Department of Medicine, Emory, University School of Medicine, Atlanta, GA, USA.
Ther Clin Risk Manag. 2009;5:789-98. doi: 10.2147/tcrm.s5318. Epub 2009 Oct 12.
Telbivudine was recently approved for the treatment of chronic hepatitis B. Phase III studies indicated its antiviral potency with 6- to 6.5-log copies/mL reductions in hepatitis B DNA levels at year 1, comparable to other potent agents such as entecavir or tenofovir. Genotypic resistance rates, however, reached 25% at year 2 in hepatitis B e-antigen positive subjects and 11% in hepatitis B e-antigen negative subjects, preventing it from becoming a preferred first-line drug for hepatitis B. Furthermore, its signature resistance mutation (a change from methionine to isoleucine at position 204 in the reverse transcriptase domain of the hepatitis B polymerase) also confers cross-resistance to entecavir, lamivudine, and emtricitabine. Telbivudine is well tolerated, with elevations in creatine phosphokinase being the most common abnormality observed in clinical trials. Most often, elevations were asymptomatic. Future research in hepatitis B will focus on the best ways to use existing therapies, including telbivudine, sequentially or in combination in order to maximize viral suppression and minimize the development of antiviral resistance.
替比夫定最近被批准用于治疗慢性乙型肝炎。III 期研究表明，其抗病毒效力在第 1 年时可使乙型肝炎 DNA 水平降低 6-6.5 对数拷贝/ml，与恩替卡韦或替诺福韦等其他强效药物相当。然而，在乙型肝炎 e 抗原阳性患者中，第 2 年的基因型耐药率达到 25%，在乙型肝炎 e 抗原阴性患者中达到 11%，这使其无法成为乙型肝炎的首选一线药物。此外，其特征性耐药突变（乙型肝炎聚合酶逆转录酶结构域第 204 位由蛋氨酸突变为异亮氨酸）也导致对恩替卡韦、拉米夫定和恩曲他滨的交叉耐药。替比夫定耐受性良好，临床试验中最常见的异常是肌酸磷酸激酶升高。大多数情况下，升高是无症状的。乙型肝炎的未来研究将集中在如何最好地使用现有疗法，包括替比夫定，按顺序或联合使用，以最大限度地抑制病毒并最小化抗病毒耐药性的发展。
