Hepatitis B

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Hepatitis B virus is an enveloped DNA virus that replicates through an RNA intermediate. Exposure can lead to transient acute infection, fulminant hepatitis, chronic infection or clinically silent resolution. Age at acquisition strongly influences persistence: perinatal infection becomes chronic far more often than adult-acquired infection.

The marker panel is a timeline rather than a collection of isolated positives. Surface antigen identifies current infection, core antibody proves natural exposure, surface antibody indicates immunity, e antigen broadly reflects active replication and HBV DNA measures viral replication directly. Treatment decisions cannot be made from ALT or HBeAg alone.

The infectious-disease emphasis is recognition, marker interpretation, transmission prevention, exposure management and reactivation risk. Detailed fibrosis staging, long-term antiviral selection, cirrhosis care and hepatocellular-carcinoma surveillance remain coordinated through hepatology.

HBV is vaccine preventable. Effective control combines universal childhood immunisation, targeted vaccination, safer blood and equipment practice, rapid post-exposure assessment, maternal viral suppression when indicated and immediate neonatal immunoprophylaxis.

Key points

HBV spreads through infected blood and body fluids by perinatal, sexual, injecting, needlestick and inadequately sterilised equipment exposure.
HBsAg indicates current infection; anti-HBc indicates natural exposure; anti-HBs alone usually indicates vaccine-derived immunity.
IgM anti-HBc supports recent acute infection but may reappear during a severe chronic flare, so interpret the whole marker pattern and clinical timeline.
Persistence of HBsAg for at least six months defines chronic infection; HBV DNA quantifies replication and informs infectivity and treatment.
First assess INR, glucose, cognition and renal function in acute jaundice, then arrange urgent liver-centre care for failure features.
Chronic treatment is specialist selected from HBV DNA, ALT, fibrosis, cirrhosis, pregnancy, renal or bone health, coinfection and future immunosuppression.
Tenofovir disoproxil 245 mg orally once daily or entecavir 0.5 mg orally once daily are established high-barrier options in suitable adults.
Vaccinate susceptible contacts, apply current UKHSA post-exposure criteria and ensure exposed infants receive the complete national perinatal schedule and follow-up testing.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Perinatal acquisition

Maternal viraemia exposes the infant around birth, and immature immune responses make chronic infection particularly likely without prompt immunoprophylaxis.

Sexual transmission

Infected blood, semen and genital secretions cross mucosa during sexual contact, with risk increasing alongside viral load and tissue trauma.

Blood exposure

Shared injecting equipment, needlestick injuries and inadequately sterilised tattoo, piercing or medical equipment can directly inoculate infectious blood.

Household contact

Shared razors or toothbrushes and contact between infected blood and broken skin can transmit HBV, whereas ordinary social contact does not.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Nuclear viral template
Relaxed circular viral DNA enters hepatocyte nuclei and forms stable covalently closed circular DNA that sustains lifelong reactivation potential.
2
Reverse transcription
Pregenomic RNA is reverse transcribed inside viral capsids, explaining why nucleos(t)ide analogues suppress replication without reliably eradicating infection.
3
Immune-mediated injury
Cytotoxic responses against infected hepatocytes create ALT elevation and necroinflammation; weak responses permit persistence while vigorous responses may cause severe hepatitis.
4
Fibrosis and oncogenesis
Repeated inflammation drives fibrotic remodelling, while viral integration and regenerative stress increase hepatocellular-carcinoma risk even without established cirrhosis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Acute hepatitis syndrome

Anorexia, nausea, fever, arthralgia, right-upper-quadrant discomfort, dark urine and jaundice follow an incubation of weeks to months.

Serum-sickness prodrome

Rash, fever and polyarthralgia can precede jaundice through circulating immune-complex deposition during acute HBV.

Silent chronic infection

Many people have normal examination and few symptoms despite replicating virus, progressive fibrosis and transmission potential.

Cirrhotic decompensationRed flag

Ascites, variceal bleeding, encephalopathy, jaundice or sarcopenia indicates advanced chronic liver disease requiring urgent specialist care.

Extrahepatic immune disease

Polyarteritis nodosa, glomerulonephritis, rash and arthralgia can reflect HBV immune-complex disease rather than direct hepatic injury alone.

Reactivation phenotypeRed flag

A sudden HBV DNA rise and ALT flare during or after immune suppression can progress to jaundice and liver failure.

Red flags requiring action

Confusion, drowsiness, asterixis, spontaneous bleeding, hypoglycaemia or rising INR requires emergency liver-failure management rather than routine outpatient referral.
A pregnant person who is HBsAg positive needs prompt specialist viral-load assessment and a documented maternal and neonatal prevention plan before delivery.
A baby born to an HBsAg-positive mother requires hepatitis B vaccine within 24 hours and HBIG when current national criteria are met.
Immunosuppression, chemotherapy or B-cell-depleting therapy can reactivate resolved or chronic HBV and should never begin without HBV marker review and a prevention plan.
New jaundice or ALT flare in chronic HBV may represent immune-active disease, resistance, non-adherence, drug injury or hepatitis D superinfection.
Occupational, sexual or household blood exposure requires same-day risk assessment because vaccine and HBIG effectiveness is time dependent.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
HBsAgFirst step
Why
Identify current hepatitis B infection in screening or diagnostic assessment.
Interpretation and limitations
Reactive HBsAg requires confirmation and clinical staging; persistence for at least six months supports chronic infection, while recent acquisition may be acute.
02
Total and IgM anti-HBc
Why
Distinguish natural exposure and support recent infection.
Interpretation and limitations
Total anti-HBc remains after natural infection but is absent after vaccination alone; IgM supports acute infection yet can be positive during severe chronic reactivation.
03
Anti-HBs
Why
Assess immunity after vaccination or resolved natural infection.
Interpretation and limitations
Anti-HBs alone usually reflects vaccination; anti-HBs with anti-HBc indicates resolved infection, although reactivation remains possible during profound immunosuppression.
04
HBeAg and anti-HBe
Why
Characterise the replicative phase alongside HBV DNA.
Interpretation and limitations
HBeAg often accompanies high replication, but precore variants replicate without it; neither marker substitutes for quantitative HBV DNA.
05
Quantitative HBV DNA
Why
Measure viraemia for infectivity, phase classification, pregnancy planning and treatment monitoring.
Interpretation and limitations
Interpret viral load with ALT, fibrosis and host context; an undetectable value on treatment means suppression, not eradication of intrahepatic viral templates.
06
Liver severity and fibrosis assessment
Why
Determine current injury, synthetic function and chronic structural damage.
Interpretation and limitations
Check ALT, bilirubin, albumin, INR, FBC and renal function, then use elastography or validated non-invasive assessment; cirrhosis changes treatment and surveillance thresholds.
07
Coinfection and baseline screen
Why
Find conditions that alter natural history or drug choice.
Interpretation and limitations
Test for HIV, HCV and hepatitis D as indicated, assess HAV immunity, pregnancy, renal and bone health, and obtain ultrasound when advanced disease or focal pathology is possible.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Other acute hepatitis

HAV, HEV, HCV, EBV, CMV and drug injury can reproduce the same jaundice and hepatitic enzyme pattern without HBV markers.

Resolved HBV

Anti-HBc with anti-HBs and absent HBsAg usually marks past infection, although occult persistence matters before immune suppression.

Vaccine immunity

Isolated anti-HBs after a documented course represents immunisation and should not be misreported as previous infectious hepatitis.

Occult infection

Very low-level HBV DNA can persist with negative HBsAg, particularly during immune suppression or when isolated anti-HBc is present.

Hepatitis D

HDV requires HBsAg and may present as severe coinfection or a sudden flare in established chronic hepatitis B.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01PATTERNRead the marker combinationFirst stepOne or more hepatitis B markers are reported as reactive or equivocal.

1Confirm which markers were actually measured, the date of exposure or previous results, vaccination history, symptoms and immune-suppression status.
2Use HBsAg to identify current infection, anti-HBc for natural exposure and anti-HBs for immunity rather than interpreting any single result in isolation.
3Add IgM anti-HBc when acute disease is possible and quantitative HBV DNA when infection, reactivation, pregnancy or treatment assessment requires replication data.
4Discuss discordant or isolated anti-HBc patterns with virology because resolved infection, occult infection, window-period disease and false reactivity require different action.

02ACUTEManage newly acquired hepatitisRecent HBV is supported by symptoms, serology or a documented new HBsAg result.

1EscalationAssess cognition, glucose, INR, bilirubin, renal function and haemodynamic state immediately, with liver-centre escalation for any failure feature.
2Provide hydration and symptom control, avoid alcohol and non-essential hepatotoxic medicines, and notify acute infectious hepatitis through the correct route.
3Seek specialist antiviral advice for fulminant, severe or protracted acute hepatitis rather than treating every uncomplicated adult infection routinely.
4Repeat HBsAg and clinical markers to document resolution or progression to chronic infection, while protecting and testing contacts.

03CHRONICStage and suppress when indicatedHBsAg persists or previous records establish chronic hepatitis B.

1Refer for HBV DNA, ALT trend, fibrosis or cirrhosis assessment, ultrasound context, coinfection testing and evaluation of renal, bone and reproductive factors.
2Treat active hepatitis, cirrhosis with detectable virus and other guideline-defined risk states using a high-barrier regimen selected by hepatology.
3Check adherence, renal function, ALT and HBV DNA after initiation, recognising that suppression prevents complications but rarely eliminates covalently closed circular DNA.
4Continue cirrhosis and hepatocellular-carcinoma surveillance according to hepatology criteria even when HBV DNA becomes undetectable.

04EXPOSUREPrevent infection after contactA needlestick, mucosal blood exposure, sexual contact or household blood contact with possible HBV occurs.

1Wash or irrigate the exposed site, document the route and time, and obtain source HBsAg plus exposed-person vaccination and anti-HBs records where lawful and feasible.
2Contact occupational health, sexual health or health protection the same day so current Green Book vaccine and HBIG criteria can be applied without delay.
3Begin or complete an age-appropriate vaccine course and give HBIG when the source, exposure and immunity matrix indicates it; do not await late serology unnecessarily.
4Arrange follow-up testing for HBV and other blood-borne viruses, and give risk-reduction advice while the outcome remains uncertain.

05PERINATALBlock mother-to-child transmissionHBsAg is detected during pregnancy or maternal infection is already known.

1Refer during pregnancy for HBV DNA, HBeAg, liver status and a specialist decision on maternal tenofovir prophylaxis according to the current viral-load pathway.
2Place a written neonatal plan in maternity records, secure vaccine and HBIG when indicated, and communicate responsibility across obstetric, neonatal and primary-care teams.
3Give the newborn monovalent hepatitis B vaccine within 24 hours of birth and HBIG at a separate site when national criteria are fulfilled.
4Complete every dose in the national infant schedule and perform the specified post-course infection and response testing; a birth dose alone is not adequate.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

A first-line high-barrier nucleotide therapy for active chronic infection, cirrhosis, selected pregnancy prevention and some reactivation-prevention pathways.

Tenofovir disoproxil fumarate

Give 245 mg orally once daily for chronic HBV when selected by a specialist; duration is usually long term and stopping requires a defined virological and clinical plan.

Check eGFR, phosphate, urinalysis and bone risk; adjust or choose an alternative in renal impairment, review nephrotoxic drugs and never stop abruptly in HBV/HIV coinfection.

A first-line high-barrier nucleoside alternative when tenofovir is unsuitable and resistance history permits effective use.

Entecavir

Give 0.5 mg orally once daily on an empty stomach in nucleoside-naive compensated disease; use the specialist 1 mg regimen for defined lamivudine resistance or decompensation.

Adjust for renal impairment, exclude untreated HIV because monotherapy can select HIV resistance, review previous lamivudine exposure and avoid unplanned withdrawal.

Finite immune-modulating option for selected compensated chronic HBV with favourable viral and host characteristics.

Peginterferon alfa-2a

Give 180 micrograms subcutaneously once weekly for 48 weeks only in carefully selected adults under specialist monitoring.

Contraindicated in decompensated liver disease and pregnancy; assess psychiatric, autoimmune, thyroid and haematological risk and monitor FBC, liver and thyroid tests.

Active and, when required, passive immunoprophylaxis after occupational, sexual, household or perinatal exposure.

Hepatitis B vaccine and HBIG after exposure

Start or boost the age-appropriate intramuscular vaccine course immediately and add the exact weight- or product-based HBIG dose only when the current UKHSA exposure matrix indicates it.

Give vaccine and HBIG at separate sites, document product and batch, complete the full schedule and check response in groups for whom post-vaccination serology is recommended.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Fulminant liver failure

Massive immune-mediated hepatocyte loss causes encephalopathy, coagulopathy, cerebral oedema, hypoglycaemia and multiorgan failure during acute or reactivated infection.

Cirrhosis

Persistent necroinflammation produces bridging fibrosis, portal hypertension, ascites, varices, encephalopathy and progressive loss of functional hepatic reserve.

Hepatocellular carcinoma

Chronic HBV increases primary liver-cancer risk through inflammation and viral integration, including in some people without cirrhosis.

Immune-complex disease

Circulating antigen-antibody complexes cause polyarteritis nodosa, glomerulonephritis, rash, arthralgia and clinically important neurological, vascular or renal injury.

Antiviral resistance

Incomplete suppression or low-barrier historical regimens select polymerase mutations, causing rebound and restricting effective future combinations.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Untreated chronic HBV needs specialist-defined serial ALT, HBV DNA and fibrosis review because phase and treatment eligibility can change over time.
During tenofovir disoproxil, monitor renal function, phosphate or tubular markers when indicated and reassess bone risk in susceptible patients.
During entecavir, follow renal function, adherence, ALT and HBV DNA, and investigate virological rebound for missed doses or resistance.
After any planned antiviral cessation, use close ALT and HBV DNA surveillance because severe relapse and hepatic decompensation can occur.
Cirrhosis and other qualifying risk groups require hepatocellular-carcinoma surveillance even during complete virological suppression.
Confirm that contacts and exposed infants complete vaccination and scheduled serology; recording a first dose is not the same as preventing infection.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Core antibody means exposure

Vaccines contain surface antigen, so anti-HBc demonstrates natural infection at some point rather than vaccine response.

Window period exists

After HBsAg disappears and before anti-HBs develops, IgM anti-HBc may be the principal marker of recent infection.

HBeAg is not viral load

Precore variants can replicate with negative HBeAg, making quantitative HBV DNA necessary for accurate activity assessment.

Suppression is not cure

Nucleos(t)ide therapy blocks replication but persistent intrahepatic templates permit rebound when effective treatment is withdrawn.

Resolved infection can reactivate

HBsAg-negative, anti-HBc-positive people remain at risk during potent immune suppression, especially B-cell-depleting treatment.

Scope boundary

Transmission, serology and exposure prevention are central here; fibrosis staging and long-term cancer surveillance remain hepatology-led.

11Common pitfallsFrequent interpretation and management errors.

01
Do not label anti-HBs alone as previous natural infection; without anti-HBc it usually represents vaccination.
02
Do not use HBeAg negativity to declare low infectivity when HBV DNA has not been measured.
03
Do not wait six months to refer a patient who already has cirrhosis, severe hepatitis, pregnancy or planned immunosuppression.
04
Do not stop tenofovir or entecavir simply because HBV DNA is undetectable; withdrawal can cause a dangerous flare.
05
Do not forget hepatitis D testing in severe, rapidly progressive or epidemiologically compatible HBV disease.
06
Do not discharge an exposed newborn after the birth dose without ownership of the complete vaccine and follow-up testing schedule.