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| Differentiating biliary atresia from other causes of infantile cholestasis: An appraisal of the histomorphological changes on liver biopsy |
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Aniket Halder1, Sabita Patra2, Bappa Mandal3, Gautam Ray4, Ranajoy Ghosh1, Suchandra Mukherjee3, Uttara Chatterjee2
1 Department of GI Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
2 Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
3 Department of Neonatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
4 Department of Pediatric Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
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| Date of Submission | 02-Mar-2022 |
| Date of Decision | 22-Aug-2022 |
| Date of Acceptance | 23-Aug-2022 |
| Date of Web Publication | 03-Feb-2023 |
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 Abstract | | |
Background: Cholestatic disorders are a significant cause of morbidity and mortality in infants. Characterization of these disorders and differentiating biliary atresia (BA) from other causes of intrahepatic cholestasis is an age-old problem. Objectives: To study the spectrum of different infantile cholestatic disorders in our population, to differentiate BA from other causes of neonatal cholestasis (NC) on a liver biopsy, and validation of the available scoring system for the characterization of these disorders. Materials and Methods: This is an observational cross-sectional study performed over a period of 3 years between 2018 and 2021, done on neonates and infants presenting with cholestatic jaundice. The changes on liver biopsy were evaluated by different histological parameters and available scoring systems to differentiate BA from non-BA causes. Correlation with clinical, biochemical, and imaging findings was done in all cases. Results: This study included 87 cases of NC, of which BA comprised 28 cases (32%), whereas idiopathic neonatal hepatitis (INH) comprised only 12 cases (14%). Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), neoductular bile plugs (P < 0.001) and bile ductular proliferation (P < 0.0001) were significantly more in BA, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequent in the non-BA group. Using the Lee and Looi scoring system, a histologic score ≥7 was helpful in identifying BA with 85.7% sensitivity, 92.6% specificity, and 90.6% accuracy. Conclusion: BA is the commonest cause of NC in neonates, whereas the frequency of INH is declining. Detailed histomorphologic analysis of liver biopsy, aided with IHC, is the cornerstone for the diagnosis of these disorders.
Keywords: Biliary atresia, conjugated hyperbilirubinemia, IHC, neonatal cholestasis, neonatal hepatitis, PFIC, scoring system
How to cite this URL:
Halder A, Patra S, Mandal B, Ray G, Ghosh R, Mukherjee S, Chatterjee U. Differentiating biliary atresia from other causes of infantile cholestasis: An appraisal of the histomorphological changes on liver biopsy. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Mar 27]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=369085 |
| Introduction | |  |
Neonatal jaundice that persists beyond 2 weeks usually indicates a severe underlying condition requiring urgent evaluation, diagnosis, and management.[1] Neonatal cholestasis (NC) is defined as persistently elevated conjugated bilirubin of more than 2.0 mg/dL or more than 20% of total bilirubin.[2] NC can be classified into obstructive and non-obstructive types with biliary atresia (BA) being the commonest obstructive etiology requiring prompt diagnosis and surgical bypass procedure.[3],[4] The non-obstructive disorders including idiopathic neonatal hepatitis (INH) are associated with much better outcomes and do not require any surgical intervention. Liver biopsy is the cornerstone of the diagnostic work-up of neonatal cholestatic disorders.[5],[6] Characterization of these cholestatic disorders remains a challenge for the clinician as well as the pathologist to date.[7],[8] After an extensive literature search, we could find only limited data on the occurrence of these disorders from India, and none from eastern India. The objectives of this study were to characterize the different cholestatic disorders in neonates and infants in our population, differentiate BA from other causes of NC in a liver biopsy by different histological parameters, and validate the available scoring system for the categorization of these disorders.
| Materials and Methods | | |
Selection of cases
This was a single-center institution-based observational cross-sectional study performed over a period of 3 years from 2018 to 2021. The study was done after obtaining requisite clearance from the institutional ethics committee and prior informed consent from the parents. Neonates and infants presenting with cholestatic jaundice of any duration in the departments of Neonatology or Hepatology and undergoing liver biopsy were initially enrolled. The cases were included mostly in a prospective manner. Retrospective cases were selected by retrieving the paraffin blocks and slides from the departmental archives and only those cases were included in which thorough clinical history and follow-up data of at least 6 months were available. Neonates or infants who died during disease evaluation or were lost to follow-up were excluded. Cases where the liver biopsy specimen was inadequate qualitatively or quantitatively were also rejected as per the established criteria. Fragmented biopsies with crush artifacts or biopsies less than 1.0 cm in size with fewer than six portal tracts in the biopsy were considered inadequate and thereby excluded.[9] The detailed demographic features and clinical presentation were noted down in a pre-designed clinical proforma.
Diagnostic workup
Routine laboratory investigations were done in all cases including a complete hemogram with reticulocyte count, liver function tests, and routine urine and stool examination. Urine and blood cultures with serological tests were done in suspected perinatal infections. Relevant chemical analysis from urine and stool samples was done in suspected metabolic disorders. An abdominal ultrasound (USG) was done in all cases. A hepatobiliary scintigraphy scan (HIDA scan) was done in all cases of suspected BA. Percutaneous liver biopsy was obtained under ultrasound guidance and after routine tissue processing, multiple step sections were taken for hematoxylin and eosin (H&E) staining, Masson trichrome, reticulin, Perl's Prussian blue, PAS with diastase and orcein. Two additional sets of sections were prepared from each block for immunohistochemistry.
Histopathopathologic evaluation
The liver biopsy slides were initially screened for the suitability of interpretation and adequacy of sectioning and staining. The length of the tissue core and the number of portal tracts present were noted. All portal tracts were observed for the number, size, and shape of portal bile ducts and ductules, and evidence of bile ductular proliferation was graded. The ductular reaction was defined as the presence of increased ductular profiles at the periphery of the portal tract around the limiting plate with portal stromal edema. Duct plate malformation (DPM) was defined as a circinate arrangement of double-layered duct profiles around a central fibrovascular core.[6] Paucity of the interlobular bile duct (PILBD) was defined as a ratio of interlobular bile ducts to portal tract ratio ≤0.5 in a minimum of five well-defined portal tracts. The presence of ductal or ductular cholestatic bile plugs was noted. The type of inflammatory cell infiltrate in the portal tracts and interface hepatitis was assessed and scored semiquantitatively as 0 (absent), 1 (mild), 2 (moderate), or 3 (marked). Portal and periportal inflammation was graded separately for neutrophils and lymphocytes as per the established criteria.[6],[7] The degree of lymphocytic lobular inflammation was also graded. The lobular hepatocytes were assessed for giant cell transformation, feathery degeneration, steatosis, and cholestasis (cytoplasmic or canalicular). Additional features evaluated were hepatocyte pseudo-rosetting, cholestatic rosette formation, extramedullary hematopoiesis (EMH), and the presence of cytoplasmic inclusions or pigments. Fibrosis was staged from 0 to 4, using the Batts–Ludwig modification of the Scheuer system on liver sections stained by Masson's trichrome stain. A histopathological scoring system by Lee and Looi[8] was followed to differentiate between BA and non-BA cases on liver histology.[7],[8] Immunohistochemistry (IHC) was done for CK7 (Sigma Aldrich) to analyze and enumerate the bile duct and ductules in all cases. IHC for CD 10, bile salt exporter protein (BSEP), and multidrug resistance protein-3 (MDR-3) were standardized and applied in to characterize different types of progressive familial intrahepatic cholestasis (PFIC). Normal liver tissue sections obtained from adult liver operated for unrelated causes (primary hepatolithiasis or liver explants) served as positive controls, whereas for negative controls, the primary antibody was omitted. The IHC slides were then interpreted as follows:
- CK7 immunostaining was done to assess and enumerate the bile duct and ductules. Bile ductular proliferation was considered to be present if the average number of ductules in the portal tract was more than five. The following criteria were used to grade the degree of bile ductular proliferation: Score 0 - the average number of bile ductules per portal tract <5; Score 1, mild - the average number of bile ductules per portal tract between 5 and 9; Score 2, moderate - the average number of bile ductules per portal tract ≥10; marked proliferation - elongated, attenuated, angulated bile ductules in addition to proliferation (average number of bile ductules perportal tract ≥10). The cases of PILBD, defined as a bile duct to portal tract ratio of 0.5 or less, were also confirmed by CK7 immunostaining.[7],[8]
- CD10, BSEP, and MDR3 staining was done for confirmation and subtyping of all suspected PFIC cases. Cases of low GGT cholestasis with bland cholestasis on liver histology, absent, or low CD10, and normal BSEP immunostaining were labeled as PFIC1, whereas cases with reduced or absent BSEP staining on the canalicular membrane were diagnosed as PFIC2. The cases with high GGT cholestasis with reduced or absent MDR-3 immunostaining were categorized as PFIC 3.
Interpretation and diagnosis
For all cases of suspected BA, liver biopsy findings were initially categorized into three headings- (1) Group A- consistent with large bile duct obstruction (LBDO); (2) Group B- indeterminate for LBDO; (3) Group C- negative for LBDO, and then correlated with the clinco-imaging features. Biopsies that showed portal expansion, bile duct proliferation, bile plugs in bile ducts or ductules, and ductular reaction were grouped into Category A, whereas those cases with no histologic features of obstruction were assigned as Category C. Category B comprised those cases of suspected BA, where histologic features of obstruction were equivocal and insufficient for definitive assignment into category C. The infant's age was taken into account while evaluating the biopsy as histologic changes and fibrosis in NC are age-dependent.[5],[6],[7] The histopathologic and immunohistochemical assessment was done independently by three pathologists (AH, UC, and RG), and discrepancies, if any, were resolved by common consensus.
All cases were followed up and clinically corroborated with relevant biochemical, serological, and imaging findings to arrive at a specific diagnosis. All cases of BA were confirmed on a peroperative cholangiogram. The diseases where no etiology was found after excluding all causes were labeled as idiopathic neonatal hepatitis (INH). Statistical analysis was done in an Excel spreadsheet. All descriptive data were summarized as median with range for continuous variables and percentages for categorical variables. Pearson's Chi-square test and Analysis of variance (ANOVA were done to study the correlation of different parameters. A P value <0.05 was considered to be statistically significant.
| Results | | |
In our study, we initially enrolled 93 cases of neonatal cholestasis, out of which 6 cases were lost to follow-up and hence excluded. Of the 87 cases, 72 cases were included in a prospective manner over 4 years. Fifteen cases were included retrospectively where clinico-radiological data and tissue blocks could be retrieved. Obstructive causes of cholestasis comprised 30 cases, of which 28 cases were BA, whereas two cases had congenital choledochal cysts. Of the 57 non-obstructive cases of cholestasis, PFIC was the commonest etiology with PFIC 2 being the most common subtype. There were only 12 cases of INH, where no definite etiology could be ascertained. The clinico-demographic profile of the cases with their final etiological diagnoses is shown in [Table 1].
Histopathologic changes on liver biopsy could correctly differentiate between BA and non-BA cases in 72/87 (82.7%) cases, whereas there were 4 cases of BA and 7 cases of non-BA, which were categorized in the gray zone [Table 2]. The two cases of congenital choledochal cysts (CCC) had histologic features indistinguishable from BA and were categorized in group A. Six patients who were misinterpreted initially were all <50 days at presentation and did not show the characteristic histologic changes of LBDO. All these six patients were confirmed as BA on peroperative cholangiogram. | Table 2: Initial categorization of cases for diagnosis of BA on liver biopsy
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Ductal cholestasis was the most consistent finding in BA, whereas ductular cholestasis, mainly within the neo-ductules in the porto-lobular interface, was seen in the majority of the cases of BA (23 cases, 82%). Bile ductular proliferation was seen in 25/28 (89.3%) cases of BA, with scores of proliferation significantly increasing with age (P < 0.5). Moderate to marked portal neutrophilic infiltrate was observed in most cases (18 cases, 64.3%). Three cases were associated with DPM. None of the cases of BA showed any steatosis, cytoplasmic inclusions, or confluent necrosis. The stages of hepatic fibrosis significantly correlated with the age of presentation with cirrhosis being diagnosed in five out of seven infants who presented after 100 days, whereas infants aged <50 days (n = 7) were found to have significantly less fibrosis (P = 0.018) [Figure 1]. The spectrum of histologic changes is shown in [Figure 2]. | Figure 2: (a) Histologic changes in BA in a 3-month-infant showing bridging fibrosis with gross nodularity at scanner power (4×, H&E); (b and c). Ductal and ductular cholestasis with marked bile ductular proliferation in BA; (d) lobular disarray, giant cell change with lobular cholestasis in INH (40×, H&E); (e) Marked fibrosis in BA (10×, Masson's trichrome); (f) IHC for CK7 showing marked bile ductular proliferation. (*BA-biliary atresia, INH-idiopathic neonatal hepatitis)
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We analyzed all histologic parameters to differentiate between the BA and the non-BA groups, which are summarized in [Table 3]. Choledochal cyst was excluded from this histologic comparison because it can be readily picked up on imaging and its histologic features mimic those of BA. Of the histologic parameters that we studied, we found that portal neutrophilic inflammation, lobular lymphocytic inflammation, ductal cholestasis, bile plugs within neoductules/neocholangioles, bile ductular proliferation, and giant cell changes significantly varied between the two groups. Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), bile plugs within neoductules/neocholangioles (P < 0.001), and bile ductular proliferation (P < 0.0001) were significantly more consistent in cases of biliary atresia, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequently found in the non-BA group. Six parameters, namely portal lymphocytic infiltration, canalicular cholestasis, cytoplasmic cholestasis, feathery degeneration, cholestatic rosettes, and EMH did not vary significantly between the two groups. Although EMH was found in 20 cases of the non-BA group, most notable in INH (n = 7) and PFIC2 (n = 9), rare foci of EMH were observed in five cases of BA as well. There was a significant difference in age-matched stage of fibrosis between the two groups (P-value = 0.0013). When compared to infants aged less than 100 days of age, the cases of BA had comparatively higher stages of fibrosis than the non-BA group. The analytical parameters to differentiate between BA and non-BA are analyzed in [Table 3] and [Table 4].
| Discussion | | |
Neonatal and infantile cholestatic disorders are a heterogeneous group of diseases with a frequency between 1:2500 and 1:5000.[10] Liver biopsy is the cornerstone in the diagnostic workup of these disorders with a primary focus to identify the obstructive etiologies, notably BA.[7] Available studies in the literature have reported BA to be the commonest cause of infantile cholestasis, followed by idiopathic NH.[11] The available literature reports NH to be around 30% of cases,[12],[13],[14],[15] but our experience shows idiopathic cases to be much lower and around 14%, which is similar to a few studies.[11],[16] This is probably due to the introduction of newer diagnostic tools and the identification of previously unrecognized diseases such as PFIC. Our study is the largest series to date from eastern India to identify and characterize these neonatal and infantile cholestatic disorders.
The age-old problem of correctly differentiating BA from non-BA cholestasis remains relevant even today. Although there are many studies that had evaluated different clinical and biochemical parameters, none of them are specific or pathognomic of BA.[17],[18],[19] In a large series by Shneider et al.,[18] age at disease onset, acholic, or pale clay stools, hepatomegaly, and weight z-score were the best clinical indicators of BA, although they documented pale clay stools in 34% cases of non-BA cases. Our findings were similar, with 82.7% of cases of BA having persistent clay-coloured stools and 33.3% of INH having intermittent acholic stools. Hepatomegaly was found in 36% of cases of BA, with the liver consistency being firm in all cases. From our experience, we suggest that persistent acholic stools and firm hepatomegaly are the best clinical pointers toward BA as reported earlier in the literature.[18],[19]
BA accounted for around 32% of the cases, which is similar to many studies available in the literature.[11],[12],[15] The incidence of BA in our series might be biased and skewed because our hospital is the largest tertiary care referral hospital in Eastern India, and a significant proportion of infants have been referred to us from other centers, thus representing the grouping of more severe cases, whereas some of the cases of infantile cholestasis with more benign causes have probably not been referred. Nevertheless, the identification of BA should be prompt from the age of presentation, so that intervention by corrective bypass surgery may be attempted as early as possible before significant fibrosis sets in. The time lag from the onset of jaundice to the age of biopsy varied from 18 to 149 days with only seven cases presenting to us at <50 days of age. The severity of fibrosis significantly correlated with the age of presentation, with as many as five cases, all >100 days having cirrhosis. In our earlier study, we noted a trend toward poor prognosis with increasing age, which correlated significantly with higher degrees of fibrosis.[6],[20] Duct plate malformation was found in three cases (10.71%) of BA, which, to our experience, is another indicator of poor survival in BA.[6],[20]
BA is not a histological diagnosis, but rather an infantile obstructive cholangiopathy that can only be correctly diagnosed by correlating the clinico-radiological features with histological findings. In this study, we found that ductal cholestasis and bile plugs within neocholangioles and ductules (ductular cholestasis) were the best histologic indicators of BA. Ductal cholestasis had 100% sensitivity and 91.5% specificity for BA, whereas bile plugs within neocholangioles had a slightly lesser sensitivity (82.1%) but very high specificity (98.3%) for BA. Moderate to marked degree of bile ductular proliferation had a low sensitivity for BA, but quite a high specificity of around 86.4%. The age-matched stage of fibrosis is also helpful in differentiating between BA and non-BA groups, specially INH. In infants aged less than 100 days of age, the cases of BA had comparatively higher stages of fibrosis (stage 2, 3, or 4 fibrosis) than the non-BA group. At the same cut-off age, we found the majority of the non-BA cases (21/25 cases) having none to mild Stage 1 fibrosis only. Nine out of 12 cases of INH had presented before 100 days of age and among them, only one case showed mild periportal fibrosis, whereas eight cases had no fibrosis on liver biopsy. Our findings are similar to previous studies by Russo et al.[7] and Rastogi et al.,[17] who showed that bile ductular proliferation, bile duct and ductular bile plugs, and portal fibrosis were the best indicators of BA. Apart from diagnosis, these features also have prognostic implications. In our previous studies, we had documented that a lower degree of fibrosis and ductular proliferation, absence of DPM, presence of large ducts, and younger age at operation were associated with better long-term outcomes.[6],[20]
We had 38 cases that were initially interpreted as 'neonatal hepatitis-like with features of significant cytoplasmic or canalicular cholestasis, lobular lymphocytic infiltration, and giant cell transformation of hepatocytes without significant bile ductular proliferation. Twenty-six cases could be etiologically specified on a detailed workup. Among the non-BA group, PFIC was the most frequent cause and the commonest etiology in our cohort. Normal GGT cholestasis presenting in infancy should always raise the suspicion for PFIC types 1 and 2. On liver biopsy, PFIC1 shows bland cytoplasmic or canalicular cholestasis, whereas the histology of PFIC 2 is similar to INH with lobular disarray, giant cell transformation, lobular inflammation, and fibrosis [Figure 3]. However, PFIC 3 cases usually present at a later age with elevated serum GGT levels with ductal cholestasis, ductal inflammation, and periductal fibrosis. We had standardized the immunostaining for CD10, BSEP (anti-ABCB11 antibody), and MDR3 (anti-ABCB4), which helped us in confirming and subtyping PFIC. Seventeen cases of PFIC had a positive family history with consanguineous marriage being documented in 15 cases. Our frequency of PFIC was the highest reported percentage to date in all published data,[11],[13],[21],[22] with PFIC 1 and 2 subtypes together contributing to 27 cases, which was 90% of the total PFIC cases, 47% of non-BA cases, and 31% of the total cohort. However, if we filter the incidence of PFIC by the age of presentation, only three cases (6.25%) of PFIC 2 presented before 100 days of age. This large percentage of PFIC 1 and 2 cases in the total cohort might be attributed to the use of immunohistochemistry in all cases of normal GGT cholestasis with bland or 'neonatal hepatitis-like' phenotype on histology, higher incidences of consanguinity in the population of our catchment area, and element of referral-bias as stated above. Metabolic causes of cholestasis in our study included two cases of galactosemia and one case each of tyrosinemia and hereditary fructose intolerance. On liver biopsy, all metabolic cases showed steatosis along with giant cell transformation (n = 2), lobular inflammation (n = 3), and fibrosis (n = 3). Therefore, the presence of steatosis on liver biopsy in infantile cholestatic disorders is a strong pointer toward metabolic liver disease. There were three cases of PILBD with one case of Alagille syndrome and two non-syndromic cases. All cases had ductopenia with a bile duct to portal tract ratio of less than 0.5 and variable degrees of cytoplasmic and canalicular cholestasis with cholestatic rosetting. None of the cases of INH or PFIC had associated ductopenia. | Figure 3: (a) Bland cholestasis in PFIC 1 (40×, H and E): (b) lobular disarray, giant cell change, and lobular inflammation in PFIC2 showing (40×, H and E); (c) BSEP immunostaining in normal controls showing chicken wire-like canalicular pattern; (d) absent BSEP canalicular staining in PFIC 2
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There were 11 cases that had been categorized as indeterminate for LBDO in the initial biopsy evaluation [Table 2], of which four cases were clinically diagnosed as BA and later underwent surgical intervention with confirmation on peroperative cholangiogram. These four cases showed overlapping features such as minimal portal expansion (n = 3), mild to moderate focal bile duct proliferation (n = 2) associated with lobular giant cell changes (n = 3), and the absence of ductal or ductular bile plugs (n = 4). Two of the four cases showed multiple incomplete portal tracts. The two cases that were misinterpreted as negative for LBDO showed small hypoplastic-appearing portal tracts without significant bile duct proliferation or ductal cholestasis. The wedge biopsies of all these cases showed features of obstructive cholangiography, suggesting that wedge biopsies are more likely to contain larger portal areas representative of the ductal changes, which may not be sampled in needle biopsies. Although bile duct proliferation, ductal/ductular bile plugs, and advanced fibrosis have been the best histologic pointers of BA as mentioned in prior studies, these findings may not be obvious in all cases, especially in needle biopsies done very early.[7],[8],[17] Therefore, the needle biopsy findings should not be evaluated in isolation, but rather should be analyzed in the light of clinical, biochemical, and imaging features. Moreover, the predictive value of needle biopsy in accurately diagnosing BA is around 80%, as in our study too, which emphasizes the importance of prelaparatomy biopsies in reducing morbidity and balancing the cost–benefit due to laparotomy in a developing country such as ours.[7],[17]
There are a few scoring systems available that help in differentiating BA from other causes of non-BA. Scoring systems by Gupta et al.[23] and EI-Guindi et al.[24] relied on multiple parameters including elaborate clinical workup details, which are often not available to us. The scoring system devised by Lee and Looi is based solely on histological parameters and hence more effective for pathologists. We used this scoring system to validate its applicability in differentiating BA from the non-BA group [Table 5]. With the seven-feature, 15-point histological scoring system, we evaluated the cut-off scores of ≥6, ≥7, and ≥8 to find the score with the best diagnostic utility to differentiate BA from other causes of intrahepatic cholestasis. We found that a cut-off score of ≥7 had the best diagnostic accuracy for identifying BA than cut-off scores of 6 or 8 (90.6% vs. 89.4% and 89.6%), thus corroborating with the findings of Lee et al.[8] After an extensive literature search and excluding the case reports, meta-analyses, and review articles, we found only eight original histopathology-based studies in the last 20 years, which evaluated the different histologic parameters for differentiating BA from non-BA causes [Table 6]. Of these, only two previous studies from India evaluated the diagnostic utility of the scoring system formulated by Lee.[25],[26] Our findings were similar to those of Lee et al.,[8] although the diagnostic accuracy was somewhat lower than the other two studies. Nevertheless, because none of the histopathological features are diagnostic of the etiology of BA, the use of scoring systems that combine and assess multiple histological features taken together is essential for arriving at the probable etiology, especially to identify the cases of BA that require urgent surgical intervention[29]. | Table 5: Evaluation of the cut-off scores for the diagnosis of BA using the scoring system by Lee et al.[8]
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 | Table 6: List of the previous histopathology-based studies differentiating BA from non-BA causes in the last 20 years
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All cases in our study were followed up for 6 months. Five out of seven cases of BA presenting at >100 days died, whereas seven cases presenting at <50 days had a better overall prognosis, in terms of clearance of jaundice at 3 months (n = 7) and survival (n = 6) post-Kasai procedure. Eleven infants of non-BA with NH had improved significantly and became jaundice free on conservative medical management within 6 months [INH, n = 7; perinatal infections, n = 3 and non-syndromic PILBD, n = 1]. Of the PFIC 1 and 2 cases, 22/27 cases had clinical improvement with UDCA, cholestyramine, and rifampicin therapy with nutritional rehabilitation at 6 months, whereas one case underwent biliary diversion surgery. One case of PFIC 3 underwent liver transplantation at our institute. Of the metabolic diseases, the case of tyrosinemia died within 4 months due to bleeding complications, whereas cases of galactosemia and hereditary fructose intolerance did well with dietary modifications.
| Conclusion | | |
BA is the commonest cause of cholestatic jaundice in neonates. The frequency of INH has declined significantly due to the advent of newer diagnostic modalities. Detailed histomorphological assessment on a liver biopsy is the cornerstone for the evaluation of infantile cholestatic disorders, and the histologic scoring system by Lee et al.[8] may be used to differentiate between BA and non-BA cases.
Acknowledgments
We acknowledge the contributions of our expert technologists Subrata Modak, Tej Narayan Mahato, and Avishek Nath, who have been instrumental in carrying out this research work.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Uttara Chatterjee,
Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ijpm.ijpm_215_22
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] |
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