妊娠同族免疫性肝病-新生儿血色病1例报告并文献复习

A case report of gestational alloimmune liver disease-neonatal hemochromatosis and literature review

目的提高对妊娠同族免疫性肝病-新生儿血色病(GALD-NH)临床特点的认识。方法对广州市妇女儿童医疗中心诊断的1例GALD-NH患儿的临床表现及尸检病理诊断过程进行回顾性分析,文献复习总结该类患儿的临床特征。结果男,生后第2 d发病,肝功能和凝血功能异常,少尿,全身水肿(大量胸腔积液、腹水),血小板减少为主要表现,积极对症治疗无效,生后43 d死亡。尸体解剖病理诊断为急性肝功能衰竭,肝外组织(胰腺、甲状腺)铁染色阳性,肝组织膜复合攻击物C5b-9免疫组化阳性,确诊GALD-NH。系统检索中国知网、维普、万方数据库、PubMed和Web of Science数据库,检索时间均从建库至2018年12月20日,12篇英文文献。报道的89例与本文病例合并后共90例NH,表现为胎儿水肿(17例)、羊水少(21例)、宫内发育迟缓(33例),生后出现铁代谢异常(65例)、肝功能衰竭(62例)、凝血机制异常(58例);肝外铁沉着阳性(48例),肝组织C5b-9免疫组化阳性14例;铁螯合剂+抗氧化治疗36例,单纯IVIG治疗4例,单纯换血治疗9例,IVIG+换血治疗20例,肝移植13例;死亡55例,存活35例,随访28例,均预后良好。结论 GALD-NH罕见,生后早期发病,以铁代谢异常、肝功能衰竭和凝血机制异常为主要表现,肝外组织铁沉着及肝活检为确诊依据,早期换血+IVIG治疗为病因治疗,病死率高,存活者预后良好。

Objective To study the clinical features of gestational alloimmune liver disease-neonatal hemochromatosis(GALD-NH),and to improve the understanding of GALD-NH.Methods Clinical manifestations and pathological diagnosis process of one patient with GALD-NH were retrospectively analyzed.The GALD-NH related literature was reviewed.Results The patient was a full-term male infant.Onset of the disease was the second day after birth.Clinical characteristics included severe liver function dysfunction,coagulation function dysfunction,oliguria,anasrca (hydrothorax and ascites),thrombocytopenia.The patient died on 43 rd day after birth.Pathological anatomy showed severe acute liver failure.Pathologic siderosis of extrahepatic tissues was positive,incluing pancreas and thyroid gland.Liver biopsy showed strong immunostaining of hepatocytes for the C5b-9 complex.Definite diagonosis of GALD-NH was made for this patient.Totally 90 patients with NH were recruited from 12 articles and our report.Main prenatal signs were hydrops fetalis(17/90),oligohydramnion(21/90),intrauterine growth retardation(33/90),and clinical process after birth developed rapidly with abnormality of iron metabolism(65/90),liver function failure(62/90) and severe coagulation function dysfunction(58/90).Extrahepatic siderosis and positive C5b-9 complex of hepatic tissue were confirmed in 48 and 14 patients respectively.The number of patients received Cocktail treatment,IVIG transfusion,blood exchange transfusion(BET),IVIG+BET and liver transplantation were 36,4,9,20 and 13,respectively.Fifty-five patients died and 35 survived.Twenty-eight of survivors were followed and the prognosis was good.Conclusion GALD-NH is rare and fatal,processing quickly after birth in multisystem injuries involving iron metabolism,liver and coagulation.Diagnosis of NH needs presence of extrahepatic siderosis.Treatment strategy includes IVIG infusion and/or BET.Mortality of GALD-NH is high,but prognosis is good for survivor.