纤维化指数有助于预测非酒精性脂肪肝孩子的肝纤维化程度

　　2009年6月2日，通过BMC Medicine五月刊的一篇研究报道得知，一个有预测性的非酒精性脂肪肝纤维化指数，能够有助于预测预测非酒精性脂肪肝孩子的纤维化程度。

　　"肝纤维化是非酒精性脂肪肝发展后的一个阶段，这与成人的肝脏引起的患病率和死亡率有关。"Valerio Nobili写到。Valerio Nobili来自意大利罗马IRCCS儿童医院。"因此，这项研究对非酒精性脂肪肝成人患者的诊治有着深远的影响，这里，我们开发了一种算法，可以在三级护理中心预测儿童肝纤维化程度。"

　　这个研究病例，囊括了136位男性，67位女性儿童非酒精性脂肪肝患者，其中141（69%）位患者通过肝活已经查出肝纤维化，这些患者的平均年龄是3.3-18周岁。

　　随肝纤维的潜在预测指数是基于生物可解性、测试简易度和成人研究结果进行确定的。这些建在的预测指数是性别、年龄、身体质量指数、腰围、谷丙转氨酶、天冬氨酸转氨酶、GGT、蛋白质、凝血酶原时间、葡萄糖、胰岛素、甘油三酯和胆固醇。这些指数通过辅助软件的阶梯式对数回归测得，并且最终的模型使用的是进行过偏离修正的阶梯式对数回归得出来的，从而产生出"非酒精性脂肪肝纤维化指数"，指数范围是0-10。

　　最终模型的预测指数包括年龄、腰围、甘油三酯水平。对于肝纤维化的预测，接受者操作特征曲线是0.85（偏离修正的置信区间是0.8-0.9）。简约拟合指数截止点是9或者更多，这类人经过肝穿检测，就是肝纤维化。对于简约拟合指数是9或者更多，阳性似然比是28.6，阳性预测值是98.5。

　　这项研究的限制性，包括高度选择序列的使用和缺乏外部交叉确认。因为大部分受测儿童是中度肝纤维化，研究者并不能预测严重的肝纤维化。而且，在这个序列中的纤维化患病率很高，这影响了研究者使用PNFI排除纤维化。

　　"PNFI是一个简单的无创指数，这个指数基于年龄、腰围和甘油三酯，能替代活检，在三级护理中心，判定非酒精性脂肪肝孩子的肝纤维化程度"研究者总结"但是，在使用这个指数之前，对外部人群必须进行PNFI交叉验证。"

　　原文：

　　Fibrosis Index May Help Predict Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease

　　June 2, 2009 - A pediatric nonalcoholic fatty liver disease (NAFLD) fibrosis index may help clinicians predict liver fibrosis in children with NAFLD, according to the results of a study reported in the May 1 issue of BMC Medicine.

　　"Liver fibrosis is a stage of...NAFLD which is responsible for liver-related morbidity and mortality in adults," write Valerio Nobili, from Pediatric Hospital IRCCS "Bambino Gesù" in Rome, Italy, and colleagues. "Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center."

　　The study sample consisted of 136 male and 67 female children with NAFLD, of whom 141 (69%) had fibrosis at liver biopsy. Age range was 3.3 to 18.0 years.

　　Potential predictors of liver fibrosis were identified based on biological plausibility, ease of testing, and evidence from adult studies. These potential predictors were sex, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), albumin, prothrombin time, glucose, insulin, triglycerides, and cholesterol. These were tested with bootstrapped stepwise logistic regression, and the final model was developed by use of bootstrapped logistic regression with bias correction, resulting in the "pediatric NAFLD fibrosis index" (PNFI) scored from 0 to 10.

　　Predictors included in the final model were age, waist circumference, and triglyceride levels. For the prediction of liver fibrosis, the area under the receiver operating characteristic curve was 0.85 (95% bootstrapped confidence interval [CI] with bias correction, 0.80 - 0.90). With a PNFI cutoff point of 9 or more, liver fibrosis could be diagnosed without performing liver biopsy. For a PNFI of 9 or more, the positive likelihood ratio was 28.6 (95% CI, 4.0 - 201.0), and positive predictive value was 98.5 (95% CI, 91.8 - 100.0).

　　Limitations of this study include use of a highly selected series and lack of external cross-validation. Because most of the children had moderate fibrosis, the investigators could not develop a predictor of severe fibrosis. Furthermore, the high prevalence rate of fibrosis in this series prevented the investigators from using PNFI to rule out fibrosis.

　　"PNFI is a simple and non-invasive index based on age, waist circumference and triglycerides that could be used in place of liver biopsy to rule in liver fibrosis in children with NAFLD followed at tertiary care centers," the study authors conclude. "However, before being employed for this purpose, PNFI must be cross-validated in external populations."

　　Internal funds (Pediatric Hospital "Bambino Gesù" and Liver Research Center) supported this study. The study authors have disclosed no relevant financial relationships.

　　BMC Med. 2009;7:21.