Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study.
Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study.
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DOI：
10.1186/s12879-018-3125-6
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发表时间：
2018-05-16
影响因子：
3.7
通讯作者：
members of the Lazio Region HCV treatment group
中科院分区：
文献类型：
--
作者：
Lanini S;Scognamiglio P;Mecozzi A;Lombardozzi L;Vullo V;Angelico M;Gasbarrini A;Taliani G;Attili AF;Perno CF;De Santis A;Puro V;Cerqua F;D'Offizi G;Pellicelli A;Armignacco O;Mennini FS;Siciliano M;Girardi E;Panella V;Ippolito G;members of the Lazio Region HCV treatment group
慢性丙型肝炎（CHC）的管理在过去几年中显著加快。目前，第二代直接作用抗病毒药物（DAAs）有望清除大多数患者的感染。在这里，我们提出了对拉齐奥临床网络数据进行的第一次分析的结果。该研究被设计成一个多中心队列：a)评估临床网络活动的前24个月治疗的进展；B)报告治疗的总体疗效；c)分析治疗后12周缺乏病毒学应答的潜在因素（SVR12）；d)评估达到SVR12的患者与未达到SVR12的患者在基线和治疗后12周的ALT变化。采用多水平混合效应logistic回归模型进行疗效分析。ALT时间变化采用患者水平随机截距和时间水平随机斜率的混合效应模型；即在治疗前或治疗后。2014年12月30日至2016年12月31日期间，5279名患者开始了DAA治疗；其中，5127人（14个临床中心）完成了为期12周的随访。SVR12的总比例为93.41% (N = 4780)， 14个临床中心之间无异质性。因严重副作用而中断治疗的患者极少（仅23例）。未经调整的分析表明，SVR12的比例根据患者的基线特征发生显著变化，但在调整潜在混杂因素后，只有遵守现行指南、肝脏疾病分期、性别、移植和HIV状态与治疗反应独立相关。ALT时间变化分析显示，大多数（但不是所有）达到SVR12的患者ALT水平正常化。我们的研究证实了DAAs在临床试验之外的非凡疗效。对于那些在DAAs时代之前被认为难以治疗且没有治疗选择的患者，DAAs的优势尤为显著。基于选择中心网络和根据疾病严重程度对患者进行优先排序的干预是成功的。需要进一步的研究来确定DAAs治疗后清除HCV是否可以阻止甚至恢复非肝硬化患者的肝纤维化和/或改善肝硬化患者的生活质量和预期。
Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy. Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.
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影响因子：
11.8
作者：
Lanini, Simone;Portella, Gina;Ippolito, Giuseppe
通讯作者：
Ippolito, Giuseppe
影响因子：
15.9
作者：
Lanini, Simone;Portella, Gina;Ippolito, Giuseppe
通讯作者：
Ippolito, Giuseppe
影响因子：
2.5
作者：
Alonso, S.;Riveiro-Barciela, M.;Fernandez-Rodriguez, C. M.
通讯作者：
Fernandez-Rodriguez, C. M.
影响因子：
3.7
作者：
d'Arminio Monforte A;Cozzi-Lepri A;Ceccherini-Silberstein F;De Luca A;Lo Caputo S;Castagna A;Mussini C;Cingolani A;Tavelli A;Shanyinde M;Gori A;Girardi E;Andreoni M;Antinori A;Puoti M;Icona Foundation and HepaIcona Study Group
通讯作者：
Icona Foundation and HepaIcona Study Group
影响因子：
3.7
作者：
Cento V;Nguyen THT;Di Carlo D;Biliotti E;Gianserra L;Lenci I;Di Paolo D;Calvaruso V;Teti E;Cerrone M;Romagnoli D;Melis M;Danieli E;Menzaghi B;Polilli E;Siciliano M;Nicolini LA;Di Biagio A;Magni CF;Bolis M;Antonucci FP;Di Maio VC;Alfieri R;Sarmati L;Casalino P;Bernardini S;Micheli V;Rizzardini G;Parruti G;Quirino T;Puoti M;Babudieri S;D'Arminio Monforte A;Andreoni M;Craxì A;Angelico M;Pasquazzi C;Taliani G;Guedj J;Perno CF;Ceccherini-Silberstein F
通讯作者：
Ceccherini-Silberstein F