuals without cirrhosis who have been on nucleos(t)ide analogue therapy for at least 3 years and who are HBeAg-negative with undetectable HBV DNA remain on or discontinue therapy? |
||
|
In adults with chronic hepatitis B, who are HBeAg-negative without cirrhosis, with sustained undetectable HBV DNA on nucleos(t)ide analogue therapy, AASLD suggests not withdrawing nucleos(t)ide analogue therapy until HBsAg loss |
Conditional |
Very low |
|
PICO Q6: Should individuals with chronic HBV without cirrhosis who cleared HBsAg and HBsAg-positive persons with HCV, HDV, and/or HIV co-infection receive surveillance for HCC? |
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In persons who achieved HBsAg loss, AASLD suggests continued HCC surveillance for those with cirrhosis, with family history of HCC, men who experienced HBsAg loss after age 40, and women who experienced HBsAg loss after age 50 |
Conditional |
Very low |
|
In persons with HBV-HDV co-infection, AASLD suggests HCC surveillance of adults independent of cirrhosis status. The decision to undertake surveillance in children should be individualized due to the risk of HCC being unknown in this population |
Conditional |
Very low |
|
In persons with HBV-HIV co-infection, AASLD suggests HCC surveillance for men ≥18 years of age and women ≥40 years of age |
Conditional |
Very low |
|
In persons with HBV-HCV co-infection, AASLD recommends treatment for HCV and suggests HCC surveillance as per criteria for HBV mono-infection |
Conditional |
Very low |
Table 1. Updated AASLD practice guideline recommendations for CHB treatment
AASLD: American Association for the Study of Liver Diseases; ALT: Alanine aminotransferase; CHB: Chronic hepatitis B; COE: Certainty of evidence; DNA: Deoxyribonucleic acid; HbeAg: Hepatitis B e (infectivity) antigen; HbsAg: Hepatitis B s (surface) antigen; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; HDV: Hepatitis D virus; HIV: Human immunodeficiency virus; IU: International unit; PICO: Population, Intervention Comparison, Outcomes; SOR: Strength of recommendation
In an interview with Omnihealth Practice, Professor Yip shared his insights on the implications of the updated AASLD/IDSA practice guidelines and how they could influence day-to-day decision-making.
Q1: What is the core philosophy driving the updated AASLD/IDSA practice guidelines?
Prof. Yip: The updated guidelines take a more pragmatic and patient-centric approach. The absolute cornerstone of this new philosophy is "shared decision-making." Rather than black-and-white rules, especially for complex patients sitting in the clinical "grey zone" (such as those in the immune-tolerant phase). Doctors are encouraged to collaboratively weigh individual risk factors with the patient. Additionally, the guidelines advocate for a more liberal approach to treatment, significantly reducing the reliance on invasive liver biopsies in favor of non-invasive tests and demographic triggers (like being over age 40).
Q2: How are these clinical guidelines developed and kept up to date?
Prof. Yip: The guidelines are crafted and continuously refined by specialized expert committees, such as the AASLD Hepatitis B Special Interest Group. Rather than a single author, it is a collaborative effort by leading hepatologists who constantly review the latest emerging clinical data. They evaluate new evidence, such as the long-term safety profiles of antiviral drugs such as TAF compared to TDF, or the reliability of new non-invasive fibrosis testing methods, to ensure the framework reflects the cutting edge of medical science.
Q3: How does the AASLD promote the adoption of these new guidelines in everyday practice?
Prof. Yip: We recognize that publishing a document is not enough. Strategic dissemination is critical for changing real-world clinical habits. The steering committees actively promote the new standards through targeted education at major medical conferences, most notably "The Liver Meeting." By deliberately curating lectures and interactive sessions that directly mirror the guideline updates, they ensure the broader medical community understands not just what the new recommendations are, but why the science changed and how to practically apply these rules to everyday patient care.
