Summary of Recommendations

Document Overview

Design and created by Guideline Central in participation with the American Association for the Study of Liver Diseases and Infectious Diseases Society of America.

Treatment of Chronic Hepatitis B

American Association for the Study of Liver Diseases

Infectious Diseases Society of America

Publication Date: Nov 4, 2025

Page Last Updated: May 5, 2026

Core Concepts Regarding Chronic Hepatitis B (CHB)

Chronic hepatitis B (CHB) is a dynamic disease that can be characterized into five phases (Table 1): immune-tolerant (hepatitis B e antigen [HBeAg]-positive, HBV DNA >10,000,000 IU/mL and normal alanine aminotransferase (ALT) defined as <35 U/L for males and <25 U/L for females); HBeAg-positive immune active (HBeAg-positive, ALT elevated 2x upper limit of normal (ULN) or greater and HBV DNA >20,000 IU/mL); HBeAg-negative immune active (HBeAg-negative, ALT elevated 2xULN or greater and HBV DNA >2000 IU/mL); inactive (HBeAg-negative, normal ALT and HBV DNA <2000 IU/mL); and hepatitis B surface antigen (HBsAg)-negative immune clearance (HBV DNA undetectable, ± antibody to HBsAg (anti-HBs)).(1) As persons transition across phases over the lifetime of their infection, regular monitoring is essential to identify when a change of management is indicated, including use of antiviral therapy.

Indeterminate phases refer to 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 (Table 1). Up to 40% of adults with CHB do not meet one or more criteria for a defined phase and are in indeterminate phases.(2, 3) Indeterminate phases are more common in persons who are HBeAg-negative than HBeAg-positive.(2-4) An alternative term used to refer to these phases is “grey zone”.

Determination of liver disease severity is integral to monitoring because of its importance to making treatment and surveillance decisions. Non-invasive tests of fibrosis, such as hepatic transient elastography or serum markers such as FIB-4 can be considered for fibrosis staging, with elastography generally showing better performance than FIB-4.(5, 6) Liver biopsy is infrequently used but is the most accurate means of defining severity of inflammation.

Two classes of drugs are approved for the treatment of CHB: peginterferon and nucleos(t)ide analogues (NAs). Peginterferon is rarely used, given its limitations of applicability, safety and tolerability, compared with NA therapy. 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). All drugs require consideration of renal function and/or dialysis. TAF is not recommended if creatinine clearance is less than 15ml/min and not yet on dialysis. ETV and TDF need dose adjustment if renal dysfunction or on dialysis, though a change in NA is preferred for those on TDF with declining renal function.

The goals of antiviral treatment are prevention of progression to cirrhosis, development of HCC and liver-related death. These clinical endpoints typically take years or decades to develop. Therefore, surrogate virological (HBV DNA undetectable by a PCR-based assay, HBeAg loss and seroconversion, HBsAg loss and seroconversion), biochemical (serum ALT normal) and infrequently, histological (improvement in necroinflammation by ≥ 2 points with no worsening of fibrosis) endpoints are used as measures of treatment efficacy.

Other goals of antiviral therapy include reduction in onward transmission (both vertical (mother-to-child) and horizontal (e.g., sexual, parenteral, nosocomial)), improvement in patient reported outcomes and quality of life as well as decreased stigma.

Increasingly, there is emphasis on the achievement of HBsAg loss as the desired endpoint for treatment (functional cure), because of its association with reduction in clinical outcomes and long-term durability, though it is recognized that functional cure is infrequent with current approved therapies, albeit higher with peginterferon than for NAs.

Shared decision making is a collaborative process where a healthcare provider and patient make informed healthcare decisions by considering clinical evidence, taking into account the individual's personal values, preferences, and circumstances, allowing the patient to actively participate in choosing the best treatment option for them.

For pregnant persons with HBV DNA levels greater than 200,000 IU/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. ( S, M )

Implementation Considerations

For pregnant persons who have been receiving HBV treatment with TDF or TAF, we suggest continuing therapy. For those receiving entecavir or other antivirals, we suggest switching to TDF or TAF, given their established efficacy and safety in pregnancy.
Amniocentesis increases the risk of perinatal transmission in those with HBV DNA >2,000,000 IU/mL. Therefore, initiating TDF or TAF early in pregnancy to achieve viral suppression should be considered when invasive procedures are anticipated. Similarly, if the pregnant individual has a high risk for preterm labor, earlier TDF or TAF treatment should be considered.
The optimal timing of initiation of TDF/TAF prophylaxis is at gestational week 28. For mothers with HBV DNA levels >200,000 IU/mL who seek perinatal care later than week 28, TDF or TAF prophylaxis should still be initiated immediately to reduce the risk of MTCT.
For mothers with HBV DNA levels >200,000 IU/mL, TDF or TAF prophylaxis should be initiated at gestational week 16 in combination with subsequent infant vaccination, if hepatitis B immune globulin (HBIG) use in the infant is unavailable.
For pregnant persons for whom the sole purpose of treatment is to prevent perinatal transmission, we suggest TDF or TAF can be discontinued at delivery.
For pregnant persons in whom treatment is discontinued, AASLD suggests HBV DNA and ALT should be monitored for withdrawal flares at intervals of 1-3 months for a period of up to six months. Treatment should be reinitiated in the event of a significant withdrawal flare (ALT ≥5 x upper limit of normal).
For breastfeeding persons who require or are on HBV treatment, AASLD suggests the use of TDF or TAF.

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. ( C, VL )

Implementation Considerations

Individuals who are viremic and in high-risk scenarios for transmission may be offered antiviral treatment to reduce risk of transmission, though there are limited data on this issue. Shared decision-making is critical to evaluate exposure and transmission risk and to consider the vaccine and immunity status of those who are potentially exposed, favoring antiviral treatment if they are unvaccinated, may have inadequate response to vaccine, have compromised immune systems, and/or have unknown vaccine status (Table 2). As risks may not always be disclosed, individuals requesting treatment for prevention of transmission can be prescribed antiviral medication.
It is essential to avoid stigmatizing practices or messages in discussions regarding horizontal transmission. People with CHB should not be restricted in their daily activities, contact sports, school activities, professional training, and should not be required to take antivirals due to risk of transmission in those settings. Within households, worksites, and other settings, routine contact, sharing meals, and hugging are not considered routes of transmission, though sharing of personal hygiene items (e.g., toothbrush, razor) should be avoided.
Most healthcare workers with CHB are not in high-risk scenarios to transmit HBV to their patients, but healthcare workers performing Society for Healthcare Epidemiology of America (SHEA) category III exposure-prone procedures are at higher risk for HBV transmission and should follow guidelines from SHEA and the Centers for Disease Control and Prevention (CDC) and may require antiviral treatment to reduce transmission risk.(34, 35) Both CDC and SHEA recommend against the need for healthcare worker disclosure to patients and staff. CHB is a protected condition by the American with Disabilities Act and people with CHB are protected from discrimination in employment, education and other areas, and all cases of discrimination should be reported to appropriate authorities.
All persons considering or initiating antiviral therapy for prevention of HBV transmission should be counseled regarding the risks of treatment cessation. The decision to continue or stop antiviral therapy should be guided by shared decision-making. If the primary indication is the reduction of horizontal transmission risk, the continuation of antiviral therapy may be revisited when transmission risks are no longer high. Examples include healthcare workers no longer engaged in category III/exposure-prone procedures and those for whom the risk of transmission has decreased via harm reduction and/or immunization of susceptible persons. The decision to continue or stop antiviral therapy should be guided by shared decision making, considering clinical factors, personal values and preferences, and potential risks of post-cessation ALT flare.

For persons in the immune-tolerant phase (defined as HBeAg-positive, HBV DNA >107 IU/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. ( C, VL )

Implementation Considerations

Accurate identification of immune-tolerant phase requires persistently normal ALT levels with HBV DNA >107 IU/mL in HBeAg-positive persons. Upper limits of normal ALT levels are 35 U/L for males and 25 U/L for females based on ≥2 measurements ≥6 months apart. HBeAg-positive individuals with ALT above ULN or with HBV DNA levels <107 IU/mL may be transitioning to immune active CHB and are not the focus of this recommendation.
Non-invasive tests of fibrosis, such as hepatic transient elastography or serum markers such as FIB-4 can be considered for fibrosis assessment, with elastography showing better performance than FIB-4. A vibration-controlled transient elastography cutoff value of 7 kPa yielded a sensitivity of 69% and a specificity of 83% for identifying F2 or higher fibrosis.
For persons younger than 40 years or without significant inflammation or fibrosis, factors to guide decision making should include age (child/adolescent versus adult), family history of HCC, and likelihood of adherence to treatment and monitoring, and prevention of transmission to others. As the duration of therapy is anticipated to be many years, addressing the need for long-term adherence and monitoring is important and particularly relevant for children and adolescents being considered for antiviral therapy.
Close monitoring is recommended if antiviral treatment is not initiated. HBV DNA and ALT levels should be tested at least every 6 months for adolescents and adults with immunetolerant CHB to monitor for transition to immune-active CHB. A similar monitoring schedule is suggested for children, though the optimal interval has not been determined.

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. ( C, VL )

Implementation Considerations

Persons who have a desire to discontinue therapy should engage in a shared decision-making process with their providers considering the benefits (HBsAg loss) and risks (hepatitis flare, liver decompensation and need for re-treatment) and need for frequent monitoring.
Those who may consider stopping treatment should meet all the following criteria:
- no history of advanced fibrosis/cirrhosis, hepatic decompensation (variceal bleed, ascites, hepatic encephalopathy, hepatorenal syndrome), HCC or extrahepatic complications of HBV.
- if HBeAg-positive at start of antiviral therapy, have seroconverted to HBeAgnegative and anti-HBe-positive for ≥1 year and have undetectable HBV DNA maintained for at least 2 years.
- If HBeAg-negative at start of antiviral therapy, the duration of undetectable HBV DNA should be at least 2 years.
- have no co-infection with human immunodeficiency virus (HIV) or hepatitis D virus (HDV).
- have a quantitative HBsAg level <100 IU/mL.
- be willing to adhere to frequent monitoring after stopping treatment.
Following withdrawal of treatment, serum ALT and HBV DNA should be monitored every 1-3 months for the initial 6 months, then every 3 months for the next 6 to 12 months. Thereafter, monitor at 3 to 6 month intervals depending on the ALT and HBV DNA values.
Treatment should be re-started immediately if any of the following criteria are met:
- an HBV DNA level ≥10,000 IU/mL (4 log IU/mL) regardless of ALT level, or
- ALT ≥5 x ULN regardless of HBV DNA or
- total bilirubin >2.5 mg/dL, or
- any symptoms of hepatic decompensation.
Treatment may also be re-started anytime for any of the following reasons: personal wish to re-start, extrahepatic complications of HBV, or if treatment initiation criteria are met (HBV DNA >2000 IU/mL and ALT >2x ULN ).

Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-Based Recommendations

Implications for:	Strong Recommendation (S)	Conditional Recommendation (C)
Patients	Most individuals in this situation would want the recommended course of action, and only a small proportion would not.	The majority of individuals in this situation would want the suggested course of action, but many would not.
Clinicians	Most individuals should receive the intervention. Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator. Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences.	Recognize that different choices will be appropriate for individual patients and that you must help each patient arrive at a management decision consistent with his or her values and preferences. Decision aids may be useful in helping individuals to make decisions consistent with their values and preferences.
Policy	The recommendation can be adopted as policy in most situations.	Policymaking will require substantial debate and involvement of various stakeholders.

Certainty in the Evidence
High	H	Low	L
Moderate	M	Very Low	VL

Source: Grading of Recommendations Assessment, Development and Evaluation Working Group (Schunemann HJ et al. Am J Respir Crit Care Med. 2006;174:605-14. Guyatt GH et al. BMJ 2008;336:924-6).

Document Overview

Document Title: Treatment of Chronic Hepatitis B

Authoring Societies

American Association for the Study of Liver Diseases

Infectious Diseases Society of America

Document Publication Date: Nov 4, 2025

Page Last Reviewed/Updated: May 5, 2026

Document Type: Guideline

Country of Publication: United States

Full Text Freely Available: Yes

Full Text Guideline: journals.lww.com/hep/abstract/9900/aasld_idsa_practice_guideline_on_treatment_of.1416.aspx

Source Citation: Ghany, Marc G.1; Pan, Calvin Q.2; Lok, Anna S.3; Feld, Jordan J.4; Lim, Joseph K.5; Wang, Su H.6,7,8; Kim, Arthur Y.9,10; Tang, Amy S.11; Nguyen, Mindie H.12,13,14; Naggie, Susanna15; Sulkowski, Mark S.16; Rodriguez-Baez, Norberto17; Chen, J.18,19; Murad, M. Hassan20,21; Mohammad, Khaled S.21,22; Terrault, Norah A.23. AASLD/IDSA Practice Guideline on treatment of chronic hepatitis B. Hepatology ():10.1097/HEP.0000000000001549, November 4, 2025. | DOI: 10.1097/HEP.0000000000001549

Supplemental Implementation Resources

Visual Brief

Document Scope, Criteria, and Use Cases

Document Objectives: Accumulating data related to prevention, surveillance and treatment of chronic hepatitis B (CHB) provided the impetus for this updated guideline, using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. This evidence-based guideline provides updated recommendations to optimize the care of persons with CHB.

Scope: Assessment and Screening, Management, Treatment

Diseases/Conditions (MeSH)

D006509 - Hepatitis B

D019694 - Hepatitis B, Chronic

D017325 - Hepatitis B Vaccines

D006515 - Hepatitis B virus

D006509 - Hepatitis B

D019694 - Hepatitis B, Chronic

D017325 - Hepatitis B Vaccines

D006515 - Hepatitis B virus

Keywords: chronic hepititis, hepatitis, hepatitis B

Target Patient Population: Patients with chronic hepatitis B

Inclusion Criteria: Male, Female, Adolescent, Adult, Child, Older Adult

Health Care Settings: Ambulatory, Hospital, Long Term Care, Outpatient

Intended Users: Nurse, Nurse Practitioner, Physician, Physician Assistant

Recommendation Development Processes & Methodology

PICO Questions

What is the optimal antiviral strategy for HBsAg-positive pregnant individuals with HBV DNA >200,000 IU/ml to prevent mother-to-child transmission of HBV?
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?
Should HBsAg-positive individuals in the immune-tolerant phase start antiviral therapy versus observation?
Should HBsAg-positive, HBeAg-negative individuals without cirrhosis and in the indeterminate phase start antiviral therapy versus observation?
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?
Should individuals with chronic HBV without cirrhosis who clear HBsAg and HBsAgpositive persons with HCV, HDV, and/or HIV co-infection receive surveillance for HCC?

Supplemental Methodology Resource: Technical Review