48周阿地富韦改善纤维化，减缓纤维进程

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48 Weeks of Hepsera (adefovir dipivoxil) Improves Fibrosis and Slows Progression of Fibrosis in Patients with HBeAg+ Chronic Hepatitis B Year one of a Phase III placebo-controlled clinical trial of Hepsera [adefovir dipivoxil (ADV)] for the treatment of HBeAg+ chronic hepatitis B infection was completed in 2001. Patients in the trial were randomized to treatment with placebo (PLB) or ADV (10 mg or 30 mg QD). Liver biopsies were performed prior to baseline and at 48 weeks of treatment. The primary efficacy endpoint was a greater than or equal to two-point improvement in the inflammatory components of the Knodell Histology Activity Index (HAI) with no progression of the fibrosis component. This was achieved by 25% (41/161) PLB treated patients, 53% (89/168) treated with ADV 10 mg QD, and 59% (98/165) treated with ADV 30 mg QD (p=<0.0001 compared to PLB). The original HAI only allows 3 stages of fibrosis (none, portal, bridging and cirrhosis). The modified HAI, also called the Ishak score has 6 stages of fibrosis, permitting better evaluation of therapy-related changes in fibrosis. The objective of this analysis is to compare changes in fibrosis, as determined by the modified HAI fibrosis score, between the PLB and ADV-treated patients. Evaluable paired baseline and week 48 biopsies were available from 441 of the 515 patients enrolled in the study (86%). The biopsies were assessed by a central histopathologist, blinded to treatment assignment and sequence. Biopsies were scored utilizing original and modified HAI scores and a ranked assessment was performed comparing the baseline to the week 48 biopsy. Possible fibrosis scores with the modified HAI are: 0 = no fibrosis; 1 = fibrous expansion of some portal areas; 2 = fibrous expansion of most portal areas; 3 = occasional bridging fibrosis; 4 = marked bridging fibrosis; 5 = incomplete cirrhosis; 6 = cirrhosis. In an intent-to-treat analysis, mean modified HAI baseline fibrosis scores were: PLB = 2.47 (62% 0-2, 30% 3-4, 8% 5-6); ADV 10 mg = 2.20 (71% 0-2, 22% 3-4, 7% 5-6); ADV 30 mg = 2.24 (65% 0-2, 30% 3-4, 4% 5-6). After 48 weeks of treatment the mean modified HAI fibrosis scores were: PLB = 2.55; ADV 10 mg = 1.95 (p=0.0007 compared to baseline); ADV 30 mg = 1.85 (p=<0.0001 compared to baseline). Significant improvement and less worsening of fibrosis occurred in the ADV 10 mg group (p=0.0006) and the ADV 30 mg group (p=<0.0001) as compared to PLB. Improvement by greater than or equal to 1 stage occurred in 19% of PLB treated patients, 35% ADV 10 mg and 41% ADV 30 mg. Worsening by greater than or equal to 1 stage occurred in 22% of PLB treated patients, 11% ADV 10 mg, and 10% ADV 30 mg. Conclusion: As judged by the modified HAI fibrosis score, there was a significant improvement and less worsening in hepatic fibrosis in patients with HBeAg+ chronic hepatitis B infection treated with ADV for 48 weeks. 01/24/03 Reference Z Goodman and others. 48 WEEKS OF ADEFOVIR DIPIVOXIL (ADV) RESULTS IN IMPROVEMENT IN FIBROSIS AND DECREASED PROGRESSION OF FIBROSIS IN A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY FOR THE TREATMENT OF PATIENTS WITH HBeAg+ CHRONIC HEPATITIS B. Abstract 841. 53rd AASLD. November 1-5, 2002. Boston, MA. Hepatology 2002: Vol 36 No 4, Pt 2 of 2.