COMMENTARY

Infectious Diseases: February 15, 2004

John Bartlett, MD

Disclosures

February 17, 2004

In This Article

Hepatitis

Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003;362:2089-2094. The authors provide a review of hepatitis B virus (HBV) based on a MEDLINE and PubMed review from 2000-03. The following summarizes this report:

Number with chronic HBV infection (global): 400 million

% of cases of liver cancer attributed to HBV (318,000 cases/year): 60%

Risk of chronicity – age at acquisition

   < 1 year: 90%
   1-5 years: 30%
   > 5 years: 2%

Prevalence of chronic HBV

   Chinese, Sub Saharan Africa – 10% to 20%
   North America, Europe, Australia: 0.2% to 0.5%

Genotypes: A-H

   A: Pandemic
   B & C: Asia
   D: Southern Europe
   E: Africa
   F: United States
   G: United States and France
   H: Central America
   Genotype: Role in treatment response is unclear (unlike in the case of hepatitis C virus [HCV])

Indications to treat

  • ALT ≥ 1.5 x upper limit of normal (ULN) + HBV DNA detectable by bDNA or hybrid capture

  • Liver biopsy optional

Treatment response

  • Seroreversion of HbeAg + undetectable HBV DNA

  • Hepatitis B e antigen (HbeAg) seronegative at baseline: undetectable DNA

  • FDA: histologic improvement

Treatment

  • Immunomodulation: Interferon meta-analysis 498 points treated 3-6 months vs 339 untreated controls.[15] (See Table 6: Outcome of Patients With HBV Treated With Interferon for 3-6 Months vs Controls.)

  • Antivirals: Nucleosides

    Lamivudine: 1-year results with 100 mg/day[16,17] -- pooled results. (See Table 7: Outcome of Patients With HBV Treated With Lamivudine or Placebo for 1 Year [Pooled Results].)

    Duration: Recommends discontinuation of 6-9 months post HBeAg seroconversion if HBeAg positive at baseline.

    Resistance: YMDD mutants -- rate is 15% to 32% at 1 year and 67% to 69% at year 5. These mutants have reduced replication capacity and show reduced DNA levels.

    2. Adefovir: 10 mg/day x 48 weeks. Initial report showed higher rates of improved histology. HBeAg seroconversion normalization of ALT and a 3-log decrease in HBV DNA with tenofovir vs placebo.[18]

    Resistance: 1.6% at 96 weeks.[19] Adefovir is active against lamivudine-resistant strains.

    3. Tenofovir: Also effective in vitro vs HBV and lamivudine-resistant mutants, but no therapeutic trial and no plans to do them.

    4. Emtricitabine: Also effective in vitro, but not active against lamivudine-resistant strains.

    5. Entecavir and telbuvidine: phase 2

Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet. 2003;362:2095-2100. This is a review of hepatitis C virus (HCV) using the same techniques by the same authors as in the review of hepatitis B. The following summarizes this report:

Number with chronic HCV infection: 170 million (global)

Risk: Primarily injection drug use

Sequelae: Cirrhosis due to fibrosis progression at a median of 30 years. Factors associated with increased rates of progression: duration infection, age, male sex, alcohol consumption, HIV coinfection, low CD4+ cell count.

Extrahepatic manifestations: 74% have at least 1 symptom

  • Rheumatic: arthralgias, myalgias, paresthesia

  • Mucocutaneous: pruritus, sicca syndrome, Raynaud's phenomenon

  • Most common symptoms in rank order: fatigue, arthralgia, paresthesia, myalgia, pruritus, sicca syndrome

  • Abnormal labs in >5%: cryoglobulin, antinuclear antibody (ANA), antibodies to smooth muscle, low thyroxine

Genotype: influence on response to therapy

Interferon response of 88%: type 2, 3
   Interferon response of 48%: type 1, 4, 5 and 6
   No impact on disease course

Pathophysiology: immune response

Tests:

  1. Anti-HIV positive at 4-10 weeks: most sensitive

  2. Qualitative HCV RNA detects at 100 copies/mL (50 IU/mL): most specific

  3. HCV RNA viral load: used to measure response to treatment

  4. Liver biopsy: severity of fibrosis as major indicator for treatment. But coefficient of variation with 15 mm bx is 55%,[20] and severe adverse effects occur in 3/1000 and death in .3/1000.[21]

Treatment:

  • Pegylated interferon alfa 2b (1.5 mcg/kg/week) + ribavirin (11 mg/kg/day)

  • Pegylated interferon alfa 2a (180 mg/week) + ribavirin (1000-1200 mg/day)

  • Rates of sustained viral response

  • See Table 8: Results of Therapeutic Interventions for HCV by Genotype

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....