Santos Stephanie A, Uriel Alison J, Park James S, Lucas Jennifer, Carriero Damaris, Jaffe David, Dieterich Douglas T
Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York 10029, USA.
Eur J Gastroenterol Hepatol. 2006 Dec;18(12):1247-53. doi: 10.1097/01.meg.0000243877.17444.5e.
In patients with chronic hepatitis B, long-term use of lamivudine is limited by resistance mutations. Adefovir dipivoxil has a very low rate of resistance, but there have been recent reports describing resistance mutations. Tenofovir disoproxil fumarate and emtricitabine show potent activity against wild-type and lamivudine-resistant hepatitis B virus.
We describe a series of seven HIV-seronegative patients who failed to achieve undetectable hepatitis B viral DNA on adefovir. No lamivudine resistance testing was performed. The antiviral regimen was changed to tenofovir (300 mg daily) and emtricitabine (200 mg daily). Variables collected included levels of hepatitis B viral DNA by polymerase chain reaction, alanine and aspartate aminotransferase, hepatitis B e antigen and hepatitis B e antibody.
The median hepatitis B viral DNA level while on adefovir was 430,000 copies/ml with a median fall in hepatitis B viral DNA levels of 2.0 log10 copies/ml. Patients were on adefovir for a median period of 10 months before a change in regimen to tenofovir and emtricitabine. This regimen change resulted in a median fall in hepatitis B viral DNA levels of 3.0 log10 copies/ml (range, 2-4) after a median treatment duration of 23 months (range, 14-28). All patients (100%) had achieved undetectable hepatitis B viral DNA levels following combination therapy. Anti-hepatitis B e seroconversion occurred in one patient. No change in serum creatinine was observed during therapy, and no significant adverse events were reported.
In patients failing to respond to adefovir monotherapy or an adefovir-containing regimen for chronic hepatitis B virus, a combination of tenofovir and emtricitabine resulted in undetectable hepatitis B viral DNA levels without any renal toxicity. Tenofovir, in combination with emtricitabine, may be an alternative treatment for those with detectable hepatitis B viral DNA on adefovir.
在慢性乙型肝炎患者中，长期使用拉米夫定受到耐药突变的限制。阿德福韦酯耐药率很低，但最近有报告描述了耐药突变情况。替诺福韦酯和恩曲他滨对野生型和拉米夫定耐药的乙型肝炎病毒均显示出强大活性。
我们描述了7例HIV血清学阴性患者，他们使用阿德福韦治疗后未能使乙型肝炎病毒DNA降至检测不到的水平。未进行拉米夫定耐药检测。抗病毒治疗方案改为替诺福韦（每日300毫克）和恩曲他滨（每日200毫克）。收集的变量包括通过聚合酶链反应检测的乙型肝炎病毒DNA水平、丙氨酸和天冬氨酸转氨酶、乙型肝炎e抗原和乙型肝炎e抗体。
使用阿德福韦时，乙型肝炎病毒DNA水平中位数为430,000拷贝/毫升，乙型肝炎病毒DNA水平中位数下降2.0 log10拷贝/毫升。在改为替诺福韦和恩曲他滨治疗方案之前，患者使用阿德福韦的中位时间为10个月。这一治疗方案的改变导致在中位治疗23个月（范围14 - 28个月）后，乙型肝炎病毒DNA水平中位数下降3.0 log10拷贝/毫升（范围2 - 4）。联合治疗后所有患者（100%）的乙型肝炎病毒DNA水平均降至检测不到。1例患者发生了抗乙型肝炎e血清学转换。治疗期间血清肌酐无变化，未报告明显不良事件。
对于慢性乙型肝炎病毒感染且对阿德福韦单药治疗或含阿德福韦方案无反应的患者，替诺福韦与恩曲他滨联合使用可使乙型肝炎病毒DNA水平降至检测不到，且无任何肾毒性。替诺福韦与恩曲他滨联合使用，可能是对阿德福韦治疗后仍可检测到乙型肝炎病毒DNA的患者的一种替代治疗方法。
