Woo Hyun Young, Park Jun Yong, Bae Si Hyun, Kim Chang Wook, Jang Jae Young, Tak Won Young, Kim Dong Joon, Kim In Hee, Heo Jeong, Ahn Sang Hoon
Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea.
Medical Research Institute, Pusan National University Hospital, Busan, Korea.
Clin Mol Hepatol. 2020 Jul;26(3):352-363. doi: 10.3350/cmh.2019.0044n. Epub 2020 May 28.
BACKGROUND/AIMS: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.
This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.
Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.
ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).
背景/目的：对于拉米夫定或替比夫定联合阿德福韦酯（LAM/LdT+ADV）挽救治疗反应欠佳的拉米夫定耐药乙型肝炎病毒（HBV）感染患者很常见。我们比较了换用恩替卡韦联合替诺福韦酯（ETV+TDF）的患者与继续使用LAM/LdT+ADV的患者。
这项前瞻性随机对照试验研究了91例接受LAM/LdT+ADV治疗至少24周后血清HBV DNA水平大于60 IU/mL的拉米夫定耐药HBV患者。患者被随机分为接受新治疗（ETV+TDF，n=45）或继续接受相同治疗（LAM/LdT+ADV，n=46）48周。排除基线阿德福韦酯耐药的患者。
与LAM/LdT+ADV组相比，ETV+TDF组有更多患者出现病毒学应答（42/45 [93.33%] 对3/46 [6.52%]，P<0.001），且血清HBV DNA水平较基线的平均下降幅度更大（-4.16对-0.37 log10 IU/mL，P<0.001）。多因素分析表明，高基线HBV DNA水平（P=0.005）和LAM/LdT+ADV维持治疗（P=0.001）与病毒学应答呈负相关。在第48周时，ETV+TDF组清除了额外的阿德福韦酯或恩替卡韦相关突变，但LAM/LdT+ADV组有4.3%的患者存在此类突变（P=0.106）。两组不良事件发生率相似。
对于对LAM/LdT+ADV反应欠佳的拉米夫定耐药HBV患者，无论HBV基因型耐药情况如何，ETV+TDF联合治疗的病毒学应答率显著高于LAM/LdT+ADV联合治疗（NCT01597934）。
