ADV Improves Liver Histology and Clinical Status

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Hepsera (adefovir dipivoxil) Improves Liver Histology and Clinical Status in Patients with HBeAg+ Chronic HBV GS-98-437 is a randomized, placebo-controlled clinical trial of adefovir dipivoxil (ADV) for the treatment of HBeAg+ chronic hepatitis B. Patients in the trial were randomized to treatment with ADV or placebo (PLB) for 48 weeks. Liver biopsies were performed at baseline and after 48 weeks of treatment. The primary efficacy endpoint was a > or= two-point improvement in the inflammatory score of the Knodell Histology Activity Index (HAI) with no progression of the fibrosis score. This was achieved by 53% (89/168) treated with ADV 10 mg QD and 25% (41/161) PLB treated patients (p<0.001). The objective of this analysis is to compare the efficacy response between ADV 10 mg and PLB treated patients with regards to baseline Knodell fibrosis scores (0/1 = no/portal fibrosis and 3/4 = bridging fibrosis/cirrhosis). Evaluable paired baseline and week 48 biopsies were available from 296 patients (88%) enrolled in the study. The biopsies were assessed by a central histopathologist, blinded to treatment assignment and sequence. Biopsies were scored utilizing Knodell HAI scores comparing the baseline to the week 48 biopsy. Change in alanine aminotransferase (ALT), serum HBV DNA (Roche AmplicorTM LLQ 400 copies/mL) and histology were evaluated in patients receiving ADV 10 mg and PLB. Results: (see table below) Conclusion: Higher absolute rates of response were seen in the baseline Knodell 3/4 (bridging fibrosis/cirrhosis) group. However, ADV 10 mg results in a consistent and significant biochemical, virological and histological response compared to PLB (ALT normalization, change in ALT, HBV DNA < 400 copies/mL, HBV DNA reduction and histological improvement) regardless of the baseline Knodell fibrosis score.

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[upload=jpg]uploadImages/20039919434998762.jpg[/upload] *comparisons of ADV 10 mg to PLB are significant (p<0.001) #M=F (missing=failure)

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Reference
P Marcellin and others. Adefovir Dipivoxil (ADV) Results in a Consistent and Significant Improvement in Liver Histology and Clinical Status Regardless of Baseline Knodell Fibrosis Score in Patients with HBeAg+ Chronic Hepatitis B. Abstract 507 (plenary session). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL, USA.