Background and Aim: Treatment for HBeAg-negative chronic hepatitis B remains unsatisfactory despite advances in antiviral therapy. The association of peginterferon-alpha-2a (PEG-IFN) with potent antivirals such as nucleoside/nucleotide analogs could improve treatment outcome in these patients. Aim of the present study was to compare the efficacy and safety of 48 weeks of combination PEG-TFN plus adefovir dipivoxil (ADV) vs. standard PEG-TFN monotherapy. Methods: A multicenter, randomized controlled trial is currently under way in Hepatology Centers in Central Italy. Patients were eligible if they had biopsy-proven HBeAg-negative chronic hepatitis B, elevated ALT levels, and quantitative serum HBVDNA i1 O 4 cpiml; co-infections with HCV, HDV or HIV were excluded. Patients were randomized at baseline to receive PEG-IFN 180 mcg/week + ADV 10mgidie or PEG-IFN monotherapy for 48 weeks, and will be 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. At present, 38 patients have completed 24 weeks of antiviral treatment. HBVDNA 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 (-4.34f1.3 Log vs -3.0&1.7 Log, respectively; p i0. 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 (1 0%) dropped out due to adverse events. PEG-TFN dose was reduced in 12 patients (22%). Conclusion: In HBeAg-negative chronic hepatitis B, 24 weeks of combination PEG-TFN+ADV treatment is safe, and results in greater HBVDNA suppression and ALT reduction than PEG-TFN monotherapy. Follow-up data will confirm whether this advantage is sustained after treatment completion.
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
DEMELIA, LUIGI;
2007-01-01
Abstract
Background and Aim: Treatment for HBeAg-negative chronic hepatitis B remains unsatisfactory despite advances in antiviral therapy. The association of peginterferon-alpha-2a (PEG-IFN) with potent antivirals such as nucleoside/nucleotide analogs could improve treatment outcome in these patients. Aim of the present study was to compare the efficacy and safety of 48 weeks of combination PEG-TFN plus adefovir dipivoxil (ADV) vs. standard PEG-TFN monotherapy. Methods: A multicenter, randomized controlled trial is currently under way in Hepatology Centers in Central Italy. Patients were eligible if they had biopsy-proven HBeAg-negative chronic hepatitis B, elevated ALT levels, and quantitative serum HBVDNA i1 O 4 cpiml; co-infections with HCV, HDV or HIV were excluded. Patients were randomized at baseline to receive PEG-IFN 180 mcg/week + ADV 10mgidie or PEG-IFN monotherapy for 48 weeks, and will be 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. At present, 38 patients have completed 24 weeks of antiviral treatment. HBVDNA 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 (-4.34f1.3 Log vs -3.0&1.7 Log, respectively; p i0. 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 (1 0%) dropped out due to adverse events. PEG-TFN dose was reduced in 12 patients (22%). Conclusion: In HBeAg-negative chronic hepatitis B, 24 weeks of combination PEG-TFN+ADV treatment is safe, and results in greater HBVDNA suppression and ALT reduction than PEG-TFN monotherapy. Follow-up data will confirm whether this advantage is sustained after treatment completion.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
