Hepatitis B virus

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Background

Microbiology

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

Investigations

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

References

  1. ^  Mustafa Sunbul. Hepatitis B virus genotypes: Global distribution and clinical importance. World Journal of Gastroenterology. 2014;20(18):5427. doi:10.3748/wjg.v20.i18.5427.