索磷布韦联合维帕他韦在慢性HCV感染患者中的治疗效果

摘要/Abstract

摘要： 目的评估NS5B抑制剂索磷布韦(sofosbuvir,SOF)和NS5A抑制剂维帕他韦(velpatasvir,VEL)联合持续治疗慢性HCV感染患者12周后的安全性和有效性。方法选取我院收治的72例慢性HCV感染患者为研究对象,采用SOF/VEL片剂的治疗方案,检测观察患者血清HCV RNA 载量、肝功能检测包含AST、ALT、总胆红素(TBil)等,进行药物安全评估。结果慢性HCV感染患者治疗第4周和第12周后血清AST、ALT、TBil水平较治疗前均明显下降(P<0.05);APRI指数也在患者治疗的第4周和第12周明显下降(P<0.05)。抗病毒治疗2 周后42例(57%)慢性HCV感染患者HCV RNA 低于最低检测下限,在继续治疗4 周、8周和12 周时低于HCV RNA检测下限的患者分别达到64例(89%)、69例(96%)和70例(97%);疗程结束后12周,分别有18例(100%)2型、43例(96%)1b型、6例(75%)3型患者获得SVR。在治疗期间有46例(64%)患者出现不良反应,常见的为头痛、疲劳、恶心、咳嗽等轻微的不良反应。结论 SOF/VEL用于慢性HCV感染患者1b、2a和3型均有效且均有较高的 HCV RNA 转阴率,早期疗效显著,不良反应发生率降低且均为轻微反应,临床用药安全性较高。

关键词: 索磷布韦, 维帕他韦, 丙型肝炎, NS5A抑制剂, NS5B抑制剂

Abstract: Objective To determine the efficacy and safety of NS5B inhibitor sofosbuvir (SOF) combined with NS5A inhibitor velpatasvir (VEL) in the treatment of patients with chronic hepatitis C virus infection (CHC).Methods A total of 72 CHC patients received SOF/VEL 400/100 mg daily for 12 weeks, The patients were then tested for serum HCV RNA and liver function, including parameters of Alanine aminotransferase (ALT), Aspartate aminotransaminase (AST), total bilirubin (TBil). The safety of the medication was also evaluated.Results Serum AST, ALT and TBIL levels of the hepatitis C patients were significantly decreased after 4 and 12 weeks of SOF/VEL treatment (P<0.05). APRI index also significantly decreased at these time points (P<0.05). HCV RNA was below the detection limit in 42 patients (57%) after 2 weeks of antiviral treatment, and in 64 (89%), 69 (96%) and 70 patients (97%) after 4, 8 and 12 weeks of continued treatments, respectively. High sustained virologic response (SVR) rates were achieved in 18 patients with genotype 2a (100%), 43 patients with genotype 1b (97%), and 6 patients with genotype 3 (75%) at the end of 12 weeks' treatment (SVR12). respectively. Adverse reactions were reported in 46 (64%) patients during the treatment, which were most commonly headache, fatigue, nausea, cough and other mild symptoms.Conclusion SOF/VEL treatment is effective in patients with genotypes 1b, 2a and 3 HCV infection. The medication also has significant early efficacy, low incidence and mild adverse reactions, and high clinical safety.

Key words: Sofosbuvir, Velpatasvir, Hepatitis C, NS5A inhibitor, NS5B inhibitor

刘阳, 许莉, 冯友成, 蒋胜昌. 索磷布韦联合维帕他韦在慢性HCV感染患者中的治疗效果[J]. 肝脏, 2021, 26(1): 33-36.

LIU Yang, XU Li, FENG You-cheng, JIANG Sheng-chang. Treatment effect of sofosbuvir combined with velpatasvir on patients with hepatitis C viral infection[J]. Chinese Hepatolgy, 2021, 26(1): 33-36.

参考文献

[1] Thrift AP, Elserag HB, Kanwal F. Global epidemiology and burden of HCV infection and HCV-related disease. Nat Rev Gastro Hepat, 2017, 14:122-132.
[2] Munro J, Briggs JD, Mccruden EA. Detection of a cluster of hepatitis C infections in a renal transplant unit by analysis of sequence variation of the NS5a gene. J Infect Dis, 1996, 174:177-180.
[3] Von Felden J, Vermehren J, Ingiliz P, et al. High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection. Aliment Pharmacol Ther,2018,47:1288-1295
[4] 佚名. 索磷布韦/维帕他韦在丙型肝炎抗病毒治疗中的应用进展. 国际流行病学传染病学杂志, 2018, 45:289-292.
[5] Rockstroh JK, Ingiliz P, Petersen J, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, in real-world patients with HIV-HCV coinfection and advanced liver disease. Antivir Ther, 2017, 22:225.
[6] Bonsall D, Black S, Howe AY, et al. Characterization of hepatitis C virus resistance to grazoprevir reveals complex patterns of mutations following on-treatment breakthrough that are not observed at relapse. Infect Drug Resist, 2018, 11:1119-1135.
[7] Hezode C, Reau N, Svarovskaia ES, et al. Resistance Analysis in Patients with Genotype 1-6 HCV Infection Treated with Sofosbuvir/Velpatasvir in the Phase 3 Studies. J Hepatol, 2018, 68:895.
[8] Degasperi E, Tosetti G, D'Ambrosio R, et al. Incidence and outcome of portal vein thrombosis in HCV cirrhotic patients treated with direct-acting antivirals: A single-center prospective 3-year study . Digest Liver Dis, 2018, 50:30.
[9] Forns X, Charlton M, Denning J, et al. Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation. Hepatology, 2015, 61:1485-1494.
[10] Abdel-Moneim A, Aboud A, Abdel-Gabbar M, et al. A sofosbuvir-based quadruple regimen is highly effective in HCV type 4-infected Egyptian patients with DAA treatment failure . J Hepatol, 2018, 68:1313-1315.
[11] Bera C, Das P, Pal S. Safety and efficacy of sofosbuvir based regimen on patients with end stage renal disease—A single centre experience. J Clin Exp Hepatol, 2017, 7:S29.
[12] Curry MP , O'Leary JG , Bzowej N , et al. Sofosbuvir and velpatasvir for hcv in patients with decompensated cirrhosis. New Engl J Med, 2015, 373:2618-2628.
[13] Von J F, Vermehren J, Ingiliz P, et al. High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection. Aliment Pharm Ther, 2018, 47.
[14] Lawitz E, Bourlière M, Han L, et al. Treatment with SOF/VEL or SOF/VEL/VOX is well tolerated and results in high SVR12 in genotype 1-6 HCV infected patients with minimal fibrosis: a retrospective analysis of the ASTRAL and POLARIS clinical studies . J Hepatol, 2017,66:S310-S311.
[15] Foster GR , Afdhal N , Roberts SK , et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med, 2015,373: 2608-2617.
[16] Kosh A , Castells L, Müllhaupt B, et al. Sofosbuvir/Velpatasvir for 12 Weeks in Genotype 1-4 HCV-Infected Liver Transplant Recipients. J Hepatol,2018,69:603-607.
[17] Gane E , Kowdley KV , Pound D , et al. Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients with HCV Genotype 2, 3, 4, or 6 Infections in an Open-label, Phase 2 Trial. Gastroenterology,2016,151:902-909.
[18] Feld J J, Jacobson I M, Hézode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med, 2015, 373:2599-2607.
[19] Bourlière M, Gordon SC , Flamm SL , et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection . New Engl J Med, 2017, 376:2134-2146.