Yang Dan-Hong, Xie Yuan-Jun, Zhao Nian-Feng, Pan Hong-Ying, Li Ming-Wei, Huang Hai-Jun
Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
World J Gastroenterol. 2015 Mar 7;21(9):2746-53. doi: 10.3748/wjg.v21.i9.2746.
To assess the efficacy of tenofovir disoproxil fumarate (TDF) in lamivudine (LAM)-resistant patients with a suboptimal response to LAM plus adefovir (ADV).
We retrospectively analyzed the efficacy of switching to tenofovir disoproxil fumarate in suboptimal responders to lamivudine plus adefovir. Charts were reviewed for LAM-resistant chronic hepatitis B (CHB) patients who visited the Zhejiang Province People's Hospital and The First Affiliated Hospital, College of Medicine, Zhejiang University, from June 2009 to May 2013. Patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM plus ADV combination therapy were included. Patients with a suboptimal response to LAM plus ADV were randomized to switch to TDF monotherapy (300 mg/d orally; TDF group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally; LAM plus ADV group) and were followed for 48 wk. Serum HBV DNA was determined at baseline and weeks 4, 12, 24, 36, and 48. HBV serological markers and biochemistry were assessed at baseline and weeks 12, 24, and 48. Resistance surveillance and side effects were monitored during therapy.
Fifty-nine patient were randomized to switch to TDF (n = 28) or continuation with LAM plus ADV (n = 31). No significant differences were found between the groups at baseline. Prior to TDF therapy, all patients had been exposed to LAM plus ADV for a median of 11 mo (range: 6-24 mo). No difference was seen in baseline serum HBV DNA between the two groups [5.13 ± 1.08 log10 copies/mL (TDF) vs 5.04 ± 31.16 log10 copies/mL (LAM + ADV), P = 0.639]. There was no significant difference in the rates of achieving complete virological response (CVR) at week 4 between the TDF and LAM + ADV groups (17.86% vs 6.45%, P = 0.24). The rate of achieving CVR in the TDF and LAM plus ADV groups was 75% vs 16.13% at week 12, 82.14% vs 22.58% at week 24, 89.29% vs 25.81% at week 36, and 96.43% vs 29.03% at week 48, respectively (P < 0.001). The rate of alanine aminotransferase normalization was significantly higher in the TDF than in the LAM plus ADV group at week 12 (75% vs 17.86%, P < 0.001), but not at week 24 (78.57% vs 54.84%, P = 0.097) or 48 (89.26% vs 67.74%, P = 0.062). Patients were hepatitis B e antigen (HBeAg) positive at baseline. There was no significant difference in HBeAg negativity between the TDF and LAM plus ADV groups at week 48 (4% vs 0%, P = 0.481). There were no drug-related adverse effects at week 48 in either group.
Switching to TDF monotherapy was superior to continuous add-on therapy in patients with LAM-resistant CHB with a suboptimal response to LAM plus ADV.
评估替诺福韦酯（TDF）对拉米夫定（LAM）耐药且对LAM联合阿德福韦酯（ADV）反应欠佳患者的疗效。
我们回顾性分析了对LAM联合ADV反应欠佳的患者换用TDF的疗效。查阅了2009年6月至2013年5月期间就诊于浙江省人民医院和浙江大学医学院附属第一医院的LAM耐药慢性乙型肝炎（CHB）患者的病历。纳入至少接受6个月LAM联合ADV治疗后血清乙型肝炎病毒（HBV）DNA仍可检测到的患者。对LAM联合ADV反应欠佳的患者被随机分为换用TDF单药治疗组（口服300mg/d；TDF组）或继续LAM（口服100mg/d）联合ADV（口服10mg/d；LAM联合ADV组），并随访48周。在基线及第4、12、24、36和48周测定血清HBV DNA。在基线及第12、24和48周评估HBV血清学标志物和生化指标。治疗期间监测耐药情况和不良反应。
59例患者被随机分为换用TDF组（n = 28）或继续LAM联合ADV组（n = 31）。两组在基线时无显著差异。在TDF治疗前，所有患者均接受LAM联合ADV治疗，中位时间为11个月（范围：6 - 24个月）。两组基线血清HBV DNA无差异[5.13 ± 1.08 log10拷贝/mL（TDF组）对5.04 ± 31.16 log10拷贝/mL（LAM + ADV组），P = 0.639]。在第4周时，TDF组和LAM + ADV组实现完全病毒学应答（CVR）的率无显著差异（17.86%对6.45%，P = 0.24）。在第12周时，TDF组和LAM联合ADV组实现CVR的率分别为75%对16.13%，第24周时分别为82.14%对22.58%，第36周时分别为89.29%对25.81%，第48周时分别为96.43%对29.03%（P < 0.）。在第12周时，TDF组丙氨酸氨基转移酶正常化率显著高于LAM联合ADV组（75%对17.86%，P < 0.），但在第24周（78.57%对54.84%，P = 0.097）或第48周（89.26%对67.74%，P = 0.062）时无差异。患者在基线时乙肝e抗原（HBeAg）阳性。在第48周时，TDF组和LAM联合ADV组HBeAg转阴率无显著差异（4%对0%，P = 0.481）。两组在第48周时均无药物相关不良反应。
对于LAM耐药且对LAM联合ADV反应欠佳的CHB患者，换用TDF单药治疗优于继续联合治疗。
