摘要
目的研究乙型肝炎病毒rtA181位点突变患者的临床特点,并初步探讨其临床治疗策略。方法对核苷(酸)类似物(NUCs)治疗过程中出现病毒学突破或治疗效果不佳的患者,进行HBV DNA P基因区NUCs相关耐药位点(共22个常见位点)的检测,其中出现rtA181位点突变者,回顾性分析其NUCs使用情况;观察部分病例改变治疗策略后的疗效,并采用描述性统计分析。结果 227例NUCs相关耐药位点变异阳性患者中出现rtA181位点突变者共103例;病例资料完整的67例患者中,单一A181T或A181V突变者21例,A181T+A181V突变者2例;A181T、A181V合并N236T突变者22例,A181T、A181V合并L180M、M204V和(或)M204I突变者13例,A181T、A181V合并其他突变者(包括L80I、V173L、S202G和M250L)者9例。5例患者单独使用拉米夫定治疗出现病毒学突破后加用阿德福韦酯,效果不佳;9例患者单独使用阿德福韦酯治疗出现病毒学突破或效果不佳加用拉米夫定,HBV DNA下降也不理想;检测HBV DNA P区NUCs相关耐药位点,均出现rtA181位点突变,改变治疗方案为阿德福韦酯加用恩替卡韦治疗3～6个月后,HBV DNA均出现显著下降,效果理想。结论拉米夫定、阿德福韦酯治疗过程中,如出现HBV DNA病毒学突破或疗效不佳,只是简单地分别加用阿德福韦酯或拉米夫定,治疗效果可能不理想;可靠的方法是检测HBV DNA P区NUCs相关耐药位点,根据耐药位点的检测结果来变更有效的治疗方案,对于合并rtA181位点突变患者,可考虑阿德福韦酯加用恩替卡韦治疗。
Objective To observe the clinical characteristics of patients with chronic hepatitis B with rtA181 mutation. Methods Twenty-two mutation sites in HBV DNA P gene correlated to nucleos（t）ide analogues （NUCs） were detected in patients who experienced virological breakthrough during NUCs treatment. The antiviml therapy and response history of patients infected with rtA181 mutation were analyzed. Treatment effect of partial patients after switching therapy strategy was also analyzed. Results Total of 103 patients were detected positively with rtA181 mutation in 227 cases with mutation sites. Among 67 cases with detailed clinical data, 21, 2, 22, 13 and 9 cases were detected positively with single A 181T/V mutation positive, A 181T ＋ A 181V mutation positive, A181T ＋ rtA181V ＋ N236T mutation positive, A181T/V ＋ L180M （M204V/I） mutation and A181T/V ＋ （LSOI, V173L, S202G, M250L） mutation positive, respectively. Among 67 cases, there were 5 patients experienced virological breakthrough during LAM treatment, 9 patients experienced virological breakthrough during ADV treatment. Treatment effect were poor in these patients after adding ADV and LAM, respectively. Total of 14 patients were detected positively with A 181 mutation. Undetected HBV DNA was achieved in all patients after ADV ＋ ETV treatment for 3-6 months. Conclusions Mutation sites in HBV DNA P gene correlated to NUCs should be detected in patients who experienced virological breakthrough during LAM or ADV treatment. If A 181 mutation was positive in these patients, treatment with ADV ＋ ETV would produce an ideal virological suppression.
出处
《中华实验和临床感染病杂志（电子版）》
CAS
2013年第2期62-65,共4页
Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)
