Cases Of Extrahepatic Biliary Atresia Research Articles

Diagnostic and Prognostic Significance of Various Histopathological Features in Extrahepatic Biliary Atresia.

Extrahepatic biliary atresia is a progressive disorder characterised by fibroinflammatory obliteration or stenosis of the extrahepatic biliary tree leading to obstruction of bile flow and cholestatic jaundice. It is the most common cause for cholestasis in newborn. Histopathological criteria for diagnosing biliary atresia from liver biopsy have not been clearly defined. This study was undertaken to analyse the significance of the various histopathological features in diagnosis and prognosis of extrahepatic biliary atresia from liver biopsy specimens. This was a retrospective study of 43 cases of extra-hepatic biliary atresia diagnosed and treated at a tertiary care hospital between January 2010 to December 2014. Formalin fixed paraffin embedded liver biopsy tissues were processed by standard technique and the slides were stained with haematoxylin and eosin. All the slides were reviewed and graded by a semi-quantitative scoring system. Features such as increased age at kasai's portoenterostomy, portal fibrosis, bile duct proliferation, cholestasis, portal inflammation and duct plate malformation were studied. Statistical analysis was worked out using SPSS 17.0 (statistical package for the social science software). Chi-square test was used to find association between various parameters with respect to mortality and Kaplan-Meier estimator was used for survival analysis of the population under study. In this study comprising of 43 cases, only 6 cases (13.95%) were alive at the end of 6 months follow-up. Twenty patients who died and the 17 cases with poor survival had greater degrees of fibrosis, bile duct proliferation and cholestasis. Majority of the cases with duct plate malformation expired inspite of earlier surgical intervention. Thus proving the association of fibrosis, bile duct proliferation, cholestasis and duct plate malformation with the survival and prognosis of biliary atresia cases. Age at surgery did not show any correlation with prognosis as cases operated even at <60 days had poor survival. From this study it can be concluded that in extrahepatic biliary atresia patients, presence of duct plate malformation, greater degrees of fibrosis, bile duct proliferation and cholestasis were strongly associated with poor prognosis.

32. The spectrum of paediatric liver disease seen in a children's hospital

Background The spectrum of hepatobiliary disease in infancy and childhood has not been reported in our population. Ours is an 830-bed hospital and academic healthcare institution for women and children in the country and the region. Aims The aim is to study the histological spectrum of paediatric hepatobiliary diseases encountered in this children's hospital. Methods The electronic histopathology record was retrospectively reviewed to identify all surgical specimens from liver, including biopsies and resection specimens, from patients under the age of 18 years over a 5-year period (from January 2009 to December 2013). Results There were 83 liver specimens over the 5-year period. 85.5% of cases were biopsies. The diagnoses of 18 cases (21.7%) were neoplasms, of which 10 were primary liver tumours (hepatoblastoma 8, hepatocellular carcinoma 1, mesenchymal hamartoma 1) and 8 were metastases (metastatic neuroblastoma 6, desmoplastic small round cell tumour 1 and germ cell tumour 1). 51.6% of cases were from infants under the age of 1 year. Non neoplastic cases accounted for 88.4% and included 25 cases of extrahepatic biliary atresia, 5 cases of choledochal cyst and 4 cases of neonatal hepatitis. 24.1% of cases were from children aged 1 to 5 years. Non neoplastic cases accounted for 50% and included 4 cases of choledochal cyst and 2 cases of autoimmune hepatitis. 24.1% of cases were from children aged 6 to 18 years. There were 3 neoplasms and three cases each of choledochal cyst, autoimmune hepatitis and graft-versus-host disease. Conclusions The most common diagnosis was extrahepatic biliary atresia (30.1%), followed by choledochal cyst (14.5%). 21.7% of cases were neoplasms, with hepatoblastoma being the most common (9.6 %), followed by metastatic neuroblastoma (7.2%).

Extra-Hepatic Biliary Atresia in Association with Polysplenia and Intestinal Malrotation

The syndromic form of biliary atresia accounts for 10-25% and is associated with a poor prognosis due to associated anomalies. We report a case of extrahepatic biliary atresia and polysplenia syndrome with jaundice since 19th day of life and who had undergone surgical correction of malrotation in the neonatal period. Inspite of successful Kasai’s portoenterostomy at 52nd day of life, the child succumbed to post-operative sepsis.

Diagnosis of neonatal cholestasis; outcome in a regional centre.

Aims Extrahepatic biliary atresia (EHBA), fatal without surgery, has a prevalence of 1 in 15000 births and an incidence of 50 cases per year. A Kasai operation before 8 weeks gives the best chance of survival with native liver. Quality clinicopathological care comprises early recognition of cholestatic jaundice, with prompt diagnosis and referral of cases of EHBA (or other causes of surgically correctable biliary obstruction) to super-regional centres for specialised surgery. This requires close cooperation between gastroenterologist and pathologist. Our aim was to assess the quality of our clinical and pathological contribution to this pathway. Methods We identified all infants over the last 12 years who had underdone liver biopsy for cholestatic jaundice. Every case had been discussed at clinicopathological conference. We examined the clinical and pathological records to establish initial diagnoses and subsequent outcome. Results *P Conclusions A close working relationship between the pathologist and the gastroenterologist at a regional centre, in partnership with the pathologists and hepatologists at super-regional centres, delivered effective care.

Coexistence of Duarte 1 and Duarte 2 variants of galactosemia with extrahepatic biliary atresia

Galactosemia is an autosomal recessive disorder caused by deficient or absent activities of one of the three enzymes involved in the galactose metabolic pathway. The predominant form is classic type galactosemia caused by severe reduction or absence of the galactose- 1-phosphate uridyl transferase (GALT) enzyme. Coexistence of extrahepatic biliary atresia (EHBA) with Duarte 1 and 2 variants of galactosemia has not been described earlier. Here we report a case of EHBA with concordant Duarte 1 and 2 variants of galactosemia in an infant with cholestasis. Genetic analysis of the index patient for galactosemia revealed presence of Duarte 1/Duarte 2 variants of galactosemia with genotype N314D-L218L/N314D-G1105C-GI391A- G1323A-5’UTR-119delGTCA. Clinical evaluation of the patient showed the presence of EHBA. Henceforth, it may be hypothesized that EHBA may have a genetic basis with simultaneous involvement of the GALT gene.

CD 56 staining in liver biopsies does not help in differentiating extrahepatic biliary atresia from other causes of neonatal cholestasis

IntroductionSeveral conditions are considered in differential diagnosis of neonatal cholestasis. Of these the most important is extrahepatic biliary atresia (EHBA), while prompt diagnosis and surgical correction of obstruction can ameliorate clinical symptoms, provides long term survival for about one fourth of patients and serves as an important bridge to transplantation for many others. From histopathologic standpoint, features of EHBA overlaps with other diagnoses and so ancillary tests such as immunohistochemical staining for CD56 is suggested by some authors as a helpful tool in differential diagnosis.Hereby we wanted to examine this staining in our center which is a referral children hospital and to prove its efficacy in our problematic cases.Materials and MethodsBy retrospective review of pathology records during 2000 to 2006 in Markaze Tebbi Koodakan (children hospital related to Tehran University of Medical Sciences), we selected 17 cases of EHBA as patients and 12 cases with other diagnoses as controls, both with some degree of bile ductular proliferation in liver biopsies. EHBA cases were all proved by surgery. Four of control cases also underwent surgery but proved to have open ducts by intra-operative cholangiography. Long term follow up and other tests ruled out EHBA in other 8 cases. Hematoxylin-Eosin stains of paraffin blocks were studied again and freshly prepared sections were immunostained for CD56.ResultsBile ducts and proliferating bile ductules were strongly positive for CD56 in 6 of 17 cases of EHBA. In 7 out of 17, positivity were seen in more than two thirds of portal tracts. In controls, one case showed strong positivity and 6 out of twelve showed positivity in more than two thirds of portal tracts. The intensity and distribution of CD56 staining did not differ significantly between two groups.DiscussionDespite findings of previous studies, we have shown that CD56 staining can not help as an ancillary test in differential diagnosis of neonatal cholestasis and perhaps other markers should be tested in this regard.

Morphological and immunohistochemical analysis of ductal plate malformation: correlation with fetal liver.

Ductal plate malformation (DPM) is the persistence of excess of embryonic bile duct structures in the portal tracts. Most of the congenital diseases of intrahepatic bile ducts represent examples of DPM at different levels of the biliary tree. The aim of the present study was to evaluate the histopathological spectrum and immunohistochemical properties of DPM in various paediatric liver diseases and compare them with those of the normal embryonic ductal plates of human fetuses. All paediatric liver biopsies and autopsied livers of infant deaths and stillbirths over a 5-year period (between 1996 and June 2001) were subjected to histopathological examination to identify ductal plate malformations. A detailed immunohistochemical analysis was carried out in 35 cases of ductal plate malformation and 25 abortuses by using antibodies against cytokeratin (CK)7, 8, 18 and 19, CD34 and type IV collagen. Thirty-nine cases of ductal plate malformation were identified which consisted of extrahepatic biliary atresia with DPM (n = 20), isolated congenital hepatic fibrosis (n = 9), autosomal recessive polycystic kidney disease (n = 5), congenital hepatic fibrosis with autosomal polycystic kidney disease (n = 2), Caroli's syndrome (n = 2) and one case of Ivemark's syndrome. The ductal plate cells stained with CK7, 8, 18 and 19 but not with CD34. DPM was present in all intrahepatic bile duct diseases included in this study and in about 26% of cases of extrahepatic biliary atresia. The cytokeratin immunophenotype of the ductal plate in pathological conditions is similar to that of normal embryonic ductal plates of fetuses after 20 weeks of gestation.

Extrahepatic biliary atresia and caudal regression syndrome in an infant of a diabetic mother

Although most cases of extrahepatic biliary atresia are thought to result from perinatal obliterating inflammation, some are associated with a faulty morphogenesis. The authors report on a baby girl of a mother with ill-managed insulin-dependent diabetes mellitus. The baby presented with sacro-coccygeal agenesis, clubfoot, and ano-urinary incontinence. In addition, there was polysplenia, no inferior vena cava, and the portal vein was grossly distorted. Progressive conjugated hyperbilirubinemia prompted liver biopsy at 4 weeks of age, showing intracanalicular cholestasis without fibrosis. The diagnosis of extrahepatic biliary atresia was confirmed during laparotomy performed for hepatoportojejunostomy. Some cases of extrahepatic biliary atresia might be part of a spectrum of malformations associated with maternal diabetes mellitus.

Bile Ducts and Ductules Are Positive for CD56 (N-CAM) in Most Cases of Extrahepatic Biliary Atresia

The diagnosis of extrahepatic biliary atresia can be challenging as the histologic features can overlap with other pediatric cholestatic liver diseases. Several previous studies have noted that biliary epithelium is positive for CD56 in the setting of extrahepatic biliary tract disease. Thus, we explored the use of CD56 in evaluating liver biopsy specimens for extrahepatic biliary atresia. A total of 22 cases were selected and immunostained for CD56, including 14 cases of confirmed extrahepatic biliary atresia and 8 cases of other cholestatic liver diseases in which the differential diagnosis included extrahepatic biliary atresia. Bile ducts and proliferating ductules were positive for CD56 in 13 of 14 cases of extrahepatic biliary atresia. The staining intensity was generally strong with most cases showing positivity in more than two thirds of portal tracts. The one negative case was a very small biopsy (<0.3 cm), and sampling may have played a role. In contrast, 4 of 8 cases in the control group were completely negative for CD56, with the remaining cases showing weak and focal positivity. In conclusion, bile ducts and ductules are CD56 positive in most cases of extrahepatic biliary atresia, and CD56 immunostaining can be a useful supplemental stain for diagnosing extrahepatic biliary atresia in its early, ductular proliferative phase when used in conjunction with traditional hematoxylin and eosin morphology and clinical information.

The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresia

The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresia

The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresia

Mutations of human jagged 1 (JAG1) gene are responsible for Alagille Syndrome (AGS), whose 2 main symptoms are intrahepatic bile duct hypoplasia and pulmonary stenosis. We examined the JAG1 mutation in extrahepatic biliary atresia (EHBA), which is similar in phenotype to AGS, although a different pathogenesis is suggested. In 102 cases of EHBA, 9 missense mutations were detected, including 2 intrafamilial expressions in the propositus and an aunt of one family. These mutations were all missense and sporadic except for those of this particular family. The JAG1 gene mutations were generally found in severely ill patients subjected to liver transplantation at less than 5 years of age. None of the 9 cases of EHBA revealed any of the 5 major symptoms of AGS nor any identical pathological findings after 3 years of follow-up. Our cases were clearly separated from AGS by pathological findings and clinical features, and could be diagnosed as EHBA and not as atypical AGS. The increase of interleukin 8 (IL-8) production induced by tumor necrosis factor α (TNF-α) in Huh 7 cells was suppressed by the coexistence of JAG1 protein. We examined the different influences between wild-type cells and the 3 kinds of mutants detected in EHBA on Huh 7 cells and found that 2 of 3 mutants showed about half of the repressed activity compared with that of wild type. In conclusion, these results suggest that the JAG1 gene abnormality may be an aggravating factor in EHBA. (H EPATOLOGY 2002;36:904-912.)

The influence of cholangitis on the prognosis of extrahepatic biliary atresia.

The prognosis of extrahepatic biliary atresia (EHBA) depends first on the progression of the basically existing disease and second on the development of preoperative existing alterations of hepatic structure. In addition there are postoperative complications which have essential influence on the prognosis of the disease. In this context ascending cholangitis poses a very important problem for children who have undergone a portoenterostomy. Both the organism and the frequency of cholangitis may play a part. This study should outline the influence of cholangitis on the prognosis. Since 1972, 146 cases of extrahepatic biliary atresia have been treated and followed up postoperatively. Children with a liver fibrosis degree IV at surgery will develop a cirrhosis in 86% of cases without additional influence of cholangitis. Children with a liver fibrosis degree II/III will develop a cirrhosis in 20% of cases without the influence of cholangitis after 15 years. But children with a fibrosis degree II/III with one or several episodes of cholangitis will develop a liver cirrhosis in 50% of cases after 12.5 years. The difference is statistically significant. In addition the frequency of cholangitis is also an important factor: The more episodes of cholangitis the greater the probability of cirrhosis.

Presence of Human Papillomavirus in Extrahepatic Biliary Atresia

ABSTRACTBackground:In a previous study the human papillomavirus DNA was detected in seven cases of so‐called idiopathic neonatal giant cell hepatitis by using nested polymerase chain reaction. The purpose of the present study was to study the prevalence and possible common causes of human papillomavirus‐associated idiopathic neonatal giant cell hepatitis and extrahepatic biliary atresia.Methods:Formalin‐fixed, paraffin‐embedded archival tissues obtained in 18 cases of extrahepatic biliary atresia were studied for human papillomavirus DNA by nested polymerase chain reaction. In addition, in situ hybridization was performed on tissue obtained in 6 cases.Results:Tissue in 16 of the 18 cases studied showed amplified human papillomavirus DNA, whereas no human papillomavirus was amplified in any of 30 control samples. Main human papillomavirus detected were types 6 and 18. Punctate intranuclear positive signals were detected in the hepatocytes after in situ hybridization for human papillomavirus DNA.Conclusions:The high prevalence of human papillomavirus DNA in liver tissue in cases of extrahepatic biliary atresia suggests a strong correlation between this disorder and idiopathic neonatal giant cell hepatitis. It further suggests that this virus may be one of the causative agents in extrahepatic biliary atresia and may represent part of the spectrum of lesions associated with neonatal human papillomavirus‐induced hepatic damage.

Presence of human papillomavirus in extrahepatic biliary atresia.

In a previous study the human papillomavirus DNA was detected in seven cases of so-called idiopathic neonatal giant cell hepatitis by using nested polymerase chain reaction. The purpose of the present study was to study the prevalence and possible common causes of human papillomavirus-associated idiopathic neonatal giant cell hepatitis and extrahepatic biliary atresia. Formalin-fixed, paraffin-embedded archival tissues obtained in 18 cases of extrahepatic biliary atresia were studied for human papillomavirus DNA by nested polymerase chain reaction. In addition, in situ hybridization was performed on tissue obtained in 6 cases. Tissue in 16 of the 18 cases studied showed amplified human papillomavirus DNA, whereas no human papillomavirus was amplified in any of 30 control samples. Main human papillomaviruses detected were types 6 and 18. Punctate intranuclear positive signals were detected in the hepatocytes after in situ hybridization for human papillomavirus DNA. The high prevalence of human papillomavirus DNA in liver tissue in cases of extrahepatic biliary atresia suggests a strong correlation between this disorder and idiopathic neonatal giant cell hepatitis. It further suggests that this virus may be one of the causative agents in extrahepatic biliary atresia and may represent part of the spectrum of lesions associated with neonatal human papillomavirus-induced hepatic damage.

Immunoreactivity of neoplastic and non-neoplastic hepatocytes for CD68 and with 3A5, Ki-M1P, and MAC387 light- and electron-microscopic findings

The immunohistochemical finding that the macrophage markers KP1, PG-M1 (both CD68) and Ki-M1P occasionally stain epithelial cells prompted a systematic immunohistochemical investigation of liver tissue with these and other macrophage markers. The material investigated comprised normal and cirrhotic liver, four hepatocellular carcinomas, including one fibrolamellar carcinoma, and liver specimens from two cases of extrahepatic biliary atresia and one case of paucity of intrahepatic bile ducts. The macrophage markers KP1, PGM1, Ki-M1P, 3A5, MAC387 and anti-lysozyme were employed. Two cases (one each of extrahepatic biliary atresia and cirrhosis) were investigated by immunoelectron microscopy to determine the subcellular site of reactivity. In the normal liver, only the Kupffer cells reacted with the macrophage markers. However, in neoplastic and non-neoplastic hepatic disorders, all the antibodies (with the exception of anti-lysozyme) stained hepatocytes in at least one case. KP1 produced particularly strong staining. Electron microscopy revealed the reaction product here to be related to lysosome-like granules in the hepatocytes. Therefore, when immunohistochemical investigation of liver biopsy specimens reveals reactivity with macrophage markers, it should be borne in mind that hepatocytes may also be reactive.

Extrahepatic biliary atresia and associated anomalies: etiologic heterogeneity suggested by distinctive patterns of associations.

Fifty-one cases of extrahepatic biliary atresia (EHBA) with associated anomalies were found in a study of EHBA (251 cases). Analysis of segregation patterns of these anomalies in individual patients suggested the existence of 2 major groups: (1) 15 cases (29.4%) with various combinations of anomalies within the laterality sequence, and (2) 30 cases (58.8%) with one or 2 anomalies mostly involving the cardiac, gastrointestinal, and urinary systems. These latter anomalies did not follow any recognizable pattern. The third group of 6 cases all had intestinal malrotation, some with preduodenal portal vein; these cases show some similarity to the laterality sequence group and may represent a more confined phenotypic result of faulty situs determination. This previously unattempted classification of patients with EHBA and associated anomalies might enable a more targeted approach towards identification of causes in this heterogeneous disorder. EHBA within the laterality sequence might prove a suitable candidate for a major gene mutation. Teratogenic, infectious and polygenic multifactorial causes might play a more significant role in EHBA associated with "nonsyndromic" organ system anomalies.

Results of Surgery in 88 Consecutive Cases of Extrahepatic Biliary Atresia

Of 88 cases of extrahepatic biliary atresia, satisfactory bile flow has been established in 46% of the patients who have undergone portoenterostomies and in 25% of patients with hepaticojejunostomies. Histological analysis of the extrahepatic biliary tissue has not shown a consistent correlation with outcome of operation, except that the patients with one or two large residual ducts lined with columnar epithelium have a better chance of developing bile flow. Cholangitis developed in 43% of the cases, and co-trimoxazole was not shown to have any beneficial effect in a small prospective trial in 18 patients. Severe haemorrhage from oesophageal varices has occurred in 4 jaundice-free survivors. Seventeen patients are now over 3 years of age and thriving but many show persistent elevation of liver enzymes.

Studies in the etiology of extrahepatic biliary atresia: Time-space clustering

Thirty new cases of extrahepatic biliary atresia in the north Texas area between 1972 and 1980 were analyzed for evidence of time-space clustering. A preponderance of affected infants from rural counties ( P −7 ) and during the fall ( P

Biliary atresia, an analysis of 30 cases.

Of 30 cases of extrahepatic biliary atresia, treated during 1973–81, twenty five were males and five were females. Two thirds of these were admitted after 90 days of age. A correct pre operative diagnosis was made in 28 patients. Wedge liver biopsy and operative cholangiograms were done in all cases. Various types of drainage procedures done in 20 patients included hepatic porto- enterostomy 13, hepatic porto- cholecystostomy 4, choledochojejunostomy 2 and choledochoduodenostomy 1. Since 1980, an operating microscope had been used for the dissection at porta hepatis.

131I rose bengal: its use in the evaluation of infantile jaundice.

One-hundred ten 131I-rose bengal studies (RBI) were performed in infants suspected of having biliary atresia. Fecal RBI excretion of less than 10% was observed in 72 of 73 cases of extrahepatic biliary atresia, but also in 10 of 37 cases of intrahepatic cholestasis of various origins. One-hundred twenty-two RBI tests were performed in children operated on for extrahepatic biliary atresia and 71 tests were performed between postsurgical weeks 3 and 8, and 51 tests were done later. Prognostically, early tests show that fecal RBI excretion of more than 15% was observed in 2 of 34 cases who were later completely jaundice-free and in only 1 of 37 cases where no bile flow restoration occurred.