Hepatology & Infectiology & Internal Medicine & Family Medicine
HBsAg (hepatitis B surface antigen)
HBsAg (Hepatitis B surface Antigen) is a hepatitis B virus (HBV) envelope protein present on the surface of full virions and secreted in large quantities into the bloodstream in the form of subviral particles (non-infectious spheres and filaments). Its detection in serum by immunoassay (ELISA or CLIA) is the reference marker of active HBV infection - whether acute or chronic. HBsAg positivity for more than six months defines chronic hepatitis B. With over 296 million chronically infected people worldwide (WHO 2019) and 820,000 deaths annually - mainly from cirrhosis and hepatocellular carcinoma (HCC) - chronic hepatitis B represents one of the most consequential viral infections worldwide. In Canada, the prevalence of chronic hepatitis B is estimated at 0.7-1.0 % of the adult population, with high-prevalence subgroups: immigrants from Southeast Asia, sub-Saharan Africa, Eastern Europe and the Middle East, aboriginal peoples, intravenous drug users, men who have sex with men and sex workers. Modern antiviral treatment - tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or entecavir - effectively suppresses viral replication in almost all treated patients, reduces the risk of cirrhosis and HCC, and can be administered indefinitely with excellent tolerability. Functional cure - defined as HBsAg seroconversion (loss of HBsAg + appearance of anti-HBs) - remains rare with current antivirals (<3 % per year), but is the focus of numerous therapeutic strategies currently under development.
Virology, serological markers and interpretation
- HBV structure, replication cycle and role of HBsAg : viral structure: HBV = partially double-stranded circular DNA virus (3.2 kb) + lipid envelope + nucleocapsid (core - HBcAg) + viral polymerase (DNA polymerase with reverse transcriptase activity) + belongs to the Hepadnaviridae family → genomes: 8 genotypes (A-H) + subgenotypes → A genotype dominant in North America + B and C genotype dominant in Asia → genotype influences response to interferon and progression to HCC (C genotype → higher risk of HCC - Chen 2006 - Gastroenterology); envelope proteins - HBsAg: the S gene encodes 3 envelope proteins: large (L-HBsAg) + medium (M-HBsAg) + small (S-HBsAg) → all three positive by standard ELISA tests → HBV produces a massive excess of non-infectious subviral particles (SVP) containing only HBsAg without viral genome → SVP/complete virions ratio: 1,000 : 1 to 100,000 : 1 → quantitative HBsAg (qHBsAg) in IU/mL: reflects cccDNA and integrated DNA load → prognostic and predictive marker of response to treatment → threshold <100 IU/mL associated with increased risk of spontaneous seroconversion → Brunetto 2010 - Hepatology + intrahepatic replication cycle : HBV → binds to the NTCP receptor (Na⁺-taurocholate cotransporting polypeptide - Yan 2012 - eLife) on hepatocytes → internalization → decapsidation → viral DNA → nucleus → conversion to cccDNA (covalently closed circular DNA) → persistent form of the virus → transcription by cellular RNA polymerase II → pregenomic RNA (pgRNA) + viral mRNA → pgRNA → nucleocapsid → viral reverse transcriptase → viral DNA → envelopment → complete virion → secretion → or return to nucleus (cccDNA amplification) → cccDNA persists for life in hepatocytes (half-lifelife of several months) → source of reactivation → not eliminated by current antivirals → major obstacle to complete virological cure → integration of viral DNA into the host genome : frequent in chronic hepatitis B → source of HBsAg transcription even without cccDNA → additional obstacle to functional cure → Levrero 2009 - Journal of Hepatology: HBV integration → mutagenic insertions → proto-oncogene activation → contribution to HCC; the 8 main HBV serological markers and their significance: HBsAg: surface protein → positive = active infection (acute or chronic) → negative + anti-HBs positive = immunity (vaccine or post-infection) → anti-HBs (anti-HBs antibodies): protective IgG → positive in isolation = vaccination + positive with anti-HBc = cure of previous infection → protective threshold: ≥10 IU/L → HBcAg (core antigen): not secreted in blood (intracellular) → not routinely dosed → total anti-HBc (IgG + IgM): marker of contact with HBV → positive in acute + chronic + cured infection → anti-HBc IgM: marker of recent acute infection (or severe reactivation) + HBeAg (e antigen): marker of active replication + high infectivity → positive in phases of immune tolerance and chronic active hepatitis HBeAg+ → anti-HBe: HBeAg → anti-HBe seroconversion → signal of reduced replication in wild-type variants → but precore (G1896A) and core promoter mutants continue to replicate without producing HBeAg → HBV-DNA (viral load): quantifies viral replication in IU/mL → IU/mL = 5.6 copies/mL → correlates with risk of liver progression → qHBsAg (quantitative HBsAg): IU/mL → marker of cccDNA + integrated DNA reservoir → used to predict response to interferon and guide treatment discontinuation
- Interpretation of common serological profiles : profile 1 - HBsAg positive + anti-HBc IgM positive + high HBV-DNA + high ALT: acute hepatitis B → check resolution at 6 months → if HBsAg still positive at 6 months → chronic hepatitis B → profile 2 - HBsAg positive + anti-HBc total positive + anti-HBc IgM negative + variable HBV-DNA + variable ALT: chronic hepatitis B → complete with HBeAg + anti-HBe + qHBsAg + biopsy/elastometry → profile 3 - HBsAg negative + anti-HBc positive + anti-HBs positive: cure of a previous infection → immunity + no treatment + screening for reactivation if immunosuppression envisaged → profile 4 - HBsAg negative + anti-HBs positive isolated : vaccination (if anti-HBc negative) → or old infection with loss of anti-HBc (rare) → profile 5 - HBsAg negative + isolated positive anti-HBc (without anti-HBs): healed old infection with loss of anti-HBs (frequent with time) → or occult infection (HBV-DNA detectable in liver but not in blood) → or false positive → or serological window of an acute infection → if immunosuppression envisaged → serum HBV-DNA + hepatological opinion + profile 6 - HBsAg negative + anti-HBc negative + anti-HBs negative : susceptible → not immunized + vaccinate → profile 7 - occult hepatitis B (OBI - Occult Hepatitis B Infection): HBsAg negative + serum HBV-DNA undetectable or <200 uiml + anti-hbc ± anti-hbs positifs → cccdna résiduel dans les hépatocytes risque de réactivation sous immunosuppression raimondo 2019 — nature reviews gastroenterology and hepatology ; interprétation selon la phase l'hépatite b chronique (terrault 2018 aasld guidelines) : 1 infection hbeag+ (anciennement « tolérance immune ») hbeag positif adn-vhb très élevé (>10⁶-10⁷ IU/mL) + normal ALT + absent or minimal fibrosis → high replication without hepatic inflammation → frequent in patients infected at birth (perinatal) + phase 2 - HBeAg+ chronic hepatitis (formerly «active immune phase»): HBeAg positive + high HBV-DNA (>2,000 IU/mL) + high ALT + liver inflammation → progression to fibrosis → indication for treatment + phase 3 - chronic HBeAg- infection (formerly «inactive carriage»): HBeAg negative + anti-HBe positive + low HBV-DNA (<2 000 uiml) + alat normale fibrose peu importante → risque faible de progression phase 4 — hépatite chronique hbeag− (hépatite anti-hbe) : hbeag négatif anti-hbe positif adn-vhb modéré (>2,000 IU/mL) + elevated or fluctuating ALAT → precore or core promoter variants → risk of progression + indication for treatment + phase 5 - HBsAg-infection (functional cure): HBsAg negative + anti-HBs ± positive + anti-HBc positive + undetectable serum HBV-DNA → residual cccDNA possible but low risk of reactivation if immunocompetent → Terrault 2018 - Hepatology: AASLD HBV Guidelines → North American reference benchmark.
Epidemiology, long-term risks, treatment and monitoring
| Domain | Data, methods and criteria | Key studies and recommendations |
|---|---|---|
| Screening, transmission and prevention - vaccination Target groups - perinatal transmission - vaccination - immunoglobulins - HBIG - screening in Canada |
HBsAg screening in Canada - indications (PHAC + CATIE + provincial guidelines): high-risk populations → systematic screening recommended : immigrants and refugees from countries with intermediate or high prevalence (>2 %) - Southeast Asia + China + Sub-Saharan Africa + Eastern Europe + Middle EastOrient + Canadian aboriginal peoples → IDUs (injecting and inhalation drug users) → MSM (men who have sex with men) → incarcerated people → sex workers → sexual partners or people from the same household as a known HBsAg carrier → people on dialysis or transplant → HIV+ patients (frequent co-infection - same transmission routes) → patients under immunosuppression or chemotherapy (reactivation of occult infection) → pregnant women : universal 1st trimester screening recommended in Canada (SOGC 2018) → infants born to HBsAg+ mothers → prophylaxis within 12h → pregnancy: all pregnant women → if HBsAg+ → HBV-DNA in 3rd trimester → if HBV-DNA >200,000 IU/mL → tenofovir from 28-32 SA to prevent perinatal transmission → infant: HBIG + vaccine within 12h of life; modes of transmission: perinatal (vertical): mother-to-child transmission most important in high endemic countries → without prevention → 90 % of infants born to HBeAg+ mothers develop chronic infection → 25-40 % of HBsAg+ / HBeAg- mothers → lower transmission but possible → prevention: HBIG (0.5 mL IM within 12h) + HBV vaccine (within 12h) → efficacy 85-95 % → reduction to 200,000 IU/mL → add TDF from 28-32 SA (Pan 2016 - NEJM) → sexual : unprotected intercourse → risk per act: 5-30 % → risk × 50-100 vs HIV → condom + vaccination → percutaneous / blood: sharing injection equipment + non-sterile tattoos and piercings + transfusions + transplants + healthcare professional (AES - accident d'exposition au sang) → HBV resists in the environment 7 days at room temperature → resistant to most common disinfectants → inactivated by hypochlorite + glutaraldehyde + heat (121°C); HBV vaccination: composition: recombinant vaccine (HBsAg produced by S. cerevisiae) → standard adult schedule: 3 doses (M0 + M1 + M6) → accelerated schedule: 3 doses in 3 weeks + booster at M12 (Engerix-B) → Twinrix (HAV + HBV): M0 + M1 + M6 → efficacy: anti-HBs ≥10 IU/L after 3 doses: 95 % in young adults + 70-90 % in >40 year olds + 50-60 % in >60 year olds + insufficient response (<10 IU/L) after full regimen → non-responders → double dose × 3 + anti-HBs test → if still negative → consider susceptible → duration of protection: anti-HBs declines over time but immunological memory persists + booster not recommended in immunocompetent general population → booster indication: dialysis patients + immunocompromised (check titer annually) → healthcare professional: check anti-HBs post-vaccination + if <10 IU/L → complete + universal infant vaccination in Canada (Programme québécois d'immunisation - PIQ): 2nd month + 4th month + 12th month → objective: global elimination of HBV by 2030 (WHO - global strategy 2016-2021); post-exposure prophylaxis (AES or unprotected exposure in a non-immune): HBIG 0.06 mL/kg IM within 24h (if available within 7 days) + start HBV vaccination → HBIG efficacy within 24h: 75 % risk reduction | Fundamental data on vaccination and prevention: WHO 2019: 296 million chronic HBV carriers worldwide → 820,000 deaths/year → universal infant vaccination = most effective strategy → Pan 2016 - NEJM (n=200 HBsAg+/HBeAg+ + high HBV-DNA pregnant women): TDF from 28 SA → transmission rate at 28 weeks of life: 0 % vs 7 % placebo → safe TDF during pregnancy → worldwide standard of care for high HBV-DNA mothers + SOGC 2018: universal screening pregnancy + management of HBsAg+ mothers in Canada + Hollinger 2003 - Journal of Hepatology: HBIG + vaccine within 12h → efficacy 85-95 % → reduced risk of perinatal transmission → Chen 2006 - Gastroenterology: genotype C → higher HCC risk than genotype B (HR 2.3) → involvement of genotyping in risk stratification + Lavanchy 2012 - Journal of Viral Hepatitis: impact of universal vaccination in Asia → 90 % reduction in HBsAg prevalence in children → Taiwan: first country to introduce universal vaccination (1984) → reduction in pediatric HCC of 75 % in 20 years (Chang 1997 - NEJM) |
| Hepatocellular carcinoma risk and monitoring CHC - cirrhosis - PAGE-B score - CU-HCC score - biannual ultrasound - AFP - REVEAL-HBV - screening |
HCC risk in chronic hepatitis B - epidemiology and risk factors: HBV is responsible for 50-55 % of HCC worldwide (GLOBOCAN 2020) → HCC can occur even without cirrhosis in hepatitis B (only in HBV among viral hepatitis - HCV requires cirrhosis) → annual HCC risk: inactive carrier (low viral load): 0.1-0.2 % per year → chronic hepatitis without cirrhosis: 0.5-1 % per year → compensated cirrhosis: 3-8 % per year → decompensated cirrhosis: 15-20 % per year → REVEAL-HBV Study (Chen 2006 - NEJM): prospective cohort of 3,653 patients + Taiwan → HBV-DNA >10⁶ copies/mL → HCC risk × 6 vs HBV-DNA 40 + male + persistent HBV-DNA + family history of HCC + genotype C + elevated ALAT → AASLD 2018: surveillance recommended if HCC risk >0.2 % per year → modalities: liver ultrasound + ± AFP (alpha-fetoprotein) every 6 months → Singal 2012 - Alimentary Pharmacology and Therapeutics: meta-analysis → biannual ultrasound → sensitivity 47-70 % for early HCC + combined with AFP → sensitivity 63-74 % → AFP alone insufficient → liver CT or MRI if nodule detected on ultrasound → LI-RADS (Liver Imaging Reporting and Data System) criteria for nodule characterization → AFP: >400 ng/mL → highly suggestive of HCC (specificity 99 % but sensitivity 20-30 % only) → AFP-L3 (lectin-bound fraction) + PIVKA-II (Protein Induced by Vitamin K Absence - des-carboxy-prothrombin): emerging complementary biomarkers → approved in Japan and the USA for HCC surveillance | Key data on HCC risk and surveillance: REVEAL-HBV 2006 - NEJM (Chen): HBV-DNA ≥ 10⁶ copies/mL → HCC RR = 6.1 (CI 95 % 2.4-15.6) → continuous dose-response relationship → basis for viral suppression as HCC prevention + Yang 2002 - NEJM (REVEAL-HBV cohort): high HBV-DNA → RR cirrhosis = 5.9 → same dose-response relationship → Papatheodoridis 2016 - Journal of Hepatology: PAGE-B score → predicts HCC risk under tenofovir or entecavir → validated in Europe + Asia → AUC 0.82 → Chang 1997 - NEJM: universal infant vaccination Taiwan → pediatric HCC reduction of 54 % at 14 years → evidence that vaccination prevents HCC + Singal 2012 - Aliment Pharmacol Ther: meta-analysis HCC surveillance → biannual ultrasound ± AFP → prolonged survival → NNS (number needed to screen) to prevent 1 death: 119 over 5 years + Llovet 2018 - Nature Reviews Disease Primers: HCC → comprehensive review + treatment options according to stage → BCLC (Barcelona Clinic Liver Cancer) staging system → curative treatment (resection + ablation + transplantation) if early stage → sorafenib + lenvatinib + atezolizumab + bevacizumab if advanced |
| Antiviral treatment of chronic hepatitis B Tenofovir - entecavir - pegylated interferon - indications - resistance - treatment discontinuation - functional recovery |
Indications for antiviral treatment (AASLD 2018 + EASL 2017 + CASL 2018): treatment recommended if any of the following conditions are met: HBV-DNA >2,000 IU/mL + ALT >1× upper limit of normal (ULN) + significant fibrosis (≥F2 at Metavir or elastometry ≥7-8 kPa) → compensated or decompensated cirrhosis + detectable HBV-DNA (at any level) → fulminant hepatitis + severe hepatic flare (ALT >10× ULN + signs of liver failure) → planned immunosuppression or chemotherapy (reactivation) → pregnant woman with HBV-DNA.HBV >200,000 IU/mL (prevention of perinatal transmission) → liver transplant → HCC → inactive carriers (HBDNA 40 years according to AASLD 2018 + significant fibrosis → nucleos(t)idic analogues (NUC) - 1st-line treatment: tenofovir disoproxil fumarate (TDF - Viread) 300 mg/d: high efficacy + very high genetic barrier to resistance (no proven cases of resistance in 15 years of use) → adverse effects: tubular nephrotoxicity (Fanconi syndrome) + reduced bone density (osteopenia + osteoporosis) → renal + bone monitoring → avoid if GFR <30 mL/min → Marcellin 2008 - NEJM (study 103/102): TDF → viral suppression (HBV-DNA undetectable) at 1 year: 76 % HBeAg+ + 93 % HBeAg- + no resistance over 8 years → tenofovir alafenamide (TAF - Vemlidy) 25 mg/d : bioequivalent to TDF in efficacy + better bone and renal profile → preferred if GFR <60 mL/min + in patients with bone or renal risk factors → not superior to TDF on viral suppression → Agarwal 2018 - Gastroenterology: TAF not inferior to TDF + better bone and renal profile → entecavir (ETV - Baraclude) 0.5 mg/d (naive) or 1 mg/d (lamivudine-refractory): high genetic barrier to resistance + very well tolerated + no bone or renal effects → Lai 2006 - NEJM: ETV vs lamivudine → viral suppression 67 % vs 36 % at 1 year + less resistance → preferred in patients with severe CKD (dose adjustment according to GFR) → lamivudine + adefovir + telbivudine: low genetic barrier → frequent resistance → abandoned as 1st-line therapy; pegylated interferon alpha-2a (PEG-IFN - Pegasys): immunomodulatory mechanism (not pure antiviral) → advantage: fixed duration of treatment (48 weeks) + higher HBsAg seroconversion rate than with NUC (4-10 % vs <1 %/year) → disadvantages: numerous adverse effects (flu-like syndrome + thrombocytopenia + leukopenia + depression + autoimmunity + thyroiditis) → contraindications: decompensated cirrhosis + psychiatric + autoimmune diseases + pregnancy → Marcellin 2004 - NEJM : PEG-IFN α-2a × 48 sem → HBeAg seroconversion 32 % vs 19 % lamivudine + HBsAg seroconversion 3 % → durable post-treatment response → EASL 2017: PEG-IFN to be preferred in young HBeAg+ patients without cirrhosis with genotype A + high ALT + moderate HBV-DNA + low qHBsAg → predictive of better response; antiviral resistances: lamivudine: resistance in 70 % at 4 years → TDF and ETV: virtually nil (<1 % in 10 years) → if NUC resistance documented → switch to TDF (if ETV resistant) or ETV (if TDF resistant - rare) → never sequential monotherapy with low genetic barrier agents (adds up resistance); NUC treatment discontinuation: controversial → EASL 2017: discontinuation possible after: HBsAg seroconversion (HBsAg loss + anti-HBs positive) → or HBeAg seroconversion confirmed for ≥12 months + HBV-DNA undetectable + ALAT normal + before any discontinuation decision → liver fibrosen assessed (elastometry) → risk of viral rebound + severe post-stoppage flare + risk of decompensation → hepatological opinion mandatory before discontinuation; functional cure - emerging goal: loss of HBsAg + ± appearance of anti-HBs → spontaneous rate under NUC: 1-3 % per year → new strategies under development: siRNA (RNA interference - inhibition of viral transcription) + capsid assembly modulators (CAM) + anti-cccDNA + NUC + PEG-IFN combinations → phase 2-3 trials underway | Fundamental treatment data: Marcellin 2008 - NEJM (studies 103 and 102): TDF × 1 year → viral suppression >90 % HBeAg- + 76 % HBeAg+ → no resistance at 8 years → histological improvement → founding reference for TDF → Lai 2006 - NEJM: ETV vs lamivudine → superior viral suppression + near-zero resistance → ETV = 2nd 1st-line agent → Agarwal 2018 - Gastroenterology: TAF not inferior to TDF + superior bone and renal profile → validation of TAF → Marcellin 2004 - NEJM: PEG-IFN α-2a → HBeAg 32 seroconversion % → reference for IFN in hepatitis B + Terrault 2018 - Hepatology (AASLD HBV Guidelines): North American reference recommendations → EASL 2017 Clinical Practice Guidelines: European reference → CASL 2018: Canadian recommendations → Papatheodoridis 2015 - Gastroenterology: tenofovir × 5 years → regression of cirrhosis in 71 % of cases + disappearance of cirrhosis in 28 % of cases (Metavir score) → histological demonstration of reversibility of fibrosis under TDF + Yang 2016 - NEJM (meta-analysis): antiviral treatment → reduction of HCC risk by 39 % + reduction of liver mortality by 34 % → efficacy of viral suppression in preventing complications |
| Hepatitis B reactivation and special situations Immunosuppression - rituximab - chemo - corticoids - prophylaxis - HDV - HCV - HIV co-infection - pregnancy - CKD |
Hepatitis B reactivation - background and prevention: definition: increase in HBV-DNA ≥2 log₁₀ IU/mL above baseline + or change from undetectable to detectable HBV-DNA + or HBsAg reappearing + or ALAT flare → populations at risk of reactivation: HBsAg+ under immunosuppression: ALL patients → antiviral prophylaxis indicated + HBsAg- / anti-HBc+ (occult infection): variable risk depending on intensity of immunosuppression → very high risk (>10 %): rituximab + ofatumumab + anthracycline-based chemotherapy → prophylaxis recommended → moderate risk (1-10 %): systemic corticosteroids >4 weeks + immune checkpoint inhibitors + tyrosine kinase inhibitors → prophylaxis to be discussed → low risk (<1 %): low-dose corticoids + methotrexate + non-routine prophylaxis → Loomba 2011 - Annals of Internal Medicine: rituximab + HBsAg- / anti-HBc+ → reactivation in 24 % without prophylaxis → prophylaxis with tenofovir or entecavir → reduction to <1 % → prophylaxis of reactivation: indications and agents: ETV or TDF depending on renal profile → start 1-4 weeks before immunosuppression → continue for full duration + 6-12 months after stopping → longer duration if rituximab (12-18 months) → never start chemotherapy without checking HBsAg + anti-HBc → Huang 2013 - Hepatology: preventive antiviral prophylaxis → reduction in risk of reactivation by 87 % + Perrillo 2015 - New England Journal of Medicine: AGA (American Gastroenterological Association) recommendations → screening algorithm + prophylaxis according to reactivation risk; HBV + VHD (hepatitis D virus) co-infection: VHD = satellite virus → requires HBsAg for replication → simultaneous co-infection (acute) → 1-5 % of chronicity only → superinfection (VHD on chronic HBV) → 70-80 % of chronicity → acceleration of cirrhosis + high risk of HCC + Rizzetto 1980 - Gut: discovery of VHD → the only effective treatment for chronic hepatitis D until 2020: PEG-IFN (48-72 weeks - response 25-30 %) → Bulevirtide (Hepcludex) 2 mg SC/d: new treatment approved by EMA (2020) + FDA (2023) → inhibitor of HDV and HBV entry into hepatocytes (inhibits NTCP receptor) → Wedemeyer 2023 - NEJM (MYR204 trial): bulevirtide 2 mg + PEG-IFN → VHD viral suppression + ALAT normalization in 72 % + bulevirtide ± PEG-IFN = reference treatment for chronic VHD + HBV + HIV co-infection: prevalence 5-10 % of HIV+ patients → TDF + (FTC or 3TC) active on both viruses → include TDF + FTC (Truvada) or TAF + FTC in ARV regimen → never treat HBV alone with lamivudine (rapid resistance) + pregnancy and HBV: TDF = antiviral of choice if maternal treatment required (pregnancy category B - large safety hindsight) → HBV-DNA surveillance in 3rd trimester + HBIG + infant vaccine from birth → Pan 2016 - NEJM: maternal TDF from 28 SA → transmission rate 0 % vs 7 % placebo; hepatitis B and CKD - dose adaptation: entecavir: dose reduction according to GFR → ETV 0.05 mg/d if GFR <10 mL/min (or dialysis) → TDF: contraindicated if GFR 15 mL/min → TAF preferred in case of CKD + ETV = 2nd option → follow-up: ALT + HBV-DNA every 3 months for 1st year + then every 6-12 months if stable + qHBsAg annually if on PEG-IFN or for NUC discontinuation + renal monitoring (creatinine + phosphorus + proteinuria) if TDF + BMD monitoring if TDF + bone risk factors + liver fibrosis by elastometry (Fibroscan) annually or every 2 years depending on score + AFP + biannual liver ultrasound if cirrhosis or HCC risk factors | Fundamental data on reactivation and special situations: Loomba 2011 - Annals of Internal Medicine: rituximab + occult HBV → reactivation 24 % without prophylaxis → reduction to 0 % with ETV/TDF → demonstration that screening + prophylaxis are essential + Perrillo 2015 - NEJM: AGA Guidelines → reactivation risk stratification algorithm + prophylaxis → global standard of care → Huang 2013 - Hepatology: preventive prophylaxis → -87 % risk of reactivation → Pan 2016 - NEJM: maternal TDF → reduction of perinatal transmission from 7 % to 0 % → approved for this indication → Wedemeyer 2023 - NEJM (MYR204): bulevirtide + PEG-IFN → 72 % VHD response → new standard of care VHD → Rizzetto 1980 - Gut: discovery of VHD → Papatheodoridis 2015 - Gastroenterology: tenofovir × 5 years → regression of cirrhosis in 71 % of patients → major histological data → Yang 2016 - NEJM meta-analysis: antiviral treatment → -39 % CHC risk + -34 % liver mortality → basis for recommendation to treat to prevent HCC; post-treatment follow-up and HBsAg seroconversion: HBsAg seroconversion rate under NUC: 1-3 %/year depending on studies → Marcellin 2016 - Lancet: tenofovir × 8 years → HBsAg loss in 13 % of HBeAg+ patients → but only 1 % HBeAg- → HBsAg seroconversion remains the ultimate goal → new emerging therapies target this goal |
ℹ️
HBsAg positive for more than 6 months defines chronic hepatitis B and requires a full workup: any HBsAg-positive finding should trigger a full serological workup (HBeAg, anti-HBe, anti-HBc, HBV-DNA, qHBsAg), liver workup (ALT, ASAT, PT, albumin, CBC-platelets), fibrosis assessment (Fibroscan or biopsy) and HCC screening if indicated. Screening of contacts (partners + family) and vaccination of non-immune patients are essential. Before any immunosuppression or chemotherapy, HBsAg and anti-HBc status must be systematically checked to prevent potentially fatal reactivation.
Situations requiring urgent medical attention
Sudden jaundice + deterioration in general condition + very high ALT (>10× normal) in a known HBsAg patient or returning from a trip to an endemic area → severe acute hepatitis B or flare of chronic hepatitis → hepatological emergencies → PT + factor V + bilirubin + HBV-DNA + anti-HBc IgM → if sign of acute hepatocellular failure (PT <50 % + encephalopathy) → transfer to liver transplant center.
HBsAg-positive or anti-HBc-positive patient starting chemotherapy, rituximab treatment, long-term corticosteroid therapy or any immunosuppressant without antiviral prophylaxis → risk of severe reactivation → urgent hepatological or infectiological consultation → initiation of entecavir or tenofovir prophylaxis before the start of immunosuppression.
Newborn of an HBsAg-positive mother without vaccination or administration of HBIG within 12 hours of life → high risk of perinatal transmission → urgent pediatrics → HBIG (0.5 mL IM) + HBV vaccine within 24h → if delay exceeded but <7 days → HBIG still useful → vaccination to be completed according to schedule.
New hepatic nodule discovered on ultrasound in a patient with chronic HBV infection, cirrhosis or at risk of HCC → hepatic CT or MRI in semi-urgent emergency (within 4 weeks) → characterization according to LI-RADS criteria → hepatology or digestive oncology opinion → do not defer exploration.
Consult at Clinique Omicron
Clinique Omicron physicians prescribe hepatitis B screening for at-risk populations, interpret the complete serological work-up (HBsAg, HBeAg, anti-HBc, HBV-DNA), initiate vaccination for non-immune individuals, refer to hepatology for patients requiring antiviral treatment, and provide biological follow-up for stable chronic carriers. Consultations are available at several points of service in Quebec, as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for information purposes only and does not replace the advice of a physician or specialist in hepatology. Any positive HBsAg result requires a full work-up and structured medical follow-up.
Omicron Clinic
Need to consult a doctor?
Treatment within 24-48 hours. In-clinic or telemedicine, anywhere in Quebec.
Insurance receipts. 7j/7. No family doctor required.