Ghany MG, Pan CQ, Lok AS, Feld JJ, Lim JK, Wang SH, Kim AY, Tang AS, Nguyen MH, Naggie S, Sulkowski MS. AASLD/IDSA Practice Guideline on treatment of chronic hepatitis B. Hepatology. 2025. Ahead of print.

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 The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA) recently 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 Recommendation Assessment, Development and Evaluation (GRADE) framework.¹ Multiple systematic reviews informed the recommendations, which are graded according to strength of recommendation and certainty of evidence.¹ The guideline is structured around six Population, Intervention, Comparison, Outcomes (PICO) questions: four address treatment initiation, continuation, or discontinuation; one addresses perinatal prevention of hepatitis B (HBV) virus transmission; and one focuses on HCC surveillance in specific clinical contexts.¹

Central to the guideline is a risk-stratified approach to treatment initiation based on HBV 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 highlights 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?
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. 2025 AASLD practice guideline recommendations for CHB

AASLD: American Association for the Study of Liver Diseases; 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; PICO: Population, Intervention Comparison, Outcomes; SOR: Strength of recommendation

 

In an interview with Omnihealth Practice, Dr. Ruveena Bhavani shared her perspectives on the 2025 AASLD/IDSA guideline for chronic hepatitis B, highlighting key considerations in treatment initiation, cirrhosis management, and long-term care.

Q1. What are the key challenges in initiating antiviral therapy in patients with chronic hepatitis B?

 Dr. Ruveena: One of the primary challenges is ensuring long-term adherence, as many patients require therapy for many years or even lifelong. Cost and sustained compliance are therefore important considerations, since treatment interruption can adversely affect outcomes. Another challenge lies in interpreting elevated alanine aminotransferase (ALT) levels among Hepatitis B patients. In some cases, ALT elevation may reflect concomitant liver conditions such as hepatic steatosis or drug-induced liver injury rather than active hepatitis B. Distinguishing the underlying cause, therefore is essential before initiating antiviral therapy.

Certain patient groups also remain nuanced despite updated guidance. For example, individuals in the immune-tolerant phase, particularly in younger patients with either minimal fibrosis or low viremia with a family history of hepatocellular carcinoma (HCC) would require careful, individualized risk assessment when determining the optimal timing for treatment.

 

Q2. How has the updated guideline influenced the management of cirrhosis and special clinical scenarios?

Dr. Ruveena: The guideline has simplified management by clearly recommending antiviral therapy for all HBsAg-positive patients with cirrhosis, regardless of ALT or viral load. In compensated cirrhosis, this supports early and proactive therapy to prevent progression and HCC. In decompensated disease, it reinforces the urgency of treatment initiation alongside careful safety monitoring and multidisciplinary care. In advanced liver disease, antiviral selection must account for renal function, bone health, age, and comorbidities. Agents with favorable renal and bone safety profiles, such as tenofovir alafenamide or entecavir, are often preferred in patients with chronic kidney disease or osteoporosis. Management, however, can be particularly challenging in patients receiving immunosuppressive therapy, where delayed initiation or premature discontinuation of prophylaxis may increase the risk of HBV reactivation, which can be severe or life-threatening.

 

Q3. How do long-term therapy and monitoring shape outcomes, and what unmet needs remain?

Dr. Ruveena: Consistent antiviral therapy, together with structured monitoring, is central to improving long-term outcomes in chronic hepatitis B infection. By maintaining viral suppression and ensuring regular reassessment, we can slow or prevent progression to cirrhosis, reduce the risk of HCC, and limit disease flares and viral transmission. Equally important is patient education, particularly for those not started on immediate treatment so that they understand the need for sustained follow-up and can recognize early signs of flare.

Despite progress, key gaps remain. Greater clarity on the role of quantitative HBsAg and HBV core-related antigen as potential treatment endpoints would be valuable, as would better definition of patient populations most likely to achieve functional cure. Continued development of novel antiviral strategies and clearer recommendations on HCC surveillance after functional cure will also strengthen long-term management.