Efficacy Of Interferon-alpha And Its Influencing Factors In Chronic Hepatitis B

To investigate the efficacy of interferon alpha (IFNa) in patients with chronic hepatitis B (CHB) and to analyze its influencing factors, a prospective study was conducted.Two hundred and eight HBeAg-positive and 78 HBeAg-negative consecutive naive CHB patients with liver biopsy proven were enrolled in this study from May, 1998 to the end of 2002. All patients were treated with IFNa 1b subcutaneously at a dose of 5 MU thrice weekly, and followed up for median 21.2 (range 12-64) months. If patients did not achieve the combined responses at the end of 6-month treatment duration the IFNa treatment would be continued ("prolonged" group) provided either HBV DNA levels or HBeAg titers were consistently decreasing, or stopped ("standard" group) owing to persistent decline in neither HBV DNA levels nor HBeAg titers recently 2 months. Patients were monitored monthly for serum alanine transaminase (ALT) activity, every 2 months for HBV DNA by a fluorescent-quantitative PCR with a detection limit of 103 copies/mL, HBeAg by an Abbott enzymimmunoassay kits (Abbott Laboratories, U.S.A.), and every 3 months during the first 12 months after cessation of therapy, and thereafter at a 6 month interval. Serum neutralizing anti-interferon antibodies (NA) were detected by a antiviral biologic neutralizing assayduring the therapy in 153 out of 238 HBeAg-positive patients and in 39 out of 78 HBeAg-negative cases. Normalization of ALT, loss of HBeAg, if positive previously, undetectable HBV DNA all three treatment end-points together was considered as combined response and non-response should be defined if none of the treatment end-points mentioned above was achieved. The sustained response implied the maintained response during 12-month treatment-free follow-up period. Relapse referred to reappearance of either elevated ALT level above 1.5 upper limit of normal, detectable serum HBV DNA, or HBeAg positivity if positive before treatment. Statistical analysis of data was performed by using the SPSS v. 10.0 program.In HBeAg-positive patients, the median treatment duration was 9.0 (range 3.0-24.0) months, with a duration of therapeutic end-point of median 6.0 (range 2.0-22.0) months among combined responders. As a result, combined responses were achieved in 67 (28.2%) at the end of 6-month treatment, in 107 (45.0%) at the end of treatment, in 131 (55.0%) patients at the end of 12 month follow-up, and in 66 (53.7%), of 123 cases who were followed-up for at least 24 months, at the end of 24 month follow-up, respectively. Relapses occurred in 19 (17.8%) at the end of 12 month follow-up and in 13 (24.1%) at the end of 24 month follow-up, respectively. The independent factors of predictive combined response, by multiple binary Logistic regression analysis, included higher histological activity index of liver necroinflammation (p=0.000), female gender (p=0.015), younger age (<20 years) (p=0.040) and NA negativity (p=0.020), except serum ALT level, AST level and HBV DNA level. Furthermore, combined response rate significantly increased up to 53.6% (67/125) in "prolonged" group at month 24 from starting of treatment, compared with 23.9% (11/46) in "standard" group (x2=11.946, p=0.001), and there was a lower relapse rate in "prolonged" group (19.5%,8/41) than in "standard" group (53.8%, 7/13) (x2=5.800,p=0.016). The present results indicated that an individualized and prolonged regimen would be a key to improve both end of treatment response and sustained response to IFNa in HBeAg-positive CHB.With regarding to HBeAg-negative patients, the treatment duration was median 9.0 (range 3.0-24.0) months, and duration of therapeutic end-point of median 6.0 (range 2.0-22.0) months among combined responders. Combinedresponse rate was 32.1 % at the end of 6-month treatment, 44.9% at the end of treatment,366.7% at the end of 12 month follow-up and 70.5% at the end of 24 month follow-up, respectively. Relapse rate was 8.6% at the end of 12 month follow-up and 5.3% at the end of 24 month follow-up, respectively. A higher HAI was the only factor pr...