HIV and Hepatitis.com Coverage of the
42nd EASL Conference
April 11 - 15, 2007, Barcelona, Spain
THE EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER

Peginterferon Alfa-2a (Pegasys) plus Adefovir Is Safe and Results in Greater Reduction in ALT and HBV DNA Suppression than Pegasys Alone

Although there have been advances in the treatment of HBeAg-negative chronic hepatitis B, the situation remains unsatisfactory. The use of peginterferonalfa-2a (PEG-IFN) [Pegasys] in combination with potent antivirals such as nucleoside/nucleotide analogs [NRTIs] could improve treatment outcome in these patients.

The objective of the current study was to compare the efficacy and safety of 48 weeks of combination PEG-IFN plus adefovir dipivoxil (ADV) vs. standard PEG-IFN (Pegasys) monotherapy.

A multicenter, randomized controlled trial is now under way in Hepatology Centers in Central Italy. Eligible patients had biopsy-proven HBeAg-negative chronic hepatitis B, elevated ALT levels, and quantitative serum HBV DNA<10^4 cp/ml. Coinfections with HCV, HDV or HIV were excluded.

Patients were randomized at baseline to receive PEG-IFN 180 mcg/week + ADV 10 mg/die or PEG-IFN monotherapy for 48 weeks, and were followed for 24 additional weeks after treatment completion. Primary endpoints are undetectable HBV DNA (<200 cp/ml) and normal ALT at end of follow-up.

Results

Fifty-four patients (70% male; median age, 48 years) have been randomized (PEG-IFN+ADV, n=29; PEG-IFN monotherapy, n=25). The two groups are comparable for all baseline variables. Mean baseline ALT levels were 3.3±3.1 times the upper normal limit.

  • 38 patients have completed 24 weeks of antiviral treatment.

  • HBV DNA is undetectable in 15/21 (71%) in the PEG-IFN+ADV group vs. 7/17 (41%) in the PEG-IFN monotherapy group (p=0.06).

  • Mean ALT levels dropped to 1.5±0.7 vs. 2.3±2.1 times the upper normal limit, respectively (p=0.057).

  • ALT normalization was achieved in 9/21 (43%) vs. 5/17 (29%), respectively (p=ns).
  • Mean viral load reduction was significantly greater in the combination than in the monotherapy group (-4.34±1.3 Log vs -3.0±1.7 Log, respectively; p<0.01).

  • Undetectable HBV DNA at week 24 was independently associated with combination treatment at multiple regression analysis including all baseline variables.

  • No patients lost HBsAg.

  • Three patients in each treatment group (10%) dropped out due to adverse events.

  • PEG-IFN dose was reduced in 12 patients (22%).
FDA-approved Treatments for
Hepatitis B
Baraclude  
(entecavir)

Epivir-HBV 
(lamivudine; 3TC)

Intron A 
(interferon alfa-2b)

Hepsera
(adefovir dipivoxil)

Pegasys
(peginterferon alfa-2a)

Tyzeka 
(telbivudine)

In conclusion, the authors wrote, “In HBeAg-negative chronic hepatitis B, 24 weeks of combination PEG-IFN [Pegasys] plus + ADV treatment is safe, and results in greater HBV DNA suppression and ALT reduction than PEG-IFN monotherapy. Follow-up data will confirm whether this advantage is sustained after treatment completion.”

Gastroenterology Unit, University Of Tor Vergata, Rome, Italy; Internal Medicine Unit, University Hospital, Cagliari, Italy; Hepatology Unit, SS. Annunziata General Hospital, Sassari, Italy; Gastroenterology Unit, Brotzu General Hospital, Cagliari, Italy; Spallanzani National Institute Of Infectious Diseases, Rome, Italy; Hepatology Unit, S. Gallicano General Hospital, Rome, Italy; Hepatology Unit, S. Giacomo General Hospital, Rome, Italy; Gastroenterology Unit, La Sapienza University, Rome, Italy; Internal Medicine Unit, Brotzu General Hospital, Cagliari, Italy.

04/27/07

Reference
P Piccolo, I Lenci, D Di Paolo, and others. Peginterferon alpha‑2a plus adefovir vs peginterferon alpha‑2a for 48 weeks in HBeAg‑negative chronic hepatitis B: preliminary 24‑week results of the PEG FOR B randomized multicenter trial. 42nd Annual Meeting of the European Association for the Study of the Liver.      April 11-15, 2007. Barcelona, Spain. Abstract 54.

 





























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