Vinciguerra Tiziana, Brunati Andrea, David Ezio, Longo Filomena, Pinon Michele, Ricceri Fulvio, Castellino Luisa, Piga Antonio, Giraudo Maria Teresa, Tandoi Francesco, Cisarò Fabio, Dell Olio Dominic, Isolato Giuseppe, Romagnoli Renato, Salizzoni Mauro, Calvo Pier Luigi
Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy.
Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy.
Pediatr Transplant. 2018 Mar;22(2). doi: 10.1111/petr.13125. Epub 2018 Jan 25.
As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.
由于小儿肝移植中的移植物存活常受进行性纤维化影响，许多中心开展了计划性肝活检。随访活检方案因中心而异，但随着移植后时间的增加，所有活检的间隔时间都逐渐延长。因此，对于那些没有肝脏损害临床或血清学迹象的儿童，需要非侵入性技术来评估移植物纤维化的进展。间接指标，如APRI，应谨慎使用，因为它们在预测纤维化方面的敏感性会受到肝病病因、纤维化严重程度和患者年龄的强烈影响。一种有效的替代方法可能是瞬时弹性成像（TE），这是一种已在成人中得到验证的非侵入性技术，它可估计肝脏组织圆柱形体积的硬度，该体积是标准穿刺活检样本大小的100倍。本研究的目的是评估TE在小儿肝移植受者中的可靠性，并将TE和APRI指数结果与肝活检的纤维化组织学评分进行比较。共研究了36例小儿肝移植受者。所有患者在肝移植后0.36至19.47年（中位时间3.02年）的1年内（中位间隔0.012个月）均接受了TE检查和活检。对活检标本进行组织学纤维化评估，并根据METAVIR标准进行分期。TE硬度值与METAVIR评分之间存在统计学显著相关性（P = 0.005）。TE诊断显著纤维化（F≥2）的诊断准确性以曲线下面积衡量（AUROC = 0.865），这表明该方法具有良好的诊断性能。与METAVIR相比，APRI在评估移植物纤维化方面不太准确（AUROC = 0.592）。TE测得的肝脏硬度临界值5.6 kPa被确定为肝活检中显著移植物纤维化（METAVIR F≥2）的最佳预测指标，其敏感性为75%，特异性为95.8%，阳性预测值为90%，阴性预测值为88.5%。这些数据表明，TE可能是小儿肝移植受者随访中评估移植物纤维化的一种非侵入性、可靠工具，可提醒临床医生肝活检的指征，以减少计划性肝活检的次数。
