Peginterferon Alfa-2b (PegIntron) plus Adefovir Strongly Reduces HBV cccDNA and Produces Clinical Benefit

The objective of the current study was to determine the virological, serological, and histological outcome, including cccDNA levels, in chronic hepatitis B patients after 48 weeks of combination therapy with pegylated interferon alfa-2b (PegIntron) plus adefovir (Hepsera), followed by 96 weeks of adefovir monotherapy.

Following is data from the final analysis of the study after 144 weeks of antiviral treatment, as presented at the 42nd Annual Meeting of the European Association for the Study of the Liver this month in Barcelona, Spain.

In this study, 26 patients received a 48-week course of PegIntron (1.5 mcg/kg) plus adefovir (10 mg) followed by 96 weeks of adefovir. 21 out of 26 subjects reached the end of the 3-year course of therapy, and triplet biopsies (baseline, week 48, and week 144) were obtained from 16 patients.

Results

• Median serum HBV DNA decreased by 4 logs.
• 43% of patients achieved undetectable HBV DNA (< 100 copies/mL) at week 144.
• 95% experienced ALT normalization.
• 2 patients developed adefovir-resistant viral strains during the third year.
• 2 out of 4 patients who seroconverted from HBsAg to anti-HBs-antibodies within the first year of combination therapy lost HBsAb during the third year.
• 11 of 13 HBeAg positive patients (85%) showed loss of HBeAg (including 5 HBeAg seroconverters to anti-HBe antibodies).
• Mean total intrahepatic HBV DNA dropped significantly from baseline to 0.87 copies/cell at week 144 in HBeAg positive patients and to 0.14 copies/cell in HBeAg negative patients.
• cccDNA dropped from 3.3 copies/cell at baseline to 0.08 copies/cell in HBeAg positive patients and from 0.2 copies/cell to 0.01 copies/cell in HBeAg negative patients.
• The median ratio of total HBV DNA and cccDNA changed significantly (P=0.041) during therapy (baseline vs week 144), indicating that not only the amount, but also the transcriptional activity, of cccDNA was reduced during the course of therapy.
• A significant reduction in both liver inflammation and fibrosis was observed.
  

Conclusion

The study authors concluded, “48 weeks of combination therapy with [PegIntron] and adefovir followed by 96 weeks of adefovir monotherapy led to substantial loss of intrahepatic HBV DNA, cccDNA, and of cccDNA replicative activity.”

They added that, “This strong reduction translated into long-term clinical benefit and demonstrates the need [for] both long-term treatment and highly active antiviral therapy (HAART) regimens in chronic hepatitis B patients.”

Department Of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Essex Pharma, Munich, Germany; Gilead Sciences, Foster City, CA, USA.

04/20/07

Reference
M Lütgehetmann, K Wursthorn, M Dandri, and others. Substantial loss of intrahepatic HBV cccDNA during antiviral combination therapy translates into long-term clinical benefit. 42nd Annual Meeting of the European Association for the Study of the Liver. April 11 - 15, 2007, Barcelona, Spain. Abstract 59.

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