Key Facts

Hepatitis B virus (HBV) infection is a major global health problem. While acute infection in adults usually resolves, chronic infection (particularly from vertical transmission) can lead to cirrhosis and hepatocellular carcinoma.

Epidemiology

An estimated 300 million people are chronically infected worldwide. UK prevalence is ~0.3% (~180,000 chronic carriers), predominantly in immigrant populations from high-endemicity countries (Sub-Saharan Africa, East/Southeast Asia). HBV is the most common cause of HCC worldwide. Universal neonatal vaccination (introduced in UK in 2017) will reduce incidence over time.

Aetiology

• Hepatitis B virus: partially double-stranded DNA virus (Hepadnaviridae family)
• Transmission: percutaneous (blood transfusion, IVDU, needlestick, tattooing), sexual, vertical (perinatal), close household contact
• NOT transmitted by: casual contact, airborne, faecal-oral, food/water

Pathophysiology

HBV infects hepatocytes and forms covalently closed circular DNA (cccDNA) in the nucleus — this is the template for viral replication and the reason HBV is difficult to eradicate. Liver damage is primarily immune-mediated: CD8+ cytotoxic T cells destroy infected hepatocytes. HBV itself is not directly cytopathic. The balance between viral replication and immune response determines outcome:

• Strong immune response: viral clearance (acute infection in adults)
• Weak/tolerant immune response: chronic infection (neonatal, immunosuppression)
• Persistent infection → chronic inflammation → fibrosis → cirrhosis → HCC

HBV integrates into host genome, directly contributing to hepatocarcinogenesis even in the absence of cirrhosis.

Acute Hepatitis B

• Incubation: 6 weeks to 6 months
• Prodrome: malaise, anorexia, nausea, myalgia
• Icteric phase: jaundice, dark urine, pale stools, RUQ pain
• Extra-hepatic: arthralgia, urticarial rash (immune complex deposition — serum sickness-like)
• ~70% subclinical; ~30% icteric; ~1% fulminant

Chronic Hepatitis B

• Often asymptomatic for years-decades
• Fatigue, RUQ discomfort
• Flares of hepatitis (raised ALT, symptoms)
• Progression to cirrhosis and decompensation

Phases of Chronic HBV

1. Immune tolerant (HBeAg+, high HBV DNA, normal ALT): minimal liver damage
2. Immune active (HBeAg+, high DNA, raised ALT): active hepatitis — treatment indicated
3. Inactive carrier (HBeAg−, anti-HBe+, low DNA <2000, normal ALT): low risk
4. HBeAg-negative chronic hepatitis (HBeAg−, fluctuating DNA/ALT): pre-core/core promoter mutants — treatment indicated

Red Flags

• Acute liver failure (encephalopathy, coagulopathy)
• Decompensated cirrhosis (ascites, variceal bleed)
• HCC (new hepatic mass, rising AFP, weight loss)
• HBV reactivation during immunosuppression (chemotherapy, anti-TNF, rituximab)

Bedside

• Risk factor assessment: country of origin, IVDU, sexual history, blood products, maternal status

Bloods

• HBV serology panel:
  • HBsAg: positive = current infection (acute or chronic); if positive >6 months = chronic
  • Anti-HBs: positive = immunity (vaccination or resolved infection); >10 mIU/mL = protective
  • Anti-HBc IgM: positive = acute infection or severe flare
  • Anti-HBc IgG: positive = ever exposed (current or past infection)
  • HBeAg: positive = high replication, high infectivity
  • Anti-HBe: positive = lower replication (seroconversion)
• HBV DNA (quantitative PCR): viral load — guides treatment and monitoring
• LFTs: ALT/AST (may be normal or raised); bilirubin, albumin, ALP
• FBC: thrombocytopaenia (cirrhosis)
• INR: synthetic function
• AFP: HCC screening
• Co-infection testing: anti-HCV, anti-HDV, anti-HIV (all recommended)
• Fibrosis assessment: FIB-4, ELF test, transient elastography (FibroScan)

Imaging

• USS abdomen: liver assessment, cirrhosis features, HCC screening
• FibroScan: liver stiffness for fibrosis staging
• CT/MRI with contrast: if HCC suspected

Special Tests

• Liver biopsy: if diagnostic uncertainty or to stage disease when non-invasive tests discordant; Ishak/METAVIR scoring
• HBV genotyping: A-H; influences treatment response to interferon (genotype A best response)
• HBV resistance testing: if treatment failure

Non-pharmacological

• Avoid/minimise alcohol: even moderate intake accelerates fibrosis
• Vaccination of contacts: sexual partners, household members, newborns of HBsAg+ mothers
• Barrier contraception: until partner vaccinated and anti-HBs >10
• Avoid sharing razors/toothbrushes: blood-borne transmission risk
• HCC surveillance: USS ± AFP every 6 months in all cirrhotics and high-risk non-cirrhotic groups
• Notify PHE: acute HBV is notifiable

Pharmacological

• Acute HBV: usually supportive; antivirals only if fulminant/severe (entecavir)
• Chronic HBV — treatment indications (NICE): HBV DNA >2000 IU/mL with raised ALT and/or significant fibrosis (≥F2)
• First-line nucleos(t)ide analogues (NAs):
  • Tenofovir disoproxil 245 mg OD (high barrier to resistance; monitor renal function and bone density)
  • Tenofovir alafenamide 25 mg OD (improved renal/bone safety profile)
  • Entecavir 0.5 mg OD (alternative first-line; high barrier to resistance)
  • Treatment is usually long-term/indefinite (suppressive, not curative)
• Pegylated interferon-alfa 2a: 180 mcg SC weekly for 48 weeks — finite course; may achieve HBeAg seroconversion or even HBsAg loss in selected patients (genotype A, high ALT, low DNA); significant side effects (flu-like, depression, cytopaenias)
• Pregnancy: tenofovir disoproxil in third trimester (if maternal DNA >200,000 IU/mL) to reduce vertical transmission; + neonatal HBV vaccine + HBIG within 12 hours of birth
• Immunosuppression/chemotherapy: screen all patients for HBsAg/anti-HBc before rituximab, anti-TNF, chemotherapy; prophylactic antivirals to prevent reactivation

Surgical/Interventional

• Liver transplantation: for decompensated HBV cirrhosis or HCC meeting criteria; post-transplant HBIG + antivirals prevent recurrence

Referral Criteria

• Hepatology referral: all chronic HBV for assessment and monitoring
• Specialist assessment for treatment: elevated ALT + DNA >2000 IU/mL, significant fibrosis, cirrhosis
• Liver transplant assessment: decompensated cirrhosis, HCC
• Antenatal screening: all pregnant women tested for HBsAg

Acute HBV in adults: >95% clear the virus spontaneously; <1% develop fulminant hepatitis. Chronic HBV: 15-40% lifetime risk of cirrhosis, HCC, or liver failure. Annual HCC risk: 0.5% in non-cirrhotic chronic HBV, 2-5% in HBV cirrhosis. HBsAg seroconversion (functional cure) occurs spontaneously in ~1% per year of chronic carriers; higher with interferon treatment. Antiviral therapy reduces but does not eliminate HCC risk. With effective viral suppression, fibrosis regression and improved survival are well-documented.

HBV Serology Interpretation

HBV Prevention