Hepatitis B virus

Background

Microbiology

• Reverse-transcription double-stranded DNA (RT-dsDNA) virus
• Genotypes A through J vary in geographic distribution and clinical severity

Clinical Presentation

Acute

• 75% are asymptomatic
• Symptoms range from self-resolving jaundice to fulminant liver failure in about 5%

Investigations

• Hepatitis B serology

Management

Acute

• Supportive care

Chronic

• HBsAg present ≥6 months
• HBV-DNA is variable
• Can be HBeAg positive or negative, with generally higher HBV DNA levels in HBeAg-positive patients
• ALT can be normal or elevated
• Liver boipsy shows chronic hepatitis and variable necroinflammation or fibrosis

Immune-active

• HBsAg present ≥6 months and HBeAg either positive or negative
• Intermittently or persistently elevated ALT and AST

Indications for treatment

• ALT ≥2x ULN or evidence of significant histologic disease, AND
• Elevated HBV DNA
  • > 2000 IU/mL if HBeAg negative
  • > 20,000 IU/mL if HBeAg positive

Immune-tolerant

• HBsAg present for ≥6 months and HBeAg positive
• HBV DNA typically over 1 million
• Normal or minimally-elevated ALT and AST
• That is, high viral load but normal ALT

Indications for treatment

• Adults >40 years, AND
• ALT rises above 2x ULN (i.e. becomes immune-active), OR
• Liver biopsy showing significant necroinflammation or fibrosis

Surveillance

• Monitor at 3 to 6 month intervals, more frequently as ALT levels rise, consider treatment if >2x ULN/

Treatment Regimens

• One of pegylated-interferon (48 weeks), tenofovir (until 12 months post-HBeAg conversion), or entecavir (until 12 months post-HBeAg conversion)
  • Peg-IFN contraindicated in autoimmune disorders, uncontrolled psychiatric disease, cyptopenia, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis
  • Peg-IFN preferred in lamivudine resistance
  • Tenofovir is safe in pregnancy
• Duration depends on what stage is being treated
  • HBeAg positive and HBV DNA >20,000 and ALT >2 ULN
    • Peg-IFN for 48 weeks
    • Tenofovir or entecavir for at least 12 months after HBeAg seroconversion (Ag to Ab)
  • HBeAg negative and HBV DNA > 2000 and ALT >2x ULN (or biopsy shows necroinflammation or fibrosis, or non-invasive testing shows fibrosis)
    • Peg-IGN for 1 year
    • Tenofovir or entecavir for many years, possibly indefinitely
• Continue HCC surveillance regardless of treatment

Inactive chronic hepatitis B

• Defined by HBeAg-negative, anti-HBeAb-positive, normal ALT, and HBV DNA <2000 IU/mL
• Monitor ALT q3mo for 1 year, then q6-12mo
• If ALT rises, check HBV-DNA and HBsAg for activity

HCC screening

• Screen if HBsAg-positive with cirrhosis, or HBsAg-positive at higher risk (Asian men >40yrs, black men >40yrs, Asian women >50yrs, family history, HDV coinfection)
• First-line is ultrasound every 6 months
• Second-line is AFP levels every 6 months

Prophylaxis in Immunosuppression

• Concern especially with chronic steroids and rituximab
• Can have the following effects
  • Asymptomatic HBV DNA and ALT
  • Hepatic failure
  • Death
• If ≥7.5mg/d should be screened
  • HBsAg +/- HBcAb if they're adding a second agent (rituximab, TNF-alpha inhibitors, or other)
  • Refer to Hepatology or Infectious Diseases
• Prophylaxis with lamivudine until 6 months after chemotherapy

Further Reading

• Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance
• Hepatitis B virus genotypes: Global distribution and clinical importance. World J Gastroenterol. 2014;20(18):5427–5434. doi: 10.3748/wjg.v20.i18.5427