Distinct effects of racial and socioeconomic disparities on biliary atresia diagnosis and outcome.

OBJECTIVES: To identify and distinguish between racial and socioeconomic disparities in age at hepatology care, diagnosis, access to surgical therapy, and liver transplant-free survival in patients with biliary atresia (BA). METHODS: Single-center retrospective cohort study of 69 BA patients from 2010 to 2021. Patients were grouped into White and non-White cohorts. The socioeconomic milieu was analyzed utilizing neighborhood deprivation index, a census tract-based calculation of six socioeconomic variables. The primary outcomes of this study were timing of the first hepatology encounter, surgical treatment with hepatic portoenterostomy (HPE), and survival with native liver (SNL) at 2 years. RESULTS: Patients were 55% male and 72% White. White patients were referred at a median of 34 days (interquartile range [IQR]: 17-65) vs. 67 days (IQR: 42-133; p = 0.001) in non-White patients. White infants were more likely to undergo HPE (42/50 patients; 84%) compared to non-White (10/19; 53%), odds ratio (OR) 4.73 (95% confidence interval: 1.46-15.31; p = 0.01). Independent of race, patients exposed to increased neighborhood-level deprivation were less likely to receive HPE (OR: 0.49, p = 0.04) and achieve SNL (OR: 0.54, p = 0.02). CONCLUSIONS: Racial and socioeconomic disparities are independently associated with timely BA diagnosis, access to surgical treatment, and transplant-free survival. Public health approaches to improve screening for pathologic jaundice in infants of diverse racial backgrounds and to test and implement interventions for socioeconomically at-risk families are needed.

The role of p.Val444Ala variant in the ABCB11 gene and susceptibility to biliary atresia in Vietnamese patients.

ABSTRACT: Biliary atresia (BA) is the most serious type of obstructive cholangiopathy that occurs in infants. BA can be the cause of death in children under 2 years if untreated early. However, the etiology of the disease is not known. BA is considered to be the result of the destruction of the bile duct system including the accumulation of bile acids. The bile salt export pump, a transporter protein encoded by the ABCB11 gene, plays the main role in the exportation and accumulation of bile acids. The p.Val444Ala variant in this gene is known to be associated with many cholestatic diseases. However, to date no study have been performed to evaluate the association of this variant with susceptibility to the risk of BA. In this study, we aimed to identify the frequency of p.Val444Ala variant and the risk of BA in Vietnamese patients.The polymerase chain reaction (PCR)- restriction fragment length polymorphism method was used to determine the frequency of alleles c.1331T>C (p.Val444Ala, rs2287622) in the ABCB11 gene in 266 Vietnamese patients with BA and 150 healthy people. The gene segment containing the variant was amplified by PCR with specific primers, after that the PCR products were cut by HaeIII restriction enzyme and analyzed on agarose gel to determine the genotypes. The frequency of alleles was assessed statistically to determine the association between these alleles and the risk of disease in patients.In our study, the frequency of alleles c.1331T>C (p.Val444Ala, rs2287622) in the ABCB11 gene was investigated the first time in the patients with BA. The results showed that CC and TC genotypes were significantly different between BA patients and healthy people (P < .01), and the C allele was associated with an increased risk of BA (odds ratio = 2.47; 95% confidence interval: 1.84-3.32; P < .01). The initial results of clinical, biochemical, and genetic analysis in our study suggested that the p.Val444Ala variant in the ABCB11 gene may be a susceptibility factor for the disease in Vietnamese patients with BA. These results provided new insights into the role of this ABCB11 variant in the pathogenesis of BA.

Biliary atresia: East versus west.

Biliary atresia (BA) is a common cause of surgical jaundice during the neonatal period. It is currently considered as a spectrum of diseases with a common final pathology characterized by obliteration of the extrahepatic biliary tract and the absence of normally branching intrahepatic ducts. Though it is a global disease that can be found in all ethnicities there are some clear differences between BA arising in the East and the West. This is likely to be related to different genetic, environmental and cultural factors. BA is more frequently found in Far Eastern infants (both Chinese and Japanese) though the syndromic associations are much less common. Many Eastern countries have national screening programmes not seen in the West possibly due to debate over its cost effectiveness in countries where incidence is low. Kasai portoenterostomy (KPE) is considered as the primary treatment of BA but its outcome still remains unsatisfactory across the region. Given the complexity of BA, it is unlikely that strategic advances could be made by the sole effort of individual countries and we believe that collaboration between the East and West is the way forward.

Can Free Carnitine or Bilirubin in Blood Be Used in Neonatal Screening for Biliary Atresia?

OBJECTIVE: To investigate the efficiency of free carnitine, unconjugated bilirubin (UBIL), bilirubin monoglucuronide (BMG), and bilirubin diglucuronide (BDG) in dry blood spots (DBSs) measured using tandem mass spectrometry (MS/MS) for screening biliary atresia (BA). MATERIALS AND METHODS: All the patients with BA, residing in Shanghai, were collected from four different children's hospitals in Shanghai from January 1, 2015, to June 30, 2017. UBILMS, BMG, BDG, and free carnitine were measured in the DBS samples of 48 patients with BA, 10,008 pediatric patients, and 52,862 newborns using MS/MS. Conjugated bilirubin was measured by MS/MS (CBMS) = BMG + BDG, and total bilirubin was measured by MS/MS (TBMS) = UBILMS + CBMS. Four hundred pediatric patients' direct bilirubin (DB) and total bilirubin (TB), measured by the clinical laboratory and MS/MS, were used as a control. RESULTS: The total number of births at the registered permanent residences in Shanghai was 233,000; among them, the occurrence of BA was in 33 patients in 2 years. Therefore, the incidence of BA in Shanghai was 1:7,060. The ratio of DB/TB and CBMS/TBMS of most patients with BA was elevated gradually in the neonatal period and higher than the normal range after 1 month after birth. The area under the receiver operating characteristic curve of DB, DB/TB, CBMS/TBMS, CBMS, and free carnitine for predicting BA was 0.98, 0.95, 0.73, 0.57, and 0.92, respectively. Using the 95% percentile as a cutoff, the sensitivity of DB and free carnitine to predict BA was 100 and 85%, respectively, and the specificity was 52 and 85%, respectively. CONCLUSION: In free carnitine, DB, and CBMS/TBMS tests, blood concentrations are elevated in all infants with BA. However, they may not be elevated while they are newborns. These tests will result in high false negatives or positives. Thus, they should not be used as newborn screening tests for BA due to their lower sensitivity and specificity.

The intragenic epistatic association of ADD3 with biliary atresia in Southern Han Chinese population.

Biliary atresia (BA) is a multifactorial pathogenic disease with possible genetic components. As a member of membrane skeletal proteins in the liver and bile ducts, a haplotype composed by five single nucleotide polymorphisms (SNPs) on adducin 3 (ADD3) has been identified as associated with BA. However, limited study was designed to further elaborate the mutual relationship amongst those replicated SNPs to disease. We selected three susceptibility SNPs in ADD3 and conducted a replication study using 510 BA cases and 1473 controls to evaluate the individual function of the SNPs and further stratified the potential roles with disease and its subclinical features. Two SNPs in ADD3 were replicated as associated with BA (1.60E-04 ≤ P≤1.70E-04, 1.33 ≤ odds ratio (OR) ≤ 1.58 for rs17095355, 2.10E-04 ≤ P≤5.30E-04, 1.26 ≤ OR ≤ 1.57 for rs2501577). Though we failed to replicate the individual association of rs10509906 to disease, the intragenic epistatic effect between rs10509906 and rs2501577 was suggested as exhibiting susceptibility to BA, further cross-validated by multifactor dimensionality reduction (MDR) (P=0.068, OR = 1.37), which may explain extra hidden heritability of ADD3 to BA. Furthermore, through subclinical stratification, we also observed the association of risk to disease mainly came from the female patients.

Ethnic Disparity in the Incidence and Outcome of Biliary Atresia in New Zealand.

To determine incidence and outcome of biliary atresia (BA) between ethnic groups in New Zealand (NZ), a retrospective review was undertaken of children with BA born between 2002 and 2014. Prioritized ethnicity was used to determine ethnicity and was compared to population data. Uni- and multivariate analyses were undertaken to determine demographic and biochemical factors associated with outcome. Overall incidence was 1 in 9181 (Maori 1 in 5285; European 1 in 16,228; P < 0.0001). Overall and transplant-free survival rates at 1, 2, and 5 years were 92%, 86%, 82% and 70%, 49%, 30% respectively with Maori having improved transplant-free survival (P < 0.05) despite European children undergoing Kasai earlier (49 vs 63 days). BA is more common in NZ than Europe and North America, which is attributable to a higher incidence in Maori but overall outcome is poorer. Maori have improved transplant-free survival compared to NZ European children but the reason is unknown.

Decreasing rate of biliary atresia in Taiwan: a survey, 2004-2009.

OBJECTIVES: The pathogenesis of biliary atresia (BA) is unclear, but epidemiological studies may help to elucidate possible causes. The goals of this study were to identify BA incidence changes in Taiwan in 2004-2009 and to survey the factors that might influence incidence changes to elucidate the possible causes of BA. METHODS: A Taiwan national registry system for BA has been established since 2004. By using data from the national registry system for BA, we identified BA incidence changes in 2004-2009. We also evaluated the correlations between BA incidences and estimated rotavirus vaccine coverage rates and between BA incidences and the gross domestic product. RESULTS: A total of 185 patients with BA were identified in 2004-2009 in Taiwan, whereas the number of live births was 1 221 189. Compared with the incidence of BA in 2004-2006 (1.79 cases per 10,000 live births), the incidence of BA in 2007-2009 (1.23 cases per 10,000 live births) was decreased significantly (P = .01). BA incidences were negatively correlated with the gross domestic product (P = .02) and marginally negatively correlated with rotavirus vaccine coverage rates (P = .07). CONCLUSIONS: A significant decrease in BA incidence in Taiwan since 2007 has been noted and may be related to improvements in the general socioeconomic status and the popularity of rotavirus vaccination. Although more evidence is needed to establish a direct correlation, this phenomenon may shed light on possible causes of and preventive interventions for BA.

Biliary atresia: a new immunological insight into etiopathogenesis.

Biliary atresia is an idiopathic neonatal cholestatic disease characterized by the destruction of both the intra- and extra-hepatic biliary ducts. There are two clinical manifestations of the disease: an embryonal subtype, which often presents at birth and is associated with congenital malformations, and a 'perinatal' subtype, which is probably an acquired disease due to unknown etiology. Over the last two decades, researchers have focused on activation of the cell-mediated immunity as the mechanism for biliary epithelial cell destruction for the latter subtype. A proposed trigger of this immune response is an initial viral infection, inducing biliary epithelial cells to become antigen-presenting cells and thus instigating immune-mediated destruction of the biliary tract. However, putative viruses have never been confirmed. More recently, a novel hypothesis - that maternal microchimerism may initiate a host immunologic response towards the bile duct epithelia - has been proposed. This paper discusses the etiology of biliary atresia in the context of the current research.

Incidence and prognostic factors associated with biliary atresia in western India.

AIM: To estimate the incidence of biliary atresia(BA) amongst neonatal cholestatic syndromes (NCS) and determine prognostic factors in BA patients who have undergone Kasai's portoenterostomy. Study design- Retrospective analysis. SETTING: Pediatric Hepatobiliary Clinic at B.J. Wadia Children's Hospital, Mumbai. METHODS AND MATERIALS: 32 patients diagnosed with BA referred to the clinic from May 2005 to July 2007 were included in the study. All patients underwent a detailed history, clinical examination and were tested for liver function tests (LFT), USG abdomen, liver biopsy, intra-operative cholangiogram and CMV tests. Patients were followed up for a period of 1 month to 7 years post operatively and complications such as cholangitis, progress to liver cell failure and cirrhosis was noted. RESULTS: Incidence of BA amongst NCS (n = 88) was 36.4%. 8 patients of BA (25%) were lost to follow up. Out of the remaining, 10 (41.7%) improved and 14 (58.3%) did not improve. The mean age of presentation was 89 + 55.8 days. 1 patient (25%) out of 4 with bile duct size of < 100 microns showed an improvement whereas 3 (37.5%) out 8 patients with bile duct size 100-200 microns showed improvement and 4 (50%) with bile duct size of > 200 microns had improvement post Kasai surgery. Those with bile duct sizes > 200 microns had better prognosis than those with sizes 100-200 microns (Odd's ratio = 1.8) and < 100 microns (Odd's ratio = 3). 12 patients (50%) were operated before 3 months of age and 50% of them responded to surgery. The remaining 12 patients were operated after 3 months of age and only 33% showed any improvement. (Odd's ratio = 2). Other parameters like SGOT (P = 0.598), SGPT (p = 0.901), total Bilirubin (p = 0.349), Direct Bilirubin (p = 0.429), Alkaline Phosphatase (p = 0.605) and GGTP (p = 0.480), cirrhosis (p = 0.417), degree of fibrosis (p = 0.384), degree of inflammation (p = 0.964) and Cholangitis (P = 0.388) had no effect on the outcome. CONCLUSION: Biliary Atresia is a common cause of NCS in India. Children with Bile duct size > 200 microns have a good prognosis. Portoenterostomy before 3 months of age has a better outcome.

Auckland paediatric liver transplant experience 1990-2000.

AIMS: New Zealand is establishing its own Paediatric Liver Transplant Service. However there have been no readily available data on the experience of New Zealand paediatric transplant recipients to date. The aim of our study was to determine numbers and indications for transplant at present, current outcomes and to estimate the likely demand for the service in the future. METHODS: A retrospective search of computerised records was performed on children cared for at Starship Hospital from 1990 to 2000. RESULTS: Seventeen children received eighteen transplants. The indication for transplantation was biliary atresia in the majority of patients (11/17, 65%). A higher proportion of Maori and Pacific Island children received transplants than would be expected from their proportion in the population (59 vs 29%, p<0.01). Significant and often multiple complications occurred post transplantation in the majority of children, but overall outcomes were good. CONCLUSIONS: A New Zealand Paediatric Liver Transplant Program is likely to perform about six transplants per year.

Kasai portoenterostomy: differences related to race.

PURPOSE: The aim of this study was to evaluate the Kasai portoenterostomy in African-American and white children with respect to differences in presentation and outcome. METHODS: A retrospective review of all children with biliary atresia who underwent a portoenterostomy at our institution over the last 15 years (n = 63) was performed. Sex, age at the time of Kasai, preoperative laboratory tests, success rates (defined as postoperative total serum bilirubin < or = 2.0 mg/dL), and survival rate were recorded. Differences between African-American (AA; n = 30) and white (W; n = 33) children were analyzed. Long-term follow-up was available on 59 of 63 patients. RESULTS: Sixty-three percent of all patients (40 of 65) were girls, and 48% were AA (30 of 63). A higher percentage of AA children (73%) were girls than were white children (55%), although this difference did not achieve statistical significance. African-Americans underwent portoenterostomy at a later age, had higher alkaline phosphatase levels, and higher AST. These differences were statistically significant. Preoperative ALT, total bilirubin level, and GGTP levels all were greater in African-Americans, although these differences did not achieve statistical significance. There was a trend toward decreased success and survival rate, although these results also were not statistically significant. CONCLUSIONS: African-Americans underwent primary therapeutic intervention for biliary atresia at an older age than white children with a trend toward less favorable results. These differences related to race may be attributed to greater difficulty in diagnosing jaundice or poorer access to health care in this patient population. Increased effort at identifying biliary atresia in AA children may lead to earlier diagnosis and treatment and improved outcomes.

Epidemiology of biliary atresia: a population-based study.

OBJECTIVE: Biliary atresia is the leading cause of extrahepatic obstructive jaundice in the newborn and is the single most frequent indication for liver transplantation in children. The cause of biliary atresia is unknown, although several mechanisms have been postulated to explain the inflammatory process that obliterates the bile ducts. Most interest has been directed toward viral infections. Information about the epidemiologic characteristics of biliary atresia in well-defined populations is lacking but is essential for developing and addressing hypotheses of causation for the disease. METHODS: Infants with biliary atresia were identified in metropolitan Atlanta from 1968 through 1993 by a population-based birth defects surveillance system that ascertains infants with serious birth defects in the first year of life using active case ascertainment. Birth prevalence rates were analyzed for spatial and temporal clustering and effects attributable to county of residence, sex, race, maternal age, parity, and birth weight. Logistic regression was used to study the independent effects of the risk factors and to look for interactions. RESULTS: Fifty-seven infants with biliary atresia were identified, for a rate of 0.73 per 10,000 live births. There was significant seasonal clustering of the disease, with rates three times higher from December through March compared with rates from April through July. Rates were significantly higher among nonwhite infants compared with white infants (0.96 vs 0.44 per 10,000 live births) and infants born at term with low birth weights (<2500 g) compared with infants born at term with normal birth weights (> or = 2500 g) (2.62 vs 0.75 per 10,000 live births). CONCLUSIONS: Our study is the first in the United States to describe the epidemiologic characteristics of biliary atresia using a population-based approach. The demonstration of significant seasonal clustering provides support for theories that biliary atresia may be caused by environmental exposure (consistent with a viral cause) during the perinatal period.