胆道闭锁患儿Kasai手术后血清肝纤维化指标对预后的评估价值

Value of serum hepatic fibrosis indexes in the prognosis assessment of children undergoing Kasai surgery for biliary atresia

目的探究胆道闭锁患儿Kasai手术后血清肝纤维化指标对预后的评估价值。方法回顾性分析2017年1月至2021年1月在安徽省儿童医院新生儿外科行Kasai手术治疗的53例胆道闭锁患儿的临床资料,其中男性23例,女性30例,手术日龄为(62.91±19.93)d。根据患儿预后分为两组:自体肝生存时间(NLS)≥2年的患儿纳为预后良好组(n=31);NLS<2年的患儿纳为预后不良组(n=22)。收集患儿的性别、手术日龄、γ-谷氨酰转肽酶(GGT)、总胆红素(TBil)、直接胆红素(DBil)、肝脏病理纤维化分级、IV型胶原、透明质酸、层粘连蛋白及Ⅲ型前胶原肽(PC-Ⅲ)等临床资料。术后采用门诊复诊、电话、微信的方式随访。Spearman秩次相关检验血清肝纤维化指标与肝脏病理纤维化分级的相关性。利用受试者工作特征(ROC)曲线分析血清肝纤维化指标对早期预后的预测能力。结果Spearman秩次相关检验发现,Kasai手术时的肝脏病理纤维化分级与透明质酸(r_(s)=0.558,P<0.001)、IV型胶原(r_(s)=0.449,P=0.004)和PC-III(r_(s)=0.426,P=0.005)呈正相关,透明质酸与GGT(r_(s)=0.588)、TBil(r_(s)=0.365)和DBil(r_(s)=0.433)呈正相关(均P<0.001),IV型胶原与GGT(r_(s)=0.696)、TBil(r_(s)=0.570)和DBil(r_(s)=0.619)呈正相关(均P<0.001),PC-III与GGT(r_(s)=0.580)、TBil(r_(s)=0.484)和DBil(r_(s)=0.538)呈正相关(均P<0.001)。与预后良好组相比,预后不良组患儿在术后1个月、3个月时的透明质酸[1个月:334.1(164.4,776.0)ng/ml比116.3(70.0,262.1)ng/ml,Z=2.66,P=0.007;3个月:394.6(161.6,800.0)ng/ml比131.9(103.2,189.4)ng/ml,Z=2.39,P=0.016]及IV型胶原[1个月:640.0(568.0,640.0)ng/ml比338.9(234.8,640.0)ng/ml,Z=2.40,P=0.016;3个月:640.0(161.6,800.0)ng/ml比277.2(167.7,495.0)ng/ml,Z=2.39,P=0.015]均增高,差异有统计学意义;预后不良组在术后3个月时的PC-III高于预后良好组[550.0(550.0,550.0)ng/ml比281.0(199.9,548.1)ng/ml],差异有统计学意义(Z=2.73,P=0.005)。术后3个月时的透明质酸预测胆道闭锁患儿Kasai术后预后的ROC曲线下面积为0.724(95%CI:0.586~0.986,P=0.006),最佳截值为215.95 ng/ml,其灵敏度和特异度分别为86.4%和83.9%。结论胆道闭锁患儿Kasai手术后3个月时较高的透明质酸水平提示预后不佳。

Objective To evaluate the prognostic value of serum hepatic fibrosis indexes in children undergoing Kasai surgery for biliary atresia.Methods Clinical data of 53 children with biliary atresia undergoing Kasai surgery in the Department of Neonatal Surgery of Anhui Children's Hospital from January 2017 to January 2021 were retrospectively analyzed,including 23 males and 30 females,aged(62.91±19.93)days.Patients were divided into two groups according to the prognosis.Patients with native liver survival(NLS)≥2 years were classified as good prognosis group(n=31),and patients with NLS<2 years as poor prognosis group(n=22).Clinical data such as gender,age of operation,gamma-glutamyl transpeptidase(GGT),total bilirubin(TBil),direct bilirubin(DBil),liver pathological fibrosis grade,type IV collagen,hyaluronic acid,laminin and type III procollagen peptide(PC-Ⅲ)were collected.Postoperative data were collected by outpatient follow-up,telephone and Wechat.Spearman rank correlation test was conducted to determine the correlation between serum liver fibrosis index and liver pathological fibrosis grade.Receiver operating characteristic(ROC)curve was used to analyze the predictive ability of serum hepatic fibrosis indexes for early prognosis.Results Spearman rank correlation test showed that the grade of liver pathological fibrosis at Kasai surgery was positively correlated with hyaluronic acid(r_(s)=0.558,P<0.001),type IV collagen(r_(s)=0.449,P=0.004)and PC-III(r_(s)=0.426,P=0.005).Hyaluronic acid was positively correlated with GGT(r_(s)=0.588),TBil(r_(s)=0.365)and DBil(r_(s)=0.433)(all P<0.001).Type IV collagen was positively correlated with GGT(r_(s)=0.696),TBil(r_(s)=0.570)and DBil(r_(s)=0.619)(all P<0.001).PC-III was positively correlated with GGT(r_(s)=0.580),TBil(r_(s)=0.484)and DBil(r_(s)=0.538)(all P<0.001).Compared with the good prognosis group,the hyaluronic acid levels of children in the poor prognosis group at 1 month and 3 months after_(s)urgery[1 month:334.1(164.4,776.0)ng/ml vs.116.3(70.0,262.1)ng/ml,Z=2.66,P=0.007;3 months:394.6(161.6,800.0)ng/ml vs.131.9(103.2,189.4)ng/ml,Z=2.39,P=0.016]and type IV collagen[1 month:640.0(568.0,640.0)ng/ml vs.338.9(234.8,640.0)ng/ml,Z=2.40,P=0.016;3 months:640.0(161.6,800.0)ng/ml vs.277.2(167.7,495.0)ng/ml,Z=2.39,P=0.015]were increased.The PC-III level in the poor prognosis group was higher than that in the good prognosis group at 3 months after surgery[550.0(550.0,550.0)ng/ml vs.281.0(199.9,548.1)ng/ml,Z=2.73,P=0.005].The area under ROC curve of hyaluronic acid at 3 months after surgery to predict the prognosis of patients with biliary atresia undergoing Kasai surgery was 0.724(95%CI:0.586-0.986,P=0.006),and the best cut-off value was 215.95 ng/ml,with sensitivity and specificity of 86.4%and 83.9%,respectively.Conclusion High levels of hyaluronic acid at 3 months after Kasai surgery in children with biliary atresia indicates poor prognosis.