Chronic Hepatitis B Infection

Aka: Chronic Hepatitis B Infection, Chronic Hepatitis B

1. See Also
   1. Viral Hepatitis
   2. Hepatitis B
   3. Chronic Hepatitis B Carrier
2. Pathophysiology
   1. Acute Hepatitis B Infection becomes chronic in 10%
   2. Chronic Hepatitis B (HBsAg present >6 months)
      1. Chronic Hepatitis B Carrier
      2. Chronic Hepatitis B Infection
         1. High viral load
         2. Elevated Liver Function Tests (ALT or SGPT)
3. Labs
   1. HBsAg positive
   2. HBeAg positive
   3. xHBeAb negative
   4. Liver Function Tests (ALT or SGPT) elevated
   5. High viral load: HBV DNA hybridization positive
   6. Evaluation for Hepatitis B complications
      1. Serum Alpha-fetoprotein
      2. Hepatic Ultrasound
      3. Liver biopsy
4. Associated Conditions
   1. Polyarteritis Nodosa
   2. Systemic Vasculitis
   3. Glomerulonephritis
5. Evaluation: Phases of Chronic Hepatitis B Infection
   1. Active Phase
      1. ALT levels increased and HBV DNA >20,000 IU/ml
      2. Treatment should be offered
   2. Inactive Phase
      1. ALT levels normal and HBV DNA <20,000 IU/ml
      2. Treatment not indicated
      3. Recheck labs every 6-12 months to screen fro re-activation
   3. Gray-Zone Phase
      1. Discoordant ALT and HBV DNA (one increased and one normal)
      2. Liver biopsy may be required to determine if treatment is warranted
   4. Immune-Tolerant Phase
      1. HBeAg positive with ALT levels normal and HBV DNA >20,000 IU/ml
      2. Treatment not indicated
      3. Recheck labs every 6-12 months to screen fro re-activation
      4. Screen for hepatocellular cancer with serial Ultrasound and Alpha-fetoprotein (every 6-12 months) - see below
6. Management
   1. See prevention below
   2. Prevent transmission to close contacts
      1. See Chronic Hepatitis B Carrier
   3. Gastroenterology Referral
   4. Vitamin E 400 IU/day
   5. Antiviral Agents
      1. Goal of therapy
         1. Viral suppression
         2. Prevention of Hepatitis B complications
         3. Seroconversion (may lag therapy completion by 6 months)
            1. HBeAg Positive genotype A: >50% seroconversion
            2. Non-A genotype: 30% seroconversion
      2. Drug Resistance
         1. Lamivudine (Epivir)
         2. Telbivudine (Tyzeka)
      3. Indications: Active Phase of Chronic Hepatitis B (see above)
         1. HBV DNA positive and
            1. Serum ALT > twice normal or
            2. Cirrhosis (not decompensated)
         2. HBe Antigen positive
            1. Serum ALT > twice normal
         3. Moderate to severe hepatitis on liver biopsy
      4. Pegylated Interferon alfa-2A (Pegasys)
         1. First-line, preferred agent
         2. Contraindicated if HIV positive or advanced liver disease
         3. Dose 180 mcg weekly for 48 weeks (costs $33,000 per year)
         4. Highest seroconversion rate of any agent and no known resistance
         5. Poorly tolerated and incredibly expensive
      5. Oral agents: Nucleotide Reverse Transcriptase Inhibitors (nRTI)
         1. Not as effective as Peg-Interferon (until 3 years of therapy, when seroconversion rates are similar)
         2. Indications
            1. Intolerance to Peg-Interferon
            2. Peg-Interferon contraindicated (severe liver disease or HIV positive status)
            3. Active Chronic Hepatitis B in first trimester pregnancy
         3. Protocol
            1. Monitor Renal Function tests during therapy
            2. Combine more than one agent if no effect on HBV DNA levels in 6-12 months
            3. Continue agents for additional 6 months beyond seroconversion
         4. Lamivudine (Epivir-HBV)
            1. Adult Dose: 100 mg daily for at least 48 to 52 weeks
            2. Viral suppression only persists while on medication
            3. Higher risk for resistance (risk at 1 year: 24%)
         5. Adefovir dipivoxil (Hepsera)
            1. Adult dose: 10 mg daily for at least 48 weeks
            2. Hadziyannis (2003) N Engl J Med 348:800-7
            3. Marcellin (2003) N Engl J Med 348:808-16
         6. Entecavir (Baraclude)
            1. Adult dose: 0.5 mg daily for more than 48 weeks
         7. Telbivudine (Tyzeka)
            1. Adult dose: 600 mg daily for at least 52 weeks
            2. Higher risk of resistance
         8. Tenefovir (Viread)
            1. Adult dose: 300 mg daily for at least 52 weeks
7. Complications: General
   1. Cirrhosis
      1. Annual risk: 12%
   2. Mortality
      1. Lifetime risk of death: 15 to 25%
8. Complications: Hepatocellular Carcinoma (Hepatoma)
   1. Risk factors for developing hepatocellular cancer in Chronic Hepatitis B patients
      1. Men over age 45 years
      2. Cirrhosis as diagnosed by liver biopsy
      3. Family History of Hepatocellular Carcinoma
      4. Coinfection with Hepatitis CVirus or Hepatitis DVirus
      5. HBV DNA Viral Load >10,000 IU/ml
      6. HBV genotype C
      7. Tobacco abuse
      8. HBeAg positive
   2. Screening for Hepatocellular Carcinoma
      1. Indications for highest risk patients as described above
      2. Protocol: Every 6-12 months (AASLD recommendation)
         1. Hepatic Ultrasound
         2. Serum Alpha-fetoprotein
   3. References
      1. Singal (2009) Aliment Pharmacol Ther 30(1): 37-47
      2. Yang (2002) N Engl J Med 347:168-74
9. Prevention: Disease progression
   1. See Prevention of Liver Disease Progression
   2. Tobacco Cessation (decreases risk of Hepatoma)
   3. Avoid Alcohol and other liver toxins
10. References
    1. Berenguer in Feldman (2002) Sleisenger GI, p. 1285-303
    2. Dienstag (1999) N Engl J Med 341:1256-63
    3. Dienstag (2008) N Engl J Med 359(14): 1486-500
    4. Lok (2001) Hepatology 34:1225-41
    5. Malik (2000) Ann Intern Med 132:723-31
    6. Singh (2008) J Antimicrob Chemother 62(2): 224-8
    7. Wilkins (2010) Am Fam Physician 81(8): 965-72