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 HIV and Coverage of the
th Annual Meeting of the American Association
for the Study of Liver Diseases
(AASLD 2009)

October 30 - November 3, 2009, Boston, MA

Review Finds Pegylated Interferon Is More Effective than Lamivudine for Chronic Hepatitis B, but Study Shows Little Activity against HBV Genotype D

SUMMARY: A systemic review of clinical trials found that pegylated interferon was more effective than the oral antiviral drug lamivudine (Epivir-HBV) at achieving endpoints including hepatitis B virus (HBV) DNA clearance and hepatitis B "e" antigen (HBeAg) seroconversion, investigators reported at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009) this month in Boston. Another study, however, showed that pegylated interferon did not work so well against HBV genotype D.

By Liz Highleyman

Two types of treatment are approved for chronic hepatitis B, directly targeted oral antiviral agents such as lamivudine (Epivir-HBV), and conventional or pegylated interferon, which stimulates immune response to HBV.

K. Mumtaz from Aga Khan University in Pakistan and colleagues performed a Cochrane review of pegylated interferon for chronic hepatitis B in adult patients. The Cochrane Collaboration is an independent network of experts that produces systematic reviews of healthcare interventions and promotes evidence-based medicine.

The investigators searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials, and the MEDLINE, EMBASE, and LILACS databases for studies published through January 2009 that compared pegylated interferon versus other therapies for adult chronic hepatitis B patients.


The researchers identified 7 trials reported in 15 publications, with a total of 2179 participants.
These studies showed evidence that pegylated interferon is superior to lamivudine in achieving outcomes including:
HBV DNA clearance: rate ratio (RR) 0.94;
HBV DNA suppression: RR 0.85;
HBeAg seroconversion: RR 0.84;
Hepatitis B surface antigen (HBsAg) loss: RR 0.97.
Adding lamivudine to pegylated interferon did not decrease the "number needed to treat" in order to produce a successful outcome.
However, adverse events were more common with pegylated interferon than with lamivudine.

Based on these findings, the researchers concluded, "Current evidence suggests that pegylated interferon is better than lamivudine when used alone or with lamivudine."

HBV Genotype D

According to a related study reported at the same conference, however, pegylated interferon is not very effective against chronic HBV genotype D infection.

O. Kurdas and colleagues from Turkey -- where genotype D is the most common form of HBV, accounting for 97% of cases -- evaluated the efficacy of pegylated interferon in eligible chronic hepatitis B patients treated at Haydarpasa Numune Education and Research Hospital between 2004 and 2007.

Eligible patients met any 2 of the following criteria: less than 60 years of age, ALT > 2 x upper limit of normal, HBV DNA < 1 million copies/mL, or fibrosis stage < 3. Patients with initial HBV DNA levels > 1 million copies/mL were pretreated with lamivudine until their viral load fell below this level, at which point they could start pegylated interferon.

A total of 28 patients (15 HBeAg positive and 13 HBeAg negative) were enrolled in the study and treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) or 1.5 mcg/kg/week pegylated interferon alfa-2b (PegIntron) for 48 weeks. Participants were followed for an average of 115 weeks after the end of therapy.

By week 12, 40% of HBeAg positive patients and 70% of HBeAg negative patients experienced at least a 2 log reduction in HBV viral load. At the end of treatment, 39% and 67%, respectively, had undetectable HBV DNA. However, only 3 HBeAg negative patients and none of the HBeAg positive participants achieved sustained virological response after completing therapy. Because of the small numbers, the differences between the HBeAg positive and HBeAg negative groups were not statistically significant. Overall, 10 patients (63%) achieved HBeAg seroconversion, but none achieved HBsAg seroconversion.

These findings led the investigators to conclude that, "Pegylated interferon therapy was found ineffective in patients with chronic hepatitis B genotype D despite young age, high ALT, low viral load, and low fibrosis scores."



K Mumtaz, S Hamid, and SM Jafri. Pegylated interferon for chronic hepatitis B in adults: a Cochrane Review. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 469.

O Kurdas, F Guzelbulut, Y Gökden, and others. PegIFNs are not satisfactory in genotype D chronic HBV infection. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 462.


























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