Approach

The main goal of treatment is to improve survival and quality of life by preventing disease progression and the development of complications. Specific management depends on whether the infection is acute or chronic. Acute infection is almost always treated with supportive care alone. Patients with chronic infection are treated with long-term antiviral therapy, if indicated. Some patients (i.e., those with acute liver failure, decompensated cirrhosis, or hepatocellular carcinoma [HCC]) may require liver transplantation. 

Acute infection

More than 95% of immunocompetent individuals with acute hepatitis B virus (HBV) infection will spontaneously achieve seroconversion in the absence of antiviral therapy.[2][29]

  • ​Supportive care is usually all that is needed in most patients with acute infection, provided that there are no signs of synthetic liver function impairment.[2][29]

  • Typically, rest, good nutrition, fluids, and avoiding alcohol or hepatotoxic drugs or supplements are enough to treat symptoms.[107]​ Symptomatic treatment (e.g., analgesic, antipyretic) may be required. The decision to hospitalise patients is made on a case-by-case basis, depending on the clinical presentation.

  • Factors associated with higher rates of spontaneous seroconversion include: older age, male sex, inactive carrier state, and lower levels of HBV DNA and quantitative hepatitis B surface antigen (HBsAg).[84]

Patients with synthetic liver function impairment, indicated by rising bilirubin and international normalised ratio (INR), require consideration of treatment with antiviral therapy to reduce the risk of fulminant liver failure and the need for liver transplantation.[2][29]

  • Initiate treatment in patients with acute liver failure or in those who have a severe, protracted course (i.e., total bilirubin level >51.3 micromoles/L (>3 mg/dL) , INR >1.5, encephalopathy, or ascites).

  • Entecavir, tenofovir disoproxil, or tenofovir alafenamide are the drugs of choice in patients with acute infection. Peginterferon alfa is contraindicated.

  • While starting antiviral therapy, simultaneously assess the patient for liver transplantation. There is a high risk of mortality in patients with liver failure who do not undergo transplantation. Manage patients in conjunction with a transplant centre.

  • Continue treatment until HBsAg clearance is confirmed, or indefinitely in patients who end up undergoing liver transplantation.

There is currently no evidence of benefit for any pharmacological treatment, including antiviral therapy, in the management of acute infection.[108][109]

Chronic infection: goals of treatment

Chronic HBV infection is defined as the presence of HBsAg for at least 6 months.[2] Long-term antiviral therapy is recommended for the treatment of chronic infection. The decision to hospitalise patients is made on a case-by-case basis, depending on the clinical presentation (e.g., complications are present).

The main goals of treatment are to improve survival and reduce morbidity from complications such as cirrhosis, hepatic decompensation, liver failure, and HCC. Additional treatment goals include:​[29]

  • Improvement of liver fibrosis

  • Improvement of HBV-associated extrahepatic manifestations

  • Improvement of health-related quality of life and patient-reported outcomes

  • Prevention of HBV transmission

  • Prevention of HBV reactivation and/or hepatitis

Surrogate markers are used to assess treatment response since HBV-related complications develop over a longer period of time. These markers include:

  • Undetectable or persistent suppression of HBV DNA

  • Normalisation of alanine aminotransferase (ALT) level

  • HBsAg loss

Confirmed loss of hepatitis B e antigen (HBeAg) and seroconversion to HBeAg antibodies (anti-HBe) with a HBV DNA level <2000 IU/mL may be used as an intermediate treatment endpoint.[29]

The ultimate goal of treatment is amelioration of hepatic dysfunction and the development of a disease-free state, marked by seroconversion from HBsAg-positive to HBsAg-negative and the production of antibodies to hepatitis B surface antigen (anti-HBs). Treatment can sometimes lead to HBeAg loss and HBeAg seroconversion to anti-HBe in individuals who are HBeAg-positive. However, overall eradication of HBV, known as virological cure, is rare with currently available treatments, so the primary goal of therapy in most patients is sustained undetectable HBsAg and serum HBV DNA. This is known as functional cure. HBsAg loss is increasingly being recognised as a surrogate marker for outcomes as it is associated with a lower risk of liver decompensation, HCC, liver transplantation, and death.[84]

​While prolonged viral suppression may reduce the rate of cirrhosis, hepatic failure, and HCC, it does not completely eliminate the risk.[110][111]​ However, there are no randomised controlled trials to support this as such trials would be prohibitively expensive and take 20-30 years.

Chronic infection: indications for antiviral therapy

In principle, all patients who are HBsAg-positive with detectable HBV DNA are candidates for antiviral therapy. However, because chronic infection is dynamic and progresses through distinct phases encompassing a wide range of clinical scenarios, recommendations for which patients should receive antiviral therapy are complex and often debated.[29]

In recent years, there has been a shift away from treatment indications being based on the phase of infection to HBV DNA level. Therefore, treatment indications currently vary across the major society guidelines, depending on when they were last updated.

  • European Association for the Study of the Liver (EASL) guidelines, last updated in 2025, acknowledge this shift and present a more simplified and pragmatic approach to treatment that avoids categorising patients according to the traditional disease phases or HBeAg status.[29] The recommendations in this topic are mainly based on this guideline.

  • World Health Organization (WHO) guidelines, last updated in 2024, largely align with the EASL recommendations, but with some key differences.[75]

  • American Association for the Study of Liver Diseases (AASLD) guidelines, last updated in 2018, base treatment indications on the phase of infection.[2] However, these guidelines are currently in the process of being updated.

Based on the latest guidance from the EASL, indications for treatment are primarily based on:[29]

  • HBV DNA level

  • ALT level

  • Fibrosis stage

  • Risk of liver disease progression and HCC

Regular monitoring and staging is therefore important to guide treatment decisions. Additional factors that may be considered before starting treatment include patient age, likelihood of response, potential adverse events, family history of HCC, and presence of HBV-related extrahepatic manifestations.[2][29]

EASL indications for initiating antiviral therapy

  • Start treatment in the following individuals:[29]

    • HBV DNA level is ≥2000 IU/mL and ALT level is above the upper limit of normal (ULN) and/or significant fibrosis is present, regardless of HBeAg status.

    • HBV DNA level detectable in the presence of cirrhosis, regardless of level of viraemia and serum ALT level.

  • Consider treatment in the following individuals:[29]

    • HBV DNA level is detectable in the presence of advanced liver disease (i.e., Metavir fibrosis score ≥F3 on liver histology or liver stiffness measurement [LSM] >8.0 kPa), regardless of level of viraemia and serum ALT level.

    • HBV DNA level is persistently low (i.e., <2000 IU/mL) and ALT level is persistently elevated. However, it is important to investigate other potential causes of liver dysfunction.

  • Consider a personalised assessment to determine whether treatment is required in individuals with HBeAg-positive or HBeAg-negative chronic infection.[29]

    • Immediate treatment can be deferred in individuals who are HBeAg-positive and age <30 years, persistently normal ALT level, no significant liver fibrosis, no family history of HCC, and no immunosuppressive condition. However, consider the benefits of early treatment.

    • Patients who are HBeAg-negative (persistent HBV DNA level <2000 IU/mL, persistently normal ALT level, no signs of liver fibrosis) do not usually require immediate treatment as they have a low risk of disease progression and transmission.

    • Treatment is recommended in individuals who are HBeAg-positive or or HBeAg-negative with the following: an increased or high risk for HCC; HBV-related extrahepatic manifestations; being considered for immunosuppressive therapy or who are immunocompromised (to prevent HBV reactivation or hepatitis). Select individuals can also be treated to prevent HBV transmission.

The WHO supports initiating treatment in all individuals with a HBV DNA level ≥2000 IU/mL and ALT level above the ULN. However, there are some key differences in their recommendations.[75][Evidence B]

  • Treatment is recommended in all individuals with significant fibrosis, regardless of HBV DNA level. However, the evidence for this recommendation in patients with a HBV DNA level <2000 IU/mL is weak.

  • Treatment is recommended in all individuals who are HBsAg-positive with a persistently elevated ALT level in geographical areas with limited access to HBV DNA testing. However, this recommendation is based on low-certainty evidence.

    • While the EASL recognises that this is a practical approach when access to treatment is unlimited, it strongly advocates for the implementation of HBV DNA testing in resource-limited settings when possible.

  • Treatment is recommended in all individuals with the following: co-infections; a family history of liver cancer or cirrhosis; immunosuppression; comorbidities; or extrahepatic manifestations (regardless of HBV DNA or ALT level or fibrosis stage).

The AASLD recommendations for initiating treatment are currently based on the phase of infection.[2]​​

  • Treatment is recommended for individuals with immune-active disease, regardless of HBeAg status. Treatment may also be considered in individuals with the following risk factors, if ALT level <2 times the ULN and the HBV DNA level is below the defined thresholds for this phase:

    • Age >40 years

    • Family history of cirrhosis or HCC

    • Previous history of HBV treatment

    • Presence of extrahepatic manifestations or cirrhosis

  • Treatment is not recommended for individuals with immune-tolerant disease, except for adults >40 years of age with normal ALT level and elevated HBV DNA level (1,000,000 IU/mL) with a liver biopsy specimen showing significant necroinflammation or fibrosis (provided other causes of liver disease have been excluded).

  • Treatment is also not recommended for adults with immune-inactive disease.

  • Assess ALT level at least every 6 months to monitor for potential transition from immune-tolerant disease to immune-active or immune-inactive disease.

  • For definitions of chronic infection phases, see Criteria.

Indications for starting antiviral therapy vary across major society guidelines. Consult your local guidelines for more information.[112]

Chronic infection: choice of antiviral therapy

There are two therapeutic options available for the treatment of chronic infection: nucleoside/nucleotide analogues and peginterferon alfa. When making a decision between the two options, take patient-specific factors (e.g., patient preferences, comorbidities, previous treatments, age, pregnancy) and treatment-specific factors into account, including:[2][29]

  • Route of administration: nucleoside/nucleotide analogues are administered orally on a daily basis, whereas peginterferon alfa is administered subcutaneously on a weekly basis.

  • Contraindications: peginterferon alfa has numerous contraindications and cautions, whereas nucleoside/nucleotide analogues have very few.

  • Potential adverse effects: nucleoside/nucleotide analogues are associated with a lower risk of adverse effects compared with peginterferon alfa.

  • Treatment duration: nucleoside/nucleotide analogues are given long-term, whereas peginterferon alfa is given for a finite period.

In general, nucleoside/nucleotide analogues are better at normalising ALT level and making HBV DNA undetectable compared with peginterferon alfa. However, there is a risk of disease flare when treatment is stopped. Peginterferon alfa increases the chance of HBsAg seroconversion compared with nucleoside/nucleotide analogues (although not significantly) and is not associated with disease flare when treatment is stopped.[Figure caption and citation for the preceding image starts]: Comparison of approved first-line treatments for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic HBV infectionRajbhandari et al. BMJ 2025; 389: e079579; used with permission [Citation ends].com.bmj.content.model.Caption@45ff69c9

​Combination therapy with a nucleoside/nucleotide analogue and peginterferon alfa is not generally recommended due to the lack of safety and efficacy data. However, combination treatment has been used in select patients with low HBsAg level under specialist guidance.[2][29]​​​ Combination treatment has not been shown to significantly increase HBsAg clearance and it is associated with an increased risk of adverse events.[113]

Chronic infection: nucleoside/nucleotide analogues

Nucleoside/nucleotide analogues inhibit HBV replication at the reverse transcription step to suppress viral replication, but do not directly affect covalently closed circular DNA (cccDNA) levels.

Drugs with a high genetic barrier to drug resistance are the preferred options (i.e., entecavir, tenofovir disoproxil, tenofovir alafenamide). Drugs with a low genetic barrier to resistance (i.e., lamivudine, adefovir, telbivudine) are generally not recommended as they can lead to resistance.[2][29][75][Evidence B]

  • Tenofovir has an excellent resistance profile in treatment-naive and treatment-experienced individuals, even with long-term therapy.[114]

  • Entecavir resistance in treatment-experienced individuals has been estimated to be 20% over 5 years.[114] Entecavir is associated with a high risk of resistance in patients who have previously been treated with lamivudine; therefore, a higher dose of entecavir may be required in these patients in order to prevent treatment failure.​[29]​​ Decisions about the best treatment regimen should be made in conjunction with an HIV specialist.

  • Entecavir and tenofovir alafenamide are the preferred options in patients with a history of renal impairment and/or osteoporosis.[2][29][75]

Nucleoside/nucleotide analogues have predictable, long-term efficacy and a favourable safety profile. However, functional cure is rare with these drugs. Long-term data over more than 5 years are available for tenofovir and entecavir.[29]

  • Virological response (undetectable HBV DNA) increases over time in treatment-naive patients, with a virological response ≥85% after 5 years of treatment (≥90% in patients who are HBeAg-negative). Long-term suppression of HBV DNA is associated with a reduced risk of liver inflammation and fibrosis, thereby preventing disease progression, and the development of cirrhosis and HCC, leading to increased survival.[29]

  • HBsAg seroclearance rate is low, ranging from 1% to 5% in 1 year (similar to the annual spontaneous HBsAg seroclearance rate without antiviral therapy). Therefore, patients are usually on treatment for many years, and sometimes lifelong, in order to prevent relapse.[84]

First-line options have been shown to be safe and effective.

  • Tenofovir disoproxil versus tenofovir alafenamide: there was no significant difference in viral suppression between tenofovir disoproxil and tenofovir alafenamide after 12 months of treatment. However, the incidence of adverse effects was lower and the rate of ALT normalisation was higher with tenofovir alafenamide.[115] Evidence suggests that switching from tenofovir disoproxil to tenofovir alafenamide can be done without a loss of efficacy in patients who are virally suppressed.[116][117][118]

  • Tenofovir disoproxil versus entecavir: tenofovir disoproxil was more likely to achieve a virological response at 48 and 96 weeks compared with entecavir. However, entecavir produced a superior biochemical response after 48 weeks compared with tenofovir disoproxil.[119]​ An umbrella review and meta-analysis identified 12 studies for quantitative analysis and found that tenofovir disoproxil was associated with a significantly lower risk of HCC compared with entecavir in most subgroups, although some studies showed no difference between the two treatments.[120]​ Tenofovir disoproxil was associated with a lower risk of recurrence and mortality after resection or ablation of HCC compared with entecavir.[121][122]

  • Tenofovir alafenamide versus entecavir: tenofovir alafenamide significantly improved 12- and 24-week complete virological response, 12-week biochemical response, and 24-week HBsAg loss compared with entecavir. However, entecavir was more effective for other longer-term parameters (i.e., 48- and 96-week complete virological response, 24-, 48-, and 96-week biochemical response, 48- and 96-week HBsAg loss, 12-, 24-, and 48-week HBeAg seroconversion).[123]

  • One Cochrane review could not determine the effect of entecavir versus no treatment or placebo on critical outcomes (i.e., all-cause mortality, serious adverse events) due to the very low certainty of available evidence, and the risk of bias and insufficient power of the included trials. Given that entecavir is a first-line treatment option in many guidelines, further evidence is needed.[124]

Adverse effects may include: nephrotoxicity and decreased bone mineral density/osteopenia (tenofovir disoproxil); hypercholesterolaemia and hypertriglyceridaemia (tenofovir alafenamide); potentially fatal lactic acidosis and severe hepatomegaly with steatosis (nucleoside analogues); pancreatitis; and severe acute exacerbations of hepatitis (after discontinuation).

  • Monitor renal function regularly during treatment. Dose adjustments of tenofovir disoproxil and entecavir may be required in patients with renal impairment, but not with tenofovir alafenamide (although it is not recommended in patients with an eGFR <15 mL/min/1.72 m²). If renal function decreases, or hypophosphataemia or osteoporosis occurs, during treatment with tenofovir disoproxil, switch to tenofovir alafenamide or entecavir.[29]

  • Monitor lipid levels regularly during treatment with tenofovir alafenamide, particularly in those at high cardiovascular risk.[125][126]

  • The risk of lactic acidosis is increased in patients with decompensated cirrhosis.[127]

Chronic infection: peginterferon alfa

Peginteferon alfa is an antiviral cytokine and immunomodulator that stimulates the immune response against HBV and enhances cccDNA degradation. The aim of treatment is to achieve long-term HBV suppression following a finite treatment duration. Variable response rates and an unfavourable safety profile limit its use.[2][29]

Predictive factors of response may be used to guide treatment.

  • Low viral load, elevated ALT level, high histological inflammatory activity, female sex, younger age, and HBV genotypes A and B have been associated with higher rates of HBeAg/anti-HBe seroconversion and HBsAg loss in individuals who are HBeAg-positive. However, HBsAg and HBV DNA levels during treatment offer better predictability of response.[29][128]​​ 

Seroconversion rates appear to be more sustained after treatment discontinuation compared with nucleoside/nucleotide analogues. However, while HBsAg loss rates are higher, the overall rate of HBsAg loss is still considered to be low.[29]

  • Evidence shows a sustained response to treatment in approximately half of the patients treated with peginterferon alfa, no disease progression, and HBsAg loss (16.2% in patients who achieved a sustained response) in a long-term follow-up study of 7 years.[129]

  • Annual rates of HBsAg clearance and seroconversion after withdrawal of peginterferon alfa were 6.9% and 4.7%, respectively, in one systematic review and meta-analysis. The pooled 1-, 3-, and 5-year sustained HBsAg clearance rates were 7.4%, 9.9%, and 13%, respectively, and the sustained HBsAg seroconversion rates were 6.6%, 4.7%, and 7.8%, respectively.[130]

  • Off-treatment HBV DNA suppression <2000 IU/mL occurs in approximately 65% of patients who achieve HBeAg to anti-HBe seroconversion.[2]

Peginteferon alfa can cause or aggravate life-threatening or fatal neuropsychiatric, autoimmune, infectious, and ischaemic disorders.[2][29]

  • It is contraindicated in autoimmune hepatitis and hepatic decompensation. Use with caution in patients with autoimmune disease, psychiatric disorders, cardiovascular disease, diabetes, infectious diseases, ischaemic disorders, seizure disorders, thyroid disorders, and renal impairment.

  • Adverse effects may include: flu-like symptoms; bone marrow suppression; CNS depression; severe dermatologic effects; gastrointestinal issues; hypersensitivity reactions; neuropsychiatric disorders; ophthalmic or pulmonary disorders; and pancreatitis.

  • Close monitoring is required during and after treatment.

Chronic infection: duration of treatment and discontinuation

Nucleoside/nucleotide analogues are usually given longer-term, although the duration of treatment is variable. Peginterferon is given for a finite treatment course of 48 weeks.[2][29]

Nucleoside/nucleotide analogues

  • Treatment is typically required for many years, or possibly lifelong in some patients.

    • Treatment can be discontinued after confirmed HBsAg loss (with or without anti-HBs seroconversion) in individuals without coexisting risk factors.[29]

    • Treatment can be discontinued in patients who are HBeAg-positive without advanced liver disease 12 months after confirmed HBeAg/anti-HBe seroconversion and undetectable HBV DNA level, provided close monitoring is possible after stopping treatment.[2][29] 

    • Treatment can be discontinued in select patients who are HBeAg-negative without advanced liver disease before HBsAg loss if HBV DNA level has been undetectable for at least 3-4 years, HBsAg level is low (e.g., <100 IU/mL), and close monitoring is possible after stopping treatment.[29] However, the AASLD recommends indefinite treatment for HBeAg-negative immune-active disease, unless there is a compelling reason to stop treatment after carefully weighing the risks and benefits.[2]

    • Finite treatment is a viable option for achieving functional cure in select patients.[131] However, this approach is still considered controversial and is not routinely recommended.

  • Only consider discontinuation after consultation with a specialist experienced in treating chronic infection, as severe hepatitis flares may occur following discontinuation.[2][29] 

Peginterferon alfa

  • Typically given for a finite period of 48 weeks. However, stopping rules can be considered based on the quantitative determinations of HBV DNA and HBsAg at weeks 12 and 24 of treatment.[2][29]

  • Consider stopping treatment in patients with negative predictors of treatment response:[29]

    • HBeAg-positive and genotype A or D: no decline of HBsAg at week 12, or HBsAg >20,000 IU/mL at week 24

    • HBeAg-positive and genotype B or C: HBsAg >20,000 IU/mL at week 12 or 24

    • HBeAg-negative and genotype D: no decline of HBsAg and HBV DNA decline is <2 log at week 12

Chronic infection: monitoring response to treatment

In patients on nucleoside/nucleotide analogues, the EASL defines treatment response as follows:[29]

  • Complete virological response: HBV DNA undetectable (i.e., <20 IU/mL)

  • Partial virological response: HBV DNA does not decline steadily and remains >2000 IU/mL

  • Virological non-response: HBV DNA decline <1 log₁₀ at 6 months of treatment

  • Virological resistance: HBV DNA increases to ≥1 log₁₀ above nadir

Definitions may vary across guidelines. For example, the AASLD define viral breakthrough as an increase in HBV DNA >1 log compared to nadir, or an HBV DNA level of ≥100 IU/mL in patients on nucleoside/nucleotide analogues with a previously undetectable level.[2]

In patients with a partial virological response or non-response, assess the patient’s adherence to treatment in the first instance. If treatment adherence is confirmed, testing for HBV variants associated with treatment resistance can be performed.[29]

The following treatment adjustments are recommended for nucleoside/nucleotide analogues:[2][29]​ 

  • If a nucleoside analogue was previously used: switch to (or consider adding-on) tenofovir disoproxil or tenofovir alafenamide

  • If tenofovir was previously used: switch to (or consider adding-on) entecavir

  • If adefovir was previously used: switch to (or consider adding-on) entecavir or tenofovir disoproxil or tenofovir alafenamide

Note that treatment does not need to be adjusted if HBV DNA level is persistently low (<2000 IU/mL) when resistance has been excluded (in the absence of advanced liver fibrosis).[29] Continue monotherapy in patients with persistent low-level viraemia on entecavir or tenofovir, regardless of ALT level.[2]

Monitor patients during treatment to assess treatment response. See Monitoring.

Chronic infection: management of patients with compensated cirrhosis

All patients require treatment. Treatment improves survival and reduces liver-related morbidity and mortality by preventing liver failure or requirement for liver transplantation.

Initiate antiviral therapy in patients with low-level viraemia (i.e., HBV DNA level <2000 IU/mL), regardless of ALT level, to reduce the risk of decompensation. If treatment is not started, patients must be monitored closely every 3-6 months for an increase in HBV DNA level and/or clinical decompensation, with treatment started if either occurs.[2][29] 

  • Entecavir, tenofovir disoproxil, and tenofovir alafenamide are first-line options.

  • While peginterferon alfa is not contraindicated in these patients, nucleoside/nucleotide analogues are considered safer. Peginterferon alfa may be considered in patients who do not have decompensated cirrhosis and/or portal hypertension.[2][132]

Discontinuation of nucleoside/nucleotide analogues is only recommended after confirmed seroconversion to anti-HBs or following HBsAg loss after at least 12 months of consolidation therapy (i.e., 12 months of persistently normal ALT level and undetectable serum HBV DNA).[2][29] 

  • Discontinuation of antiviral therapy in patients with compensated cirrhosis was associated with a high risk of relapse (virological relapse 55%, clinical relapse 44%), but the incidence of adverse events was generally low and controlled. The rate of HCC after discontinuation of antiviral therapy was 9%.[133]

  • Monitor patients at least every 3 months for 1 year after stopping therapy to check for viral rebound that could lead to decompensation.[2]

Chronic infection: management of patients with decompensated cirrhosis or acute-on-chronic liver failure

All patients require treatment. Treatment improves survival and reduces liver-related morbidity and mortality by preventing liver failure or requirement for liver transplantation.

Initiate antiviral therapy as soon as possible, and assess the patient for liver transplantation. There is some debate about whether individuals with an undetectable HBV DNA level require treatment. However, do not delay treatment if results are not immediately available, or it is not possible to closely monitor HBV DNA level.[2][29]

  • Entecavir, tenofovir disoproxil, and tenofovir alafenamide are first-line options.

    • Nucleoside/nucleotide analogues have been shown to improve outcomes (e.g., improved liver function, reduced risk of HCC, increased survival, and increased transplant-free survival) in patients with decompensated cirrhosis or acute-on-chronic liver failure, especially with early treatment.

    • Tenofovir disoproxil and entecavir are equally effective in improving virological response, liver function, and survival among patients with acute-on-chronic liver failure.[134]

  • Peginterferon alfa is contraindicated in these patients due to safety concerns.

    • High rates of serious adverse events, including sepsis and the risk of hepatic decompensation, have been reported.[135]

  • Lifelong treatment is recommended, regardless of ALT or HBV DNA levels, or HBeAg status. The goal is to achieve an undetectable HBV DNA level, ideally within 12 months of treatment. Adjustments to treatment may be considered if this is not achieved.[2]

Antiviral prophylaxis (e.g., a nucleoside/nucleotide analogue plus hepatitis B immunoglobulin [HBIG]) is recommended in patients who undergo liver transplantation to prevent recurrence.[29] 

  • HBIG may be discontinued after transplantation under certain circumstances. Consult a specialist for guidance on the most appropriate regimen.[29]

  • Similar recurrence and overall survival rates have been reported in patients on a nucleoside/nucleotide analogue alone compared with those on a nucleoside/nucleotide analogue plus HBIG.[136]

Chronic infection: management of patients with HCC

Initiate antiviral therapy in patients with HCC, regardless of HBV DNA level. Tenofovir disoproxil is the recommended treatment for tertiary prophylaxis after curative treatment for HCC (e.g., surgery, locoablative therapy).[29]

See Hepatocellular carcinoma.

Chronic infection: management of patients with HIV co-infection

HBV has no significant effect on the natural history of HIV, but HIV and its treatment may profoundly affect the natural history of HBV. Patients may have an accelerated progression of liver disease, as well as increased risk for HCC and liver-related mortality.[84] Reactivation of HBV may also occur.[137]

All patients who are HBsAg-positive and living with HIV should receive HBV-specific antivirals incorporated into their antiretroviral therapy (ART), regardless of HBV DNA level, ALT level, or CD4 cell count.[2][29][138]

  • Initiate ART, regardless of CD4 cell count, according to current local HIV guidelines and under specialist guidance.

  • Make sure that the ART regimen includes drugs that are active against both viruses, including two drugs with activity against HBV. The preferred regimen includes tenofovir disoproxil or tenofovir alafenamide plus emtricitabine or lamivudine as the backbone. In patients already on ART, review the regimen to make sure it includes drugs with HBV activity. Do not discontinue ART.

  • Treatment monitoring is the same as for patients who are not living with HIV.

See HIV in adults.

Chronic infection: management of patients with hepatitis C virus (HCV) co-infection

In general, the indications for treatment are the same as those for chronic HBV monoinfection. However, patients who are HBsAg-positive with chronic HCV co-infection must also be treated with HCV-specific direct-acting antiviral (DAA) therapy according to current local hepatitis C guidelines and under specialist guidance.[2][29] 

  • Nucleoside/nucleotide analogues are also recommended during DAA therapy in patients who are HBsAg-positive with cirrhosis to prevent HBV reactivation. They can also be given to patients who do not meet the indications for treatment for chronic HBV monoinfection in order to prevent HBV reactivation during DAA therapy.[29]

  • The rate of HBV reactivation is higher in patients receiving DAA therapy compared with those receiving peginterferon alfa for the treatment of hepatitis C.[139]​​

See Hepatitis C.

Chronic infection: management of patients with hepatitis D virus (HDV) co-infection

Fulminant hepatitis can be seen in patients with HDV co-infection.[140]​ 

Consider HDV-specific antiviral therapy for all patients with chronic HBV infection, regardless of whether they have cirrhosis, according to current local hepatitis D guidelines and under specialist guidance.[2][29] 

  • Treatment options include peginterferon and/or bulevirtide depending on local guidelines and availability of these drugs.

  • Nucleoside/nucleotide analogues are recommended in addition to HDV antiviral therapy in patients with compensated or decompensated cirrhosis, or patients without cirrhosis if the HBV DNA level is ≥2000 IU/mL.

See Hepatitis D.

Chronic infection: management of pregnant women

Chronic infection during pregnancy has been associated with an increased risk of gestational diabetes, preterm delivery, pre-eclampsia, and eclampsia.[141]

Antiviral prophylaxis is recommended in all pregnant women who are HBsAg-positive with a HBV DNA level >200,000 IU/mL, or a positive HBeAg status regardless of HBV DNA level (in areas where HBV DNA testing is unavailable), to reduce the risk of perinatal transmission. Prophylaxis is also recommended in pregnant women with chronic hepatitis, in accordance with the recommendations for non-pregnant women.[2][29][75][77]

  • Peripartum antiviral prophylaxis has been shown to be highly effective at reducing the risk of perinatal transmission, and considered safe with no increased risk of infant or maternal safety outcomes.[142][143]

  • One Cochrane review found no evidence to demonstrate or disprove any benefit for antiviral therapy for the prevention of perinatal transmission in pregnant women with HIV and HBV co-infection.[144]

Ideally, antiviral prophylaxis should be started before the last trimester, usually in the second trimester or at 28-32 weeks' gestation (depending on guidelines), and discontinued at birth to 3 months postpartum or upon completion of the infant HBV vaccination series.[2][29]​​[75]

  • Tenofovir disoproxil or tenofovir alafenamide are the preferred first-line options. Evidence shows that tenofovir disoproxil and tenofovir alafenamide significantly reduce the rate of perinatal transmission, are equally effective at reducing perinatal transmission, and are considered safe for the mother and baby.[145][146][147][143][148]

  • Lamivudine is an alternative option. It can be given during the third trimester of pregnancy and demonstrates safety and reduction in perinatal and intra-uterine transmission of HBV when given with infant hepatitis B vaccination and HBIG.[2][149][150][151][152]

  • Women who become pregnant while receiving tenofovir may continue on this treatment. However, switching to tenofovir is recommended in women who become pregnant while receiving other drugs. Tenofovir can be continued long-term after delivery to maintain viral suppression.[2][29] 

Caesarean section delivery may be considered in select patients in order to reduce the risk of perinatal transmission.[153]

  • The American College of Obstetricians and Gynecologists (ACOG) suggest that caesarean delivery be reserved for obstetric indications for caesarean delivery only.[77]

  • European guidelines do not recommend caesarean section to reduce the risk of perinatal transmission in women who are HBsAg-positive. However, caesarean section may be considered in Asian women who are HBeAg-positive with a high HBV DNA level who have not received antiviral therapy during pregnancy. Recommendations for patients with HDV co-infection are the same as those with HBV infection.[154]

Chronic infection: management of breastfeeding women

Encourage breastfeeding of infants born to mothers who are HBsAg-positive, unless there are contraindications, or the mother presents with cracked nipples and/or the infant has oral ulcers and the mother has detectable HBV DNA level.[77][154]

  • Breastfeeding after neonatal immunoprophylaxis does not increase transmission rates compared with not breastfeeding.[146]

Antiviral therapy is not contraindicated during breastfeeding.[2][154]

  • Antivirals are minimally excreted in breast milk and are unlikely to pose a significant risk to the infant. However, the risks associated with low-level exposure are unknown.

  • Tenofovir can be continued safely during breastfeeding.[29][155]

Chronic infection: management of children

Chronic infection typically runs an asymptomatic course in most children. A conservative approach to treatment is usually acceptable in children owing to a paucity of clinical data and therapeutic options. A provider experienced in treating children must initiate treatment, if indicated. Follow-up of children through to adulthood is important.[2][29] 

Consider antiviral therapy in HBeAg-positive children aged ≥2 years who have an elevated ALT level (>1.3 times the ULN for at least 6 months) and a measurable HBV DNA level. The HBV DNA level is generally very high in children. Therapy may be deferred until other aetiologies of liver disease and spontaneous HBeAg seroconversion are excluded in patients with a HBV DNA level <10⁴ IU/mL.[2]

  • Tenofovir disoproxil, entecavir, and lamivudine are approved in the US for use in children ≥2 years of age. Tenofovir alafenamide is approved for children ≥6 years of age. Peginterferon alfa is approved for use in children aged ≥3 years of age. Approval age cut-offs may vary in other countries.

  • Duration of nucleoside/nucleotide analogue treatment studied in children is 1-4 years. However, HBeAg seroconversion may be used as a therapeutic endpoint, continuing for a further 12 months of consolidation (as per adults). The treatment course of peginterferon alfa in children is 48 weeks.[2]

  • Combination therapy with a nucleoside/nucleotide analogue and peginterferon alfa has been shown to be more effective than peginterferon alfa monotherapy in children in terms of serological response and viral suppression. However, combination therapy is not recommended and more studies are needed.[156]

A detailed discussion on the management of children is beyond the scope of this topic.

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