儿童肝脏酶学异常328例病因分析

目的探讨儿童肝脏酶学异常的病因。 方法对2001年11月至2004年10月以肝脏酶学异常为主要原因,收住复旦大学附属儿科医院的328例患儿通过查阅病历进行回顾性分析。 结果328例患儿中52例(15.9%)未能明确病因,38例存在肝脏酶学异常重叠性疾病(11.6%)。引起儿童肝脏酶学异常的前6位疾病(有重叠)分别为巨细胞病毒(CMV)肝炎(156例)、乙型病毒性肝炎(46例)、甲型病毒性肝炎(30例)、胆管闭锁(30例)、肝豆状核变性(12例)、糖原累积病(12例);CMV肝炎是1岁以下儿童肝脏酶学异常最常见的病因,3岁以上儿童肝脏酶学异常以甲、乙型病毒性肝炎为主。 结论儿童肝脏酶学异常的病因多种多样,仍需深入研究;以CMV肝炎为首因的婴儿肝病综合征及以甲、乙型病毒性肝炎为主的病毒性肝炎是儿童肝脏酶学异常的主要病因,加强上述疾病的防治具有重要意义。     

婴儿巨细胞病毒肝炎的血清学诊断

巨细胞病毒(cyto megalo virus,简称CMV)是通过胎盘引起胎儿宫内感染的重要病毒之一。亦可在围产期使新生儿从产道或产后从母乳、母亲及护理人员口腔及呼吸道分泌物中获得感染,致使胎儿在出生后及婴儿早期即出现症状,可侵犯多器官(1),但以肝脏为主,是婴儿病毒性肝炎的一个重要原因。目前国内对婴儿巨细胞病毒肝炎的诊断已开始作了很多工作(2～4)。我们应用酶联葡萄球菌A蛋白免疫吸附试验(ELISA),测定患儿双份血清的CMV抗体及母亲血清CMV抗体,探讨婴儿巨细胞病毒肝炎的血清学诊断方法,报告如下。     

婴儿巨细胞病毒性肝炎(上)

图1CMV结构示意图婴儿巨细胞病毒性肝炎(infantilecytomegalovirus hepatitis,简称婴儿CMV肝炎)是指在婴儿期(包括新生儿期)发生、由人巨细胞病毒(humancytomegalovirus,CMV)引起的肝脏疾病,是目前我国儿科、婴儿期中最常见的一种肝脏疾病。要充分认识此病,必须熟悉:①CMV的生物学特性;②婴儿肝脏的解剖、生理和婴儿CMV肝炎的发病机理;③其他相关的医学知识。CMV的生物学特性一、CMV的病毒结构CMV为8种人疱疹病毒中的一种,人与动物均可感染,有很多种属,但各有其物种特异性,只有人巨细胞病毒(HCMV)感染人类;鼠巨细胞病毒(MCMV)…     

淤胆型婴儿巨细胞病毒性肝炎肝胆核素显像及意义

目的　探讨淤胆型婴儿巨细胞病毒 (CMV)肝炎患儿核素肝胆显像的变化及临床意义。方法　应用StarcamXR/T4 0 0型SPECT仪对 4 6例淤胆型婴儿CMV肝炎患儿行肝胆动静态显像 ,观察肝摄取和排泄功能与血清总胆红素值、肝酶 (ALT、γ GT)活性、肝脏病理征 (肝肿大、质地改变 )之关系。结果　 4 6例淤胆型婴儿CMV肝炎均有不同程度肝摄取和排泄异常 ,其中 2 8例肠道放射性时相延迟 ,18例肠道无放射性。此 18例患儿经治疗后再次核素肝脏显像检查肠道显影。结论　肝摄取和排泄功能与肝细胞损害和胆汁淤积程度密切相关 ;核素肝脏显像能评价肝胆损害程度 ,对肝外胆道闭锁鉴别具有实用价值。     

儿童肝炎疫苗的使用问题

病毒性肝炎无特效药物治疗,历来是危害人类健康的重大问题。儿童是病毒性肝炎特别是甲、乙型病毒性肝炎的好发人群,主动免疫是预防病毒性肝炎的重要措施,目前研究成熟供儿童使用的预防病毒性肝炎疫苗仅有甲型肝炎(甲肝)疫苗和乙型肝炎(乙肝)疫苗。现就儿童肝炎疫苗使用问题作一     

婴儿巨细胞病毒性黄疸肝炎特异性IgG多肽抗体检测及临床意义

本文观察了30例婴儿巨细胞病毒性黄疸肝炎患儿血清抗巨细胞病毒(CMV)多肽抗体变化,并与10例婴儿无症状巨细胞病毒感染者比较,旨在探讨抗CMV多肽抗体与婴儿巨细胞病毒性黄疸肝炎疾病发生之关系。 材料与方法 一、研究对象 婴儿巨细胞病毒性黄疸肝炎患儿(肝炎组)30例,为本院住院患儿,平均月龄为3月;婴儿无症状CMV感染者(无症状组)10例,为     

小儿感染及传染性疾病诊治进展

现对 2 0 0 0年我国小儿感染及传染性疾病的诊断和治疗进展作一回顾。1　病毒性疾病1 1　病毒性肝炎　对慢性乙型病毒性肝炎的治疗 ,近年来成人应用拉米夫定疗效显著 ,2 0 0 0年 9月在上海举行的国际肝炎肝癌会议上对于拉米夫定的应用效果予以肯定 ,目前对于拉米夫定应用后造成的ＹＭＤＤ变异的研究仍为热点 ,但仍缺乏在儿童中的应用经验。近年来 ,丙型肝炎有增多趋势。商庆华等的研究发现儿童慢性乙肝 (ＣＨＢ)中庚型肝炎病毒 (ＨＧＶ)感染常见 ,ＨＧＶ感染对ＣＨＢ患儿肝脏损害及乙型肝炎病毒 (ＨＢＶ)复制无明显影响 ,认为ＨＧＶ对肝脏的…     

常见小儿感染性肝脏疾病的肝功能障碍

肝脏是机体代谢最为活跃的器官 ,参与各种物质的合成和分解、运输和贮存 ,并具有分泌、排泄和生物转化等功能。在儿童时期 ,肝脏的结构和功能继续发育和完善 ,因而较成人更易受到病理因素的影响和侵害。本文将简介儿科常见感染性肝脏疾病所致肝功能障碍的表现特点。1　病毒性肝炎病毒性肝炎是一组由嗜肝病毒引起的以肝细胞损害为主的肝脏疾病 ,主要病原有甲、乙、丙、丁戊型肝炎病毒 (HAV、HBV、HCV、HDV和HEV)。小儿各型肝炎的特点及急性肝炎肝功障碍详见本期继续教育一文。慢性肝炎根据肝损害程度分为轻、中、重度[1 ] 。重度慢性肝…     

小儿病毒性肝炎356例临床分析

目前小儿病毒性肝炎(下称肝炎)仍以甲、乙型多见。其双重感染越来越引起人们关注,我院近3年中收治356例,分析如下。1990年1月～1992年12月我院共住院肝炎患者3904例,其中小儿356例,男224例,女132例。年龄6个月～12岁。诊断甲肝255例,占71.6％。按甲、乙型双重感染诊断标准,225例中,双重感染(包括混合感染和重叠感染)43例。乙肝67例,占18.3％,其中急性42例,CAH4例,CPH14例,抗HAV-IgM和HBVM均阴性者34例,占8.1％。符合重症者8例。发热、呕吐、腹痛、腹泻较成人多见而明显。黄疸     

急性白血病伴慢性肝病患儿的非甲非乙型肝炎

在联合化疗的急性白血病儿童中肝脏损害常见,除药物对肝脏的直接毒性作用外,病毒性肝炎被认为是引起这种肝脏损害的重要原因。本文作者在意大利米兰大学儿科103例急性白血病患儿中,选择了伴慢性肝病(转氨酶增高3倍,持续6个月以上)肝脏中HBsAg阴性的11例急性淋巴细胞白血病儿童,在停止治疗期间对非甲非乙型(NANB)肝炎感染有关的抗原抗体系统进行了研究。11例患儿中,8例男性,3例女性。年龄4～14岁(平均8.6岁)。化疗时间30～87个月(中位数45个月)。9例在抗白血病治疗初期接受过1～7次输血,2例从未输血。研究与方法按Alberti等法在患儿的血清和肝脏中研究与NANB肝炎有关的抗原抗体系统。通过间接免疫荧光技术用NANB抗原阳性的肝脏作为基质检测血清中NANB抗体。通过直接的免疫荧光技术在11例儿童的肝活检标本中寻找NANB抗原,低温切片(厚4μm)未加固定,用荧光素结合的NANB抗体在37℃染色45分钟(从患输血后NANB,肝炎距其急性发病后8个月康复的病人身上获得的抗血清用来制备     

Long-term evolution of chronic hepatitis B in children with antibody to hepatitis B e antigen

The aim of this study was to evaluate the long-term outcome of chronic hepatitis B in 27 children who had increased alanine aminotransferase activity and antibody to hepatitis B e antigen in serum from the time of their first clinical observation. Initial histologic changes were consistent with chronic active hepatitis in 13 cases (three with associated cirrhosis) and with persistent or lobular hepatitis in the remaining cases. On the basis of virologic testing, three groups of patients were identified: (1) two children had hepatitis delta antigen in the liver and anti-delta antibody in serum, and both had severe hepatitis; (2) 10 children had hepatitis B virus DNA in serum, and 60% of them had active hepatitis; (3) 15 patients had no hepatitis B virus DNA, and 33% of them had active hepatitis. During a follow-up period of 12 months to 12 years (mean +/- SD: 6.1 +/- 2.4 years), the disease remained active in both children with anti-delta antibody, but they had no major complaints. In all eight patients who could be followed in group 2, test results became negative for hepatitis B virus DNA and alanine aminotransferase activity normalized within 4 years; biochemical remission was delayed in three patients with higher hepatitis B virus DNA levels on entry, and one of these patients had a severe exacerbation of disease activity before remission. In group 3, a total of 10 patients (71%) achieved biochemical remission within 1 year, and two within 26 months; only two patients, who were transfused at birth, had long-lasting liver damage. These results indicate a trend to early remission of liver disease in children with chronic hepatitis B with antibody to hepatitis B e antigen without delta virus infection. Antiviral therapy aimed at accelerating the termination of hepatitis B virus replication may be indicated only in those with higher levels of hepatitis B virus DNA.     

Acute viral hepatitis: aetiology and evolution.

Over a period of three and a half years, 348 consecutive children with acute hepatitis were studied. There were 205 boys and 143 girls aged from 3 months to 12 years old. The most common type was hepatitis A, of which there were 281 cases, 81% of the total; there were 41 in the under 4 years old age group (63% of that group), 99 in the 5-8 year old age group (87% of that group) and 141 in the 8-12 year old age group (83% of that group). Hepatitis B occurred in 29 (8% of the total), and non-A, non-B hepatitis occurred in 35 (10%). All the children with hepatitis A and all but one with hepatitis B recovered. There were three deaths from fulminant hepatitis, one in the group with hepatitis B and two with non-A, non-B. Clearance of the hepatitis B surface antigen was fast, by six months 26 patients having cleared the antigen and 21 (77%) being positive for hepatitis B surface antibody. One patient became a carrier of hepatitis B surface antigen.     

Efficacy of interferon-α2b treatment in children with chronic hepatitis B who have previously undergone therapy for cancer

BACKGROUND: The aim of the present study was to evaluate the efficacy of treatment with recombinant interferon (IFN)-alpha2b in 12 children with chronic hepatitis B who had previously undergone therapy for cancer. METHODS: Nine children had acute leukemias and the other three children had solid tumors. The mean (+/-SD) age of the children was 8.4+/-3.8 years (range 4-16 years). All cases were hepatitis B virus (HBV)-DNA positive and 11 were hepatitis B e antigen (HBeAg) positive. One was anti-HBe positive (mutant strain). Four cases were anti-delta IgG positive. Liver biopsy revealed chronic hepatitis B in 11 patients and cirrhosis in one patient. Interferon-alpha2b was given at a dose of 5 MU/m2 three times a week, subcutaneously, for 12 months. RESULTS: Elimination of serum HBV-DNA was obtained in three cases, but a further three patients demonstrated a marked decrease in HBV-DNA levels after therapy. Three of 11 patients seroconverted from HBeAg to anti-HBe. Alanine aminotransferase (ALT) levels returned to normal in three of nine cases in whom the ALT levels were high before treatment. At the end of therapy, the mean histologic activity index score was significantly diminished (P = 0.0039). CONCLUSIONS: In conclusion, a 12 month course of IFN-alpha2b induces some beneficial effects on virologic, biochemical and histologic indices in children with chronic hepatitis B who have previously undergone therapy for cancer.     

巨细胞病毒特异性IgG抗体亲和力测定及其临床意义

目的     

Blood levels of leukotrienes (LTC4, D4, E4, B4) and synthesis of leukotriene B4 by peripheral leukocytes in children with acute A and B hepatitis

Leukotrienes (LTs) are cell-membrane derived lipid inflammatory mediators, synthesized and eliminated by the liver. LTs have effects on liver cells in some pathological conditions. In this study, we measured plasma endogenous and liberated leukotriene (LT) concentration in peripheral blood leukocytes stimulated in vitro by the calcium ionophore (CaA23187) and platelet-activating factor (PAF). Production of LTs was measured in type A (n=37) and type B (n=10) acute hepatitis patients and control subjects (n=10). LTs levels were measured by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The concentration of LTB4 measured in plasma and stimulated peripheral blood leukocyte supernatants of children with hepatitis A infection was found to be statistically elevated and in positive correlation with serum alanine aminotransferase (ALT) levels. In plasma samples of hepatitis B patients, LTC4 and LTE4 were measured in significantly elevated concentrations. These results suggest that LTB4 may be a critical mediator of hepatitis A virus-induced hepatocellular injury.     

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 14000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1–7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P<0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P<0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.Abbreviations anti-HBc IgM IgM antibody to hepatitis B core antigen - HBeAg hepatitis B antigen - HBcAg hepatitis B core antigen - HBV hepatitis B virus - ALT alanine aminotransferase - CAH chronic active hepatitis - CPH chronic persistent hepatitis     

小儿血友病93例临床分析

目的分析93例血友病患儿的诊断及治疗经验。方法对患儿的发病年龄、病例特点、实验室检查进行分析。结果血友病甲78例(84%),血友病乙15例(16%),其中重型45例(48%),中型33例(35%),轻型14例(15%),亚临床型1例(1%)。各种类型的出血为小儿血友病的主要表现,重型多见于婴幼儿,其中6例发生颅内出血(6%);关节病变及严重关节畸形多见于年长儿,共6例(6%)。初次出现出血症状的中位年龄为1.5(0～12.0)岁,但初次诊断的中位年龄为5.4(0.4～12.0)岁。延迟诊断的原因多种多样。结论延迟诊断、延误因子替代治疗是导致脏器出血和关节畸形的主要原因。     

Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children

Ganciclovir treatment in children with cytomegalovirus (CMV) infection is still controversial and only indicated in selected cases. The aim of thi study was to evaluate clinical and demographic features of CMV hepatitis in immunocompetent children and to determine the effect of ganciclovir treatment in these patients retrospectively. The study was carried out in a group o 29 children with CMV hepatitis. All the patients were investigated for signs of infection, inborn errors of metabolism, genetic diseases, extrahepatic biliary atresia and other causes of hepatitis. Two patients with congenital CMV infection and two patients with biliary atresia were excluded from the study group. The patients included in the study were divided into two groups: non-cholestatic hepatitis (n=16) as Group I and cholestatic hepatitis (n=9) as Group II. Four (25%) patients in the non-cholestatic group and four (44.4 in the cholestatic group were treated with ganciclovir for a median of 21 days. The mean age was 9.6+/- 10.9 months (median age 6 months) in Group I, while cholestatic hepatitis patients in Group II were significantly younger, with a mean age of 2.7+/-0.9 months (p<0.01). The most prominent symptoms at admission were diarrhea and vomiting (25%) in Group I. In Group I, all cases (100%) and in Group II, three of four cases (75%) treated with ganciclovir had recovery from acute CMV hepatitis. In the non-cholestatic group, no relapses were observed while one patient in the cholestatic group relapsed and progressed into chronic liver disease. Patients who received supportive treatment showed a marked decrease in GGT, ALT, AST and bilirubin levels spontaneously and no relapses of hepatitis were observed in at least one year of follow-up. Although ganciclovir therapy is not indicated particularly in immunocompetent cases, since most were self-limited infections, in case of progressive and persistent hepatitis, such as in our cases, ganciclovir was a treatment option; no side effect due to ganciclovir therapy was observed in our cases. Although ganciclovir seems to be effective in progressive CMV hepatitis, multicenter randomized studies in a large study group are necessar to determine the efficacy and indications for ganciclovir treatment.     

Dengue virus infection: a major cause of acute hepatic failure in Thai children

BACKGROUND: Acute hepatic failure (AHF) can be caused by a variety of viruses, drugs, toxins and metabolic disorders. AIMS: A prospective study was conducted to determine the aetiology and outcome of AHF in Thai children aged 1-15 years. METHODS: All serum samples were tested for anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, anti-HEV IgM and anti-dengue IgG and IgM. Further individual investigations were done according to the clinical impression. RESULTS: Forty subjects were enrolled from 14 centres during February 2000 to December 2001. Five cases were excluded owing to a lack of evidence of encephalopathy. The causes of AHF were dengue infection in 12 (34.3%), Wilson disease in 2 (5.7%), T-cell lymphoma in 2 (5.7%), ischaemic hepatitis in two (5.7%), haemophagocytic syndrome in one (2.8%), CMV in 2 (5.7%), Reye syndrome in one (2.8%) and unknown in 13 (37.1%) patients. The fatality rate was 68.6%. Eight of 24 (33.3%) deaths were caused by dengue infection. CONCLUSIONS: Improvements in sanitation and socio-economic status as well as the implementation of hepatitis B vaccine in the Extended Programme on Immunization (EPI) are likely to be the reasons for the observed absence of AHF caused by hepatitis A and B. The study showed that dengue infection, on the other hand, was a major cause of AHF in Thailand.