Lucan · Conditions

Chronic hepatitis B

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Australian guidance: GESA Australian Consensus Recommendations Hep B 2022

1. Definition and epidemiology

Chronic hepatitis B (CHB) is defined by the persistence of hepatitis B surface antigen (HBsAg) in serum for more than six months following infection with hepatitis B virus (HBV). In Australia, the estimated prevalence of CHB in 2020 was approximately 0.9% of the population, representing around 230,000 people, with Aboriginal and Torres Strait Islander people and those born overseas in endemic regions disproportionately affected. Worldwide, the World Health Organization estimates 296 million people were living with CHB in 2019, with approximately 820,000 deaths annually attributable to cirrhosis and hepatocellular carcinoma (HCC).

2. Pathophysiology

HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. Following hepatocyte entry via the NTCP (sodium taurocholate cotransporting polypeptide) receptor, viral DNA is transported to the nucleus and converted to covalently closed circular DNA (cccDNA), which forms a stable episomal reservoir that persists despite antiviral therapy and drives chronic infection. The outcome of acute infection is strongly age-dependent: perinatal transmission leads to chronicity in up to 90% of cases, whereas adult-acquired infection progresses to chronicity in only 1 to 10% of individuals. This difference reflects the immature neonatal immune system failing to mount an effective cytotoxic T-lymphocyte response against infected hepatocytes. In CHB, ongoing immune-mediated hepatocyte destruction produces cycles of necroinflammation and regeneration that drive progressive hepatic fibrosis, cirrhosis and ultimately HCC, consistent with the framework described in Robbins Ch 18 Liver and Gallbladder. HBV is not directly cytopathic; liver injury is immunologically mediated. Integration of HBV DNA into the host genome, though not required for viral replication, is a key driver of hepatocarcinogenesis.

3. Clinical presentation and diagnostic criteria

Most adults with CHB are asymptomatic and unaware of their infection. Symptomatic patients may report fatigue, right upper quadrant discomfort, or features of decompensated cirrhosis such as jaundice, ascites, or variceal bleeding in advanced disease. Extrahepatic manifestations, including polyarteritis nodosa and membranous glomerulonephritis, occur via immune complex deposition. Diagnosis requires HBsAg positivity confirmed on two separate occasions at least six months apart, or HBsAg positivity with negative anti-HBc IgM (indicating chronic rather than acute infection). Chronic infection is classified into four phases based on the interplay of viral replication markers and immune activity: immune tolerant, immune active (HBeAg-positive), immune control (HBeAg-negative chronic infection), and immune escape (HBeAg-negative chronic hepatitis with ongoing viraemia).

4. Investigations and AU-specific cutoffs

Initial assessment in a confirmed HBsAg-positive patient should include the following panel, as recommended by ASHM:

  1. Serology: HBeAg and anti-HBe to determine phase of infection
  2. HBV DNA (quantitative): Medicare funds testing once per year for patients not on treatment and four times per year for those on treatment
  3. Full blood count including platelet count (thrombocytopaenia suggests portal hypertension)
  4. Liver function tests and INR
  5. Serum alpha-fetoprotein (AFP)
  6. Liver ultrasound to assess for cirrhosis and HCC
  7. Co-infection screen: hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), and HIV
  8. Renal function and serum phosphate (especially if tenofovir disoproxil fumarate is being considered)
  9. Non-invasive fibrosis assessment: APRI score (APRI 1.0 or less makes cirrhosis unlikely); FibroScan (result greater than 12.5 kPa is consistent with cirrhosis)

Phase-defining HBV DNA thresholds in AU practice: immune tolerant phase features HBV DNA greater than 10^7 IU/mL with normal ALT; immune active (HBeAg-positive) features HBV DNA greater than 20,000 IU/mL with elevated ALT (above 30 IU/L in men, above 19 IU/L in women); immune escape phase (HBeAg-negative chronic hepatitis) features HBV DNA greater than 2,000 IU/mL with elevated ALT.

5. Management

Management decisions hinge on phase of infection, degree of fibrosis, and the presence of cirrhosis. Treatment is not required in the immune tolerant or immune control phases provided HBV DNA thresholds and ALT are stable, but regular monitoring is mandatory.

Treatment is indicated in the immune active or immune escape phases, and in all patients with cirrhosis regardless of HBV DNA level. Patients with severe exacerbation, co-infection with HIV or HDV, pregnancy, immunosuppression, or confirmed HCC should be referred to a specialist. In Australia, patients requiring treatment are referred to a section 100 community prescriber or specialist for initiation of therapy.

Key principles of AU management per GESA 2022 and ASHM guidance: - Suppress viral replication to undetectable HBV DNA to reduce the risk of cirrhosis, hepatic decompensation, and HCC - Treat co-factors that accelerate fibrosis: optimise glycaemic control, reduce alcohol, address obesity - Screen and vaccinate household and sexual contacts for susceptible individuals (HBsAg, anti-HBc, anti-HBs panel) - Notify CHB to the state or territory health department as it is a notifiable disease

6. Pharmacology and AU PBS notes

First-line agents (preferred for treatment-naive patients):

Second-line agents (not preferred as monotherapy for first-line treatment):

Antiviral therapy suppresses but does not eradicate cccDNA; lifelong treatment is generally required unless durable HBeAg seroconversion or HBsAg loss is achieved.

7. Complications and monitoring

Complications: - Cirrhosis and portal hypertension (ascites, variceal haemorrhage, spontaneous bacterial peritonitis, hepatic encephalopathy) - Hepatocellular carcinoma: the single most important long-term complication, occurring even in the absence of cirrhosis in HBV - Hepatic flares (immune reactivation), which may cause acute-on-chronic liver failure - Reactivation in the context of immunosuppression or chemotherapy (screen all patients commencing immunosuppression for CHB with HBsAg and anti-HBc) - Extrahepatic manifestations: membranous glomerulonephritis, polyarteritis nodosa, cryoglobulinaemia

HCC surveillance schedule (AU, per ASHM/Cancer Council 2023):

Six-monthly liver ultrasound with or without AFP is recommended in: - All patients with established cirrhosis - Anyone aged 40 years or older with a family history of HCC (consider commencing 10 years before earliest family case) - Sub-Saharan African people aged 20 years or older - Aboriginal and Torres Strait Islander people aged 50 years or older - Aboriginal and Torres Strait Islander people aged 40 years or older with high-risk features - Asian-Pacific males aged 40 years or older - Asian-Pacific females aged 50 years or older

On-treatment monitoring schedule:

Practise this in Lucan

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.