Relationship between phenotype and genotype of ABCB11 deficiency in siblings and literature review / 中华儿科杂志

Objective@#To explore the relationship between genotype and phenotype of ABCB11 deficiency.@*Methods@#Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene’ or 'bile salt export pump’, 'cholestasis’ and 'child’ as key words.@*Results@#The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood.@*Conclusions@#The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.

Association between enterohepatic circulation of bile acid and cholestatic liver disease / 临床肝胆病杂志

The development of cholestatic liver disease is closely associated with the enterohepatic circulation disorder of bile acid.This article elaborates on metabolism of bile acid,enterohepatic circulation-related mechanism of hereditary cholestasis,molecular regulation of related transporters,and association between current therapeutic regimens and enterohepatic circulation,in order to investigate the pathogenesis of cholestatic liver disease and provide a basis for the research on new drugs or therapies.

Continuous intra-tracheal gas insufflation during mechanical ventilation in juvenile piglets with acute lung injury induced by endotoxin / 中华急诊医学杂志

Objective To evaluate the effects of continuous intra-tracheal gas insufflation (TGI) during mechanical ventilation for protecting the juvenile piglets with acute lung injury (ALI) induced by endotoxin. Method Twelve healthy juvenile piglets were anesthetized and mechanically ventilated at 2 cmH2O PEEP with 10 cmH2O peak inspiration pressure. The piglets were challenged with lipopolysaccharide (LPS) and randomly (random number) assigned to two groups (n = 6 each): (1) piglets treated with mechanical ventilation alone (group MV) and (2) piglets treated with TGI by continuous airway flow of 2 L/min (group TGI). FiO2 was set at 0.4 to avoid oxygen toxicity, and the piglets were continuously monitored with an oxygen analyzer. Results Tidal volume, ventilation efficacy index and mean airway pressure were significantly improved in piglets of TGI group (P < 0.01 or P < 0.05). Four hours after ALI, pH decreased to below 7.20 in piglets of MV group, and was higher in piglets of TGI group (P < 0.01). Similarly, PaCO2 was stable and was significantly lower in piglets of TGI group than that in piglets of MV group (P < 0.01). PaO2 and PaO2/FiO2 increased in piglets of TGI group (P < 0.05). There were no significant differences in heart rate, respiraaatory rate, mean arterial pressure, central venous pressure, dynamic lung compliance and mean resistance of airway between two groups. Lung histopathological changes showed severe inflammation,and intra-alveolar hemorrhage and interstitial patchy hemorrhage were ameliorated and the lungs were more homogenously expanded in piglets of TGI group. Conclusions Continuous TGI during MV can significantly improve gas exchange and ventilation efficacy, and may provide a better treatment for acute lung injury.