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Background: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children., Methods: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography., Results: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002)., Conclusion: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Inflammation and immune dysregulation persuade biliary duct injury in biliary atresia (BA), a leading cause of pediatric liver transplantation given lack of specific biomarkers. We aimed to determine associations between systemic cytokine profiles and clinical parameters in BA patients and to identify potential BA biomarkers., Methods: Systemic levels of 27 cytokines were measured in 82 BA patients and 25 healthy controls using a multiplex immunoassay. Relative mRNA expressions of candidate cytokines in 20 BA livers and 5 non-BA livers were assessed using quantitative real-time PCR., Results: Higher levels of 17 cytokines including IL-1β, IL-6, IL-7, IL-8, IL-9, IL-2, IL-15, eotaxin, IP-10, MCP-1, MIP-1α, MIP-1β, G-CSF, IL-1ra, IL-4, IL-5, and IL-10 and lower levels of IFN-α and PDGF were significantly associated with BA. In BA patients, increased levels of IL-7, eotaxin, IP-10, and IL-13 were significantly associated with unfavorable outcomes including jaundice, fibrosis, and portal hypertension. Indeed, systemic levels of those cytokines were significantly correlated with clinical parameters indicating jaundice, fibrosis, and hepatic dysfunction in BA patients. Out of 27 cytokines, 4 (IL-8, IP-10, MCP-1, and PDGF) had potential as sensitive and specific biomarkers of BA. Of these, higher IL-8 levels were significantly associated with reduced survival of BA. In BA livers, relative mRNA expressions of IL-8, IP-10, and MCP-1 were significantly up-regulated., Conclusions: Higher levels of several cytokines including inflammatory cytokines, immunomodulatory cytokines, chemokines, and anti-inflammatory cytokines and lower levels of growth factors would reflect inflammatory and immune responses related to BA development. Among 27 cytokines, plasma IL-8 might have great potential as a diagnostic and prognostic biomarker for BA., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation., (© 2021. The Author(s).)

This study aimed to determine whether circulating levels of clusterin (CLU), an extracellular chaperone implicated in cholestatic and fibrotic processes, are associated with clinical parameters of post-operative BA patients and could serve as a BA biomarker. Ninety-six BA patients and 56 healthy controls were recruited. Circulating CLU levels were measured using enzyme-linked immunosorbent assay. Circulating CLU levels were significantly reduced in BA patients - especially those with worse outcomes including jaundice, severe liver fibrosis, and late-stage of hepatic dysfunction. Multivariate linear regression analysis revealed that circulating CLU levels were negatively associated with outcome parameters indicating jaundice status, degree of fibrosis, and liver dysfunction, but positively correlated with serum albumin and platelet number of BA patients. Lower circulating CLU levels were considerably associated with poor survival of post-operative BA patients. Receiver-operating characteristic curve analysis demonstrated a diagnostic value of circulating CLU as a non-invasive indicator for poor outcomes of BA patients (AUC = 0.85), with a sensitivity of 81.5% and a specificity of 73.5%. All findings indicate that reduced circulating CLU might reflect poor outcomes of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

Background: The prognosis of biliary atresia (BA) remains difficult to predict. This study evaluated the roles of hepatocyte growth factor (HGF) and its receptor (C-met) towards clinical outcome and native liver survival., Methods: Hepatic HGF and C-met expression were determined using immunohistochemistry from liver biopsies of 41 BA patients during Kasai operation, and 17 non-cholestatic patients. The HGF and C-met expression was visually scored as per its intensity and percentage of stained area. BA patients were classified as high- and low-HGF and C-met receptor status. Native liver survival was compared between the two groups at 3-year follow-up. Data are shown as median and range., Main Results: Median age of BA patients was 2 (1-6) months. Hepatic HGF and C-met staining scores of BA patients were higher than those of non-cholestatic patients (P < 0.0001). There was a correlation between HGF and C-met staining scores (spearman r = 0.77, P < 0.0001). However, there was no association between their expression and early outcome at 6 months post-op. Mean follow-up time was 68.6 months. Survival analysis revealed that native liver survival at 1 year and 3 years were 88% and 77%, respectively. Additionally, 82.6% (19/23) of patients in the low-HGF group survived with native liver, compared with 66.7% (10/15) of those in high-HGF group (P = 0.436). For C-met expression, 78.6% (22/28) of low-score and 70% (7/10) of high score groups survived with native liver (P = 0.673)., Conclusions: Strong expression of hepatic HGF and its receptor in BA patients was demonstrated. However, the expression was not associated with the early outcome and native liver survival. These results suggest that HGF involved in the liver pathology of BA but its expression cannot be used as a prognostic indicator. Small sample size of patients was a main limitation. Further studies are warranted to validate our findings.

Background: Glypican-3 plays a vital role in regulating embryonic morphogenesis of the liver. This study aimed to investigate associations of hepatic expressions of glypican-3 and alpha-smooth muscle actin with clinical parameters in biliary atresia., Methods: Liver specimens were obtained from 20 biliary atresia infants and 7 non-biliary atresia controls. Relative mRNA expressions of glypican-3, alpha-smooth muscle actin, and signaling molecules of Wnt/β-catenin were measured using real-time polymerase chain reaction. Protein expressions of glypican-3 and alpha-smooth muscle actin were examined using immunohistochemistry. Masson's trichrome staining was conducted to evaluate the stage of liver fibrosis., Results: Up-regulation of glypican-3 mRNA expression was observed in biliary atresia livers, and its expression was positively associated with alpha-smooth muscle actin, β-catenin, c-Myc, and cyclin D-1. Immunostaining scores of glypican-3 and alpha-smooth muscle actin were significantly increased in biliary atresia livers. Biliary atresia patients with poor outcomes had significantly greater glypican-3 expression than those with good outcomes, consistent with hepatic alpha-smooth muscle actin expression analysis. Hepatic glypican-3 expression was associated with age, albumin, aspartate transaminase, and alkaline phosphatase in biliary atresia patients, while hepatic alpha-smooth muscle actin expression was correlated with alkaline phosphatase in the patients. Moreover, glypican-3 and alpha-smooth muscle actin expressions were positively associated with fibrosis stage in biliary atresia livers. There was a positive relationship between glypican-3 and alpha-smooth muscle actin expression in biliary atresia livers. Combined high expressions of glypican-3 and alpha-smooth muscle actin were associated with poor survival., Conclusion: Hepatic overexpressions of glypican-3 and alpha-smooth muscle actin were associated with hepatic dysfunction and the degree of liver fibrosis in biliary atresia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Biliary atresia (BA) is a chronic obstructive liver disease, leading to advanced liver failure. Mitochondria dysfunction-mediated aberrant telomere length has been implicated in various pathological processes including cholestasis. Herein, we aimed to investigate associations between mitochondrial DNA (mtDNA) copy number, oxidative DNA damage, telomere length, and disease severity in BA patients. mtDNA copy number and relative telomere length (RTL) were assessed using real-time PCR. Circulating 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured using ELISA. Our findings showed that BA patients had significantly lower mtDNA copy number and RTL than healthy controls, whereas plasma 8-OHdG levels were significantly elevated in BA patients. mtDNA copy number was remarkably reduced in advanced BA patients. Furthermore, mtDNA copy number was independently associated with age and degree of liver fibrosis in BA patients. Decreased mtDNA copy number was significantly associated with elevated risks of BA, severe fibrosis, jaundice, and hepatic dysfunction. Low mtDNA copy number can be utilized to distinguish patients with poor-outcome from those with good-outcome. Survival curve analysis revealed that low mtDNA copy number was significantly associated with poor survival of BA patients. Interestingly, there was a positive association between mtDNA copy number and plasma 8-OHdG in BA patients, while a negative association of mtDNA copy number with RTL was observed in BA patients. Alternatively, RTL was negatively correlated with plasma 8-OHdG in BA patients. These data demonstrated relationships between leukocytes mtDNA copy number, oxidative stress, telomere length, and clinical parameters in BA patients. Accordingly, our findings indicate that mtDNA copy number may serve as a potential biomarker reflecting BA severity., (Copyright © 2019 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Background: Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients., Methods: One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography., Results: BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P < 0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1 ± 2.1 vs. 27.9 ± 2.5 ng/mL, P < 0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r = 0.491, P < 0.001), alanine aminotransferase (r = 0.448, P < 0.001), total bilirubin (r = 0.303, P = 0.002), alkaline phosphatase (r = 0.414, P < 0.001), and liver stiffness values (r = 0.455, P < 0.001). There was a negative correlation between serum HSP70 and serum albumin (r = -0.434, P = 0.001)., Conclusion: Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

Objective: Biliary atresia (BA) is a progressive fibroinflammatory liver disease. Autotaxin (ATX) has a profibrotic effect resulting from lysophosphatidic acid activity. The purpose of this study was to examine ATX expression and ATX promoter methylation in peripheral blood leukocytes and liver tissues from BA patients and controls and investigate their associations with outcome parameters in BA patients., Methods: A total of 130 subjects (65 BA patients and 65 age-matched controls) were enrolled. DNA was extracted from circulating leukocytes and liver tissues of BA patients and from and age-matched controls. ATX promoter methylation status was determined by bisulfite pyrosequencing. ATX expression was analyzed using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay., Results: Decreased methylation of specific CpGs were observed at the ATX promoter in BA patients. Subsequent analysis revealed that BA patients with advanced stage had lower methylation levels of ATX promoter than those with early stage. ATX promoter methylation levels were found to be associated with hepatic dysfunction in BA. In addition, ATX expression was significantly elevated and correlated with a decrease in ATX promoter methylation in BA patients compared to the controls. Furthermore, promoter hypomethylation and overexpression of ATX were inversely associated with jaundice status, hepatic dysfunction, and liver stiffness in BA patients., Conclusion: Accordingly, it has been hypothesized that ATX promoter methylation and ATX expression in peripheral blood may serve as possible biomarkers reflecting the progression of liver fibrosis in postoperative BA. These findings suggest that the promoter hypomethylation and overexpression of ATX might play a contributory role in the pathogenesis of liver fibrosis in BA., Competing Interests: The authors have declared that no competing interests exist.

Alu and LINE-1 elements are retrotransposons with a ubiquitous presence in the human genome that can cause genomic instability, specifically relating to telomere length. Genotoxic agents may induce methylation of retrotransposons, in addition to oxidative DNA damage in the form of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Methylation of retrotransposons induced by these agents may contribute to biliary atresia (BA) etiology. Here, we investigated correlations between global methylation, 8-OHdG, and relative telomere length, as well as reporting on Alu and LINE-1 hypomethylation in BA patients. Alu and LINE-1 hypomethylation were found to be associated with elevated risk of BA (OR = 4.07; 95% CI: 2.27-7.32; P < 0.0001 and OR = 3.51; 95% CI: 1.87-6.59; P < 0.0001, respectively). Furthermore, LINE-1 methylation was associated with liver stiffness in BA patients (β coefficient = -0.17; 95% CI: -0.24 to -0.10; P < 0.0001). Stratified analysis revealed negative correlations between Alu and LINE-1 methylation and 8-OHdG in BA patients (P < 0.0001). In contrast, positive relationships were identified between Alu and LINE-1 methylation and relative telomere length in BA patients (P < 0.0001). These findings suggest that retrotransposon hypomethylation is associated with plasma 8-OHdG and telomere length in BA patients.

Objective: The purpose of this study was to investigate the association of telomere length in peripheral blood leukocytes with the severity of biliary atresia (BA)., Methods: One hundred and fourteen BA patients and 114 age-matched healthy controls were enrolled. Relative telomere length (RTL) was assessed using a quantitative real-time polymerase chain reaction. Multivariate regression analysis was used to estimate RTL as an independent risk factor of BA. Receiver operating characteristic curve analysis was used to calculate the accuracy of biomarkers in the prediction of liver cirrhosis., Results: BA patients had significantly shorter telomeres than healthy controls (p < 0.0001). The RTL in BA patients with jaundice was considerably lower than that of patients without jaundice (p = 0.005). Moreover, RTL was markedly shorter in patients with cirrhosis (F4), as compared to patients with mild fibrosis (F2) and non-fibrosis (F0-F1, p < 0.0001). Logistic regression analysis indicated that short RTL was associated with a higher risk of liver cirrhosis in BA. Tertile analysis showed a dose-response effect for this association (p trend < 0.0001). Additionally, RTL in BA children revealed a negative correlation with age (r = -0.50, p < 0.001). We noted an association between reduction of RTL and liver stiffness scores, adjusted for age and gender (b = -0.01, p < 0.0001). Short RTL can be employed to distinguish cirrhosis patients from non-cirrhosis patients (AUC = 0.78). Further analysis showed a linear correlation between leukocyte RTL and liver RTL in BA patients (r = 0.83, p < 0.001)., Conclusion: The findings of this study provide evidence that telomere shortening is associated with an elevated risk of liver cirrhosis in BA.

Background: We determined the relationship between serum sclerostin and disease severity of biliary atresia (BA)., Methods: Seventy postoperative BA patients and 35 controls were recruited. Serum sclerostin, C-terminal telopeptide of type I collagen (CTX), and osteocalcin were analyzed using ELISA. Bone mineral density (BMD) of the lumbar spine was measured by dual energy X-ray absorptiometry., Results: BA patients had significantly higher serum sclerostin than controls. Serum sclerostin was markedly elevated in jaundice patients compared with jaundice-free patients. Serum osteocalcin was not different, whereas serum CTX was greater in BA patients than controls. BMD of jaundice patients was significantly lower than jaundice-free patients. Additionally, serum sclerostin was correlated with biochemical parameters and BMD in BA., Conclusion: Increased sclerostin levels were associated with liver dysfunction and the severity of BA, suggesting that sclerostin may reflect the deterioration of hepatic function and the outcome in postoperative BA., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To analyze serum periostin and liver stiffness in postoperative biliary atresia (BA)., Methods: A total of 60 BA patients and 14 controls were enrolled. Serum periostin levels were analyzed by ELISA. Liver stiffness measurement was determined by transient elastography., Results: Biliary atresia patients had significantly higher periostin and liver stiffness values than controls. Serum periostin levels were remarkably increased in BA patients with jaundice compared to those without jaundice. Moreover, serum periostin was correlated with liver stiffness., Conclusions: Serum periostin was associated with liver stiffness in BA. Thus, serum periostin has potential as a parameter reflecting the severity in BA.

Objective: To investigate correlation of serum autotaxin and disease severity in biliary atresia (BA)., Methods: Eighty postoperative BA patients and 15 controls were recruited. Serum autotaxin levels were determined by enzyme-linked immunosorbent assay., Results: BA patients had greater serum autotaxin and liver stiffness than controls. Serum autotaxin and liver stiffness were markedly elevated in BA patients with jaundice compared to those without jaundice. Furthermore, serum autotaxin was correlated with liver stiffness and biochemical parameters in BA., Conclusions: Elevated serum autotaxin was correlated with hepatic dysfunction in BA. Accordingly, serum autotaxin is a promising biomarker reflecting the severity in BA.

Objectives: Soluble receptor for advanced glycation end products (sRAGE) has emerged as a possible biomarker of several disease conditions, including liver injury. This study was aimed to assess serum sRAGE and liver stiffness in biliary atresia (BA)., Design and Methods: Forty postoperative BA patients and 20 controls were enrolled. Serum sRAGE levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography., Results: BA patients had higher serum sRAGE and liver stiffness values than controls (P<0.001). Serum sRAGE and liver stiffness values were significantly elevated in BA patients with jaundice compared to those without jaundice (P<0.001). Additionally, serum sRAGE was correlated with liver stiffness and serum total bilirubin (r=0.65, P<0.001 and r=0.71, P<0.001, respectively)., Conclusion: Serum sRAGE was associated with the severity of BA. Accordingly, serum sRAGE and liver stiffness may serve as indicators reflecting the severity and the development of hepatic fibrosis in postoperative BA., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Biliary atresia (BA) is an intractable neonatal inflammatory and obliterative cholangiopathy, leading to progressive fibrosis and cirrhosis. Adiponectin, an anti-inflammatory adipokine, is known to play a possible role in liver diseases. The objective of our study was to determine the relationship between adiponectin gene polymorphisms and BA susceptibility., Methods: A total of 106 BA patients and 107 healthy controls were included in this study. Two single nucleotide polymorphisms (SNPs) of the adiponectin gene, +45T/G (rs2241766) and +276G/T (rs1501299), were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis., Results: Genotype distributions of +45 T/G and +276 G/T SNPs were seen in the Hardy-Weinberg equilibrium for both BA patients and controls. The frequency of the G/G genotype at +276G/T was significantly higher in BA patients than in the controls (P=0.009). Regarding +45T/ G in BA patients, the frequency of the T/T genotype tended to be lower than in the controls, but the difference was not significant. Moreover, the G allele at +276G/T in BA patients was more common than in the controls (P=0.0043). In contrast, the frequency of the T allele at +45T/G was not significantly different between BA patients and the controls. None of the haplotypes studied was found to significantly influence the risk of BA., Conclusions: +276G/T SNP is strongly associated with BA, particularly with the G allele. We postulate that the +276G/T adiponectin gene polymorphism confers increased susceptibility to BA.

Introduction: Biliary atresia (BA) is a fatal disease in children. Its main pathological feature is progressive immune-mediated cholangiopathy. Interleukin (IL)-12, IL-18, and interferon-gamma (IFN-gamma) play important roles in various immunological diseases., The Objective: was to investigate whether these serum markers were associated with clinical outcome in BA., Methods: Serum levels of IL-12, IL-18, and IFN-gamma were determined using enzyme-linked immunosorbent assay from 46 BA patients (median age of 9 years) and 19 normal controls. The BA patients were then categorized into three groups according to their outcome: jaundice-free (29 cases), mild to moderate jaundice (10 cases), and marked jaundice (7 cases). The comparisons of serum IL-12, IL-18, and IFN-gamma levels among groups of the patients were performed using one-way analysis of variance with post-hoc tests. Data are expressed as mean + standard deviation., Results: Serum IL-18 and IFN-gamma in BA patients were higher than the normal controls (IL-18: 113.3 + 82.6 vs. 80.5 + 9.9 pg/mL, p = 0.011 and IFN-gamma: 41.7 + 5.1 vs. 38.0 + 1.9 pg/mL, p < 0.001). There was no difference in serum IL-12 between BA and controls. Further analysis demonstrated that, in BA patients, only serum IL-18 levels significantly increased with the degree of jaundice (test for trend, p = 0.004)., Conclusions: Serum IL-18 and IFN-gamma levels were increased in medium-term survivors of BA. The elevated serum IL-18 in BA patients was associated with worse clinical outcome. These results suggest that IL-18 and IFN-gamma play roles in the pathophysiology of BA. Additionally, IL-18 is likely to be involved in the disease progression., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background and Aim: Biliary atresia (BA) is an intractable neonatal liver disease characterized by progressive fibrosclerotic obliteration of the extrahepatic biliary tree. The aim of this study was to evaluate serum galectin-3 in postoperative BA patients and the association between galectin-3, clinical outcome and liver stiffness score., Methods: 58 BA patients post Kasai operation and 20 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into 2 groups according to their serum total bilirubin (TB) levels (TB<2 mg/dL, no jaundice vs. TB≥2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT<45 IU/L, normal ALT vs. ALT≥45 IU/L, elevated ALT). Serum galectin-3 levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography (FibroScan)., Results: BA patients had higher serum galectin-3 levels (5.1±0.3 vs. 3.8±0.4 ng/mL, p=0.01) and greater liver stiffness values than healthy controls (29.7±3.0 vs. 5.1±0.5 kPa, p<0.001). Serum galectin-3 levels were markedly elevated in BA patients with jaundice compared to those without jaundice (6.4±0.5 vs. 4.4±0.3 ng/mL, p=0.001). Furthermore, BA patients with elevated ALT displayed significantly higher levels of serum galectin-3 than those with normal ALT (5.9±0.4 vs. 3.8±0.3 ng/mL, p=0.001). Additionally, BA patients with portal hypertension had considerably higher serum galectin-3 levels than those without portal hypertension (6.1±0.4 vs. 3.7±0.3 ng/mL, p<0.001)., Conclusions: Increased serum galectin-3 is associated with a poor outcome in postoperative BA patients. Serum galectin-3 could be used as a biochemical parameter reflecting the deterioration of liver function and the severity of liver fibrosis in postoperative BA., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Biliary atresia (BA) is a neonatal liver disorder characterized by chronic inflammation and obliteration of extrahepatic bile ducts. The purpose of the study was to investigate serum matrix metalloproteinase-3 (MMP-3) in postoperative BA patients and the association of MMP-3 with clinical outcome and liver stiffness score., Methods: Fifty-eight BA patients post-Kasai operation and 20 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (TB < 2 mg/dL, no jaundice vs. TB ≥ 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT < 45 IU/L, normal ALT vs. ALT ≥ 45 IU/L, elevated ALT). Serum MMP-3 levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by FibroScan., Results: BA patients had greater MMP-3 levels (10.8 ± 1.0 vs. 7.9 ± 0.8 ng/mL, P = 0.02) and higher liver stiffness values than controls (29.7 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum MMP-3 levels were significantly elevated in BA patients with jaundice when compared with those without jaundice (15.3 ± 2.2 vs. 8.5 ± 0.8 ng/mL, P = 0.004). In addition, BA patients with elevated ALT had higher levels of serum MMP-3 than those with normal ALT (12.4 ± 1.5 vs. 8.3 ± 0.9 ng/mL, P = 0.02). Moreover, BA patients with portal hypertension displayed higher serum MMP-3 than those without portal hypertension (13.5 ± 1.5 vs. 7.4 ± 0.8 ng/mL, P = 0.001). There was also a correlation between serum MMP-3 and liver stiffness scores (r = 0.448, P ≤ 0.001)., Conclusion: Serum MMP-3 was associated with hepatic dysfunction and liver stiffness in postoperative BA patients. Accordingly, MMP-3 could play a role in the pathophysiology of hepatic fibrosis in BA after Kasai operation.

Purpose: Biliary atresia (BA) is one of the most serious liver disorders in children. The aims of the present study were to investigate circulating levels of osteopontin in BA children compared with healthy controls and to evaluate the relationship between circulating osteopontin and therapeutic outcome of BA patients., Methods: Fifty-nine BA patients post-Kasai operation and 13 healthy children were recruited. The patients were divided into two groups according to their serum total bilirubin levels (TB < 2, jaundice-free vs. TB ≥ 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 45, normal ALT vs. ALT ≥ 45 IU/L, elevated ALT). Plasma osteopontin levels were analyzed using commercial enzyme-linked immunosorbent assay., Results: The circulating osteopontin was higher in BA children compared with that of healthy controls (146.9 ± 19.1 vs. 28.0 ± 8.4 ng/mL, P = 0.001). The BA patients with persistent jaundice had more increased plasma osteopontin levels than those without jaundice (157.8 ± 47.9 vs. 27.5 ± 6.4 ng/mL, P = 0.001). Furthermore, plasma osteopontin levels in BA patients with elevated ALT were significantly higher than those with normal ALT (103.2 ± 29.2 vs. 24.5 ± 7.9 ng/mL, P = 0.01). In addition, circulating osteopontin was positively correlated with serum total bilirubin (r = 0.526, P < 0.001) and with serum ALT (r = 0.575, P < 0.001). Subsequent analysis showed that the BA patients with portal hypertension had more elevated plasma osteopontin compared to those without portal hypertension (116.7 ± 31.1 vs. 19.5 ± 9.3 ng/mL, P = 0.01)., Conclusion: Increased circulating osteopontin was associated with the development of hepatic dysfunction and portal hypertension in BA patients. Circulating osteopontin may serve as a possible marker reflecting disease severity and monitoring the disease progression in postoperative BA patients.

Background: Biliary atresia (BA) is a progressive inflammatory disorder of the extrahepatic bile ducts leading to the obliteration of bile flow. The purpose of this study was to determine serum adiponectin in BA patients and to investigate the relationship of adiponectin with clinical parameters and liver stiffness scores., Methods: Sixty BA patients post Kasai operation and 20 controls were enrolled. The mean age of BA patients and controls was 9.6 ± 0.7 and 10.1 ± 0.7 years, respectively. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ≥ 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness < 7 kPa vs. significant fibrosis, liver stiffness ≥ 7 kPa). Serum adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were examined by transient elastography (FibroScan)., Results: BA patients had markedly higher serum adiponectin levels (15.5 ± 1.1 vs. 11.1 ± 1.1 μg/ml, P = 0.03) and liver stiffness than controls (30.1 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum adiponectin levels were significantly elevated in BA patients with jaundice compared with those without jaundice (24.4 ± 1.4 vs. 11.0 ± 0.7 μg/ml, P < 0.001). In addition, BA patients with significant liver fibrosis had remarkably greater serum adiponectin than insignificant fibrosis counterparts (17.7 ± 1.2 vs. 9.4 ± 1.1 μg/ml, P < 0.001). Subsequent analysis revealed that serum adiponectin was positively correlated with total bilirubin, hyaluronic acid, and liver stiffness (r = 0.58, r = 0.46, and r = 0.60, P < 0.001, respectively)., Conclusions: Serum adiponectin and liver stiffness values were higher in BA patients compared with normal participants. The elevated serum adiponectin levels also positively correlated with the degree of hepatic dysfunction and liver fibrosis. Accordingly, serum adiponectin and transient elastography could serve as the useful non-invasive biomarkers for monitoring the severity and progression in postoperative BA.

Aim: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls., Methods: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundice status. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa)., Results: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001)., Conclusion: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

Background and Aim: Biliary atresia (BA) is a chronic progressive inflammatory disorder of the extrahepatic and intrahepatic biliary system in children. The aim of the present study was to investigate circulating endoglin levels in BA patients compared with healthy controls and to determine the relationship between plasma endoglin levels and outcome parameters of BA patients after Kasai operation., Methods: Fifty-five postoperative BA patients and 14 healthy controls were recruited. The patients were divided into two groups based on their serum total bilirubin levels (TB<34.2, no jaundice vs. TB>or=34.2 micromol/L, persistent jaundice) and serum alanine aminotransferase (ALT<45, normal ALT vs. ALT>or=45 IU/L, high ALT). Circulating endoglin levels were analyzed by enzyme-linked immunosorbent assay., Results: Average levels of plasma endoglin were significantly higher in BA patients compared to healthy controls (7.8+/-0.4 vs. 6.5+/-0.4 ng/mL; P=0.02). BA patients with persistent jaundice had higher plasma endoglin levels than those without jaundice (9.2+/-0.8 vs. 6.9+/-0.3 ng/mL; P=0.006). Furthermore, the concentrations of plasma endoglin in BA patients with high ALT were significantly higher compared to those with normal ALT (8.5+/-0.5 vs. 6.3+/-0.5 ng/mL, P=0.003). In addition, BA patients with portal hypertension had more elevated plasma endoglin levels than those without portal hypertension (8.8+/-0.6 vs. 6.1+/-0.3 ng/mL, P=0.001). Plasma endoglin was positively correlated with serum ALT (r=0.36, P=0.007) and serum GGT (r=0.44, P=0.001)., Conclusion: High circulating endoglin correlated with a poor outcome for BA. Plasma endoglin can be utilized as a potential biomarker reflecting the severity of ongoing liver injury and biliary obstruction in BA patients after Kasai procedure.

Objective: The purpose of this study was to investigate the association between cyclooxygenase-2 (COX-2) expression and clinical outcome in biliary atresia (BA) patients., Methods: Six months after surgery, twenty-eight BA patients were divided into three groups according to their liver function tests: group A with satisfactory liver function (n=11), group B with moderate liver dysfunction (n=8), and group C with severe liver dysfunction (n=9). COX-2 expression was determined by immunohistochemistry. Choledochal cysts (n=5) and normal liver samples (n=4) served as controls., Results: Our data have shown that the intrahepatic biliary epithelium in BA specimens expressed COX-2. The mean immunoreactive score of COX-2 in BA patients was significantly higher than that in choledochal cyst and normal liver (4.0+/-0.6, 0.9+/-0.3, and 0.7+/-0.3, respectively, p<0.002). Strong expression of COX-2 was observed in BA patients with severe liver dysfunction. Subgroup analysis showed that the mean COX-2 immunoreactive scores of patients in group A, B, and C were 2.1+/-0.6, 3.6+/-1.1, and 5.9+/-0.9, respectively. The COX-2 immunoreactive score in BA patients with severe liver dysfunction was higher than in patients with satisfactory liver function (p<0.005)., Conclusion: Increased COX-2 expression of biliary epithelial cells at the time of Kasai operation was associated with an adverse therapeutic outcome in BA, suggesting that COX-2 could play a plausible role in the liver pathology of BA.

Background and Aim: Biliary atresia (BA) is one of the most serious liver disorders in children. The purposes of the present study were to investigate serum levels of bone morphogenetic protein 7 (BMP7) in BA children compared with healthy controls and to evaluate the association between serum BMP7 and the clinical outcome of BA patients post Kasai operation., Methods: Sixty-two BA patients post Kasai operation and 14 healthy controls were enrolled. The patients were divided into two groups according to their serum total bilirubin levels (TB<2, no jaundice vs. TB> or =2 mg/dL, persistent jaundice) and alanine aminotransferase levels (ALT<45, normal ALT vs. ALT> or =45 IU/L, elevated ALT). Serum BMP7 levels were determined by commercial enzyme-linked immunoabsorbent assay., Results: The mean serum BMP7 was higher in BA patients compared with that of healthy controls (35.4+/-3.6 vs. 20.6+/-2.7 pg/mL, p=0.002). The BA patients with persistent jaundice had more elevated serum BMP7 levels than those without jaundice (59.5+/-6.5 vs. 20.3+/-1.6 pg/mL, p=0.001). There was also a correlation between serum total bilirubin and serum BMP7 levels (r=0.57, p<0.001). Moreover, the levels of serum BMP7 in BA patients with elevated ALT were significantly higher than those with normal ALT (41.6+/-4.7 vs. 22.4+/-4.2 pg/mL, p=0.003). Additionally, BA patients with portal hypertension had higher increased serum BMP7 levels compared to those without portal hypertension (45.3+/-4.9 vs. 18.7+/-2.8 pg/mL, p<0.001)., Conclusion: The significant increment of serum BMP7 was associated with a deterioration of hepatic function and the progression of liver fibrosis. Serum BMP7 could be used as a prognostic marker to reflect disease severity and monitor disease progression in BA patients post Kasai operation., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)

Objective: Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Macrophage migration inhibitory factor (MIF) is an important mediator of inflammation and immune response in various diseases. The objective of this study was to examine the possible roles of MIF in BA., Methods: Forty-eight BA paediatric patients who had undergone a Kasai operation and 22 healthy children were recruited. The mean ages of the patients and controls were 8.47 +/- 0.74 and 7.64 +/- 0.41 years, respectively. The patients were categorised into two groups according to their serum levels of total bilirubin (TB) (TB < 2 mg/dL; no jaundice, and TB >/= 2 mg/dL; persistent jaundice). The serum MIF levels were determined using commercially available enzyme-linked immunosorbent assay., Results: The mean serum MIF level of the BA children was higher than that of healthy controls (0.43 +/- 0.04 ng/mL [corrected] vs. 0.27 +/- 0.02 ng/mL; [corrected] p < 0.001). However, there was no difference in serum MIF levels between BA patients with jaundice and those without jaundice. Further analysis revealed that there was no difference in serum MIF levels of BA patients without portal hypertension compared to that of BA patients with portal hypertension., Conclusion: MIF production was elevated in BA patients compared to normal controls. It is likely that MIF plays a role in the pathophysiology of post-operative BA patients. However, the elevated MIF levels are not associated with either jaundice status or portal hypertension.

Purpose: Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) have been implicated in osteoclastogenesis. However, the relationship between the OPG-RANKL system and bone status in biliary atresia (BA) has not, as yet, been clarified. Thus, the aim of this study has been to evaluate the relationship between the OPG-RANKL system and bone mineral metabolism in patients with BA., Methods: Fifty patients with BA and 13 healthy controls were investigated. The mean age of BA patients and controls was 7.3 +/- 0.6 and 8.0 +/- 1.1 years, respectively. Serum levels of OPG, RANKL, osteocalcin, and C-terminal telopeptide of type I collagen (CTX) were measured by sandwich enzyme-linked immunosorbent assay. Bone mineral density (BMD) of the lumbar spine was determined by dual energy X-ray absorptiometry., Results: Biliary atresia patients had significantly elevated serum OPG levels compared with controls (4.0 +/- 0.3 vs. 3.0 +/- 0.3 pmol/L, P = 0.02) and serum OPG levels in BA patients with jaundice were higher than in those without jaundice (4.6 +/- 0.4 vs. 3.6 +/- 0.4 pmol/L, P = 0.04). Likewise, serum RANKL levels were significantly higher in BA patients than in controls (2.9 +/- 0.2 vs. 1.2 +/- 0.7 pmol/L, P = 0.001). In addition, serum RANKL levels were increased in BA patients with jaundice compared to those without jaundice, but this difference was not statistically significant (3.2 +/- 0.3 vs. 2.7 +/- 0.2 pmol/L, P = 0.2). The serum osteocalcin levels in BA patients were not significantly different from those in the healthy controls, whereas the serum CTX levels were elevated in BA patients compared with the controls (0.4 +/- 0.1 vs. 0.2 +/- 0.1 ng/mL, P = 0.02). Furthermore, BMD of BA children with jaundice was significantly lower than that of BA children without jaundice (P = 0.0005). BMD of BA patients was inversely correlated with serum levels of OPG (r = -0.452, P < 0.001)., Conclusion: Elevated serum OPG levels are associated with reduced BMD and the outcome of BA. The increase of serum OPG in BA patients with severe disease could reflect a compensatory response to bone loss.

Background/aims: The purpose of this study was to investigate the relationship between basic fibroblast growth factor (bFGF) and clinical outcome in biliary atresia (BA) patients after surgical treatment., Methodology: Sixty-five pediatric patients with BA post Kasai operation and 12 healthy children were recruited. The patients were categorized into 2 groups according to their serum levels of total bilirubin (TB < 2, no jaundice vs. TB > or = 2mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs. ALT > or = 100 U/L). The serum bFGF levels were determined by enzyme-linked immunosorbent assay., Results: The mean serum bFGF level of the BA patients was higher than that of normal controls (14.2 +/- 1.6 vs. 9.0 +/- 2.2 pg/mL, p < 0.03). Serum bFGF levels in the persistent jaundice group were significantly higher than those without jaundice (17.6 +/- 3.1 vs. 11.9 +/- 1.5 pg/mL, p < 0.04). Additionally, patients with serum ALT > or = 100 U/L had higher serum levels of bFGF than those with serum ALT < 100 U/L (19.0 +/- 2.4 vs. 8.9 +/- 1.6 pg/mL, p < 0.0005). In the no jaundice group, serum bFGF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (15.8 +/- 2.2 vs. 8.6 +/- 1.9 pg/mL, p < 0.02)., Conclusions: The significant elevation in bFGF levels is associated with the presence of PH and the severity of hepatic damage. bFGF may play a role in the pathogenesis of progressive inflammation and the perpetuation of PH in BA patients after Kasai procedure.

Aim: To investigate circulating leptin levels in biliary atresia (BA) patients and the association of leptin with bone mineral density (BMD) and the severity of BA., Methods: We have examined 50 patients with BA and 15 matched healthy controls. Serum leptin, osteocalcin and C-terminal telopeptide of type I collagen (CTX) levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). BMD of the lumbar spine was measured by dual energy X-ray absorptiometry., Results: Serum leptin levels of BA patients were lower than those of healthy controls (2.7 +/- 0.3 vs. 7.1 +/- 1.7 ng/mL, p = 0.0001). Among the BA patients, serum leptin levels were significantly lower in patients with jaundice than patients without jaundice (1.7 +/- 0.2 vs. 3.4 +/- 0.4 ng/mL, p = 0.001). BMD of BA patients was correlated (p < 0.001) with leptin levels, age and BMI (r = 0.55, r = 0.75 and r = 0.58, respectively). The serum CTX levels were significantly higher in jaundice patients compared with jaundice-free patients and the healthy controls (0.6 +/- 0.2 vs. 0.2 +/- 0.1 ng/mL, p = 0.01), whereas the serum osteocalcin levels in BA patients were not different from those in the controls., Conclusion: Circulating leptin levels are correlated with BMD and the presence of jaundice in BA, suggesting that the leptin may play a physiological role in maintaining bone mass of BA patients with jaundice.

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.

Objective: Connective tissue growth factor (CTGF) has been proposed to play a key role in the pathogenesis of hepatic fibrosis in biliary atresia (BA). The aim of the present study was to determine the single nucleotide polymorphism (SNP) in the promoter region of CTGF gene in a Thai population, and to investigate the possible role of CTGF promoter polymorphism in the susceptibility of BA., Material and Method: Genomic DNA was obtained from 84 patients with BA and 142 healthy controls. The -447 G/C and -132 C/G in CTGF promoter were amplified and examined by amplification-refractory mutation system (ARMs) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The test of Hardy-Weinberg equilibrium (HWE) was performed using HWE program of SNPAnalyzer. Statistical analysis was carried out with SPSS and Epi Info., Result: According to the previous experiment, there were two SNPs, which were at position -447 and -132 on the promoter. However, there was only one SNP at the position -447 in the Thai population. No significant differences in genotype and allele frequency were observed between BA and controls or with BA subgroups., Conclusion: The present study demonstrated that CTGF polymorphism at -447 G/C was not associated with BA and the jaundice status of the postoperative BA patients.

The purpose of this study was to determine the possible role of serum levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) in the pathogenesis of the progressive inflammation and fibrosis in biliary atresia (BA). Serum concentrations of TIMP-1 were measured in 57 BA patients and 15 healthy controls using commercially available enzyme-linked immunosorbent assays. The mean ages of the BA patients and the controls were 6.1 +/- 0.6 and 6.7 +/- 1.1 years, respectively. The patients were categorized into two groups according to their clinical outcomes: patients with jaundice (total bilirubin > or = 2 mg/dl) and patients without jaundice (total bilirubin < 2 mg/dl). In our study, serum levels of TIMP-1 were significantly higher in the BA patients than in healthy subjects (4.8 +/- 0.4 vs. 3.5 +/- 0.3 ng/ml, respectively; p < 0.05). Additionally, serum levels of TIMP-1 significantly increased in the BA patients with jaundice in comparison to those without jaundice (6.3 +/- 0.7 vs. 3.1 +/- 0.3 ng/ml, respectively; p = 0.001). Patients with persistent jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Furthermore, patients with portal hypertension (PH) had higher TIMP-1 levels than those without PH (5.3 +/- 0.4 vs. 1.9 +/- 0.3 ng/ml, respectively; p < 0.001). It is concluded that serum levels of TIMP-1 increased in patients with BA. The significant increase in TIMP-1 levels is related to the presence of PH and the severity of jaundice. The elevated TIMP-1 levels may reflect the degree of hepatic fibrosis and development of PH. The data suggest that TIMP-1 may play a role in the pathophysiology of post-Kasai BA.

Biliary atresia (BA) is a neonatal obliterative cholangiopathy of unknown etiology. Despite the Kasai procedure, hepatic fibrosis and portal hypertension (PH) still occur. Interleukin-8 (IL-8) is an important mediator of inflammation and immune response in human disease. The objective of this study was to investigate the potential role of IL-8 in the pathogenesis of the progressive, sclerosing, inflammatory process and fibrosis in BA. A total of 60 pediatric patients with BA and 15 healthy children were evaluated. The mean ages of BA patients and controls were 6.3 +/- 0.6 and 6.7 +/- 1.1 years, respectively. The patients were classified into two groups according to their clinical outcomes: patients with jaundice (total bilirubin +/- 25.5 micromol/l) and patients without jaundice (total bilirubin < 25.5 micromol/l). The IL-8 levels in serum samples were determined by commercially available enzyme-linked immunosorbent assay. Serum IL-8 levels were higher in the BA patients than in healthy children (236.2 +/- 60.1 vs. 34.5 +/- 12.1 pg/ml, P < 0.001). Patients with jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Serum IL-8 levels in the jaundice group were significantly higher than in those without jaundice (516.5 +/- 130.0 vs. 49.3 +/- 10.4 pg/ml, P < 0.0005). Furthermore, patients with PH had higher IL-8 levels than those without PH (378.1 +/- 102.2 vs. 106.6 +/- 48.4 pg/ml, P < 0.005). In the jaundice-free group, IL-8 levels were elevated in patients with PH compared with those without PH (79.0 +/- 17.4 vs. 19.7 +/- 5.8 pg/ml, P < 0.005). The present study demonstrated elevation of serum IL-8 levels in children with BA. Serum IL-8 levels were also higher in patients with jaundice compared with patients without jaundice. These findings suggest that IL-8 may play a significant role in the pathogenesis of BA.