婴儿胆汁淤积症的病因研究进展

婴儿胆汁淤积症是一类多因素引起的以高胆红素血症为临床特点的综合征,病因谱广泛,包括感染、中毒、肝内外胆管发育异常及遗传代谢缺陷等.感染、胆道闭锁患儿占胆汁淤积症患儿半数以上,除了常见病因,citrin缺陷症、Alagille综合征、进行性家族性胆汁淤积症等新病因不断被认识,这些疾病临床症状与胆道闭锁相似,预后及治疗各不...     

遗传代谢相关的婴儿胆汁淤积症

胆汁淤积症是婴儿期较常见的疾病,在引起婴儿胆汁淤积症的病因中,遗传代谢异常受到了越来越多的关注,如Citrin缺陷导致的新生儿胆汁淤积症、进行性家族性肝内胆汁淤积症等。在临床上,遇到婴儿胆汁淤积症的患儿除考虑感染因素外,应注意遗传代谢因素。     

婴儿胆汁淤积性肝病的治疗

婴儿胆汁淤积性肝病的病因复杂,临床主要表现为高结合胆红素血症、粪便颜色改变、胆汁酸增加,可伴或不伴肝大,质地异常,肝功能异常;部分患儿还可伴皮肤瘙痒、营养不良等表现。治疗的主要原则为保肝、利胆、营养和病因治疗。预后因病因而异。     

新生儿及婴儿胆汁淤积症诊断方法及流程进展

<正>胆汁淤积症(cholestasis)是以高结合胆红素血症为主要临床表现的综合征~([1]),病因复杂;除胆道闭锁(biliary atresia,BA)、早产儿静脉营养相关、感染等病因外,多种导致胆汁淤积症的遗传学病因,逐渐被认识。尽早确定病因,是改善患儿预后的关键,但目前国内关于新生儿及婴儿胆汁淤积症的临床诊断流程尚未达成共识。本文就胆汁淤积症不同诊断方法进展及国内外诊断管理方案最新     

婴儿巨细胞病毒感染并血液系统损害

目的　探讨巨细胞病毒 (CMV)感染致小婴儿血液等多系统损害。方法　对 7例CMV感染并多系统损害患儿的临床及实验室资料进行回顾性分析。结果　 7例均证实为CMV感染 ,并两个系统以上损害 ,部分患儿以血液系统损害为首发表现。结论　婴儿CMV感染同时并多系统损害 ,用一般病因难以解释 ,追踪观察为巨细胞病毒感染应尽早治疗干预     

婴儿巨细胞病毒感染的血液系统损害

目的 探讨巨细胞病毒(CMV)感染致小婴儿血液等多系统损害。方法 对7例CMV感染并多系统损害患儿的临床及实验室资料进行回顾性分析。结果 7例均证实为CMV感染，并两个系统以上损害，部分患儿以血液系统损害为首发表现。结论婴儿CMV感染同时并多系统损害，用一般病因难以解释，追踪观察为巨细胞病毒感染应尽早治疗干预。     

早产儿胃肠外营养相关性胆汁淤积症临床研究

目的 探讨生后早期使用静脉营养的早产儿胆汁淤积症的临床特点,分析胃肠外营养相关性胆汁淤积症(parenteral nutrition associated cholestasis,PNAC)的相关因素及防治措施.方法 回顾性分析2011年1月至2016年4月出生并在盛京医院住院治疗的早产儿,生后均早期使用静脉营养2周,后出现胆汁淤积,共89例,分为两组,PNAC组即符合PNAC诊断(未发现其他导致胆汁淤积原因)41例,多病因组(除胃肠外营养因素还有其他病因)48例.通过病例对照研究分析其临床特点.结果 早产儿胆汁淤积症的男女比例为2.18:1,平均胎龄(31.05 ±2.15)周,平均出生体重(1360.55±421.14)g,静脉营养平均使用时间为(26.22±9.78)d.PNAC组根据丙氨酸氨基转移酶是否升高又分为肝炎组与非肝炎组,两组在胎龄、静脉营养开始时间、生后黄疸出现时间、开奶时间、氨基酸起始剂量及脂肪乳最大剂量方面的差异均有统计学意义,(P＜0.05);根据胃肠外营养时间分为长期组(≥20d)与短期组(＜20 d),长期组的谷丙转氨酶、谷草转氨酶、总胆红素、直接胆红素及胆汁酸水平均高于短期组,但P均≥0.05.多病因组患儿多合并感染,依次为细菌感染(75.0％)、真菌感染(20.83％)、巨细胞病毒感染(8.33％)和梅毒感染(2.08％)等.PNAC组和多病因组其他并发疾病的发生率差异无统计学意义.在预后方面,两组患儿经过保肝治疗后肝功能均较前明显好转,PNAC组的各项指标较多病因组降低更为显著(P＜0.05).结论 PNAC是早产儿胆汁淤积症发生的主要因素,PNAC早产儿肝损伤程度与胃肠外营养开始时间、使用时间、肠内喂养时间、氨基酸起始剂量及脂肪乳最大剂量有关.经保肝对症治疗后肝功能可以明显恢复,且效果优于多病因所致的胆汁淤积症.     

与感染相关的婴儿肝炎综合征

与感染相关的婴儿肝炎综合征可由多种病原引起,包括嗜肝病毒及非嗜肝病毒、细菌、弓形体、梅毒螺旋体等.主要临床表现为婴儿期(包括新生儿期)发病,肝功能异常,肝大、质地改变,伴有肝细胞性黄疸(血结合胆红素和未结合胆红素均增高).需要与遗传代谢病、药物引起的肝损伤或肝胆系统先天畸形鉴别.治疗原则为保肝、利胆、营养和病因治疗.预后因病原而异.     

婴儿胆汁淤积症的诊断与治疗

婴儿胆汁淤积症是婴儿期的常见病,由多种原因引起,临床表现为黄疸,瘙痒、粪便颜色改变、肝大或质地变化及血生化异常.根据胆汁淤积的部位分为肝细胞性胆汁淤积、胆管性胆汁淤积和混合性胆汁淤积.早期正确的诊断有助于选择恰当的治疗方法,改善预后.     

Citrin蛋白缺乏致新生儿肝内胆汁淤积症:更新的认识

Citrin蛋白缺乏所致新生儿肝内胆汁淤积症是由SLC25A13基因突变导致的常染色体隐性遗传病,主要表现为黄疸消退延迟、肝功能异常及高氨基酸血症,确诊依赖基因分析。Citrin蛋白缺乏是中国新生儿肝内胆汁淤积症的重要病因之一,近年来对该病的报道越来越多。文章综述Citrin蛋白缺乏所致新生儿肝内胆汁淤积症的流行病学、发病机制、临床特点、诊治进展等。     

Coincidence of congenital toxoplasmosis and biliary atresia in an infant.

A 4-week-old infant presenting with neonatal cholestasis was found to have congenital toxoplasmosis and biliary atresia. This is the first patient in which their coincidence is reported. Because biliary atresia can coexist with either congenital infection or inborn errors of metabolism, evaluation for an obstructive etiology of jaundice in infants with a recognized cause of intrahepatic cholestasis is necessary.     

婴儿胆汁淤积性肝病在中国的研究现状的可视化分析

目的展现中国关于婴儿胆汁淤积性肝病的研究情况,描绘该领域的研究趋势,提供未来研究的可能方向。方法采用共词分析法,于2016年10月以"胆汁淤积"及"婴儿"等关键词在中国知网(CNKI)及万方数据库进行文献检索及筛选,通过Excel2010建立高频关键词共现矩阵,使用Ucinet 6.0及Netdraw绘制高频关键词可视化网络图。结果共纳入相关文献383篇。共现分析图显示,在整个国内研究领域中以"婴儿""胆汁淤积"为核心,"婴儿肝炎综合征""新生儿""肝内""胆道闭锁""遗传代谢""肝炎""巨细胞病毒""黄疸""结合胆红素"为主要研究热点,其余大部分研究集中在"肠外营养""肝胆显像""(基因)突变""肝活检"等方面,而关于疾病的外科诊断技术以及疾病的治疗的研究较少。结论中国关于婴儿胆汁淤积性肝病的研究热点集中于病因学及鉴别诊断,基因诊断是近年来的关注点,有关治疗的研究尚有待加强,新的诊断技术是未来主要的研究方向。     

A Case of Lipoid Congenital Adrenal Hyperplasia Presenting with Cholestasis

Background

Lipoid congenital adrenal hyperplasia, is the rarest and usually the most severe form of adrenal steroidogenic defect,which may presents as infantile cholestasis.

Case Presentation

Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment.

Conclusion

Congenital adrenal hyperplasia as one of the causes of neonatal cholestasis should be kept in mind, whenever there are also electrolytes abnormalities.     

Resurgence of congenital syphilis: diagnosis and treatment

Despite comprehensive antenatal screening recommendations and inexpensive treatment, congenital syphilis has long been and continues to be a public health concern, causing substantial morbidity and adverse outcomes. The following article reviews syphilis etiology and presentation, clinical disease, laboratory diagnosis, and treatment of congenital syphilis. A case will be presented describing a 31-week male infant exposed to infectious syphilis in utero. The neonate presented with classic signs of infection at birth. After initial serology testing of the infant, appropriate treatment was commenced. The infant received crystalline penicillin G for a period of ten days in consultation with pediatric infectious disease specialists. As expected, the infant's rapid plasma reagin (RPR) titers declined by three and six months of age. An interdisciplinary approach provided safe and optimal care for this infant. He was discharged, stable, and thriving at 38 weeks corrected age. Long-term multidisciplinary management and follow-up were arranged.     

α1-抗胰蛋白酶缺乏症合并胆道闭锁1例报告及文献复习

目的探讨α1-抗胰蛋白酶缺乏症合并胆道闭锁的临床特点及早期诊断。方法回顾性分析1例α1-抗胰蛋白酶缺乏症合并胆道闭锁患儿的临床资料,并复习国内外相关文献。结果患儿,男,新生儿期即出现黄疸、肝脏肿大,血清谷丙转氨酶及谷草转氨酶升高、总胆红素和直接胆红素升高、γ-谷氨酰转肽酶增高,行十二指肠引流未引流出胆汁,手术探查、术中胆道造影及术后病理证实为胆道闭锁。基因检测发现SERPINA1突变,明确诊断为α1-抗胰蛋白酶缺乏症合并胆道闭锁。复习国内外文献,α1-抗胰蛋白酶缺乏性肝病患儿主要表现为胆汁淤积性黄疸、肝脾肿大、低白蛋白血症、血清谷丙转氨酶及谷草转氨酶升高、维生素K缺乏或肝脏合成功能障碍导致的凝血异常疾病;若早期不能及时诊断及进行干预治疗可引起进行性肝病或肝硬化。结论对不明原因胆汁淤积性肝病的患儿应积极寻找病因,必要时行基因检测,及早诊断、治疗,改善预后。     

Life-Threatening Intracranial Bleeding in a Newborn with Congenital Cytomegalovirus Infection: Late-Onset Neonatal Hemorrhagic Disease

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.     

Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.     

18q21杂合缺失致婴儿肝内胆汁淤积症伴智能发育落后1例病例报告

目的： 报告1例18q21杂合缺失致ATP8B1缺陷病（婴儿肝内胆汁淤积症）合并皮特-霍普金斯综合征（PHS）。 方法：总结患儿的临床特征、染色体芯片和基因检查结果。 结果：男,3个月2 d,因皮肤巩膜黄染2月余就诊。体重4 kg（＜P3）。颜面、躯干和四肢皮肤轻中度黄染,巩膜中度黄染,手心和足心无黄染。血清总胆红素明显升高,以直接胆红素升高为主,ALT、AST、总胆汁酸（TBA）、甲胎蛋白（AFP）升高,谷氨酰转肽酶（GGT)和白蛋白（ALB）正常,提示为低GGT胆汁淤积症。染色体芯片分析发现,患儿18号染色体长臂（18q21.2-q21.33）缺失11.6 Mb,8号染色体短臂（8p23.2）缺失961 kb。18号染色体缺失区域包含ATP8B1及TCF4基因,可分别解释肝内胆汁淤积症和PHS表现。ATP8B1基因测序发现两个SNP,经Mutationtaster软件预测为非致病性。口服熊去氧胆酸及补充脂溶维生素,1岁龄黄疸消退,肝功能指标恢复正常。随访至2岁10个月,身高90 cm（P3~P10）,体重12 kg（P3~P10）,头围42.5 cm（＜P3）,呈特殊面容（嘴宽大,唇厚,鼻梁宽而高,鼻尖突出,下颌略微前突）,有明显的智力发育落后,便秘严重。 结论：采用染色体芯片技术和基因测序确诊了1例婴儿期肝内胆汁淤积症合并PHS病例,提示原因不明的胆汁淤积,应重视分子学诊断,常规的基因外显子测序技术可能会漏诊一些染色体片段缺失的病例,应联合使用染色体芯片技术。     

Management of cholestasis in infants with very low birth weight

Infants with very low birth weight (VLBW) are at increased risk of cholestasis when compared with older infants and children. Factors associated with this increased risk of cholestasis include immaturity of the biliary excretory system, a diminished immune response to sepsis, an increased incidence of necrotizing enterocolitis and short bowel syndrome, as well as an increased exposure to parenteral nutrition (PN). The current literature on cholestasis in VLBW infants and the factors that mediate the initiation and progression of cholestatic liver damage is reviewed. A protocol for managing infants with cholestatic jaundice is presented, and a case report is included that shows use of the protocol to normalize the bilirubin in a VLBW infant with severe cholestatic jaundice.