D'Ambrosio Roberta, Degasperi Elisabetta, Aghemo Alessio, Fraquelli Mirella, Lampertico Pietro, Rumi Maria Grazia, Facchetti Floriana, Grassi Eleonora, Casazza Giovanni, Rosenberg William, Bedossa Pierre, Colombo Massimo
Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, Milan, Italy.
Division of Gastroenterology and Endoscopy, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
PLoS One. 2016 Jun 15;11(6):e0155967. doi: 10.1371/journal.pone.0155967. eCollection 2016.
Liver biopsy (LB) has lost popularity to stage liver fibrosis in the era of highly effective anti-hepatitis C virus (HCV) therapy, yet diagnosis of persistent cirrhosis may have important implications following HCV eradication. As performance of serological non-invasive tests (NITs) to predict residual fibrosis in non-viremic HCV patients is unknown, we investigated accuracy of NITs to predict residual fibrosis in cirrhotics after a sustained virological response (SVR) to interferon (IFN).
Thirty-eight patients with a pre-treatment histological diagnosis of cirrhosis and a 48-104 months post-SVR LB were tested with APRI, CDS, FIB-4, FibroQ, Forns Score, GUCI Index, King Score, Lok Index, PLF, ELF. In 23 (61%) patients, cirrhosis had histologically regressed.
All NITs values declined after SVR without any significant difference between regressors and non-regressors (AUROC 0.52-0.75). Using viremic cut-offs, PPV ranged from 34% to 100%, with lower NPV (63% - 68%). NITs performance did not improve using derived cut-offs (PPV: 40% - 80%; NPV: 66% - 100%). PLF, which combines several NITs with transient elastography, had the best diagnostic performance (AUROC 0.75, Sn 61%, Sp 90%, PPV 80%, NPV 78%). After treatment, none of the NITs resulted significantly associated with any of the histological features (activity grade, fibrosis stage, area of fibrosis).
The diagnostic estimates obtained using both viremic and derived cut-off values of NITs were suboptimal, indicating that none of these tests helps predicting residual fibrosis and that LB remains the gold standard for this purpose.
在高效抗丙型肝炎病毒(HCV)治疗时代,肝活检(LB)在肝纤维化分期中的应用已不如以往普遍,但持续性肝硬化的诊断在HCV根除后可能具有重要意义。由于血清学非侵入性检测(NITs)预测非病毒血症HCV患者残余纤维化的性能尚不清楚,我们研究了NITs预测干扰素(IFN)治疗获得持续病毒学应答(SVR)后肝硬化患者残余纤维化的准确性。
对38例治疗前经组织学诊断为肝硬化且SVR后48 - 104个月接受LB检查的患者进行了APRI、CDS、FIB-4、FibroQ、Forns评分、GUCI指数、King评分、Lok指数、PLF、ELF检测。23例(61%)患者的肝硬化在组织学上有所消退。
SVR后所有NITs值均下降,消退组与未消退组之间无显著差异(曲线下面积[AUROC]为0.52 - 0.75)。使用病毒血症临界值时,阳性预测值(PPV)范围为34%至100%,阴性预测值(NPV)较低(63% - 68%)。使用衍生临界值时,NITs的性能并未改善(PPV:;NPV:66% - 100%)。结合多种NITs与瞬时弹性成像的PLF具有最佳诊断性能(AUROC 0.75,敏感度[Sn] 61%,特异度[Sp] 90%,PPV 80%,NPV 78%)。治疗后,没有一种NITs与任何组织学特征(活动度分级、纤维化分期、纤维化面积)显著相关。
使用NITs的病毒血症临界值和衍生临界值获得的诊断估计均不理想,表明这些检测均无助于预测残余纤维化,LB仍是为此目的的金标准。