Persico Marcello, Rosato Valerio, Aglitti Andrea, Precone Davide, Corrado Mariano, De Luna Antonio, Morisco Filomena, Camera Silvia, Federico Alessandro, Dallio Marcello, Claar Ernesto, Caporaso Nicola, Masarone Mario
Internal Medicine and Hepatology Division, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
Internal Medicine and Hepatology Department, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Antivir Ther. 2018;23(2):129-138. doi: 10.3851/IMP3186.
Direct antiviral agents (DAA) demonstrated high efficacy among HCV-infected patients in registered trials. Nevertheless, the impact of these therapies on liver stiffness measurement (LSM) and liver functionality in 'real-life' is not well-known. The aim of the present study was to evaluate the sustained virological response (SVR) impact on LSM and clinical parameters of DAA-therapy on a real-life population of HCV patients with F3/F4 fibrosis.
A total of 749 HCV genotype 1-4 patients with F3/F4 hepatitis undergoing antiviral therapy were consecutively enrolled in four centres of hepatology in Italy. Clinical, biochemical and imaging data were collected at the baseline (T0), at the end of treatment (EoT) and after 12 weeks (SVR12).
Out of 749 patients, 69.7% were F4 and 30.3% were F3. SVR12 was reached in 97.5%. LSM significantly decreased from T0 to EoT (P<0.001), whereas, it did not from EoT to SVR12 (P= not significant). Moreover, in F4 no significant differences were found in Child and MELD between T0, EoT and SVR12 (P= not significant). At the univariate analysis of clinical and liver parameters, baseline high glucose (P<0.005), type 2 diabetes (P<0.001), low alanine aminotransferase (ALT; P<0.001), low platelets (P<0.005), and the presence of esophageal varices (EV; P<0.001) were found to be associated with a lack of a significant EoT LSM improvement. At multiple regression, ALT (P<0.05), diabetes (P<0.005) and EV (P<0.05) were inversely associated with significant LSM reduction.
Virological response to DAA is associated with fibrosis regression and recovery of liver functionality and this can be detected as early as EoT. HCV eradication is associated with a rapid and significant clinical improvement that lasts over time and seems to be negatively influenced by diabetes and EV.
在注册试验中，直接抗病毒药物（DAA）在丙型肝炎病毒（HCV）感染患者中显示出高效性。然而，这些疗法在“现实生活”中对肝脏硬度测量（LSM）和肝脏功能的影响尚不清楚。本研究的目的是评估持续病毒学应答（SVR）对LSM的影响以及DAA疗法对HCV F3/F4纤维化患者实际人群临床参数的影响。
意大利四个肝病中心连续纳入了749例接受抗病毒治疗的HCV 1-4型F3/F4肝炎患者。在基线（T0）、治疗结束时（EoT）和12周后（SVR12）收集临床、生化和影像学数据。
749例患者中，69.7%为F4，30.3%为F3。97.5%的患者达到了SVR12。LSM从T0到EoT显著下降（P<0.001），而从EoT到SVR12则没有下降（P=无显著性差异）。此外，在F4患者中，Child和MELD在T0、EoT和SVR12之间没有显著差异（P=无显著性差异）。在对临床和肝脏参数的单变量分析中，发现基线高血糖（P<0.005）、2型糖尿病（P<0.001）、低丙氨酸转氨酶（ALT；P<0.001）、低血小板（P<0.005）以及食管静脉曲张（EV；P<0.001）与EoT时LSM无显著改善相关。在多元回归分析中，ALT（P<0.05）、糖尿病（P<0.005）和EV（P<0.05）与LSM显著降低呈负相关。
对DAA的病毒学应答与纤维化消退和肝功能恢复相关，这早在EoT时就能检测到。HCV根除与迅速且显著的临床改善相关，这种改善会持续一段时间，并且似乎受到糖尿病和EV的负面影响。
