Choi Kanghyug, Lee Han Min, Jun Baek Gyu, Lee Sae Hwan, Kim Hong Soo, Kim Sang Gyune, Kim Young Seok, Kim Boo Sung, Jeong Soung Won, Jang Jae Young, Kim Young Don, Cheon Gab Jin
Departments of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
Departments of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Korean J Gastroenterol. 2015 Jan;65(1):35-42. doi: 10.4166/kjg.2015.65.1.35.
BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the management of drug-resistant chronic hepatitis B. However, it remains unclear whether TDF-nucleoside analogue combination therapy provides better outcomes than TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.
This retrospective cohort study included 76 patients receiving TDF-based rescue therapy for more than 12 months. Suboptimal response was defined as serum HBV-DNA level of > 60 IU/mL during prior rescue therapy. Multi-drug resistance was defined as the presence of two or more drug resistance-related mutations confirmed by mutation detection assay. The relationship between baseline characteristics and virologic response (HBV DNA < 20 IU/mL) at 12 months were evaluated using logistic regression analysis.
Fifty-five patients (72.4%) were suboptimal responders to prior rescue therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%) received combination therapy with nucleoside analogues. Virologic response at 12 months was not significantly different between the TDF monotherapy group and TDF-nucleoside analogue combination therapy group (p = 0.098). The serum HBV DNA level was reduced to -4.49 ± 1.67 log10 IU/mL in the TDF monotherapy group and to -3.97 ± 1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy group at 12 months (p = 0.18). In multivariate analysis, female sex (p = 0.032), low baseline HBV-DNA level (p = 0.013), and TDF monotherapy (p = 0.046) were predictive factors for virologic response at 12 months.
TDF monotherapy showed similar efficacy to that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.
背景/目的：富马酸替诺福韦二吡呋酯（TDF）在耐药慢性乙型肝炎的治疗中起着关键作用。然而，TDF与核苷类似物联合治疗是否比TDF单药治疗能带来更好的疗效仍不明确。本研究旨在比较TDF单药治疗与TDF - 核苷类似物联合治疗在耐药慢性乙型肝炎患者中的疗效。
这项回顾性队列研究纳入了76例接受基于TDF的挽救治疗超过12个月的患者。疗效欠佳定义为在先前的挽救治疗期间血清HBV - DNA水平>60 IU/mL。多药耐药定义为通过突变检测试验确认存在两个或更多与耐药相关的突变。使用逻辑回归分析评估基线特征与12个月时病毒学应答（HBV DNA<20 IU/mL）之间的关系。
55例患者（72.4%）对先前的挽救治疗疗效欠佳，26例（34.2%）存在多药耐药。42例患者（55.3%）接受了核苷类似物联合治疗。TDF单药治疗组和TDF - 核苷类似物联合治疗组在12个月时的病毒学应答无显著差异（p = 0.098）。12个月时，TDF单药治疗组血清HBV DNA水平降至-4.49±1.67 log10 IU/mL，TDF - 核苷类似物联合治疗组降至-3.97±1.69 log10 IU/mL（p = 0.18）。在多变量分析中，女性（p = 0.032）、低基线HBV - DNA水平（p = 0.013）和TDF单药治疗（p = 0.046）是12个月时病毒学应答的预测因素。
在耐药慢性乙型肝炎患者中，TDF单药治疗与TDF - 核苷类似物联合治疗疗效相似。
