Echocardiographic detection of intrapulmonary shunting in a patient with hepatopulmonary syndrome: case report and review of the literature

Transthoracic echocardiography is a useful tool in the evaluation of patients with intrapulmonary and intracardiac shunts. We describe a case of a 49-year-old female with severe hypoxemia in the setting of aortic stenosis and cirrhosis of the liver. The use of agitated saline contrast during an echocardiography study helped to establish the diagnosis of intrapulmonary arteriovenous shunting consistent with the hepatopulmonary syndrome, thereby confirming the etiology of her symptoms and laboratory findings. This case report highlights the utility of echocardiography in diagnosing intrapulmonary shunts and assists in the understanding of the pathophysiology of hypoxemia in such patients.     

Cardiac anomalies associated with Escobar syndrome: A case report and a review of the literature

Rationale:Escobar syndrome (ES) is an autosomal recessive disorder. It is highly characterized by facial abnormalities, congenital diaphragmatic muscle weakness, myasthenic-like features, and skin pterygiums on multiple body legions. ES is a rare condition associated with many external and internal abnormalities. The internal malformations described in ES affect many organs including the heart, lungs, esophagus, liver, spleen, and intestine. The purpose of this paper is to explore the cardiac manifestations associated with ES.Patient concerns:A 3.5-year-old girl, who was born for double first cousins, was admitted to the hospital for neuromuscular evaluation of multiple congenital contractures.Diagnosis:The girl was diagnosed with ES and isolated dextrocardia which is a rare cardiac manifestation. However, to the best of our knowledge, no similar cases have been reported to date, and this case is thus believed to be very rare.Interventions:The patient underwent an operative intervention to correct the bilateral fixed flexion deformity at her knees which was related to the posterior bilateral fibrotic bands/pterygia.Outcomes:Post-operatively, complete knee extension was obtained, the patient was fitted with a cast and extension night splint. She was discharged alive and had no complications. The patient was followed regularly in the orthopedic clinic and had periodic physiotherapy sessions.Conclusions:ES and isolated dextrocardia concurrence in the presented case resulted from different pathogenic mechanisms. Our findings suggest that ES might be caused by dysfunction in the acetylcholine receptor throughout fetal life, which may have affected muscle strength and movement. Other cardiac conditions include hypoplastic left-sided heart, Hypertrophic cardiomyopathy, patent ductus arteriosus, and heterotaxia.     

Rapid onset of intrapulmonary arteriovenous shunting after surgical repair of tetralogy of Fallot with pulmonary atresia

We describe a 2-year-old girl with tetralogy of Fallot and pulmonary atresia, palliated as a neonate with a right modified Blalock Taussig shunt, who developed severe cyanosis following total correction in the absence of corresponding evidence of parenchymal lung disease on the chest X-ray. Selective pulmonary angiography showed new intrapulmonary shunting involving only the right middle and lower lobes only. The cyanosis resolved rapidly subsequent to inhalation of nitric oxide. To our knowledge, this is the first documented case of rapid onset of localised intrapulmonary right-to-left shunting, involving only two lung lobes, following biventricular repair for complex congenital heart disease.     

Hypertrophic osteoarthropathy in a child with biliary atresia

Hypertrophic osteoarthropathy is a syndrome characterized by clubbing of the digits of the hand/foot, periosteal reaction and arthralgia or arthritis which is usually secondary to cyanotic congenital heart disease and chronic pulmonary infections. This syndrome rarely occurs in association with chronic liver disease in childhood. Here, we report on a child with biliary atresia who developed arthralgia and arthritis during follow‐up and which was diagnosed as hepatic hypertrophic osteoarthropathy. It is emphasized that hypertrophic osteoarthropathy should be considered in the differential diagnosis of arthralgia and arthritis in children with long‐standing chronic liver diseases, especially if finger clubbing is also present.     

Epidemiological features of biliary atresia in Taiwan, a national study 1996-2003

Background and Aim: The incidence of biliary atresia (BA) varies among different countries. It is supposed to be higher in Asian countries than in Western countries; however, the incidence of BA in Taiwan has not been well investigated. The aim of this study was to analyze the epidemiological characteristics and the incidence of BA in Taiwan. Methods: National Health Insurance (NHI) was implemented in Taiwan in 1995, and covers most of the population (>99%). We use the NHI database to investigate the epidemiological features of BA and compare Taiwan's annual BA incidence with that of other countries. Results: We identified 327 new BA cases during the period from 1996 to 2003. The overall incidence of BA was 1.46 cases per 10 000 live births (0.89–1.90 per 10 000). The estimation was 1.32–1.65 per 10 000 after adjustment for the misdiagnosis rate. The peak incidence occurred in 2002 (1.90 per 10 000), accompanying Taiwan's dengue fever epidemic in 2002. The 5‐year overall survival rate during 1999–2003 was higher than that during 1996–1998 (74.8% vs 61.1%, P = 0.014). Conclusion: Taiwan has the second‐highest incidence of BA reported in world literature. Viral infection outbreaks remain a potential candidate as a cause of BA. The management of BA has been improving, with a better 5‐year overall survival rate.     

Biliary atresia with associated structural malformations in Canadian infants

Background: Biliary atresia (BA) is associated with extrahepatic congenital malformations in a minority of affected infants. The term commonly applied to this subgroup is ‘BASM’ for biliary atresia splenic malformation syndrome, as spleen abnormalities are prominent. Aims and methods: To examine clinical outcome in Canadian BA patients with extrahepatic congenital malformations in the Canada‐wide BA database of patients born between 1985 and 2002, and additionally, to recharacterized the syndrome. Patients had ≥1 of the following: a/polysplenia, abnormal abdominal situs, intestinal malrotation, abdominal vascular anomaly or congenital heart disease. Results: Among 328 BA patients, 44 (13%) had associated congenital abnormalities. Intra‐abdominal anomalies included polysplenia (n=25), abnormal abdominal situs (n=9), intestinal malrotation (n=19), portal vein anomaly (n=12), hepatic artery anomaly (n=3) and inferior vena cava interruption (n=20). Twenty‐six patients had cardiac malformations including pulmonary stenosis (n=11), ventricular septal defect (n=10), atrial septal defect (n=7), total anomalous pulmonary venous return (n=3), double outlet right ventricle (n=3), tetralogy of Fallot (n=2), atrioventricular canal (n=2), dextrocardia (n=2), bicuspid aortic valve (n=2), hypoplastic left heart (n=1) and partial anomalous pulmonary venous return (n=1). Age at Kasai operation, performance of liver transplant, overall survival, post‐Kasai native liver survival and transplant survival were comparable to isolated BA. Presence of polysplenia or complex cardiac disease did not reduce post‐Kasai native liver survival. Three patients had ≥2 typical abnormalities without polysplenia: thus, splenic malformations are not essential to this BA subgroup. Hierarchical cluster analysis demonstrated characteristic abnormalities grouped in a multiplicity of combinations, consistent with a spectrum of defective lateralization. Conclusion: We suggest that the acronym ‘BASM’ be redefined as ‘biliary atresia structural malformation’.     

Portal vein thrombosis associated with antiphospholipid syndrome

Received: April 25, 2000 / Accepted: October 6, 2000     

ANKRD1 and SPP1 as diagnostic markers and correlated with immune infiltration in biliary atresia

The diagnosis of biliary atresia (BA) remains a clinical challenge, reliable biomarkers that can easily distinguish BA and other forms of intrahepatic cholestasis (IC) are urgently needed.Differentially expressed genes were identified by R software. The least absolute shrinkage and selection operator regression and support vector machine algorithms were used to filter the diagnostic biomarkers of BA. The candidate biomarkers were further validated in another independent cohort of patients with BA and IC. Then CIBERSORT was used for estimating the fractions of immune cell types in BA. Gene set enrichment analyses were conducted and the correlation between diagnostic genes and immune cells was analyzed.A total of 419 differentially expressed genes in BA were detected and 2 genes (secreted phosphoprotein 1 [SPP1] and ankyrin repeat domain [ANKRD1]) among them were selected as diagnostic biomarkers. The SPP1 yielded an area under the curve (AUC) value of 0.798 (95% confidence interval [CI]: 0.742–0.854) to distinguish patients with BA from those with IC, and ANKRD1 exhibited AUC values of 0.686 (95% CI: 0.616–0.754) in discriminating BA patients and those with IC. Further integrating them into one variable resulted in a higher AUC of 0.830 (95% CI: 0.777–0.879). The regulatory T cells, M2 macrophages cells, CD4 memory T cells, and dendritic cells may be involved in the BA process. The ANKRD1 and SPP1 was negatively correlated with regulatory T cells.In conclusion, the ANKRD1 and SPP1 could potentially provide extra guidance in discriminating BA and IC. The immune cell infiltration of BA gives us new insight to explore its pathogenesis.     

Identification of signature of gene expression in biliary atresia using weighted gene co-expression network analysis

Biliary atresia (BA) is the most common cause of obstructive jaundice during the neonatal period. This study aimed to identify gene expression signature in BA. The datasets were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis identified a critical module associated with BA, whereas Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed the functions of the essential modules. The high-connectivity genes in the most relevant module constructed protein–protein interaction networks via the string website and Cytoscape software. Hub genes screened by lasso regression consisted of a disease classification model using the randomforest method. Receiver operating characteristic curves were used to assess models’ sensitivity and specificity and the model was verified using the internal and external validation sets. Ten gene modules were constructed by WGCNA, of which the brown module had a strong positive correlation with BA, comprising 443 genes. Functional enrichment analysis revealed that module genes were mainly involved in biological processes, such as extracellular matrix organization, cell adhesion, inflammatory response, and the Notch pathway (P < .001), whereas these genes were involved in the metabolic pathways and cell adhesion molecules (P < .001). Thirty-nine high-connectivity genes in the brown module constructed protein-protein interaction networks. keratin 7 (KRT7) and C-X-C motif chemokine ligand 8 (CXCL8) were used to construct a diagnostic model that had an accuracy of 93.6% and the area under the receiver operating curves for the model was 0.93. The study provided insight into the signature of gene expression and possible pathogenesis of BA; furthermore, it identified that the combination of KRT7 and CXCL8 could be a potential diagnostic model for BA.     

Phenotypic characterization of mononuclear infiltrate present in liver of biliary atresia

The liver tissue of 26 chidren with biliary atresia was compared to that of 20 adults with autoimmune chronic active hepatitis, 20 adults with chronic hepatitis due to hepatitis B infection, and 5 children with ₁-antitrypsin deficiency in terms of the number and type of mononuclear cells in portal and lobular areas of each using a panel of specific monoclonal antibodies that recognize different cell surface epitopes. All of the tissues studied were obtained at time of liver transplantation. In addition the livers of 5 adults biopsied for hepatomegaly but found to have no histologic liver disease were used as normal controls for this study. The results demonstrate that liver tissue obtained from children with end-stage biliary atresia is more like normal liver in terms of the number and type of mononuclear cells present than in either of the two types of adult liver diseases. Moreover although the liver of children with end-stage ₁-antitrypsin deficiency is more like that of normal liver than either of the two adult liver diseases studied in terms of the number and type of mononuclear cells within the liver, it is less similar to that of normal adult liver than is liver tissue obtained from children with biliary atresia. These findings suggest that as a morphologic basis biliary atresia is unlikely to be due to either a viral or an autoimmune attack upon the liver.This work was supported in part by grants AA04425-07 and NIDDK DK32556-05.     

Induction of innate immune response and absence of subsequent tolerance to dsRNA in biliary epithelial cells relate to the pathogenesis of biliary atresia

Background/Aims: Biliary epithelial cells (BECs) possess negative regulatory mechanisms of Toll‐like receptor (TLR)‐based tolerance to bacteria (e.g. endotoxin tolerance). Viral infections of the Reoviridae genus with a dsRNA genome are suspected to be part of the aetiology of biliary atresia (BA), but the negative biliary mechanisms remain unexplored. Methods: Cultured human intrahepatic BECs (HIBECs) pretreated with polyinosinic–polycytidylic acid [poly(I:C)] (a synthetic analogue of viral dsRNA) for 24 h were exposed to poly(I:C) in fresh medium. The activation of nuclear factor‐κB (NF‐κB) and the expression of myxovirus resistance protein A (MxA) and tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) mRNAs were evaluated. Moreover, after the pretreatment, the transition of these molecules was examined in poly(I:C)‐free conditions. Results: Treatment with poly(I:C) significantly upregulated NF‐κB activity in fresh HIBECs, and pretreatment failed to show tolerance to poly(I:C). The production of MxA and TRAIL was also preserved. Moreover, upregulation in the pretreated HIBECs was well preserved in poly(I:C)‐free medium for at least 72 h. Conclusions: BECs fail to show tolerance to poly(I:C), and once innate immunity is activated it is sustained in poly(I:C)‐free conditions, suggesting that the initiation of the immune response to dsRNA in HIBECs and its presence after the clearance of virus are closely associated with the progression of BA.     

不同时期婴幼儿胆道闭锁活体肝移植的预后情况:单中心101例经验分析

目的对上海交通大学医学院附属仁济医院肝脏外科2010年前后婴幼儿胆道闭锁活体肝移植预后进行比较分析,旨在探讨不同时期手术的预后情况。方法回顾分析2006年10月至2012年12月间101例婴幼儿胆道闭锁活体肝移植病例资料。根据移植年份的不同将病例资料分为2006-2009年和2010-2012年2组,分析并比较2组术前一般资料、术中情况和预后情况。行Kaplan-Meier生存分析,计量资料的统计采用t检验,计数资料采用Fisher确切概率法和卡方检验。结果 2组术前一般资料差异无统计学意义。2010-2012年组受者术中出血量(t=2.05,P=0.04)和供肝冷缺血时间(t=3.25,P0.01)显著低于2006-2009年组。2010-2012年组受者术后胆道并发症(χ2=4.27,P=0.04),肺部感染并发症(χ2=4.47,P=0.03)和急性排斥反应(P=0.03)的发生率显著低于2006-2009年组。2010-2012年组受者术后生存情况明显好于2006-2009年组。2010-2012年组术后1、2年累积生存率分别为88.4%和88.4%,而2006-2009年组为84.4%和75%。结论外科技术和围手术期管理经验的积累,以及逐渐完善和规范的随访可提高手术成功率和术后生存率,并降低围手术期并发症的发生率。     

内镜下逆行胰胆管造影术在完全性内脏反位中的临床应用价值

目的评价在完全性内脏反位(SIT)患者中进行经内镜逆行胰胆管造影术(ERCP)的有效性和安全性。方法回顾性分析2008年12月至2018年12月在杭州市第一人民医院消化内镜中心行ERCP治疗的SIT患者的资料,评估插镜成功率、插管成功率、治疗成功率和并发症发生情况。结果共有10例SIT患者进行了11例次ERCP,其中胆总管结石7例,胆总管结石合并胆总管下端狭窄1例,胆总管下端恶性狭窄1例,胆总管下端良性狭窄1例。所有患者采用常规左侧卧位,插镜成功率为100%,胆道插管的成功率为100%,总体治疗成功率为100%,有2例放置金属支架的患者术后出现腹痛,给予保守治疗后好转。结论在SIT患者中施行ERCP安全有效。     

Gastric microcirculatory disturbance and behaviour of leucocytes after thermal injury: Intravital observation of arteriovenous shunting channels in the gastric submucosal layer

In order to investigate the pathogenesis of acute gastric mucosal lesion after thermal injury, microcirculatory disturbance was assessed and observation of the behaviour of leucocytes was performed. Gastric blood flow decreased at 15 min post-thermal injury, and partially improved at 2 h; however, it decreased again at 5 h post-thermal injury. Mucosal microcirculatory disturbance was observed by using vascular labelling with monastral blue B. Deposits of monastral blue B were observed centring mainly on collecting venules but were also observed in the capillaries. Submucosal microcirculatory disturbance was observed through an intravital microscope. The irregularity of the wall and segmental constriction in the venules and presence of an arteriovenous shunting channel was observed in the submucosal layer at 5 h post-thermal injury. The percentage of rolling or sticking leucocytes that passed the confluence of a prevenule and a venule were significantly increased at 5 h after thermal injury. The present study revealed depression of gastric blood flow, mucosal and submucosal microcirculatory disturbance, and a significant increase of rolling and sticking leucocytes in the peripheral part of venules after thermal injury. Leucocyte-endothelial interactions may occur under such conditions and this interaction may play an important role in inducing the microcirculatory disturbance that results in an acute gastric mucosal lesion after thermal injury. The present study also demonstrated the possibility of intravital study of gastric submucosal arteriovenous shunting channels.     

Reovirus serotype 3 infection in infants with extrahepatic biliary atresia or neonatal hepatitis

Infection with reovirus serotype 3 (reo 3) has been postulated to be associated with extrahepatic biliary atresia (EHBA) in infants, and with neonatal hepatitis (NNH). We have investigated this association by assaying antireo 3 antibodies in sera from infants (aged < 4 months) with EHBA (n= 40), NNH (59), cholestatic liver disease due to other causes (61) and control infants with no liver disease (138). Antireo 3 immunoglobulins (Ig) of the G, A and M classes were measured by enzyme-linked immunosorbent assay. No differences in the prevalence of antireo 3 IgG or IgA were found between any of the four groups. A significantly higher prevalence of positive antireo 3 IgM was found in infants with EHBA (12/40), NNH (12/59) or cholestatic liver disease associated with parenteral nutrition (7/17), alpha-1 antitrypsin deficiency (4/15) or a variety of other causes (15/29) compared with control infants (13/138). These data support an association between reovirus 3 infection and cholestatic liver disease in infants. The nature of this association may differ for EHBA, NNH and cholestatic liver disease due to other causes, and remains to be determined.