Efficacy of direct-acting antiviral agents in treatment of chronic hepatitis C and its effect on liver stiffness and aspartate aminotransferase-to-platelet ratio index
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摘要:
目的探讨目前直接抗病毒药物(DAA)治疗方案下,慢性丙型肝炎患者真实世界病毒应答情况及对肝硬度值和天门冬氨酸/血小板比值指数(APRI)的影响。方法连续性纳入2018年4月1日-2018年11月30日在天津市第三中心医院接受DAA治疗的慢性丙型肝炎患者,应用无干扰素方案的DAA治疗12~24周,评估治疗结束后第12周病毒学应答情况,对比基线及治疗结束后12周肝硬度值和APRI的变化。计量资料两组间比较采用Wilcoxon秩和检验。结果共纳入212例慢性丙型肝炎患者,其中肝硬化患者占35. 4%,基因1b、2a、3a、6a型分别占75. 0%、18. 4%、4. 2%及2. 4%。174例患者完成了DAA治疗疗程及治疗后12周随访。在DAA治疗结束和治疗结束后12周获得持续病毒学应答(SVR)的比例分别为98. 3%及95. 4%。基因1b型、2a型、3a型及6a型患者的SVR12分别为96. 3%、93. 1%、80. 0%及100%。治疗结束后12周肝硬度值较基线[9. 8(6. 9~16. 3) kPa vs 11. 4(7. 7~19. 1) kPa,Z=-2. 5,P=0. 0...
Abstract:Objective To investigate the real-world viral response of chronic hepatitis C( CHC) patients receiving direct-acting antiviral agent( DAA) treatment and its effect on liver stiffness measurement( LSM) and aspartate aminotransferase-to-platelet ratio index( APRI). Methods The CHC patients who were consecutively admitted to Tianjin Third Central Hospital from April 1,2018 to November30,2018 and received DAA treatment were enrolled,and all patients were treated with DAA( without interferon) for 12-24 weeks. Virologic response was evaluated at week 12 after treatment ended,and the changes of LSM and APRI from baseline to week 12 after treatment were compared. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups. Results A total of 212 CHC patients were enrolled in our study,among whom 35. 4% had liver cirrhosis,and the patients with genotype 1 b,2 a,3 a,or 6 a accounted for75. 0%,18. 4%,4. 2%,and 2. 4%,respectively. Of all patients,174 completed the course of DAA treatment and the 12-week follow-up,and among these patients,98. 3% achieved sustained virologic response( SVR) at the end of DAA treatment and 95. 4% acquired SVR at week 12 after the treatment ended. Among the patients with genotype 1 b,2 a,3 a,or 6 a,96. 3%,93. 1%,80. 0%,and 100%,respectively,achieved SVR at week 12 after the treatment ended. There were significant reductions in LSM [9. 8( 6. 9-16. 3) kPa vs 11. 4( 7. 7-19. 1) kPa,Z =-2. 5,P = 0. 012]and APRI [0. 34( 0. 25-0. 64) vs 0. 76( 0. 56-2. 25),Z =-6. 6,P < 0. 001]from baseline to week 12 after the treatment ended. The patients were divided into groups according to the presence or absence of liver cirrhosis at baseline,and the results showed that from baseline to week 12 after treatment ended,the non-liver cirrhosis group had a significant reduction in LSM[7. 6( 6. 6-10. 7) k Pa vs 8. 8( 7. 2-13. 0) kPa,Z =-2. 7,P = 0. 007],while the liver cirrhosis group had no significant change in LSM [17. 4( 12. 7-22. 1) kPa vs 19. 8( 12. 8-24. 9) kPa,Z =-1. 4,P = 0. 152]. There was a significant reduction in APRI from baseline to week 12 after treatment ended in the liver cirrhosis group [0. 73( 0. 52-1. 34) vs 1. 37( 0. 80-2. 11),Z =-3. 4,P <0. 001] and the non-liver cirrhosis group [0. 29( 0. 21-0. 36) vs 0. 54( 0. 31-0. 95),Z =-6. 8,P < 0. 001]. Conclusion In this real-world study,CHC patients treated with DAA achieve a high overall virological response rate,with significant improvements in LSM and APRI at week 12 after treatment ends.
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Key words:
- hepatitis C,chronic /
- antiviral agents /
- sustained virologic response /
- treatment outcome
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[1] Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015:A modelling study[J]. Lancet Gastroenterol Hepatol,2017,2(3):161-176. [2] GONZALEZ HC,DUARTE-ROJO A. Virologic cure of hepatitis C:Impact on hepatic fibrosis and patient outcomes[J].Curr Gastroenterol Rep,2016,18(7):32. [3] PERZ JF,ARMSTRONG GL,FARRINGTON LA,et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide[J]. J Hepatol,2006,45(4):529-538. [4] D'AMBROSIO R,DELLA CORTE C,COLOMBO M. Hepatocellular carcinoma in patients with a sustained response to antihepatitis C therapy[J]. Int J Mol Sci,2015,16(8):19698-19712. [5] ARIMA Y,KAWABE N,HASHIMOTO S,et al. Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C[J]. Hepatol Res,2010,40(4):383-392. [6] WEI L,CHENG J,LUO Y,et al. Efficacy and safety of paritaprevir/ritonavir/ombitasvir combined with dasabuvir in noncirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection:A randomized,doubleblind,placebo-controlled study-China data[J]. Chin J Hepatol,2018,26(5):359-364.(in Chinese)魏来,成军,罗燕,等.在初治和经治丙型肝炎病毒基因1b型慢性感染的非肝硬化亚洲成年患者中评价奥比帕利联合达塞布韦治疗的有效性和安全性:随机、双盲、安慰剂对照研究[J].中华肝脏病杂志,2018,26(5):359-364. [7] Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association. The guideline of prevention and treatment for hepatitis C:A 2015 update[J]. J Clin Hepatol,2015,31(12):1961-1979.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.丙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1961-1979. [8] European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018[J]. J Hepatol,2018,69(2):461-511. [9] European Association for Study of Liver,Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines:Non-invasive tests for evaluation of liver disease severity and prognosis[J]. J Hepatol,2015,63(1):237-264. [10] DUAN Z,JIA JD,HOU J,et al. Current challenges and the management of chronic hepatitis C in mainland China[J]. J Clin Gastroenterol,2014,48(8):679-686. [11] AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance2018 update:AASLD-IDSA recommendations for testing,managing,and treating hepatitis C virus infection[J]. Clin Infect Dis,2018,67(10):1477-1492. [12] CHAN A,PATEL K,NAGGIE S. Genotype 3 infection:The last stand of hepatitis C virus[J]. Drugs,2017,77(2):131-144. [13] AMPUERO J,REDDY KR,ROMERO-GOMEZ M. Hepatitis C virus genotype 3:Meta-analysis on sustained virologic response rates with currently available treatment options[J].World J Gastroenterol,2016,22(22):5285-5292. [14] FOSTER GR,AFDHAL N,ROBERTS SK,et al. Sofosbuvir and Velpatasvir for HCV genotype 2 and 3 infection[J]. N Engl J Med,2015,373(27):2608-2617. [15] SEZAKI H,SUZUKI F,HOSAKA T,et al. Initial-and retreatment effectiveness of glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C virus-genotype 1/2/3infections[J]. J Gastroenterol,2019,54(10):916-927. [16] RYDER SD,IRVING WL,JONES DA,et al. Progression of hepatic fibrosis in patients with hepatitis C:A prospective repeat liver biopsy study[J]. Gut,2004,53(3):451-455. [17] HOEFS JC,SHIFFMAN ML,GOODMAN ZD,et al. Rate of progression of hepatic fibrosis in patients with chronic hepatitis C:Results from the HALT-C Trial[J]. Gastroenterology,2011,141(3):900-908. [18] NAKAGOMI R,TATEISHI R,MASUZAKI R,et al. Liver stiffness measurements in chronic hepatitis C:Treatment evaluation and risk assessment[J]. J Gastroenterol Hepatol,2019,34(5):921-928. [19] CASTERA L. Noninvasive methods to assess liver disease in patients with hepatitis B or C[J]. Gastroenterology,2012,142(6):1293-1302. [20] KIM WR,BERG T,ASSELAH T,et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients[J]. J Hepatol,2016,64(4):773-780. [21] CHOU R,WASSON N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection:A systematic review[J]. Ann Intern Med,2013,158(11):807-820. [22] JIN CT,GUO LW,LIANG WF. Research progress on non-invasive serum markers for liver fibrosis assessment in patients with chronic hepatitis B[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition),2018,12(1):11-14.(in Chinese)金彩婷,郭利伟,梁伟峰.慢性乙型病毒性肝炎肝纤维化无创性血清诊断指标研究进展[J/CD].中华实验和临床感染病杂志(电子版),2018,12(1):11-14. [23] Review Panel for Liver Stiffness Measurementt. Recommendations for the clinical application of transient elastography in liver fibrosis assessment[J]. Chin J Hepatol,2013,21(6):420-424.(in Chinese)肝脏硬度评估小组.瞬时弹性成像技术诊断肝纤维化专家意见[J].中华肝脏病杂志,2013,21(6):420-424. [24] BACHOFNER JA,VALLI PV,KRGER A,et al. Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4score and aspartate aminotransferase-platelet ratio index[J]. Liver Int,2017,37(3):369-376. [25] TAG-ADEEN M,SABRA AM,AKAZAWA Y,et al. Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement[J]. Hepat Med,2017,9:45-53. [26] MORISHIMA C,SHIFFMAN ML,DIENSTAG JL,et al. Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis C[J]. Am J Gastroenterol,2012,107(9):1388-1398. [27] CHU CY,CHENG CH,CHEN HL,et al. Long-term histological change in chronic hepatitis C patients who had received peginterferon plus ribavirin therapy with sustained virological response[J]. J Formos Med Assoc,2019,118(7):1129-1137. -
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