Cai Shaohang, Yu Tao, Jiang Yegui, Zhang Yonghong, Lv Fangfang, Peng Jie
Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China.
Clin Exp Med. 2016 Aug;16(3):429-36. doi: 10.1007/s10238-015-0373-2. Epub 2015 Jul 12.
This study compared virologic response to entecavir monotherapy and de novo lamivudine plus adefovir (LAM + ADV) combination therapy in patients with chronic hepatitis B (CHB) with high viral load (HVL). Hepatitis B e antigen (HBeAg)-positive patients [hepatitis B virus (HBV) DNA levels >1 × 10(7) copies/ml] were assigned to LAM + ADV or entecavir treatment. The primary efficacy endpoint measure of the multicenter prospective cohort study was proportion of patients with CHB with virologic response, defined as HBV DNA <300 copies/ml at week 48. During treatment, 39.1 % (18/46) of patients in the LAM + ADV group and 48.1 % (25/52) of those in the entecavir group achieved virologic response in week 48 (P = 0.37). A baseline alanine aminotransferase (ALT) level ≥5 × ULN (upper limit of normal) or baseline serum HBV DNA level <8 log10 IU/ml could predict virologic response at week 48 (P = 0.025). The mean reduction in HBV DNA was comparable (P = 0.45); no significant difference was found in the proportion of ALT normalization (P = 0.46) or HBeAg seroconversion (P = 0.88). Two cases of genotypic resistance were found (rtM204 V + rtL180 M and rtA181T/V) in the LAM + ADV group, with a resistance rate of 4.3 %; there was no genotypic resistance in the entecavir group (P = 0.13). De novo LAM + ADV combination therapy is as effective as entecavir monotherapy in HBeAg-positive patients with CHB with HVL. Moreover, genotypic resistance was only found in the LAM + ADV group at week 48. Baseline ALT levels ≥5 ULN or baseline serum HBV DNA levels <8 log10 IU/ml were favorable predictors of virologic response in CHB with HVL.
本研究比较了高病毒载量（HVL）的慢性乙型肝炎（CHB）患者接受恩替卡韦单药治疗和初治拉米夫定联合阿德福韦酯（LAM + ADV）治疗的病毒学应答情况。将乙肝e抗原（HBeAg）阳性患者[乙肝病毒（HBV）DNA水平>1×10⁷拷贝/ml]分配至LAM + ADV或恩替卡韦治疗组。这项多中心前瞻性队列研究的主要疗效终点指标是CHB患者的病毒学应答比例，定义为第48周时HBV DNA<300拷贝/ml。治疗期间，LAM + ADV组39.1%（18/46）的患者和恩替卡韦组48.1%（25/52）的患者在第48周时达到病毒学应答（P = 0.37）。基线丙氨酸氨基转移酶（ALT）水平≥5×ULN（正常上限）或基线血清HBV DNA水平<8 log₁₀ IU/ml可预测第48周时的病毒学应答（P = 0.025）。HBV DNA的平均下降幅度相当（P = 0.45）；ALT正常化比例（P = 0.46）或HBeAg血清学转换比例（P = 0.88）未发现显著差异。LAM + ADV组发现2例基因型耐药（rtM204V + rtL180M和rtA181T/V），耐药率为4.3%；恩替卡韦组未发现基因型耐药（P = 0.13）。初治LAM + ADV联合治疗在HBeAg阳性的HVL CHB患者中与恩替卡韦单药治疗效果相当。此外，仅在第48周时LAM + ADV组发现基因型耐药。基线ALT水平≥5 ULN或基线血清HBV DNA水平<8 log₁₀ IU/ml是HVL CHB患者病毒学应答的有利预测指标。
