摘要目的 通过观察新生儿citrin缺陷肝内胆汁淤积症(NICCD)的肝穿刺活检病理标本,探讨肝病变的组织学特点及其诊断价值.方法 对10例NICCD患儿的肝穿刺标本进行HE、组织化学和免疫组织化学(EnVision法)等染色,应用聚合酶链反应(PCR)和PCR-限制性片段长度多态性方法常规筛查SLC25A13的2个等位基因的突变情况以确切诊断,在光镜下观察肝脏病变的特征.结果 10例NICCD均经基因检测予以确诊.乙型肝炎表面抗原、乙型肝炎核心抗原、PAS-D和铜的免疫组织化学与组织化学染色均为阴性.NICCD肝脏的主要病理组织学改变有大泡和微泡混合型肝细胞内脂肪沉积、坏死性炎性病变、胆汁淤积、胆栓形成和肝纤维化等并存而组成四联图像.其中,肝纤维化随病程的发展而加重,可最终导致肝硬化.结论 肝穿刺活检对NICCD的临床诊断应依据四联图像,尤以大泡和微泡混合型肝细胞内脂肪沉积为特点,与伴有脂肪性肝炎病理改变的其他各种肝病鉴别;提示应进行基因检测以确诊NICCD;可根据炎性反应和纤维化的发展趋势推测NICCD的预后.

abstractsObjective To investigate the diagnostic value of histopathological changes in the liver of patients with neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD).Methods Liver specimens from 10 cases of NICCD were evaluated by hematoxylin-eosin stain,histochemistry and immunohistochemistry(EnVision method).SLC25A13 mutation analysis was performed to correlate with histopathology.Results Most specimens showed varying degrees of fat deposition in hepatocytes,necrotic inflammation,cholestasis and fibrosis(so-called tetralogy).The combination of the above four histological changes was highly characteristic for NICCD.With the progression of the disease,hepatic fibrosis deteriorated and ultimately led to cirrhosis.Conclusions NICCD should be suspected in the presence of cholestasis during infancy.A liver biopsy must be performed to rule out other liver diseases.The tetralogy of the hepatic histopathological changes has a highly diagnostic value for NICCD,which is also practical for accurately assessing the degree of inflammation and fibrosis,and similarly the progression of hepatic cirrhosis.