Hepatitis B and hepatitis D

• Hepatitis B is a DNA virus (Hepadnaviridae) with a stubborn covalently closed circular DNA (cccDNA) reservoir in liver cells; it is spread by blood, sexual and perinatal routes and is the leading infectious cause of cirrhosis and liver cancer worldwide.
• About 90% of infants infected at birth but less than 5% of healthy adults become chronically infected; the result depends mainly on age at infection and immune competence.
• Diagnosis rests on a panel: HBsAg (surface antigen) shows infection, anti-HBs shows immunity, anti-HBc shows exposure, HBeAg/anti-HBe and HBV DNA show replication. There is a window period in acute infection when only anti-HBc IgM is positive.
• Chronic infection moves through clinical phases (immune tolerant, immune active, inactive carrier, HBeAg-negative) that are tracked with ALT, HBV DNA and fibrosis assessment; treatment is reserved for immune-active disease and special groups.
• First-line treatment is entecavir, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF); lamivudine, adefovir and telbivudine are no longer recommended because of resistance.
• Hepatitis D is a defective virus that can only infect someone who is HBsAg positive; it usually makes the disease far worse and is treated with pegylated interferon (peg-IFN) and, where licensed, bulevirtide.

By the end of this page you should be able to:

1. Explain how hepatitis B spreads, why a newborn is so likely to become chronically infected, and what cccDNA means for cure.
2. Draw the serologic time course of acute hepatitis B, including the window period, and interpret the common marker combinations.
3. Describe the phases of chronic hepatitis B and say which ones need treatment.
4. State when to treat chronic hepatitis B according to the AASLD 2018 guidance and the EASL 2017 guideline (HBV DNA, ALT, fibrosis), and name the first-line drugs with doses and resistance profiles.
5. Manage acute hepatitis B, HBV in pregnancy, HBsAg-positive patients on immunosuppressive therapy, and HBV with HIV or hepatitis D.
6. Outline prevention: vaccination schedules, newborn prophylaxis within 12 hours, post-exposure prophylaxis, and screening.

Every HBV-infected person carries the virus as covalently closed circular DNA (cccDNA) inside hepatocytes. This episomal DNA acts as the transcription template for new virions and is the reason that current drugs suppress, but rarely eliminate, infection: clearance of HBsAg ("functional cure") leaves cccDNA behind, and "true cure" would require its elimination.^[1]

Chronic HBV is further divided by HBeAg status and clinical phase:

• HBeAg-positive chronic infection (historically "immune tolerant"): high HBV DNA, normal ALT, little inflammation.
• HBeAg-positive chronic hepatitis ("immune active"): high HBV DNA, elevated ALT.
• HBeAg-negative chronic infection ("inactive carrier"): low HBV DNA, normal ALT.
• HBeAg-negative chronic hepatitis ("immune active"): moderate HBV DNA, elevated ALT.

EASL 2017 adds a fifth, HBsAg-negative phase (resolved infection with anti-HBc, with or without anti-HBs).^[5]

HBV is a DNA virus that replicates through reverse transcription of an RNA intermediate, a strategy it shares with retroviruses. Its life cycle matters clinically: the viral polymerase has no proof-reading function, so mutations arise, and lamivudine resistance emerges readily. The gene that codes for hepatitis B core antigen also codes for HBeAg, so loss of HBeAg signals a change in viral replication.^[3][4]

Genotypes. Ten genotypes (A to J) have been identified; genotypes A through H are found in the United States, where A, B and C predominate. Genotype influences disease course and interferon response: genotype A (versus B to D) is associated with higher rates of HBeAg and HBsAg loss on interferon, and genotype C progresses to cirrhosis and hepatocellular carcinoma more readily than genotype B in Asian cohorts. Genotype F is linked to a higher incidence of hepatocellular carcinoma in some populations.^[1]

HBsAg quantification. Quantitative HBsAg reflects cccDNA and intrahepatic DNA but also measures antigen produced from integrated viral DNA, which limits its specificity as a replication marker. Levels vary by genotype.^[1]

WHO's 2024 estimate is 296 million people chronically infected with hepatitis B, causing an estimated 820,000 deaths in 2019, mainly from cirrhosis and liver cancer; an older EASL estimate put the global figure at over 250 million. The burden falls hardest on the WHO African, South-East Asian and Western Pacific regions.^[2][5][7]

Prevalence by HBsAg positivity is classified as high (at least 8%), intermediate (2 to 7%) or low (less than 2%). In low-prevalence countries most chronic carriers are immigrants or children of immigrants from high-prevalence countries.^[1][3]

Transmission is by perinatal, percutaneous and sexual routes, and through close person-to-person contact in households; in endemic areas perinatal transmission is dominant. The virus survives outside the body for prolonged periods, and blood, semen, saliva, vaginal secretions and tears are all infectious. In low-prevalence countries injection drug use, sexual exposure and household or needle-sharing contact account for most cases.^[1][3][4]

A special group is health care and public safety workers: transmission from an infected worker to a patient is rare, and an HBsAg-positive worker with serum HBV DNA below 1,000 IU per mL may perform exposure-prone procedures under guidance.^[1]

There is no modifiable risk factor for the host beyond exposure. Risk comes from exposure and from biological susceptibility:

• Newborns of HBsAg-positive mothers, especially those who are HBeAg positive: a 70 to 90% chance of infection, and up to 90% of those children become chronically infected.^[7]
• Infants and children under 5: a 25 to 30% chance of chronicity after infection.^[1]
• Immunocompetent adults: less than 5% become chronically infected; more than 95% clear the virus.^[1][3]
• Immunosuppressed adults: a higher risk of chronicity than healthy adults.^[1]
• Vertical transmission is the dominant driver of the chronic disease burden in endemic regions, and the perinatal rate is far higher from HBeAg-positive mothers.^[2][7]

WHO estimated that in 2022 only 45% of infants received a timely hepatitis B birth dose, falling to 18% in the African region, and that only 10% of the 296 million carriers had been diagnosed.^[2]

HBV is not directly cytopathic: liver injury is immune-mediated, and the balance between viral replication and host response determines phase, flares and progression. Chronic inflammation with failed clearance drives cirrhosis and cancer.^[1]

After exposure the incubation period is about 12 weeks (the range is usually given as 1 to 6 months, and varies between sources). HBsAg is the first marker detectable, 1 to 12 weeks after infection, and ALT rises in the replicative phase. Most adults have an asymptomatic or mild self-limited illness; a serum-sickness-like illness with fever, arthralgias and rash can appear in the prodrome. Less than 1% develop fulminant hepatitis with hepatic encephalopathy, coagulopathy or ascites.^[3][4][7]

The window period is the gap between disappearance of HBsAg and appearance of anti-HBs, when anti-HBc (especially IgM) may be the only marker.^[3]

HBsAg persistence for at least 6 months defines chronic infection. The dynamic phases are the practical framework for follow-up and treatment (summarised from AASLD 2018, Table 6):

• Immune-tolerant (HBeAg-positive): HBsAg for at least 6 months, HBeAg positive, HBV DNA typically above 1 million IU/mL, normal ALT, no fibrosis.^[1]
• Immune-active (HBeAg-positive): HBV DNA above 20,000 IU/mL, ALT above the upper limit of normal, with inflammation.^[1]
• Inactive carrier (HBeAg-negative, anti-HBe positive): HBV DNA below 2,000 IU/mL, persistently normal ALT.^[1]
• HBeAg-negative immune-active: HBV DNA above 2,000 IU/mL, elevated ALT.^[1]
• Resolved (HBsAg loss): sustained loss of HBsAg with undetectable HBV DNA; cccDNA persists, and the risk of hepatocellular carcinoma falls but does not disappear, especially after age 50 or with cirrhosis.^[1]

ALT behaves in phases, and cut-offs for decisions are taken as 35 U/L for men and 25 U/L for women (AASLD 2018); EASL and WHO guidance phrase thresholds differently, so follow local practice.^[1]

• Cirrhosis and decompensation: a 15 to 40% risk of progression to cirrhosis in chronic infection, higher with genotype C and co-infection.^[8]
• Hepatocellular carcinoma: the main cause of death, with risk from integrated HBV DNA even after HBsAg loss.^[1]
• Fulminant hepatitis in acute infection is rare (about 1% of acute cases or fewer, with some series reporting less than 0.5%) but carries high mortality and needs transplant assessment.^[4]
• Postpartum flares occur in about a quarter of women.^[1]
• With HBsAg loss the disease generally stabilises; HCC risk persists with age, cirrhosis or HDV/HCV co-infection.

About 20% of patients with HBV infection develop immune-mediated extrahepatic disease, driven by circulating immune complexes containing HBsAg and/or HBeAg.^[7]

• Serum sickness-like prodrome of acute infection appears in 10 to 30% of those who acquire acute hepatitis B, 1 to 6 weeks before clinical hepatitis: a symmetric inflammatory arthritis of the small joints of the hands and feet, fever and a maculopapular, petechial, purpuric or urticarial rash, sometimes with glomerular or angio-oedematous involvement. It is non-destructive and resolves at the onset of clinical hepatitis.^[7]
• Polyarteritis nodosa (PAN) is a rare but serious systemic vasculitis of small and medium vessels that presents within 4 months of clinical onset; ANCA and complement are normal and angiography may show microaneurysms. Treatment combines antiviral therapy, immunosuppression and plasma exchange; prognosis is poor (mortality up to 50%) without treatment.^[7]
• HBV-associated glomerulonephritis, most often membranous nephropathy or membranoproliferative glomerulonephritis, occurs mainly in children in endemic areas, where it often remits; adults may progress to renal failure. Genotype A carries a higher incidence of membranous and membranoproliferative disease.^[7]
• Mixed cryoglobulinaemia (mainly HCV, occasionally HBV or HIV), neurologic disease, papular acrodermatitis of childhood (Gianotti-Crosti syndrome) and other autoimmune phenomena are also reported but are less well established.^[7]

Because extrahepatic disease is an indication for antiviral treatment independent of liver severity in both AASLD 2018 and EASL 2017 guidance, HBV replication should be suppressed.^[1][5]

The main traps are distinguishing acute from chronic disease and an HBsAg-positive carrier state from active hepatitis. ALT alone is unreliable: immune-tolerant carriers have high HBV DNA but normal ALT, and inactive carriers have low HBV DNA and normal ALT. Clinical clues help:

• Acute infection follows exposure and is usually self-limited in adults.
• Chronic infection is marked by HBsAg for at least 6 months.
• Resolving infection is HBsAg negative, anti-HBc positive and anti-HBs positive.
• Vaccinated people are anti-HBs positive with no anti-HBc.
• Isolated anti-HBc needs careful interpretation (see below).

A negative HBsAg does not always mean no infection: HBV DNA can be present at low levels in occult infection, and serologic gaps (the window period) can hide infection. Anti-HBc is therefore screened in blood donors and before immunosuppression.

Isolated anti-HBc has several explanations: past infection with waning immunity (common in endemic areas), long-past chronic infection that cleared HBsAg (yet still at HCC risk), window-phase acute infection (IgM positive) or, rarely, a false-positive test in a low-prevalence person. Low-level HBV DNA (20 to 200 IU/mL) is common when anti-HBs is negative. In an immunosuppressed person, screen with HBV DNA and consider prophylaxis rather than assuming immunity.

• ALT and AST (upper limit of normal taken as 35 U/L for men and 25 U/L for women for decision-making). ALT is used, with HBV DNA, to judge immune activity; a single value is less useful than trend. AST above ALT, and a falling platelet count, suggest advanced fibrosis.^[1]
• HBV DNA by real-time PCR (sensitive to 5 to 10 IU/mL) is the central virologic test for infectivity, staging and response.
• Fibrosis assessment: liver biopsy is the only test that grades both fibrosis and inflammation; non-invasive tests are preferred in practice. Transient elastography is more accurate than serum scores (APRI, FIB-4) for predicting significant or advanced fibrosis, though high ALT can overestimate fibrosis. Treat if non-invasive testing shows at least F2.^[1]
• HCC surveillance: ultrasound of the liver every 6 months, with or without alpha-fetoprotein, in all HBsAg-positive patients with cirrhosis, and in high-risk groups (Asian or Afro-American men over 40, Asian women over 50, anyone with a first-degree relative with HCC, or HDV co-infection). AFP alone is used where ultrasound is unavailable. Children with advanced fibrosis or a family history of HCC are screened similarly.^[1]
• qHBsAg is useful in selected settings (peg-IFN stopping rules, risk stratification) but measures integrated DNA as well as cccDNA.^[1]
• HDV screening in all HBsAg-positive patients at risk, or universally where feasible.^[1][2]

Chronic infection is diagnosed when HBsAg persists for at least 6 months. Staging requires:

1. HBeAg/anti-HBe status.
2. HBV DNA level.
3. ALT trend (not a single value).
4. Fibrosis assessment (elastography or biopsy).
5. Testing for HIV, HCV and HDV where indicated.
6. Documentation of cirrhosis (compensated or decompensated).

AASLD further defines the "inactive" state as HBeAg negative, anti-HBe positive, HBV DNA below 2,000 IU/mL and persistently normal ALT.^[1]

More than 95% of immunocompetent adults clear acute infection. Management is supportive (rest, fluids, avoid hepatotoxins, monitor). Antiviral therapy is not generally needed, but is reasonable in:

• acute liver failure or a severe/protracted course: total bilirubin above 3 mg/dL (or direct bilirubin above 1.5 mg/dL), INR above 1.5, encephalopathy or ascites;
• patients who may need transplantation, where lower HBV DNA is desirable.

When treated, the preferred drugs are entecavir, TDF or TAF; interferon is contraindicated because of the risk of worsening hepatitis. Treatment continues until HBsAg clears or indefinitely after transplantation. Lamivudine-based criteria (bilirubin above 10 mg/dL, INR above 1.6) define severe disease in some sources.^[1][3][7]

A 2023 review and national guidelines also frame severe acute disease as two of the following three: bilirubin above 10 mg/dL, INR above 1.6 and hepatic encephalopathy.^[3]

Indications (AASLD 2018) for adults with immune-active disease are HBV DNA above 2,000 IU/mL (HBeAg negative) or above 20,000 IU/mL (HBeAg positive) with ALT of two or more times the upper reference limit, or evidence of significant histologic disease with elevated HBV DNA. TDF, TAF and entecavir are preferred first-line; therapy reduces liver-related complications.^[1]

EASL 2017 frames the typical indication as HBV DNA above 2,000 IU/mL, elevated ALT and/or at least moderate histological lesions; all cirrhotic patients with detectable HBV DNA should be treated regardless of ALT. Additional indications include prevention of mother-to-child transmission with high viremia and prevention of reactivation with immunosuppression.^[5]

Taken together, the practical rule used in most algorithms is: treat if (HBV DNA above 2,000 IU/mL + elevated ALT) or at least fibrosis F2, or cirrhosis with any detectable DNA, or any high-risk factor (co-infection, family history, extrahepatic manifestations, immune suppression).

WHO 2024 simplified eligibility further, and now supports treatment if any of four conditions are met: significant fibrosis (APRI above 0.5 or elastography above 7 kPa) regardless of DNA/ALT; HBV DNA above 2,000 IU/mL with ALT above the upper limit of normal; co-infection, family history, immune suppression, comorbidities or extrahepatic manifestations regardless of DNA/ALT; or persistently abnormal ALT alone where DNA testing is unavailable. This broader approach is expected to capture about half of all HBsAg-positive people.^[2]

Who not to treat: immune-tolerant adults are not treated under AASLD 2018; instead monitor ALT every 6 months, with biopsy/therapy considered for those over 40 with active histology. EASL allows treatment of HBeAg-positive immune-tolerant patients over 30 may be treated if there are advanced lesions.^[1][5]

Other independent indications include active extrahepatic manifestations, fibrosis F2 or worse, and cirrhosis with any detectable HBV DNA.

• Lamivudine (100 mg daily), adefovir (10 mg daily) and telbivudine (600 mg daily) are no longer recommended, because of rapid selection of resistance (lamivudine resistance reaches around 90% by 4 years in HIV co-infection, and entecavir resistance appears in about half of lamivudine-resistant patients by 5 years). EASL 2017 states the same: lamivudine, adefovir and telbivudine are not recommended.
• Combination therapy is not generally recommended for treatment-naive patients when a high-barrier drug is used.^[5]
• Response on therapy: HBV DNA suppression rates on TDF/TAF are 76 to 93% and on entecavir 61 to 91% depending on HBeAg status; HBeAg seroconversion occurs in roughly a fifth to a third of treated patients; HBsAg loss is uncommon (well under 1% to low single digits per year).^[1]
• All nucleos(t)ide analogues require dose adjustment when creatinine clearance falls below 50 mL/min (except TAF, not used below 15 mL/min or on dialysis).^[1]
• Antiviral therapy does not eliminate HCC risk: surveillance continues in at-risk people.^[1]

• HBeAg-positive patients who are not cirrhotic, after seroconversion to anti-HBe on a nucleos(t)ide analogue, may discontinue after at least 12 months of consolidation (normal ALT and undetectable HBV DNA for that whole period); otherwise treat to HBsAg loss. Cirrhotic patients who seroconvert should usually be treated indefinitely because of decompensation risk.^[1]
• HBeAg-negative patients are generally treated indefinitely, unless there is a compelling reason to stop; discontinuation in cirrhosis is not recommended. Stopping can be considered after confirmed HBsAg loss.^[1]
• Anyone who stops must be monitored every 3 months for at least 1 year (monthly for 6 months in cirrhotics) for recurrent viremia, ALT flares and decompensation. Viral rebound and flares are common.^[1]
• WHO's newer approach treats longer in some programmes, but AASLD's standard stopping rules above are the reference for most settings.^[2]

All patients should be screened for HBsAg and anti-HBc (total IgG) before starting any immunosuppressive, cytotoxic or immunomodulatory drug, because reactivation occurs in 41 to 53% of HBsAg-positive patients on anticancer therapy.^[1]

• HBsAg-positive patients receive prophylaxis before (ideally about a week before) treatment, throughout, and for at least 6 months afterwards (12 months after anti-CD20 therapy such as rituximab).
• HBsAg-negative, anti-HBc-positive patients are lower risk: they may be monitored (HBsAg, HBV DNA, ALT every 1 to 3 months) with on-demand therapy, except those receiving anti-CD20 antibody therapy or undergoing stem cell transplantation, who should receive prophylaxis.^[1]
• Use high-barrier drugs: entecavir, TDF or TAF (not lamivudine). Preferred drug choice here is supported by meta-analyses showing reduced reactivation, hepatitis and mortality.^[1]
• Reactivation is defined as a rise in HBV DNA from baseline (or the appearance of detectable HBV DNA/HBsAg seroreversion in HBsAg-negative, anti-HBc-positive patients) with a hepatitis flare (ALT at least 3 times baseline and above 100 U/L); liver failure occurs in up to 13.9% of HBsAg-positive cancer patients with reactivation in pooled data.^[1]

• Screen all pregnant women for HBsAg (and, by current guidance, core total antibody and surface antibody if testing history is incomplete). HBV vaccination is safe in pregnancy.^[1][7]
• Third-trimester antiviral therapy is recommended when HBV DNA exceeds 200,000 IU/mL, to reduce mother-to-child transmission; TDF is preferred because of potency and resistance profile, started in the second trimester through delivery. AASLD supports stopping antiviral treatment at delivery or up to 4 weeks postpartum; extending treatment 2 to 12 weeks postpartum did not prevent postpartum flares.^[1]
• Without prophylaxis, transmission occurs in 70 to 90% of infants born to HBeAg-positive mothers and 10 to 20% to HBeAg-negative mothers (some series report higher rates). Even with immunoprophylaxis, a small proportion of infants, about 9% in one estimate, are infected when maternal viral load is very high. Perinatal (and later childhood) infection leads to chronicity in about 90% of newborns, 25 to 30% of children under 5 and only about 5% of adults.^[7]
• Newborn management: give HBIG plus monovalent HBV vaccine within 12 hours of birth, then complete the three-dose series, and test for response at 9 to 15 months. Infants of mothers whose HBsAg status is unknown should be vaccinated promptly, and low-birth-weight infants (below 2,000 g) should receive HBIG plus vaccine within 12 hours. Breastfeeding is not prohibited.^[1][7]
• Postpartum flares affect about 25% of women; monitor closely for up to 6 months. Women with cirrhosis should be managed in high-risk obstetric practice and treated with TDF. Breastfeeding while on antiviral therapy has supporting clinical safety data.^[1]
• WHO 2024 also allows prophylaxis for all HBsAg-positive pregnant women where testing for HBV DNA or HBeAg is unavailable, preferably from the second trimester to delivery or completion of the infant series.^[2]

All HIV-HBV co-infected patients should receive antiretroviral therapy that includes two drugs active against HBV: tenofovir (TDF or TAF) plus lamivudine or emtricitabine. Lamivudine monotherapy selects resistance in up to 90% by 4 years, and entecavir may induce HIV resistance mutations, so it is only used with a fully suppressive antiretroviral regimen. Adefovir and telbivudine are not recommended. Treat indefinitely, and monitor flares when antiretrovirals are changed; never stop HBV-active drugs without substituting another.^[1]

WHO recommends TAF or TAF-containing dual regimens preferentially where renal or bone risk exists, and TDF plus lamivudine/emtricitabine otherwise. Treatment continues with monitoring for virologic response and adverse events.^[1][2]

HDV is a defective RNA virus that can only infect an HBsAg-positive person; it packages itself in hepatitis B surface antigen and uses HBV's entry receptor. It causes two distinct patterns:

• Co-infection (simultaneous with HBV): often severe or fulminant, but recovery usually clears both viruses.
• Super-infection (HDV in a person already chronically infected with HBV): usually becomes chronic and drives very rapid progression to cirrhosis and a higher risk of hepatocellular carcinoma. About 50 to 70% of HBsAg-positive, HDV-infected people develop cirrhosis within 5 to 10 years, a three-fold increase over HBV alone. Global HDV prevalence among HBsAg carriers is estimated at 4.5% (roughly 12 million people), though under-reporting makes this uncertain. The global prevalence of active infection is about 0.16%.^[8]

Diagnosis: screen all HBsAg-positive people, and screen universally where possible, prioritising those born in HDV-endemic regions, people who inject drugs, men who have sex with men, people with HIV or HCV, haemodialysis recipients, people with advanced liver disease and those already on HBV treatment. Test with anti-HDV antibody (total) first, then HDV RNA if positive; reflex testing following a positive HBsAg (and RNA following a positive antibody) is recommended. AASLD 2018 advised screening of at-risk groups rather than everyone; the 2024 WHO and EASL 2023 guidance favour broader testing.^[1][2][6]

Treatment: the cornerstone remains pegylated interferon (peg-IFN alfa, 180 micrograms weekly) for 48 weeks (12 months), or for 12 to 18 months with continued viral suppression; up to around 25 to 29% achieve an off-treatment virologic response (undetectable HDV RNA at 24 weeks), but relapse is common. Nucleos(t)ide analogues have no effect on HDV and are only added when HBV DNA is raised. Peg-IFN is contraindicated in decompensated cirrhosis.

Bulevirtide, an entry inhibitor approved by the European Medicines Agency in 2020 in some countries, blocks NTCP and suppresses HDV replication; EASL 2023 suggests long-term treatment at 2 mg subcutaneously once daily (a single-guideline figure; check the current label), alone or combined with peg-IFN alfa, for patients with compensated disease where available. Optimal duration and stopping rules are still being defined. AASLD 2018 noted that new agents (entry inhibitors, prenylation inhibitors) were in early trials.^[1][6][7]

Given the poor outcomes and limited treatment efficacy, patients with hepatitis D should be managed in specialist centres.

In many high-burden regions (sub-Saharan Africa, South-East Asia), HBsAg testing and HBV DNA quantification are scarce; simplified pathways are essential.

• Clinical and non-invasive assessment: use APRI (above 0.5) or elastography (above 7 kPa, where available) to identify significant fibrosis, which alone indicates treatment under WHO 2024. Where DNA testing is unavailable, treating on persistently abnormal ALT alone captures about 20% of carriers.^[2]
• First-line drugs: TDF and entecavir have the same high barrier to resistance; TDF plus lamivudine or emtricitabine (from existing HIV programmes) are acceptable alternatives when TDF monotherapy is not procured, and TAF is reserved for renal or bone risk.^[2]
• Mother-to-child prevention: prioritise the timely birth dose, which remains the most important intervention where coverage is still only 45% globally; where HBeAg/HBV DNA testing is unavailable, prophylactic tenofovir for all HBsAg-positive pregnant women from the second trimester (WHO 2024 conditional recommendation) plus infant immunoprophylaxis is a pragmatic option.^[2]
• Point-of-care and reflex testing: POC HBV DNA assays and reflex HBV DNA after a positive HBsAg result improve linkage to care without extra visits.^[2]
• HBV/HIV co-infection is common in these regions; ART backbones should already contain tenofovir plus lamivudine/emtricitabine, which treats both.^[1]
• HCC surveillance with ultrasound is often unavailable; in some regions AFP every 6 months is the fallback, though sensitivity is limited.^[1]
• Vaccination coverage gaps are the rate-limiting step: only 18% birth-dose coverage in the African region in 2022.^[2]

• Screen all persons born in countries with HBsAg prevalence of at least 2%, US-born people whose parents were born in high-endemicity regions, pregnant women, people needing immunosuppressive therapy, men who have sex with men, people who inject drugs, recipients of blood and organ donations, dialysis patients, people with chronic liver disease or HIV, household and sexual contacts of carriers, and health care and public safety workers at risk.^[1]
• Screen with both HBsAg and anti-HBs; add anti-HBc for HIV-positive people, those about to receive immunosuppression, donated blood and organs.^[1]
• HBV vaccination does not produce anti-HBc, so anti-HBc means exposure.

• Universal infant vaccination with a birth dose within 24 hours, followed by completion of the series. Only monovalent HBV vaccine is used under 6 weeks of age; combination vaccines (including combination hepatitis A/B) are used later.^[1]
• Standard series: 3 doses at 0, 1 and 6 months; an alternate 4-dose schedule at 0, 7, 21 to 30 days and 12 months is used for the combination hepatitis A/B vaccine in adults; a 2-dose schedule at 0 and 1 month is approved for adults (HEPLISAV-B).^[1]
• Newborns of HBsAg-positive mothers should receive HBIG plus HBV vaccine within 12 hours, then complete the series, with post-vaccination testing at 9 to 15 months. Low-birth-weight infants (below 2,000 g) of HBsAg-positive mothers get HBIG plus vaccine within 12 hours followed by the standard 3-dose schedule; premature or low-birth-weight infants of HBsAg-negative mothers should be vaccinated before 1 month of age or at discharge.^[1]
• Post-vaccination serologic testing (anti-HBs 1 to 4 months after the last dose) is recommended for health care workers, sexual partners of carriers, dialysis patients and immunocompromised people (including HIV), with a responder defined as anti-HBs above 10 mIU/mL (or above 100 mIU/mL by some schedules). Non-responders repeat the series, with double dosing for immunocompromised patients or those with cirrhosis.^[1][3]
• Boosters are not recommended for immunocompetent people whose primary series was completed; an immunocompromised responder should receive a booster when anti-HBs falls below 10 mIU/mL; dialysis patients are tested annually.^[1]
• Adult vaccination is offered to all susceptible adults (universal adult vaccination is recommended), and to everyone at risk: multiple partners, sexually transmitted infection clinics, household contacts, men who have sex with men, people who inject drugs, dialysis patients, travellers to endemic countries, people with diabetes aged 19 to 59, health care workers, prisoners, and others.^[1]
• HBV vaccination during pregnancy is safe and effective.

• For unimmunised or incompletely immunised people exposed percutaneously, mucosally or sexually to an HBsAg-positive (or HBsAg-unknown) source: give HBIG plus vaccine (or vaccine alone, depending on immune status) within 24 hours. The maximum effective interval is unlikely to exceed 7 days for percutaneous exposure and 14 days for sexual exposure. If the exposed person is already immune, no treatment is needed. For people who are HBsAg positive, management follows the occupational health/PEP protocol.^[1]
• Everyday, household and food contact is safe: HBsAg-positive adults and children can participate in all activities, including contact sports and school, sharing food and utensils, with only standard precautions. HBIG is not required for everyday contact.^[1]

• Any suspected acute liver failure, fulminant hepatitis, or decompensated cirrhosis.
• Cirrhosis, advanced fibrosis (F3 or more), or suspected hepatocellular carcinoma.
• Extrahepatic manifestations (PAN, nephropathy).
• HIV or hepatitis D co-infection.
• Pregnancy with high viraemia.
• Before starting immunosuppressive or cytotoxic therapy, if support is needed for prophylaxis and monitoring.
• Uncertainty about pathogenesis or phase, or expected non-response.

Plain text references (no live links in this draft): cirrhosis and portal hypertension; hepatocellular carcinoma; hepatitis A; hepatitis C; HIV infection; acute liver failure; renal disease (membranous nephropathy); pregnancy and infections; vaccination; immune suppression and infection risk.

• Hepatitis B is an enveloped DNA virus with a cccDNA reservoir; true virologic cure is not achieved by current drugs.
• Infection risk of chronicity is age-dependent: about 90% of newborns, 25 to 30% of children under 5, less than 5% of healthy adults.
• The serologic triad is HBsAg (infection), anti-HBs (immunity), anti-HBc (exposure); HBeAg/anti-HBe and HBV DNA reflect replication; remember the window period.
• Chronic phases are immune tolerant, immune active, inactive carrier and HBeAg-negative disease; follow with trend ALT, HBV DNA and fibrosis.
• Treat immune-active disease, cirrhosis with detectable DNA, fibrosis F2 or worse, extrahepatic manifestations, and during immunosuppression or pregnancy with high viraemia.
• AASLD 2018: treat if HBV DNA above 2,000 (HBeAg negative) or 20,000 IU/mL (HBeAg positive) with ALT of two or more times the upper reference limit or significant histology; EASL 2017: treat HBV DNA above 2,000 IU/mL with elevated ALT or significant lesions; all cirrhotics with detectable DNA.
• First-line: peg-IFN for 48 weeks in selected patients, or entecavir 0.5 mg (1 mg if resistance-experienced), TDF 300 mg, or TAF 25 mg daily; avoid lamivudine, adefovir and telbivudine.
• Stop nucleos(t)ide analogues cautiously: 12 months consolidation after HBeAg seroconversion in non-cirrhotic disease; treat HBeAg-negative disease and cirrhosis indefinitely unless HBsAg is lost.
• Newborns of HBsAg-positive mothers need HBIG plus vaccine within 12 hours; vaccinate all infants at birth and complete the series.
• Post-exposure prophylaxis with HBIG plus vaccine works if given within 24 hours.
• Hepatitis D co-infection makes disease much worse; treat with peg-IFN 48 weeks (and bulevirtide where licensed) and refer.
• HCC surveillance with ultrasound every 6 months continues in all at-risk patients even after HBsAg loss.
• Vaccinated people have anti-HBs only; resolved infection has anti-HBs and anti-HBc; isolated anti-HBc needs interpretation, not dismissal.