Gut microbiome in biliary atresia

The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age. We retrospectively analyzed perioperative, laboratory, and outcome parameters of all biliary atresia patients in The Netherlands between January 1987 and June 2015 with NLS of at least 2 years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS-). We included 100 patients. Upon a median follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively. Six months post-Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared with NLS- patients (each P < 0.05). Cox regression could only assess a significant effect of COJ on continued NLS. Main indications for LTx after the age of 2 were irreversible jaundice and portal hypertension. Eighty-seven percent of patients with 2-year NLS reach adult age and more than 50% with their native liver. A pre-transplant mortality of 6%, however, exists among patients who reach the age of 2 years with their native livers. Early life parameters, other than COJ, did not have a significant effect on continued NLS after 2 years of age.

Hepatic fibrosis scores and serum biomarkers in pediatric hepatology.

Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia

Biliary atresia (BA) is the most common cause of obstructive jaundice in infants. Although the Kasai procedure has greatly improved the prognosis, most patients still need liver transplantation (LT) for long-term survival. The pathogenesis of BA has not been fully clarified, and liver fibrosis in BA is far beyond biliary obstructive cirrhosis. Literature reviews were underwent through PubMed. Persistent inflammation, immune response, biliary epithelial-mesenchymal transition, matrix deposition, decompensated angiogenesis, and unique biliary structure development all contribute to the fibrosis process. Observed evidences in such fields have been collected and form the backbone of this review. Interactions of the multiple pathways accelerate this process. Understanding the mechanisms of the liver fibrosis in BA may pave the way to improved survival after the Kasai procedure.

ObjectivesThough the prevalence of biliary atresia (BA) in the Middle East is low, its role in causing life-threatening liver diseases is disproportionately high. This study aimed to assess the prevalence, clinical presentations, diagnosis, surgical interventions, and long-term outcomes including survival rate, and to analyze prognostic factors affecting the survival of infants with BA in Bahrain.MethodsA retrospective cohort review of cases of infants diagnosed with BA between January 1993 and December 2021 at Salmaniya Medical Complex, Bahrain, was conducted. Demographic, clinical, laboratory, imaging, and histopathological data were analyzed. Outcomes measured included 5-year native liver survival (NLS) and overall liver survival (OLS) rates.ResultsOut of 27 infants diagnosed with BA, 26 were included in the study. The overall prevalence was 0.007% and was significantly higher among Bahraini (0.006%) compared to the non-Bahraini population (0.001%), p< 0.001. Most patients had clay-colored stool (19 of 22; 86.4%) and hepatomegaly (18; 81.8%). Kasai procedure was performed in 23 (88.5%) patients and primary liver transplant (LT) in three. Ten (38.5%) infants required LT after the Kasai procedure. The median age at diagnosis was 56 days with interquartile range (IQR) of 30–90, and the median age at the Kasai procedure was 61 days (IQR = 56–90). NLS and OLS rates were 53.8% and 65.4%, respectively. The overall mortality rate was 34.6%. Six of the 13 (46.2%) patients who were subjected to Kasai procedure alone died awaiting LT donors. Infants with lower birth weight and older age at diagnosis had significantly better odds of survival (p< 0.029 and p< 0.044, respectively).ConclusionsBA is uncommon among infants in Bahrain. Despite effective treatment options, late diagnosis can lead to significant morbidity and mortality. Our study found a relatively low prevalence of NLS (53.8%) and OLS (65.4%). Since the majority of the diagnosed patients had presented with clay-colored stools, implementing an infant stool card for screening may be beneficial in raising parental awareness and detecting BA early. Early detection and treatment using novel therapies are likely to improve the survival rates.

Early diagnosis of biliary atresia

&lt;p&gt;Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor β-chain variable regions (TRBVs).&lt;/p&gt;&lt;p&gt;Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD.&lt;/p&gt;&lt;p&gt;Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group.&lt;/p&gt;&lt;p&gt;Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.&lt;/p&gt;

Increasing calories, decreasing morbidity and mortality: Is improved nutrition the answer to better outcomes in patients with biliary atresia?

Outcomes in biliary atresia (BA) have been well-documented in large national cohorts from Europe, North America, and East Asia. Understanding the challenges that preclude success of the Kasai portoenterostomy (KPE) is the key to improve the overall outcomes of BA and implementing intervention strategies. Here, we analyzed the data from the Saudi national BA study (204 BA cases diagnosed between 2000 and 2018) to identify the prognostic factors of BA outcomes. One hundred and forty-three cases underwent KPE. Several prognostic factors (center case load, congenital anomalies, serum gamma-glutamyl transferase, use of steroids, ascending cholangitis post-operatively, and degree of portal fibrosis at time of KPE) were investigated and correlated with the primary outcomes of interest: 1) success of KPE (clearance of jaundice and total serum bilirubin <20 mmol/l after KPE), 2) survival with native liver (SNL), and 3) overall survival. Use of steroids after KPE was associated with clearance of jaundice, 68% vs. 36.8% in the BA cases that did not receive steroids (P = 0.013; odds ratio 2.5) and a significantly better SNL rate at 2 - and 10-year of 62.22% and 57.77% vs. 39.47% and 31.57%, respectively (P = 0.01). A better 10-year SNL was observed in centers with caseload <1/year (group 1) as compared to centers that performed ≥1/year (group 2) [45.34% vs. 26.66%, respectively; P = 0.047]. On comparison of the 2 groups, cases in group 1 had KPE at significantly earlier age (median 59.5 vs. 75 days, P = 0.006) and received steroids after KPE more frequently than group 2 (69% vs. 31%, P < 0.001). None of the remaining prognostic variables were identified as being significantly related to BA outcome. Steroids use post-KPE predicted clearance of jaundice and better short- and long-term SNL. There is a need to establish a national BA registry in Saudi Arabia aiming to standardize the pre- and post-operative clinical practices and facilitate clinical and basic research to evaluate factors that influence BA outcome.

Timing for Orthotopic Liver Transplantation in Children With Biliary Atresia: A Single-Center Experience

Nature or Nurture in the Pathogenesis of Biliary Atresia?

Viral infections may have an important role in the pathogenesis of biliary atresia, and related clinical outcomes. In this research for determination of the possible role of HBV, HCV, HCMV, adenovirus, and BK virus infections in biliary atresia related clinical complications, the molecular and antigenic prevalence of these viral agents were studied. In this retrospective study, 34 formalin fixed paraffin embedded (FFPE) biopsy and autopsy liver tissue samples of neonates with biliary atresia were evaluated. The molecular prevalence of these viral infections was assayed by different PCR and RT-PCR methods. The antigenic prevalence of HBV, HCV, and HCMV infections was also studied in these liver tissue samples by immunohistochemistry (IHC) method. HBV, HCV, and adenovirus genomes were detected in 9%, 6%, and 6% of liver autopsy and biopsy tissues of infants with biliary atresia, respectively. HBV and HCV co-infection was confirmed in 6% of FFPE samples. The genome of other investigated viruses was not detected in FFPE liver tissues. Detection of viral infection in FFPE liver tissue samples of newborns with biliary atresia, suggests the need for complete studies for the determination of accurate role of these viral infections in pathogenesis of biliary atresia.

Biliary atresia in England and Wales: results of centralization and new benchmark

Objective To investigate the correlation between the remnants of extrahepatic bilie duct with the prognosis of biliary atresia after Kasai operation. Methods From Sep.2005 to Sep.2011, 93 cases of biliary atresia [51 boys and 42 girls, ages at operation: 61 days(40-121 days)] in Tongji Hospital Affiliated of Tongji Medical College of Huazhong University of Science and Technology were operated with Kasai procedure, and the diagnosis of type Ⅲ biliary atresia was based on the cholangiography and the intraoperative findings.According to whether there was fibrotic remnant plates of porta hepatis or not, type Ⅲ biliary atresia cases were grouped into 2 subtypes: subtype A, in which there was fibrotic remnant plates of porta hepatis(n=80); subtype B, in which there was no fibrotic remnant plates, but solid cords structure like hepatic duct was observed(n=13). Specimens of the remnants were colleted in operation and pathologic section detected the degree of bile ductular proliferation in the remnants.Postoperatively, all of the patients were followed up.The contents included the cholangitis occurrence rate, the jaundice disappearance rate and survival rate during postoperative 2 years. Results The patients had more bile ductular proliferation in subtype A(χ2 =18.49, P 0.05). The jaundice disappearance rate in postoperative 6 months of subtype A was higher than the rate of subtype B(χ2 =9.19, P<0.05). The survival rate during postoperative 2 years of subtype A was higher than the rate of subtype B(χ2 =4.49, P<0.05). Conclusions There are higher jaundice disappearance rate and 2 years survival rate in type Ⅲ biliary atresia with the fibrotic remnant plates of porta hepatis, which suggest that there is more bile ductular proliferation in the extrahepatic remnants which is good for biliary drainage in subtype A after Kasai operation, and it can slow down hepatic injury and have a long-term good life quality. Key words: Biliary atresia; Kasai operation; Fibrotic plate; Prognosis

Gut Microbiota Dysbiosis Associated with Persistent Fatigue in Hematopoietic Cell Transplantation Survivors