| Theme | Cutting Edge : Pathogenesis and Treatment of Hepatitis B | |
|---|---|---|
| Title | Three-year Assessment of Entecavir Therapy in Chronic Hepatitis B Patients | |
| Publish Date | 2009/06 | |
| Author | Yasuhito Tanaka | Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences |
| Author | Motokazu Mukaide | Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences |
| Author | Fuminaka Sugauchi | Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences |
| Author | Masashi Mizokami | Research Center for Hepatitis & Immunology, International Medical Center of Japan Kohnodai Hospital |
| [ Summary ] | To assess the frequency of entecavir-resistance (ETVr) during a three-year ETV therapy and mechanisms of association between specific substitutions and viral breakthrough (BT), we conducted a cross sectional study of 100 patients with chronic hepatitis B including 41 lamivudine (LVD)-refractory patients and 59 naĩve patients. Three-dimensional homology modeling of HBV reverse transcriptase (RT) was used to investigate the mechanisms of resistance. ETVr substitutions (T184SCGA/ILFM,S202G/C) were only found in the group of LVD-refractory patients; in 4.9% at baseline and emerged in 14.6%, 24.4% and 44.8% at weeks 48, 96, and 144, respectively. Evidence of BT was observed in 26.8% of the LVD-refractory group during the 60-144 week period of ETV therapy. Multivariate logistic regression analysis of groups adjusted for age, gender, HBV DNA and LVD-resistance (LVDr, M204V and/or L180M),indicated that the ETVr substitutions (T184SCGA/ILFM and S202G) were associated with BT (adjusted OR: 141.12,95% CI: 6.94-2,870.2: and OR: 201.25,95% CI:11.22-3,608.65,respectively). In conclusion, the combination of clinical observations and molecular modeling indicates that ETV should be considered as a first option for nucleoside-naĩve patients whereas alternative therapeutic strategies should be developed for those with LVDr. | |