早产儿急性肝功能衰竭

目的 探讨妊娠同族免疫性肝病-新生儿血色病（GALD-NH）的临床特点,提高对该疾病的认识,为新生儿肝功能衰竭提供鉴别诊断思路。方法 新生儿重症监护室（NICU）收治的1例早产儿,生后持续血小板减少、凝血功能障碍、低蛋白血症,伴胆汁淤积、腹水。新生儿科联合医学影像科、口腔科、超声诊断科多学科讨论,制定进一步诊疗方案。结果 患儿生后早期出现肝功能衰竭,经多学科讨论,考虑GALD-NH可能。完善口腔黏膜活检,未发现阳性结果。腹部（肝脾、胰腺）MRI显示肝、脾T2WI弥漫性信号减低。肝穿刺病理显示肝细胞局灶性颗粒样铁沉积,明确诊断为GALD-NH。结论 新生儿肝功能衰竭除需考虑感染性肝病、胆道系统阻塞性肝病、遗传性代谢性疾病外,还需考虑妊娠同族免疫性肝病。     

新生儿特发性含铁血黄素沉着症1例报告并文献复习

目的探讨新生儿特发性含铁血黄素沉着症的诊断和治疗。方法回顾分析1例新生儿特发性含铁血黄素沉着症患儿的临床资料,并复习相关文献。结果女性患儿,胎儿期及出生时检查未见明显异常;生后4小时起出现皮肤黄染,并进行性加重,经换血及白蛋白输注等治疗未见改善。肝脏病理提示肝细胞弥漫性气球样变伴多核巨肝细胞转化,肝细胞内胆汁淤积伴毛细胆管扩张,胆栓形成,可见散在髓外造血灶,肝细胞内大量棕黄色颗粒沉着;普鲁士蓝染色显示为铁沉着。确诊为特发性含铁血黄素沉着症,随后加用N-乙酰半胱氨酸治疗,病情渐改善。结论新生儿含铁血黄素沉着症是新生儿期表现为伴有肝外含铁血黄素沉积的重度肝病,肝脏病理检查见肝细胞内铁沉积为确诊金标准。     

婴儿急性特发性血小板减少性紫癜与巨细胞病毒感染的相关性探讨

目的探讨婴儿急性特发性血小板减少性紫癜(AITP)与巨细胞病毒(CMV)感染的相关性、临床特点及治疗。方法对于AITP患者,应用ELESA方法测CMVIgG、IgM,对仅CMVIgG阳性者,再予CMVDNAPCR检测,同时予肝功能检测。对于CMVIgG或CMVDNAPCR阳性而无肝功能损害,均予地塞米松(Dex)+静注人血丙球(IVIG)常规治疗,而对同时有肝功能损害者分析予Dex+IVIG+阿托莫兰或Dex+IVIG+阿托莫兰+更昔洛韦(GCV)治疗。结果仅CMV感染而无肝功能损害与非CMV感染的AITP患者经正规治疗后,两组血小板升至正常时间差异无显著性,而肝功能异常时,两组血小板升至正常及肝功能恢复时间有显著性差异。结论婴儿AITP与CMV感染密切相关,若合并有其它脏器损害需联合应用GCV治疗,否则只需常规治疗。     

胰高糖素-胰岛素疗法对肝功衰竭的临床及实验研究进展

目前对急性肝功衰竭的治疗虽采用换血、换血浆、体外活性炭灌注、人工肝装置等方法,除对改善神志有些作用外,存活率仍未见明显提高。     

新生儿肝衰竭1例

患儿男,足月儿,28日龄,因发现皮肤黄染20 d、腹胀15 d入院。患儿生后1周起病,以皮肤黄染、肝脾大、大量腹水、肝功能异常进行性加重至肝衰竭、严重凝血功能障碍、血小板减少为主要表现。给予抗感染、限液利尿、保肝利胆、间断放腹水、换血,以及静脉注射免疫球蛋白、白蛋白、血浆等多种血制品治疗,病情无好转,入院第24天家属决定放弃治疗行临终关怀。患儿肝组织和父母血家系全外显子组测序未找到可以解释患儿肝衰竭的致病变异,最终尸体解剖肝组织病理提示先天性肝纤维化(congenital hepatic fibrosis, CHF)。鉴于CHF导致新生儿肝衰竭罕见,今后仍需对CHF病例的转归及其致病基因进一步研究。该文对新生儿肝衰竭的鉴别诊断进行重点描述,并介绍其多学科诊疗思路。[中国当代儿科杂志,2024,26 (2):213-218,V]     

非生物型人工肝／血液净化治疗儿童急性肝衰竭技术规范--上海交通大学附属儿童医院重症医学科诊疗技术规范

1.1急性肝衰竭的定义肝衰竭是指各种原因引起的严重肝脏损害，导致合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿，出现以凝血机制障碍、黄疸、肝性脑病、腹水等为主要表现的一组临床症候群。急性肝衰竭（ acute livre failure， ALF）可能是肝脏本身疾病引起，也可能是肝外疾病导致多器官功能障碍综合征（ multiple organ dysfunction syndrome，MODS）的一部分。目前尚未统一ALF的定义，儿童急性肝衰竭（ pediatrci acute livre failure，PALF）通常定义为：原先无肝脏损害，8周内突发严重肝功能障碍，注射维生素K1无法纠正的凝血障碍，凝血酶原时间（ PT ）＞20 s或国际标准化比值（ INR）＞2.0，可无肝性脑病；或肝性脑病合并凝血障碍，P T＞15 s或INR＞1.5［1］。     

以急性肝功能衰竭为首发表现的噬血细胞综合征11例临床分析

目的：通过对11例以急性肝功能衰竭为首发症状的噬血细胞综合征(hemophagocytic syndrome,HPS)患儿的临床特征进行分析,提高对本病的早期识别。方法收集中国医科大学附属盛京医院2011年9月至2015年2月收治的以急性肝功能衰竭为首发表现的 HPS 患儿11例,对其临床表现、实验室检查结果、治疗方法、预后进行综合分析。结果 HPS 可以急性肝功能衰竭为首发症状,其特点为凝血功能严重异常,ALT、AST 升高,纤维蛋白原降低。11例患儿均有大于1周的热程和脾脏肿大;治疗上在应用肾上腺皮质激素及静注丙种球蛋白等抑制单核巨噬细胞系统的激活,早期依托泊苷进行化疗等基础上积极予以保肝降酶等综合治疗,部分病例伴有严重出血倾向,予血浆置换及连续血液透析滤过治疗。11例患儿中,存活1例,4例因多脏器功能衰竭死亡,自动出院6例随访均死亡。结论不明原因急性肝功能衰竭并伴有发热和血细胞减少的患儿应警惕 HPS,进行早期诊断和治疗以降低病死率。     

HLH-2004方案治疗儿童噬血细胞综合征40例临床分析

目的探讨儿童HLH的临床特征、发病危险因素、实验室特点以及采用HLH-2004方案治疗的疗效和预后情况。方法回顾分析2011年1月至2014年12月收治的40例HLH患儿的临床资料。诊断标准和治疗方案按照国际组织细胞协会HLH-2004方案。结果 40例HLH患儿中,男24例、女16例,发病中位年龄1岁(4个月～10.5岁);2例有明确家族史,27例有明确诱因。主要临床表现为发热、肝脾肿大、出血、肺浸润、胸腔积液、中枢神经系统病变、皮疹等。实验室检查血细胞减少、肝功能异常、凝血异常、高三酰甘油血症、铁蛋白升高,骨髓可见噬血细胞。35例患儿采用HLH-2004方案治疗。存活26例,死亡14例。死亡原因主要为感染、弥散性血管内凝血和多脏器衰竭。结论儿童HLH病情凶险,临床表现复杂,须尽早采用HLH-2004方案诊疗。     

COG6基因新突变致新生儿期起病的先天性糖基化障碍1例并文献复习

目的：诊断1例COG6基因复合杂合突变所致的先天性糖基化障碍（CDG）,为CDG患儿的的早期诊断、制定干预措施和结局预测提供依据。方法： 总结1例携带有COG6复合杂合突变的CDG患儿的临床表型、家系sanger验证信息、影像学表现、实验室检查和随访信息,对COG6及其他Golgi复合体（COG）基因突变所致CDG的疾病表型行文献复习。结果：患儿因早产、生后反复气促吐沫1月余就诊,主要表现为不明原因反复高热伴肝酶异常,皮肤少汗,异常面容,并存在心、肺、肾、凝血和神经系统异常。行核心家系全外显子组检测发现COG6基因复合杂合突变c.511C>T （p.R171X）和c.540G>A （p.E180E）,c.511C>T 来源于母亲,是人类基因突变数据库（HGMD）已报道的CDGⅡ型的致病突变;c.540G>A 来源于父亲,为新发突变。汇总专业版HGMD已报道的COG6-CDG 患儿9例加本文1例共10例表型（CDGⅡ型）,异常面容,可表现为肝、皮肤、心脏、肾脏、骨骼、关节、凝血、免疫、神经系、听力和视觉异常或其他畸形等,多数患儿生长发育迟缓,预后不良,5例病死,存活者均进展为严重肝功能障碍伴反复感染。比COG-CDG其他亚型,临床表现更丰富、病情偏重且预后差。结论：新生儿期表现为不明原因高热伴肝酶异常,皮肤少汗,肌张力异常,或存在心、肾、免疫和凝血等多器官和系统功能异常的患儿,应高度怀疑COG6-CDG,此类患儿多数生长发育迟缓,预后不良,新生儿期通过基因测序可早期诊断。     

4例EB病毒感染相关急性肝功能衰竭患儿的临床特点分析

4例EB病毒感染相关急性肝功能衰竭患儿中男2例、女2例,年龄10（8.5~44）个月。3例诊断为传染性单核细胞增多症（IM）,其中2例符合噬血细胞淋巴组织细胞增生症（HLH）诊断标准;1例诊断为EBV既往感染。4例患儿的血EBV-DNA载量均阳性。4例患儿入院时均有发热、肝大、黄疸,3例患儿具有脾大、腹水或者呕吐症状,2例患儿有颈淋巴结大、皮疹或胸水,1例患儿出现消化道出血或者2期肝性脑病。4例患儿的异型淋巴细胞计数均 < 10%,仅1例出现白细胞升高和血小板减少;4例患儿的转氨酶10~100倍升高、以直接胆红素为主的总胆红素3~5倍升高、乳酸脱氢酶数10倍升高、凝血酶原时间显著延长。4例患儿均静脉给予阿昔洛韦或更昔洛韦抗病毒、促肝细胞生长因子促进肝细胞生长以及激素减轻炎症反应等治疗;2例加用血浆置换治疗,其中1例联合连续性静脉-静脉血液透析滤过治疗;2例HLH患儿按照HLH 2004方案化疗。3例存活,1例HLH因多脏器功能衰竭死亡。EB病毒感染可以引起儿童急性肝功能衰竭,早期给予包括血液净化治疗在内的综合治疗手段可能对预后有益。     

Neonatal liver cirrhosis without iron overload caused by gestational alloimmune liver disease

Gestational alloimmune liver disease has emerged as the major cause of antenatal liver injury and failure. It usually manifests as neonatal liver failure with hepatic and extrahepatic iron overload, a clinical presentation called neonatal hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected during pregnancy and who presented at birth with liver cirrhosis and mild liver dysfunction. Liver biopsy showed the absence of iron overload but strong immunostaining of hepatocytes for the C5b-9 complex, the terminal complement cascade neoantigen occurring specifically during complement activation by the immunoglobulin G-mediated classic pathway, which established the alloimmune nature of the hepatocyte injury. The infant survived with no specific therapy, and follow-up until 36 months showed progressive normalization of all liver parameters. This case report expands the recognized clinical spectrum of congenital alloimmune liver disease to include neonatal liver disease and cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost importance regarding the necessity for immunotherapy in further pregnancies to avoid recurrence of alloimmune injury.     

Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG

We evaluated the effects of platelet transfusions and intravenous immunoglobulin (IVIG) in neonates with fetal and neonatal alloimmune thrombocytopenia (FNAIT) with and without antenatal treatment with IVIG. Records of neonates with FNAIT admitted between January 2000 and November 2005 were reviewed. The patients were divided into group I, treated antenatally with IVIG for known FNAIT, and group II, postnatally diagnosed with FNAIT. The primary outcome was the time interval to reach a platelet level above 100 × 10⁹/L in relation to the type of treatment. Nineteen neonates with FNAIT were identified, 13 in group I and 6 in group II. In group I, four children were born with a platelet count above 100 × 10⁹/L and never needed treatment, and four received a single matched platelet transfusion at birth with a maintained response. Five neonates received IVIG and one matched transfusion, with all but one rapidly responding. In antenatally treated cases, postnatal IVIG had no apparent effect on the platelet count. In group II, two neonates died on day 1 with severe intracranial hemorrhage. Two of the four other patients responded to a number of unmatched platelet transfusions, with one neonate rapidly responding after one matched transfusion, while another needed nine matched transfusions before a persistent adequate platelet count was reached after 9 weeks. Postnatal IVIG had no apparent effect on the platelet count in any of our cases. In neonates with FNAIT treated antenatally with IVIG, neonatal management using a single matched platelet transfusion was adequate in all cases. In neonatally diagnosed cases not treated before birth, multiple matched platelet transfusions may be required. We found no evidence to support the use of IVIG in neonates with FNAIT.     

Pathology teach and tell: neonatal hemochromatosis with massive hepatic necrosis

Neonatal hemochromatosis (NH) is an uncommon disorder clinicopathologically defined by severe liver disease of intrauterine onset associated with extrahepatic siderosis that spares reticuloendothelial elements. NH phenotypically is a similar disorder to hereditary hemochromatosis. However, its extremely early onset of liver failure makes it notably unique. Massive liver necrosis in the newborn is a rare occurrence, but whenever present hemochromatosis should be considered in the differential diagnosis. Herein, we report a case of neonatal hemochromatosis that had massive hepatic necrosis with sparing only little parenchyma. The outcome was fatal within the first month of life.     

PATHOLOGY TEACH AND TELL: NEONATAL HEMOCHROMATOSIS WITH MASSIVE HEPATIC NECROSIS

Neonatal hemochromatosis (NH) is an uncommon disorder clinicopathologically defined by severe liver disease of intrauterine onset associated with extrahepatic siderosis that spares reticuloendothelial elements. NH phenotypically is a similar disorder to hereditary hemochromatosis. However, its extremely early onset of liver failure makes it notably unique. Massive liver necrosis in the newborn is a rare occurrence, but whenever present hemochromatosis should be considered in the differential diagnosis. Herein, we report a case of neonatal hemochromatosis that had massive hepatic necrosis with sparing only little parenchyma. The outcome was fatal within the first month of life.     

Neonatal Hemochromatosis, Renal Tubular Dysgenesis, and Hypocalvaria in a Neonate

We report a neonate with neonatal hemochromatosis (NH), renal tubular dysgenesis (RTD), and hypocalvaria. NH is a fatal condition of the newborn, characterized by severe idiopathic liver failure of intrauterine onset and siderosis, intra- and extrahepatic, with sparing of the reticuloendothelial system. RTD is characterized by short, abnormally developed cortical tubules that lack proximal tubule differentiation. Although both NH and RTD have been reported as entities with a genetic component, similar findings can be secondary to in utero insults. Hypocalvaria has been reported in association with fetal hypoxia including that secondary to angiotensin converting enzyme inhibitors. This 38-week-old infant died at 8.5 h. The small nodular liver weighed 44 g. Grossly, the kidneys were normal. Hypocalvaria was present. Microscopically, the hepatic parenchyma was distorted by fibrous tracts, proliferation of bile ducts, and abundant iron deposition in hepatocytes. Extrahepatic siderosis in the pancreas, myocardium, and other organs was consistent with NH. Proximal convoluted tubules were not seen on routine stains and markers for proximal tubules were negative. Previous reports have linked NH with RTD and RTD with hypocalvaria. This infant had all three of these rare conditions, which have been hypothesized or shown to be due to genetic factors, hypoxia, or drugs. The etiology in this case is unknown. Received May 20, 1997; accepted August 15, 1997.     

不同方法对重症新生儿高胆红素血症的疗效观察

探讨不同治疗方法对重症新生儿高胆红素血症的治疗效果 ,将 43例重症新生儿高胆红素血症患儿 (达换血标准 )按治疗方法分为 3组。光疗组 1 5例 ,予以药物治疗及光疗直至退黄 ;丙球组 1 6例 ,药物及光疗同前组 ,另加静脉输注丙种球蛋白(简称丙球 )× 3d ;换血组 1 2例 ,予以换血 ,换血前后药物治疗及光疗同前二组。所有三组患儿分别于治疗前 ,治疗后第 1d、4d、7d测血胆红素。结果 :( 1 )血清胆红素值 :治疗第 1d换血组明显低于丙球组及光疗组 (P均 <0 0 1 ) ,但光疗组与丙球组之间无统计学意义 (P >0 0 5) ;治疗第 4d、7d三组间比较均有显著性差异 (P均 <0 0 1 ) ;( 2 )所需光疗时间及黄疸消退时间 :换血组明显低于丙球组及光疗组 (P均 <0 0 1 ) ,但光疗组与丙球组之间无统计学意义 (P >0 0 5) ;( 3)临床情况 :43例患儿黄疸均消退 ,换血组 1 2例无胆红素脑病、贫血发生 ;丙球组胆红素脑病 2例 ,明显贫血 5例 ;光疗组胆红素脑病 3例 ,明显贫血 5例 ,亦因拒绝输血而未予纠正。结论 :换血疗法仍然是治疗重症新生儿黄疸的最佳选择     

Disparate clinical presentation of neonatal hemochromatosis in twins

Neonatal hemochromatosis (NH) is a rare disease of gestation that results in fetal liver injury and extrahepatic siderosis. The etiology of NH is not fully understood. However, the rate of recurrence of NH in the pregnancy after an affected one is approximately 80%. A spectrum of liver disease has been recognized, spanning from liver failure in the fetus or neonate to infants that survive with medical therapy. Here we report on 2 sets of fraternal twins, each set with a gross disparity in the severity of presentation: 1 infant with liver failure and the other nearly unaffected. These findings suggest a need to look carefully for subclinical disease in the siblings of patients with NH by using sensitive tests such as those for ferritin and alpha-fetoprotein. They also suggest that affected infants may be missed when using routine clinical testing, which would lead to the apparent rate of recurrence, understating the actual recurrence rate.     

Pre-operative time course changes in liver function tests in biliary atresia: Its usefulness in the discrimination of biliary atresia in early infancy

In order to investigate the possibility of early discrimination of extrahepatic biliary atresia from other cholestatic diseases, a series of results of liver function tests in infants with cholestatic diseases were reviewed. The results of routine liver function tests (LFT) recorded in patients' charts were reviewed within 12 weeks after birth in 47 infants with extrahepatic biliary atresia (BA), 10 infants with neonatal hepatitis (NH) and 130 age-matched control infants (CO) without cholestatic diseases. The mean of each test value for each week after birth was derived from the actual data examined in each infant. No differences were observed between BA and CO in the levels of aminotransferases within 2 weeks after birth. Total bilirubin and direct bilirubin levels were significantly different between BA and CO within 1 week after birth (16.1 ± 3.2 mg/dL vs 11.1 ± 4.5 mg/dL, 4.6 ± 2.6 mg/dL vs 0.7 ± 0.3 mg/dL, respectively) The direct bilirubin-total bilirubin ratio exceeded 25% within the first week in BA. The individual values of direct bilirubin (DB) exceeded 2 mg/dL within the first week in all infants with BA, while none of the individual values exceeded 1.6 mg/dL in CO. Gamma-glutamyl transpeptidase levels were significantly different between BA and CO at 4 weeks (432 ± 272 IU/L vs 79 ± 43 IU/L) and thereafter; and were significantly different between BA and NH at 6 weeks (314 ± 232 IU/l vs 69 ± 58 IU/L) and thereafter. These data suggest that the determination of direct bilirubin within 1 week after birth can detect extrahepatic biliary atresia patients from those with physiologic jaundice, and γ-glutamyl transpeptidase levels may discriminate BA from NH at no later than 6 weeks of age.     

Neonatal haemochromatosis associated with gastroschisis

We describe, to our knowledge, the first case of progressive neonatal liver failure due to neonatal haemochromatosis (NH) occurring in an infant with a gastroschisis and review the literature regarding these two conditions. A 1,665 g male infant with antenatally diagnosed gastroschisis was born with a severe coagulopathy, anaemia, thrombocytopenia, hypoglycaemia and jaundice. He developed progressive liver failure, complicated by necrotising enterocolitis. Serum ferritin was elevated at 1,459 μg/L. He died on day 40 and a limited post-mortem examination confirmed significant hepatic siderosis with fibrosis and cholestasis, and siderosis of the pancreas. Although no genetic aetiology for gastroschisis has been identified, an occasional inherited tendency has been observed. There is also evidence to support an autosomal recessive inheritance in NH.     

Effect of intravenous gammaglobulin (IVIG) on the platelet count in patients with Wiskott-Aldrich syndrome

The ability of IVIG to increase platelet counts in patients with idiopathic thrombocytopenic purpura suggests its potential usefulness in other disease states characterized by low platelet counts. This possibility was evaluated in nine patients with the Wiskott-Aldrich syndrome (WAS) who received IVIG, at a dose of 400 mg/kg every 4 weeks. The mean platelet count prior to institution of IVIG was 32,000/cumm (range 2,400 to 98,000). Following administration of IVIG, the platelet count ranged between 5,000 and 85,000/cumm. There were no immediate increases in platelet counts after IVIG infusion in any patient who had serial platelet counts. During treatment, patients were not given any routine platelet transfusions for low platelet counts. However, while on IVIG, two patients showed a good response to platelet transfusion prior to surgical procedures. In conclusion, chronic IVIG therapy does not appear to affect platelet counts in patients with the Wiskott-Aldrich syndrome.