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。
Objective The aim of this study was to investigate the clinical antiviral efficacy of dalatavir(DCV)and asulivir(ASV)combination in the treatment of na ve patients with chronic hepatitis C(CHC)with genotype 1b infection.Methods 53 na ve 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 na ve patients with CHC with genotype 1b infection is definitely efficacious,without renal function injury,while the NS5A mutations needs further investigation.
作者
张珂瓈
童静
李昌平
Zhang Keli;Tong Jing;Li Changping(Department of Gastroenterology,Affiliated Hospital,Southwest Medical University,Luzhou 646000,Sichuan Province,China)
出处
《实用肝脏病杂志》
CAS
2024年第6期840-843,共4页
Journal of Practical Hepatology
基金
四川省科技厅科研计划项目(编号:2019YFS0038)。
