Analysis Of Clinical Characteristics Of 709 Cases With Neonatal Intrahepatic Cholestasis Caused By Citrin Deficiency

Obejective:To summarize the clinical characteristics of Neonatal Intrahepatic cholestasis caused by Citrin deficiency(NICCD),and to provide evidences for clinical diagnosis and treatment of NICCD.Methods:Based on the principles and methods of Cochrane systematic reviews,we searched Pubmed,VIP,WANFANG and CNKI databases,from 2000 to June 2018.Descriptive systematic evaluation was used to clarify the clinical features of NICCD.Result:1.General information and clinical manifestations: 71 literatures met the inclusion criteria,including 709 children with NICCD,mainly in China(74.6%)and Japan(20.3%).The ratio of male to female was 1.44:1,onset time of 94.43% of NICCD patients was within 3 months of age.The common clinical manifestations were jaundice in skin and sclera(95.12%),hepatomegaly(75.2%),chubby face(73.21%),splenomegaly(52.68%),growth retardation(52.53%),steatorrhea(50.88%)and pottery stool(45.92%);cataract(14.29%)and subcutaneous bleeding spots(13.72%)were relatively rare.2.Biochemical and physicochemical characteristics: The proportions of increased direct bilirubin,total bilirubin,alanine aminotransferase and aspartate aminotransferase were 83.94%,95.61%,65.74% and 86.93% respectively;cases with DB/TB < 0.67 and AST/ALT > 2 accounted for 84.52% and 67.68%;cases with elevated gamma glutamyl transpeptidase and alkaline phosphatase accounted for88.64% and 84.03%;cases with decreased albumin,anemia and fasting hypoglycemia accounted for 71.72%,49.74% and 57.44% partly;cases with high cholesterol,plasma ammonia and lactate accounted for 34.64%,58.7% and 79.93%;theproportion of high alpha-fetoprotein and coagulation disorder was 97.47% and68.83%.3.Therapy: A total of 63 literatures reported the therapy of 651 children with NICCD.34.41% of them were fed with lactose-free diet,65.59% were fed with lactose-free and medium-chain triglyceride-rich diet;57.3% received ursodeoxycholic acid,36.25% of whom were given fat-soluble vitamins meanwhile,42.7% of all the patients did not receive any medication.4.Prognosis: 559 of 709 NICCD children(78.84%)had jaundice subsided and liver function level returned to normal after treatment(rate of improvement within 1year old and over 1 year old was 34.7% and 1.61%,63.69% of the children improved at unknown time).4.11% and 0.36% of all improved children have preference for high-protein diet and progressed to Adult-Onset Type ? Citrullinemia.There were35 deaths(4.94%)among 709 children with NICCD(37.14% deaths from liver failure,17.14% deaths from cirrhosis and 45.72% deaths from other causes);55 cases(7.76%)were lost to follow up.Conclusion:NICCD mostly occurs within 3 months of age.Its clinical manifestations include juandice,hepatomegaly,chubby face,splenomegaly,growth retardation,steatorrhea,pottery stool,cataract and subcutaneous bleeding spots.The biochemical characteristic was that DB,TB,ALT,AST,GGT and ALP were significantly increased,DB/TB < 0.67 and AST/ALT > 2 were common;It also contains low albumin,hypoglycemia,anemia,high cholesterol,elevated plasma ammonia and lactate,significantly increased AFP and coagulation disorder.The therapy for NICCD is dietary adjustment coordinating with freeing gallbladder.Most children with NICCD have a good prognosis,but there were still a few deaths.