接受达拉他韦和阿舒瑞韦治疗的初治基因1b型慢性丙型肝炎患者疗效评价*

doi:10.3969/j.issn.1672-5069.2024.06.011

摘要/Abstract

摘要： 目的观察应用达拉他韦(DCV)联合阿舒瑞韦(ASV)治疗初治的基因1b型慢性丙型肝炎(CHC)患者的临床疗效。方法 2019年10月～2021年10月我院诊治的初治的基因1b型CHC患者53例,均接受DCV和ASV联合治疗24周,随访24周。采用RT-PCR法检测血清HCV RNA载量,采用测序法分析HCV NS5A耐药相关突变(RAS),采用放射免疫分析法检测血清透明质酸(HA)、Ⅲ型前胶原(Pc-Ⅲ)、Ⅳ型胶原(Ⅳ-c)和层粘连蛋白(LN)水平。结果在治疗1周、2周、4周、8周、12周、24周和随访时,53例CHC患者血清HCV RNA转阴率分别为3.7%、9.4%、43.3%、69.8%、83.0%、94.3%和94.3%,血清HCV RNA载量分别为(5.8±0.1)lg IU/ml、(5.3±0.6)lg IU/ml、(3.5±0.5)lg IU/ml、(2.2±0.6)lg IU/ml、(1.0±0.2)lg IU/ml、(0.7±0.5)lg IU/ml和(0.7±0.4)lg IU/ml,均显著低于基线水平【(6.1±0.4)lg IU/ml,P＜0.05】;在治疗24周和随访时,血清AST水平分别为(22.7±11.4)U/L和(20.9±9.9)U/L,显著低于基线水平【(63.5±6.6)U/L,P<0.05】,血清ALT水平分别为(19.3±10.7)U/L和(19.2±8.5)U/L,均显著低于基线水平【(80.2±65.3)U/L,P＜0.05】;在治疗过程中,估算的肾小球滤过率(eGFP)和血常规指标无显著性变化;在治疗结束和随访时,血清Pc-Ⅲ、HA和Ⅳ-c水平均显著低于基线水平(P＜0.05);3例(5.6%)患者出现NS5A耐药位点突变,其中1例(1.8%)患者同时存在L31Y和Y93H位点突变,2例(3.7%)患者存在Y93H突变。结论 DAC联合ASV治疗初治治疗的基因1b型感染的CHC患者近期疗效良好,无肾功能损伤表现。个别病例出现的NS5A耐药位点突变的意义还需要进一步研究。

关键词: 慢性丙型肝炎, 1b基因型, 达拉他韦, 阿舒瑞韦, 治疗, 初治

Abstract: Objective The aim of this study was to investigate the clinical antiviral efficacy of dalatavir (DCV) and asulivir (ASV) combination in the treatment of naïve patients with chronic hepatitis C (CHC) with genotype 1b infection. Methods 53 naïve patients with CHC and genotype 1b infection were enrolled in our hospital between October 2019 and October 2021, and all of them received the combination regimen of DCV and ASV therapy for 24 weeks, and were followed-up for 24 weeks. Serum HCV RNA loads, blood biochemical indexes and liver fibrosis index levels were detected. The drug resistance-related mutations of NS5A were detected by direct sequencing. Results At week 1, 2, 4, 8, 12 and 24 treatment, and at the end of 24 week follow-up, serum HCV RNA loss rates in the 53 patients with CHC were 3.7%, 9.4%, 43.3%, 69.8%, 83.0%, 94.3% and 94.3%, and serum HCV RNA loads were (5.8±0.1)lg IU/ml, (5.3±0.6)lg IU/ml, (3.5±0.5)lg IU/ml, (2.2±0.6)lg IU/ml, (1.0±0.2)lg IU/ml, (0.7±0.5)lg IU/ml and (0.7±0.4)lg IU/ml, all significantly lower than [(6.1±0.4)lg IU/ml, P＜0.05] at baseline; at treatment week 24 and at the end of follow-up, serum AST levels were (22.7±11.4)U/L and (20.9±9.9)U/L, both significantly lower than [(63.5±6.6)U/L, P<0.05], and serum ALT levels were (19.3±10.7)U/L and (19.2±8.5)U/L, both significantly lower than [(80.2±65.3)U/L, P＜0.05] at baseline; there were no obvious changes as respect to estimated glomerular filtration rate and blood routines during the treatment; at the end of treatment and follow-up, serum liver fibrosis indexes, such as Pc-III, HA and IV-c levels decreased greatly (P＜0.05); the drug resistance-related mutations of NS5A was found in 3 cases (5.6%), out of which, the L31Y and Y93H simultaneous mutation in one case, and Y93H mutation in two cases. Conclusion The combination of DAC and ASV in treatment of naïve patients with CHC with genotype 1b infection is definitely efficacious, without renal function injury, while the NS5A mutations needs further investigation.

Key words: Hepatitis C, Genotype 1b, Dalatavir, Asurivir, Therapy, Naïve

张珂瓈, 童静, 李昌平. 接受达拉他韦和阿舒瑞韦治疗的初治基因1b型慢性丙型肝炎患者疗效评价^*[J]. 实用肝脏病杂志, 2024, 27(6): 840-843.

Zhang Keli, Tong Jing, Li Changping. Antiviral efficacy of dalatavir and asulivir combination in the treatment of naïve patients with chronic hepatitis C with genotype 1b infection[J]. Journal of Practical Hepatology, 2024, 27(6): 840-843.

参考文献

[1] 李生浩, 张黎, 张瑞仙. 1990-2019年中国丙型病毒性肝炎疾病负担评估. 中国感染控制杂志, 2022, 21(10):971-976.
[2] Du G, Li X, Musa TH, et al.The nationwide distribution and trends of hepatitis C virus genotypes in mainland China. J Med Virol, 2019, 91(3):401-410.
[3] Lee MH, Yang HI, Lu SN, et al.Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma. Int J Cancer, 2014, 135(5):1119-1126.
[4] Barnett PG, Joyce VR, Lo J, et al.Effect of interferon-free regimens on disparities in hepatitis C treatment of US veterans. Value Health, 2018, 21(8):921-930.
[5] 中华医学会肝病学分会和感染病学分会.《丙型肝炎防治指南》2019年更新版.实用肝脏病杂志,2020,23(1):S33-52.
[6] Lazarus JV, Roel E, Elsharkawy AM. Hepatitis C virus epidemiology and the impact of interferon-free hepatitis C virus therapy. Cold Spring Harb Perspect Med, 2020, 10(3):a036913.
[7] Martinez MA, Franco S. Discovery and development of antiviral therapies for chronic hepatitis C virus infection. Adv Exp Med Biol, 2021, 1322:139-157.
[8] Feld JJ, Jacobson IM, Hézode C, et al.Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med, 2015, 373(27):2599-2607.
[9] Andrieux-Meyer I, Tan SS, Thanprasertsuk S, et al. Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial. Lancet Gastroenterol Hepatol, 2021, 6(6):448-458.
[10] Welzel TM, Asselah T, Dumas EO, et al.Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously untreated patients with hepatitis C virus genotype 1b infection without cirrhosis (GARNET): a single-arm, open-label, phase 3b trial. Lancet Gastroenterol Hepatol, 2017, 2(7):494-500.
[11] Parlati L, Hollande C, Pol S. Treatment of hepatitis C virus infection. Clin Res Hepatol Gastroenterol, 2021, 45(4):101578.
[12] Isakov V, Paduta D, Viani RM, et al. Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV). Eur J Gastroenterol Hepatol, 2018, 30(9):1073-1076.
[13] Lancaster K, Rhodes T, Rance J. Towards eliminating viral hepatitis: Examining the productive capacity and constitutive effects of global policy on hepatitis C elimination. Int J Drug Policy, 2020, 80:102419.
[14] 杨仕贵. 消除病毒性肝炎公共卫生威胁,机遇与挑战并存. 中华疾病控制杂志, 2021, 25(7):749-752.
[15] 饶慧瑛, 李明阳, 魏来. 消除丙型肝炎,我们的进展、挑战和希望. 中华肝脏病杂志, 2020, 28(10):809-811.
[16] Toyoda H, Kumada T, Tada T, et al.Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B. J Hepatol, 2017, 66(3):521-527.
[17] Lu Y, Jin X, Duan CA, et al. Cost-effectiveness of daclatasvir plus asunaprevir for chronic hepatitis C genotype 1b treatment-naïve patients in China. PLoS One, 2018, 13(4):e0195117.
[18] Dietz C, Maasoumy B. Direct-Acting antiviral agents for hepatitis C virus infection-from drug discovery to successful implementation in clinical practice. Viruses, 2022, 14(6):1325.
[19] Yamane D, McGivern DR, Masaki T, et al. Liver injury and disease pathogenesis in chronic hepatitis C. Curr Top Microbiol Immunol, 2013, 369:263-288.
[20] Yeh ML, Kuo HT, Huang CI, et al. Eradication of hepatitis C virus preserve liver function and prolong survival in advanced hepatocellular carcinoma patients with limited life expectancy. Kaohsiung J Med Sci, 2021, 37(2):145-153.
[21] Mazzaro C, Quartuccio L, Adinolfi LE, et al. A review on extrahepatic manifestations of chronic hepatitis C virus infection and the impact of direct-acting antiviral therapy. Viruses, 2021, 13(11):2249.
[22] 李建国, 曾国芬, 曾映夫, 等. 直接抗病毒药对慢性丙型肝炎患者外周血单个核细胞频率及其活化因子sCD14s、CD163的影响. 中华肝脏病杂志, 2020, 28(12):1018-1022.
[23] Signorovitch JE, Betts KA, Song Y, et al.Comparative efficacy and safety of daclatasvir/asunaprevir versus IFN-based regimens in genotype 1b hepatitis C virus infection. J Comp Eff Res, 2015, 4(6):593-605.
[24] 冯亦农, 王泽红, 周丽, 等. 达拉他韦联合阿舒瑞韦治疗基因1b型慢性丙型肝炎13例报告. 临床肝胆病杂志, 2018, 34(12):2650-2652.
[25] Sato K, Uraoka T. Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus.World J Gastroenterol, 2018, 24(38):4304-4310.
[26] Teraoka Y, Uchida T, Imamura M, et al.Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure. J Gen Virol, 2018, 99(8):1058-1065.

接受达拉他韦和阿舒瑞韦治疗的初治基因1b型慢性丙型肝炎患者疗效评价^*

Antiviral efficacy of dalatavir and asulivir combination in the treatment of naïve patients with chronic hepatitis C with genotype 1b infection

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张少博, 张树庚, 刘连新. 免疫治疗肝细胞癌肝移植患者现状和前景展望^*[J]. 实用肝脏病杂志, 2024, 27(6): 801-803.
[2]	郑浩, 张树庚, 王嘉倍, 郭亚飞. 肝移植术治疗肝细胞癌患者肿瘤复发再治疗策略^*[J]. 实用肝脏病杂志, 2024, 27(6): 804-807.
[3]	朱泽斌, 张树庚, 刘连新. 靶向和免疫治疗原发性肝癌:肝移植术前降期治疗应用进展^*[J]. 实用肝脏病杂志, 2024, 27(6): 808-811.
[4]	张天挺, 许晶, 姜正伟, 嵇卉. 丙酚替诺福韦联合肝爽颗粒治疗慢性乙型肝炎患者疗效及其对肝纤维化指标的影响^*[J]. 实用肝脏病杂志, 2024, 27(6): 820-823.
[5]	张丽, 冯禧轩, 刘飞, 延欢欢. 丙酚替诺福韦联合PEG-IFNα-2b治疗慢性乙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 824-827.
[6]	何振文, 徐刚, 孟华, 陈辉, 周庆坤. 艾米替诺福韦再治疗低病毒血症的慢性乙型肝炎患者临床疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 828-831.
[7]	朱中华, 胡均贤, 李炎. 索非布韦/达克拉韦治疗CHC患者血清血管性血友病因子和可溶性血管黏附因子1水平变化^*[J]. 实用肝脏病杂志, 2024, 27(6): 836-839.
[8]	乔进, 赵彦, 窦志华. 半量索磷布韦联合全量达卡他韦治疗终末期肾病合并慢性丙型肝炎患者疗效和耐受性评价^*[J]. 实用肝脏病杂志, 2024, 27(6): 844-847.
[9]	李靓, 段丽祥, 孙晓红. NucliSens miniMag与QIAamp系统检测血清丙型肝炎病毒RNA效能比较^*[J]. 实用肝脏病杂志, 2024, 27(6): 848-851.
[10]	陈蓉蓉, 蒋黎黎, 曹利华. 自身免疫性肝炎患者血清细胞因子水平变化及其与治疗应答的关系研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 852-855.
[11]	高宇, 杨磊, 胡光明, 孙占虎, 周涛, 肖杰. 自身免疫性肝炎患者血清巨噬细胞迁移抑制因子和白细胞介素-21水平变化及其对治疗应答的影响^*[J]. 实用肝脏病杂志, 2024, 27(6): 866-869.
[12]	武羽, 韩宇星, 徐曼曼, 焦婧然, 杨雪, 段小宛, 陈煜. DRG付费改革背景下慢加急性肝衰竭患者费用盈亏分析^*[J]. 实用肝脏病杂志, 2024, 27(6): 882-886.
[13]	马莉, 顾中盛, 李想. 内镜下套扎联合奥曲肽和埃索美拉唑治疗肝硬化并发食管静脉曲张破裂出血患者临床疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 903-906.
[14]	武文华, 蔡芝芳, 李亚萍, 贾晓黎, 党双锁. 肝动脉化疗栓塞联合射频消融治疗原发性肝癌患者血清炎症因子变化及其对远期生存率的影响^*[J]. 实用肝脏病杂志, 2024, 27(6): 927-930.
[15]	唐浩, 宋文渊, 程千里, 曾凯, 文拔辉. CT三维可视化指导腹腔镜精准肝段切除联合纤维胆道镜取石治疗复杂性肝胆管结石患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 939-942.