聚乙二醇干扰素或利巴韦林剂量对接受过治疗的慢性丙型肝炎和晚期肝纤维化患者使用特拉匹韦治疗疗效的影响：一项多中心队列研究
Effect of Peginterferon or Ribavirin Dosing on Efficacy of Therapy With Telaprevir in Treatment-Experienced Patients With Chronic Hepatitis C and Advanced Liver Fibrosis: A Multicenter Cohort Study.
作者信息
Janczewska Ewa, Flisiak Robert, Zarebska-Michaluk Dorota, Kozielewicz Dorota, Berak Hanna, Dobracka Beata, Librant-Suska Marta, Lojewski Wladyslaw, Jurczyk Krzysztof, Musialik Joanna, Postawa-Klosińska Barbara, Wroblewski Jacek, Augustyniak Krystyna, Dudziak Marek, Olszok Iwona, Ruszala Agata, Pisula Arkadiusz, Lapinski Tadeusz, Kryczka Wieslaw, Horban Andrzej, Dobracki Witold
机构信息
From the ID Clinic, Myslowice, Poland (EJ, AP); Klinika Chorob Zakaznych i Hepatologii, Uniwersytet Medyczny, Białystok, Poland (RF, TL); Uniwersytet J. Kochanowskiego i Wojewodzki Szpital Zespolony, Kielce, Poland (DZ-M, WK); Department of Infectious Diseases and Hepatology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland (DK); Hospital of Infectious Diseases, Warsaw, Poland (HB); Infectious Diseases Clinic, Wroclaw, Poland (BD, WD); Poradnia Wirusowych Zapalen Watroby SU, Kraków, Poland (ML-S); NZOZ Poradnia Chorob Watroby, Zielona Gora, Poland (WL); Department of Infectious Diseases, Hepatology, and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland (KJ); Department of Gastroenterology and Hepatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland (JM); Department of Basic Biomedical Science, School of Pharmacy, Division of Laboratory, Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland (JM); Oddzial Obserwacyjno-Zakazny, Szpital im. Zeromskiego, Kraków, Poland (BP-K); Oddzial Obserwacyjno-Zakazny, Szpital Wojewodzki, Koszalin, Poland (JW); Oddzial Chorób Zakaznych, Walbrzych, Poland (KA); Klinika Chorob Infekcyjnych i Alergologii WIM, Warsaw, Poland (MD); Oddzial Obserwacyjno-Zakazny, Szpital Rejonowy, Raciborz, Poland (IO); Ośrodek Leczenia WZW, Centrum Medyczne, Lancut, Poland (AR); Warsaw Medical University and Hospital of Infectious Diseases, Warsaw, Poland (AH); and Faculty of Health Science, Medical University, Wroclaw, Poland (WD).
出版信息
Medicine (Baltimore). 2015 Sep;94(38):e1411. doi: 10.1097/MD.0000000000001411.
We investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis.Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets <100,000/mm or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received <60% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%).Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level <35 g/L and/or platelet count <100,000/mm) group.Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.
我们研究了利巴韦林和聚乙二醇干扰素剂量降低对接受特拉匹韦三联疗法的晚期肝纤维化经治患者的完全早期病毒学应答和持续病毒学应答（SVR）的安全性、有效性及影响。对211例曾接受聚乙二醇干扰素和利巴韦林治疗失败、有桥接纤维化（F3，n = 68）或肝硬化（F4，n = 143）的患者开始进行治疗，其中包括103例（49%）无应答者（NR）、30例（14%）部分应答者（PR）和78例（37%）复发者（REL）。40例患者存在肝功能受损（ILF），血小板<100,000/mm³或白蛋白<35 g/L。丙型肝炎病毒亚型分布为：1a、1b或1型，分别有10例（5%）、187例（89%）和14例（6%）患者亚型未确定。治疗起始采用标准剂量的聚乙二醇干扰素α - 2a或α - 2b、利巴韦林和特拉匹韦。总体SVR24率为56%，肝硬化患者（NR：35%，PR：40%，REL：63%）低于有桥接纤维化的患者（NR：50%，PR：75%，REL：75%）。SVR24概率最低的是伴有ILF的NR患者（26%）。接受利巴韦林总剂量<60%对比>60%的NR患者，SVR24率显著降低（分别为23%对比44%），接受利巴韦林总剂量<80%对比>80%的患者也如此（分别为33%对比48%）。聚乙二醇干扰素总剂量降低后，SVR24显著下降，比较接受总剂量<60%对比>60%的患者时（NR：0%对比44%；REL：33%对比68%）以及接受总剂量<80%对比>80%的患者时（NR：17%对比50%；REL：46%对比71%）均是如此。31例患者（15%）观察到严重不良事件。4例患者死亡。所有死亡受试者均为ILF组的肝硬化患者（基线血清白蛋白水平<35 g/L和/或血小板计数<100,000/mm³）。利巴韦林剂量降低对REL患者的疗效无影响，但对NR患者有影响。聚乙二醇干扰素剂量降低使所有组的SVR24率下降，尤其是既往NR患者。ILF增加了发生致命并发症的风险且实现SVR24的概率较低。一种解决办法可能是为经治患者，尤其是肝硬化患者，广泛且早期提供新型高效安全的无干扰素联合治疗方案。
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