Current concept about postoperative cholangitis in biliary atresia

Background  Postoperative cholangitis characterized by fever and acholic stool and positive blood culture is a common and serious complication following Kasai’s operation for biliary atresia. The aim of this review was to describe the pathogenesis, clinical manifestations, medical treatment and outcome of postoperative cholangitis. Data sources  Articles on biliary atresia retrieved from Pubmed and MEDLINE in the recent 10 years were reviewed. Results  The pathogenesis of postoperative cholangitis is still controversial. Recent methods for the diagnosis of postoperative cholangitis include urinary sulfated bile acids (USBA) and magnetic resonance cholangiopancreaticography (MRCP). High-dose steroids and oral antibiotics have been used to reduce the incidence of postoperative cholangitis, and recurrent cholangitis leads to a lower survival rate. Conclusions  Cholangitis is one of the most important determinants of long-term survival after the Kasai’s procedure. The knowledge on postoperative cholangitis has been increasing in the past 10 years, showing a lower incidence of the disease and better therapeutic results.     

Coincidental cases of primary sclerosing cholangitis and biliary atresia in siblings?

Familial cases of primary sclerosing cholangitis or biliary atresia have been reported, although genetic influences and immunopathological abnormalities in these diseases are considered to be obscure. We report a case of primary sclerosing cholangitis and biliary atresia in siblings with the observation of HLA-DR antigen expression in the abnormal bile duct epithelial cells.     

Elevation of serum stem-cell factor in postoperative biliary atresia

BACKGROUND: Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Stem-cell factor (SCF) has been implicated in the development of fibrosis in various diseases. The objective of the present study was to examine the significant role of SCF in BA. METHODS: Fifty-seven pediatric patients with BA after Kasai operation and 30 healthy children were recruited. The mean ages of BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years, respectively. The patients were categorized into two groups according to their serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or = 100 U/L). The serum SCF levels were determined on commercially available enzyme-linked immunosorbent assay. RESULTS: The mean serum SCF level of the BA children was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3 pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL, respectively; P = 0.002). In addition, serum SCF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001). CONCLUSION: The current study showed that BA patients had higher serum SCF levels compared with controls. The significant elevation in SCF levels is associated with the presence of PH and the degree of hepatic injury. These findings suggest that SCF may play a part in the pathogenesis of hepatic fibrosis in BA patients after Kasai procedure.     

Efficacy of urinary sulfated bile acids for diagnosis of bacterial cholangitis in biliary atresia

This study evaluated the efficacy of measuring urinary sulfated bile acids (USBA) for diagnosis of bacterial cholangitis in patients with biliary atresia. Eight infants with biliary atresia were recruited. The USBA level was measured when they were admitted to hospital with a fever of unknown origin. Clinical manifestations and laboratory data were reviewed. The standard USBA value for each patient (S-USBA) was defined as the level measured when they had no fever, and USBA ratio (R-USBA) was calculated as the USBA level during the febrile episode divided by the S-USBA. Then R-USBA values were compared between febrile episodes with and without cholangitis to assess the diagnostic ability of USBA. Twenty-three febrile episodes occurred in eight patients during a 15-month period. Nine episodes were diagnosed as being due to cholangitis, five were due to non-cholangitis, and nine were of undetermined origin. The R-USBA value ranged from 1.5 to 15.4 during cholangitis episodes and from 0.4 to 1.2 during non-cholangitis febrile episodes. When fever was of undetermined origin, R-USBA was found to be increased during some episodes and not in others. USBA increased immediately in patients with cholangitis. The measurement of USBA is a useful non-invasive test for cholangitis in patients with biliary atresia who had undergone Kasai’s operation.     

Bacterial cholangitis in patients with biliary atresia: impact on short-term outcome

 Bacterial cholangitis (BC) is a common complication in patients with biliary atresia (BA) and is characterized by fever, acholic stools and positive blood cultures. The diagnosis is often empirical because the yield of blood cultures is low. It is difficult to differentiate BC from other febrile episodes. In order to characterize the clinical and laboratory features of BC in patients with BA, identify risk factors, and correlate cholangitis with outcome, 37 patients with BA from 1993 to 1998 who underwent a Kasai operation in our hospital were studied. The follow-up period ranged from 6 to 59 months. A total of 107 febrile episodes were documented in these patients. The diagnostic criteria for cholangitis were fever, increased jaundice, or acholic stools. The clinical features, laboratory data, results of bacterial cultures, and outcomes were analyzed retrospectively. A total of 107 febrile episodes, including 78 bouts of cholangitis and 29 non-cholangitis infections, were found in 34 patients. Patients with BC had higher postoperative bilirubin levels (P=0.02) and less frequent use of prophylactic antibiotics (P=0.05) than those with non-cholangitis infections. Abnormal white blood cell counts (>12,000 or <4,000 mm³) tended to be present in patients with BC (P=0.08). There were no statistical differences in the risk factors and laboratory data between culture-positive (n=16) and -negative (n=62) cholangitis cases. The occurrence of cholangitis significantly reduced survival in both patients with good (P=0.03) and inadequate bile flow (P=0.03). All 9 patients who had never had cholangitis survived during the follow-up period. Repeated attacks of BC further decreased survival probability. The responsive organisms were mainly enteric bacteria, including Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumanni, and Salmonella typhi. The sensitivity tests justified empirical therapy with ceftriaxone. The effectiveness of prophylactic trimethoprim-sulfamethoxazole or neomycin warrants further studies. BC was a highly prevalent postoperative complication in patients with BA, especially those with inadequate bile drainage. It significantly affected early mortality. Aggressive and complete treatment with empirical ceftriaxone was appropriate.     

Outcome of biliary atresia in Malaysia: A single-centre study

Aim:   This study aimed to determine the outcome of the operation of children with biliary atresia (BA) at a tertiary paediatric referral centre in Malaysia.
Methods:   A prospective study on all patients with BA referred to the University of Malaya Medical Centre (UMMC), Kuala Lumpur, from 1996 to 2005 was conducted. Survival with native liver, liver transplantation (LT) or death at 2 years of age was determined.
Results:   The median age at referral of the 57 patients with BA seen at University of Malaya Medical Centre was 62 days. Kasai procedure was not performed in nine patients who were all referred late (median age of referral 180 days). The median age at hepatoportoenterostomy (HPE) of the remaining 48 patients was 70 days. A total of 53 (93%) patients had type 3 BA, while only 1 (2%) patient had BA splenic malformation. At 2 years, the survival rate with native liver for the 48 patients who had HPE was 37%, while the overall survival (native liver and LT) rate was 40%. Two of the four patients who had LT survived with a liver graft at 2 years.
Conclusions:   The 2-year survival with native liver following corrective surgery for BA in UMMC, Malaysia, compares favourably with other international figures, but the overall survival rate was adversely affected by a lack of timely LT. The outcome of BA in Malaysia may be further improved by increasing the awareness among child-health professionals on the importance early referral for appropriate surgery in infants suspected of having BA.     

术前营养状态对胆道闭锁术后胆管炎的影响研究

目的 探讨胆道闭锁患儿术前营养状态对术后胆管炎发生的影响.方法 对2014年1月至2014年12月底收入我院的66例经手术探查确诊为Ⅲ型胆道闭锁的患儿采用STRONGKid方法进行营养不良风险评估并分组:低度营养不良风险组,中度营养不良风险组及重度营养不良风险组.通过门诊及电话进行随访,随访内容为首次发生胆管炎的时间,早期胆管炎发生情况及术后3个月内发生胆管炎的次数,术后6个月内黄疸消退情况.结果 低度营养不良风险患儿0例,中度营养不良风险患儿30例(45.5％),重度营养不良患儿36例(54.5％).中度营养不良组首次发生胆管炎的时间(44.31±18.75)d明显晚于重度营养不良组(26.75±7.96)d,P=0.002;中度营养不良组早期胆管炎的发生率13.3％明显低于重度营养不良组66.7％,P=0.04;重度营养不良组患儿术后3个月内胆管炎的平均发生次数(2.11次/人)明显高于中度营养不良组(1次/人),中度营养不良组术后6个月黄疸清除率60.0％高于重度营养不良组16.7％,P=0.014.结论 胆道闭锁患儿术前合并重度营养不良易于发生早期胆管炎且反复发生,中度营养不良组的患儿首次发生胆管炎的时间明显晚于重度营养不良组,重度营养不良组术后黄疸清除率明显低于中度营养不良组.     

Magnetic compression anastomosis for postoperative biliary atresia

We report a case of successful magnetic compression anastomosis (MCA) for obstructed cyst‐jejunostomy in a young woman who had undergone surgery for type 1 biliary atresia (BA) on day 78 of life. A 16‐year‐old girl was admitted with obstructive jaundice. Jaundice resolved with percutaneous trans‐hepatic cholangiodrainage (PTCD) but contrast medium injected from the PTCD tube did not flow through the anastomosis. Magnets were placed on each side of the anastomosis, in the cyst and the jejunum, to compress the partition. On postoperative day (POD) 6, the anastomosis was recanalized and the PTCD tube placed trans‐anastomotically until POD 245. The patient remained free from jaundice after removal of the PTCD tube. MCA can be a useful and less invasive procedure for treating biliary tract anastomotic obstruction in patients with BA.     

胆道闭锁Kasai术后胆管炎的病因及诊治进展

胆道闭锁是威胁新生儿生命的严重先天性肝内、外胆管畸形,目前针对该疾病的治疗主要依靠Kasai手术,即肝门-空肠吻合术纠正发育不良的胆道系统,胆管炎是胆道闭锁Kasai术后最常见且较难处理的并发症,发病机制尚未完全清楚,多种因素如肠道细菌的上行感染、肝内胆管发育异常及手术损伤、肠道内容物反流等都可影响疾病的发生发展。而胆管炎的首发时间、发生次数可影响术后原生肝脏功能,对其进行及时诊治尤为重要。Kasai术后胆管炎的诊断缺乏特异性,主要依据临床表现、生化异常以及手术史,对于难治性胆管炎应考虑完善放射性同位素肝胆成像、经皮胆道造影和小肠镜检查。其防治重点在于围术期的术前护理、术式改进和术后护理以及疾病随访过程中的药物防治等。     

Additional congenital anomalies in babies with gut atresia or stenosis: when to investigate, and which investigation

A wide variety of additional congenital anomalies occur in babies born with a gut atresia or stenosis. The specific pattern of anomalies depends on the location of the atresia. The serious nature of many of them makes perioperative diagnosis imperative. Eighty-six babies born with pure oesophageal atresia (OA), duodenal atresia (DA) or stenosis, or jejuno-ileal atresia (JIA) have been studied. These, combined with over 2,000 cases in the literature, have been used to develop a protocol to optimally investigate babies with gut atresia for associated anomalies. The authors recommend routinely obtaining anterio-posterior and lateral chest and abdominal radiographs for babies with pure OA, DA and intestinal atresia, making sure the entire spine can be visualised. Cardiac and renal ultrasonography (US) should be routine in all babies with pure OA or DA. A micturating cystourethrogram should be done in those babies with abnormal urinary tract US or an associated anorectal anomaly. A sweat test should be obtained in babies with JIA, and a rectal biopsy should be taken in babies with the combination of Down's syndrome and DA to exclude Hirschsprung's disease.     

血清内毒素水平在胆道闭锁患儿术后的意义

目的探讨血清内毒素(ET)、透明质酸(HA)与胆道闭锁(BA)患儿术后肝损害、肝纤维化的关系。方法以行肝门空肠吻合(Kasai)术后的BA患儿为BA组(n=38),正常体检儿童(n=12)为对照组;BA患儿根据其胆红素水平再分成黄疸组(n=14)和无黄疸组(n=24)。由自动生化仪测肝功能,鲎三肽基质显色法测ET水平、放射免疫法测HA水平。结果 BA组患儿存在肝损害,血清ET、HA水平均较正常对照儿童高(P<0.05);BA组患儿中,黄疸患儿的肝损害较无黄疸者重,血清ET、HA水平也较无黄疸者高,差异均有统计学意义(P<0.05);血清ET水平与血清总胆红素、谷草转氨酶及HA水平呈正相关(P<0.05)。结论血清ET水平与术后BA患儿肝损害和肝纤维化密切相关,可作为术后判断BA患儿预后的有用指标。     

57例胆道闭锁术后近期疗效及部分影响预后因素分析

为了解胆道闭锁术后近期疗效及部分影响预后的因素，对1990年1月－2001年12月收治的胆道闭锁患儿57例进行分析。男32例，女25例；平均手术年龄81天（33－223天）；36例行Kasai术。测定13例患儿血清巨细胞病毒的DNA、抗CMV－lgG和lgM抗体和肝活检组织和CMV抗原表达。结果：Kasai术后总的胆汁排出率为53．8％，总的黄疸消退率为33．3％。激素治疗有促进胆汁引流作用。60天以内手术组疗效明显好于90天以后手术组。CMV感染组术后疗效较非感染相差。提示在目前国内尚未广泛开展肝移植的情况下，早期诊断、及早手术及加强术后抗感染和抗病毒治疗对提高其生存率意义重大。     

Hedgehog 通路在先天性胆道闭锁发病机制中研究进展

先天性胆道闭锁(congenital biliary atresia,CBA)是一种新生儿早期胆管疾病,导致肝内肝外胆管不同程度的闭锁并造成肝组织纤维化伴肝胆管不可逆性损伤。它是新生儿阻塞性黄疸和小儿肝移植最主要的原因。其发病机制目前尚未研究清楚,是遗传与环境因素共同作用导致的复杂疾病。Hedgehog信号通路在哺乳动物胚胎发育、器官形成及发育中有重要作用。近期研究发现,Hedgehog信号通路在CBA的发生过程中也发挥重要作用。Hedgehog通路的激活会影响胚胎肝脏发育、增强肝胆管纤维化的发生并且阻碍胆管形态的形成,从而导致CBA的发生。文章重点介绍Hedgehog通路在CBA形成过程中所起的重要作用。     

先天性小肠闭锁术后肠动力功能障碍的原因探讨

目的探讨小肠闭锁术后发生肠动力功能障碍的原因及手术切除病变肠管范围。方法对小肠闭锁手术切除小肠标本15例及对照组6例非肠道或神经系统疾病死亡的足月新生儿尸检小肠标本肠壁S-100蛋白、α-平滑肌肌动蛋白（α-SMA）和c-kit蛋白进行免疫组化研究。观察闭锁两端肠壁肠神经系统（ENS）、平滑肌和肠间质细胞（ICCs）病理改变及其分布范围，并行统计学处理。结果闭锁近端肠壁S-100、α-SMA和c—kit阳性表达明显低于对照组。随远离盲端，以上指标呈逐渐增加趋势。在闭锁近端16cm、远端4cm处，三者病变总体趋于正常。结论小肠闭锁两端肠壁与肠动力密切相关的ENS、平滑肌和ICCs均存在病变。是小肠闭锁术后发生肠道动力功能障碍的原因。在患儿小肠长度允许的情况下．切除闭锁近端肠管16cm以上，而远端切除4cm．可减少或避免术后肠动力功能障碍的发生。     

Implication of early‐onset biliary atresia and extrahepatic congenital anomalies

Background: The aim of the present study was to determine the rate of early‐onset biliary atresia (BA) and its implications, for embryonic‐type BA in Taiwan, a high‐prevalence area for BA. The relationship between the timing of disease onset and congenital extrahepatic anomalies was also identified. Methods: Medical records of 130 infants born in Taiwan with biliary atresia between January 1996 and December 2005 were reviewed retrospectively. The gold standard for the diagnosis of biliary atresia was intraoperative cholangiography. As well as medical records review, abdominal imaging and echocardiograms were performed to determine other structural anomalies. Early‐onset BA was defined as acholic stool and cholestatic jaundice observed before 2 weeks of age. Results: On review of onset of acholic stool and cholestatic jaundice before 2 weeks of age, 31 patients (23.8%) were defined as having early‐onset BA. Twenty patients (15.4%) had major congenital extrahepatic anomalies. One (0.7%) had biliary atresia splenic malformation syndrome (BASM). Both early‐onset and late‐onset BA may be associated with other structural anomalies. Patients with early‐onset BA had a higher probability of having major extrahepatic anomaly (9/31 vs 11/99, P= 0.046). Situs anomalies accompanying major gastrointestinal (GI) tract anomalies occurred only in early‐onset BA patients. Conclusions: After comprehensively investigating the timing of onset and associated congenital extrahepatic anomalies in BA patients in Taiwan, only one BASM with double spleen was detected. A total of 23.8% of patients had early‐onset BA, and this group of patients is prone to extrahepatic anomalies. Situs anomalies accompanying major GI tract anomaly may be indicative of embryonic‐type early‐onset BA.     

Relationship between prognosis of biliary atresia and infection of cytomegalovirus

Background  The etiology of biliary atresia is still unknown. It is generally accepted that virus infection may be one of the important causes that lead to biliary atresia. This study aimed to illustrate the relationship between infection of cytomegalovirus and prognosis of biliary atresia. Methods  From January 2002 to March 2004, 27 patients who had undergone Kasai’s procedure because of biliary atresia were investigated for cytomegalovirus-IgG, IgM and pp65, and their mothers were also examined for confirmation of cytomegalovirus infection. The patients were divided into three groups: infection free group, cytomegalovirus positive group and cytomegalovirus infection group. The rate of jaundice disappearance and the incidence of reflux cholangitis were analyzed statistically. The histopathological changes of the liver were also analyzed. Results  The positive expression of cytomegalovirus-IgM and cytomegalovirus-pp65 in the patients was higher than that in their mothers (48% versus 14.81% and 37% versus 3.78%, respectively). Compared with the other two groups (80% in the infection free group, and 82% in the cytomegalovirus positive group), the rate of jaundice disappearance after operation in the cytomegalovirus infection group (36%) was significantly lower (P<0.05), and the incidence of reflux cholangitis was higher (P<0.05). Histopathological examination also showed that the degree of liver fibrosis and inflammation was more serious (P<0.05). Conclusions  There is a strong correlation between cytomegalovirus infection and a lower rate of jaundice disappearance, also a higher post-operational reflux cholangitis. Liver fibrosis seems to be more severe in biliary atresia patients with cytomegalovirus infection.     

Answered and unanswered controversies in the surgical management of extra hepatic biliary atresia

Almost a half-century since Kasai described the portoentersotomy for extrahepatic biliary atresia (EHBA), some questions about the management of this condition have been resolved and many are unanswered. The most useful diagnostic steps to aid in the diagnosis are debated. Sonography can be helpful but its sensitivity and selectivity are arguable with strong advocates for its effectiveness. Likewise, the magnetic resonance imaging has forceful advocates but also has not been universalized. The liver biopsy, done commonly before an operation for cholestasis, is often not discriminating. The radionuclide scan hepatobiliary iminodiacetic acid (HIDA) scan after phenobarbital stimulation is helpful if negative, but false positive results are common. It is agreed to proceed expeditiously to the operation in the cholestatic infant after a prompt investigation. The proposal to avoid this step and provide liver transplantation as initial management for EHBA has been suppressed by several clinical findings. The Kasai procedure has not worsened the outcome of eventual liver transplantation. The Kasai, even if it eventually fails, will often buy time and allow the child to grow before transplantation is needed. Multiple reoperations prior to the transplant are discouraged. Revisions to improve bile flow have not gained wide popularity. Use of a stoma to divert the bile has been largely abandoned. The need for frozen section examination of the liver at the site chosen for the portoenterostomy is no longer demanded. The preferred type of intestinal conduit is argued. Unanswered questions about the post-operative management include the role of steroids and of prophylactic antibiotics. The Biliary Atresia Research Consortium, a multi-institutional National Institutes of Health (NIH)-supported project, will address many of the unanswered issues.