Hepatitis B treatment

3TC (lamivudine, Epivir / Zeffix) is licensed as a treatment for hepatitis B in an increasing number of countries. It may be prescribed to people with chronic hepatitis B virus infection with liver damage, liver inflammation or fibrosis. The standard dose for hepatitis B infection is 100mg once daily. 3TC can also improve liver function in patients co-infected with HIV.1

A number of trials have found that 3TC normalises liver function in the majority of people with hepatitis B. Clinical trials have found improved liver function in more patients taking 3TC than placebo, and less progression to fibrosis and liver cancer.2 3 However, some experts have questioned the appropriateness of once-daily, single drug therapy due to the likelihood of hepatitis B patients developing drug resistance in the long term.

Resistance to 3TC in the hepatitis B virus usually occurs in the YMDD domain.4 Resistance emerges more slowly in the hepatitis B virus than in HIV. 3TC resistance appears to emerge more quickly in individuals with a higher body mass index, suggesting that resistance to 3TC may develop if the dose of 3TC used is not large enough.

The inclusion of 3TC in antiretroviral therapy regimens for co-infected individuals has also been questioned, since this would lead to 3TC monotherapy for hepatitis B and the possibility of resistance developing.5 6 Combination approaches to hepatitis B treatment are being explored, using adefovir (Hepsera), tenofovir (Viread), interferon alfa (Roferon-A / Viraferon) or famciclovir (Famvir) alongside 3TC.

Patients infected with the hepatitis B virus may experience a flare-up of hepatitis B when they stop 3TC treatment.7 Additionally, cases of hepatitis B flare-up in HIV co-infected patients receiving 3TC have been reported in the absence of any evidence of 3TC resistance. This is probably caused by the reconstitution of the immune system before the 3TC has time to control the HBV.8 9 A possible way to avoid this is to combine 3TC with tenofovir in co-infected patients, to delay the addition of other anti-HIV drugs until the HBV is controlled, or to assess the extent of liver damage before initiation of antiretroviral therapy.

References

  1. Dore GJ et al. Dual efficacy of lamivudine treatment in HIV / hepatitis B virus coinfected persons in a randomized, controlled study (CAESAR). J Infect Dis 180: 607-613, 1999
  2. Dienstag JL et al. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 341: 1256-1263, 1999
  3. Lai CL et al. A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med 339: 61-68, 1999
  4. Bourne NE et al. Prolonged lamivudine therapy for chronic hepatitis B: safety, efficacy on HBV, variant emergence, and seroconversion. Twelfth International Conference on Antiviral Research, Jerusalem, abstract S74, 1999
  5. Hoff J et al. Evaluation of chronic hepatitis B virus (HBV) infection in coinfected patients receiving lamivudine as a component of anti-human immunodeficiency virus regimens. Clin Infect Dis 32: 963-969, 2001
  6. Neau D et al. Hepatitis B exacerbation with a precore mutant virus following withdrawal of lamivudine in a human immunodeficiency virus-infected patient. J Infect 41: 192-194, 2000
  7. Bessesen M et al. Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine. Clin Infect Dis 28: 1032-1035, 1999
  8. Drake A et al. Immune reconstitution hepatitis in HIV and hepatitis B coinfection, despite lamivudine therapy as part of HAART. Clin Infect Dis 39: 129-132, 2004
  9. Bellini C et al. Frequent liver dysfunction after lamivudine withdrawal in HIV-hepatitis B coinfection. Antivir Ther 8: S464, 2003
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