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Milan Jirsa Milan Jirsa Jií Bronsky Lenka Dvoáková Jan perl Vít majstrla Jií Horák Jií Nevoral Martin Hebícek 《World journal of gastroenterology : WJG》2014,20(19):5867-5874
AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC. 相似文献
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Guo-Hua Li Shi-Jia Huang Xiang Li Xiao-Song Liu Qiao-Ling Du 《World journal of gastroenterology : WJG》2020,26(46):7338-7351
BACKGROUNDIntrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.AIMTo investigate the link between the gut microbiota and serum metabolome in ICP patients.METHODSIn this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated.RESULTSThe Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome.CONCLUSIONOur study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP. 相似文献
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探讨血中总胆汁酸(TBA),血清抑制素A(INH-A)及可溶性细胞间黏附因子-1(sICAM-1)水平对妊娠合并肝内胆汁淤积症(ICP)病人病情严重程度的评估价值,选取本院100例ICP患者作为观察组,50例健康体检者作为对照组。结果显示,与对照组比较,观察组患者TBA,INH-A,sICAM-1显著增高,其中,重度组显著高于轻度组;联合TBA、INH-A、sICAM-1检测对诊断ICP病情程度进行诊断的敏感度、特异度及AUC均高于各指标单独诊断(P<0.05)。结果提示,TBA、INH-A、sICAM-1联合检测可作为评估ICP患者病情严重程度的重要指标。 相似文献
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Binita M. Kamath Philip Stein Roderick H. J. Houwen Henkjan J. Verkade 《Liver international》2020,40(8):1812-1822
Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are rare, inherited cholestatic liver disorders that manifest in infants and children and are associated with impaired bile flow (ie cholestasis), pruritus and potentially fatal liver disease. There are no effective or approved pharmacologic treatments for these diseases (standard medical treatments are supportive only), and new, noninvasive options would be valuable. Typically, bile acids undergo biliary secretion and intestinal reabsorption (ie enterohepatic circulation). However, in these diseases, disrupted secretion of bile acids leads to their accumulation in the liver, which is thought to underlie pruritus and liver‐damaging inflammation. One approach to reducing pathologic bile acid accumulation in the body is surgical biliary diversion, which interrupts the enterohepatic circulation (eg by diverting bile acids to an external stoma). These procedures can normalize serum bile acids, reduce pruritus and liver injury and improve quality of life. A novel, nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT), a key molecule in the enterohepatic circulation that reabsorbs bile acids from the intestine. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of paediatric cholestatic liver diseases. This review explores the rationale of inhibition of the IBAT as a therapeutic target, describes IBAT inhibitors in development and summarizes the current data on interrupting the enterohepatic circulation as treatment for cholestatic liver diseases including ALGS and PFIC. 相似文献
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Svenja Sydor Paul Manka Lea van Buren Sarah Theurer Suzan Schwertheim Jan Best Janette Heegsma Ali Saeed Diana Vetter Martin Schlattjan Anna Dittrich Maria I. Fiel Hideo A. Baba Alexander Dechêne Francisco J. Cubero Guido Gerken Ali Canbay Han Moshage Scott L. Friedman Klaas Nico Faber Lars P. Bechmann 《Liver international》2020,40(9):2172-2181
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[目的]评估丁二磺酸腺苷蛋氨酸(SAMe)治疗胆汁淤积性肝炎的效果及不良反应。[方法]68例胆汁淤积性肝炎患者被随机分为治疗组(38例)和对照组(30例)。2组均予常规保肝治疗,治疗组加用SAMe针剂1.0g/d静脉滴注,对照组加用苦黄针剂30ml/d静脉滴注,2组疗程均为4周。观察2组治疗前后临床症状与体征、生化指标[总胆红素(TBil)、直接胆红素(DBil)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酸转肽酶("-GT)、总胆汁酸(TBA)]、疗效及不良反应。[结果]治疗后治疗组TBil、DBil、"-GT及TBA下降程度明显高于对照组(P0.05或P0.01);其灰白便和皮肤瘙痒改善率也明显高于对照组(P0.05或P0.01);治疗组总有效率为84.2%,明显高于对照组的60.0%(P0.05)。2组患者耐受性良好,均无严重不良反应发生。[结论]SAMe治疗胆汁淤积性肝炎有确切的疗效,且安全性好。 相似文献
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The following is a case review of portal vein cavernous malformation presenting with intermittent cholestasis and jaundice in a 4 year old child. Correct assessment was supported by radiology, later laparoscopy, yet hindered by histopathology representative Wilson’s disease and elevated urinary copper excretion. During surgical procedure the stenosis of the common bile duct secondary to extremely dilated portal vein reticulation was solved by Roux-en-Y choledochojejunostomy. After a one-year follow up the child remains asymptomatic. 相似文献