Changes in branched-chain amino acids in an infant with maple syrup urine disease during perioperative pediatric liver transplant: A case report.

An 11-month-old female infant diagnosed with classic subtype IB maple syrup urine disease underwent living donor liver transplantation. Blood samples for plasma amino acid analysis were collected during the three phases of the operation. Despite the perioperative prophylactic administration of 12.5% hypertonic dextrose solution with insulin and a 20% intralipid emulsion, the blood levels of the branched-chain amino acids increased dramatically during surgery, consistent with an acute intraoperative metabolic decompensation. However, these blood levels normalized soon after liver transplantation with an excellent outcome. We suggest that the occurrence of an intraoperative metabolic crisis during liver transplantation is not necessarily a sign of graft failure.

Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: Expert review on behalf of the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood.

Decreased circulating clusterin reflects severe liver complications after hepatoportoenterostomy of biliary atresia.

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.

Detection of reflux-symptom association in children with esophageal atresia by video-pH-impedance study.

BACKGROUND: Children with esophageal atresia (EA) have risk of gastroesophageal reflux disease (GERD), suggesting reflux monitoring for prompt management. AIM: To evaluate GERD in children with EA and specific symptom association from combined Video with Multichannel Intraluminal Impedance and pH (MII-pH) study. METHODS: Children diagnosed with EA with suspected GERD and followed up at King Chulalongkorn Memorial Hospital between January 2000 and December 2018 were prospectively studied. All underwent esophagogastroduodenoscopy with esophageal biopsy and Video MII-pH study on the same day. Symptoms of GERD which included both esophageal and extra-esophageal symptom were recorded from video monitoring and abnormal reflux from MII-pH study based on the statement from the European Paediatric Impedance Group. Prevalence of GERD was also reported by using histopathology as a gold standard. Endoscopic appearance was recorded using Los Angeles Classification and esophagitis severity was graded using Esohisto criteria. RESULTS: Fifteen children were recruited with age of 3.1 (2.2, 9.8) years (40%, male) and the common type was C (93.3%). The symptoms recorded were cough (75.2%), vomiting (15.2%), irritability or unexplained crying (7.6%) and dysphagia (1.9%) with the symptom-reflux association of 45.7%, 89%, 71% and 0%, respectively. There were abnormal endoscopic appearance in 52.9%, esophagitis in 64.7% and high reflux score in 47.1%. Video MII-pH study has high diagnostic value with the sensitivity, specificity and accuracy of 72.7%, 100% and 82.4%, respectively. CONCLUSION: Prevalence of GERD in children with EA was high. Video MII-pH study to detect GERD in children with EA had high diagnostic value with the trend of specific symptom association.

Hepatic expression of HGF/C-met and native liver survival in biliary atresia.

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.

Spleen and Liver Stiffness to Detect Esophageal Varices in Children with Biliary Atresia.

OBJECTIVES: The aim of the study was to determine the accuracy of noninvasive parameters, such as liver (LS) and spleen stiffness (SS) to detect esophageal varices (EV) in children with biliary atresia (BA). METHODS: Children with BA between 2000 and 2015 were recruited. All underwent esophagogastroduodenoscopy and transient elastography. Demographic data, laboratory investigations, alanine transferase-to-platelet ratio index (APRI), and Varices Prediction Rule (VPR) score were collected. RESULTS: A total of 51 children (mean age 10.63 years, standard deviation (SD) = 6.08 years; 53% boys) were enrolled. There were differences in onset and outcome of portoenterostomy, spleen palpablility, platelet count, albumin, LS, SS, and VPR between the varice and varice-free groups (P < 0.05). In the varice group, the median LS was 18.12 (interquartile ratio, IQR 13.15-19.12) and the median SS was 46.85 (IQR 25.95-54.55) kPa. In the varice-free group, the median LS was 7.85 (IQR 5.88-16.75) and the median SS was 16.54 (IQR 11.75-21.75) kPa. Both LS and SS were higher in the varice than the varice-free group (P < 0001). The area under the receiver operating characteristic curve of LS, SS, spleen palpability, platelet count, APRI, and VPR were 0.734, 0.870, 0.817, 0.810, 0.751, and 0.794, respectively. Using a cut-off value of 12.5 kPa for LS, the sensitivity and specificity were 80 and 70%, respectively. Using a cut-off value of 28.9 kPa for SS, the sensitivity and specificity were 75 and 87%, respectively. Combination of LS and SS to diagnose varices increased the specificity to 93%. CONCLUSIONS: SS as a single marker had the best diagnostic value to predict esophageal varices in children with BA. The combination of SS and LS furthermore, increased the diagnostic yield.

Diagnosis and management of children with Blue Rubber Bleb Nevus Syndrome: A multi-center case series.

BACKGROUND: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations. AIMS: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied. PATIENTS AND METHODS: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS. RESULTS: Eighteen patients diagnosed with BRBNS were included. Cutaneous venous malformations were observed in 78% and gastrointestinal venous malformations in 89%. Lesions were also found in other organs including muscles, joints, central nervous system, eyes, parotid gland, spine, kidneys and lungs. Gastrointestinal lesions were more common in the small intestine than in stomach or colon. The management varied significantly among centers. Endoscopic therapy and surgical therapy alone failed to prevent recurrence of lesions. In younger children and in patients with musculoskeletal or other organ involvement, sirolimus was used with 100% success rate in our series (5 patients treated) although poor compliance with subtherapeutic sirolimus trough levels led to recurrence in a minority. CONCLUSIONS: Considering the multi-organ involvement in BRBNS, diagnosis and management requires a multidisciplinary approach. The treatment includes conservative, medical, endoscopic and surgical options. Prospective multicenter studies are needed to identify the optimal management of this rare condition.

Hepatic autotaxin overexpression in infants with biliary atresia.

BACKGROUND: Autotaxin (ATX) is a secreted glycoprotein that is involved in the development of hepatic fibrogenesis via the enzymatic production of lysophosphatidic acid. The aim of this study was to investigate hepatic expression of ATX in biliary atresia (BA) compared with non-BA liver controls and to examine the association between ATX expression and clinical outcome in BA. METHODS: Liver specimens from BA infants (n = 20) were compared with samples from infants who underwent liver biopsy for reasons other than BA (n = 14) and served as controls. Relative mRNA and protein expression of ATX were quantified using real-time polymerase chain reaction (PCR) and immunohistochemistry. Masson's Trichrome staining was performed to determine the degree of liver fibrosis. RESULTS: Quantitative real-time PCR demonstrated overexpression of ATX mRNA in BA livers. In immunohistochemical evaluation, ATX was positively stained on the hepatic parenchyma and the biliary epithelium in BA patients, as compared to non-BA controls. The immunostaining score of ATX in BA livers was also significantly higher than that observed in non-BA livers (P < 0.001). Subgroup analysis revealed that ATX expression in the patients with poor outcomes was significantly greater than in those with good outcomes (P = 0.03). Additionally, there was a positive correlation between hepatic ATX expression and Metavir fibrosis stage in BA livers (r = 0.79, P < 0.001). DISCUSSION: This study found that mRNA and protein expression of ATX were increased in BA livers. High hepatic ATX expression at the time of Kasai operation was associated with liver fibrosis and outcome in BA, suggesting that ATX may serve a role as a promising biomarker of the prognosis in biliary atresia.

Elevated serum heat shock protein 70 and liver stiffness reflect hepatic dysfunction and severity in postoperative biliary atresia.

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.

Prognostic values of serum bilirubin at 7th day post-Kasai for survival with native livers in patients with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a serious liver disease with uncertain prognosis. The objective of this study was to investigate prognostic values of the >20 % decrease in serum total bilirubin (TB) at 7th day post-op regarding early outcome and 5-year survival with native liver in BA. METHODS: Biliary atresia patients undergoing Kasai operation between 2000 and 2014 were reviewed. The ratio of serum TB at 7th day post-op to pre-op TB levels (TB7/TB0) was calculated for every patient. TB7/TB0 ratio of <0.8 indicated the >20 % decrease in serum TB. At 6th month following Kasai operation, outcome of BA patients were categorized into good outcome (TB < 2 mg % or clinically jaundice free) and poor outcome (TB > 2 mg % or clinically jaundice). For outcome analysis, logistic regression was used. For survival analysis, Cox regression was applied. RESULTS: There were 133 BA patients (M:F = 68:65) undergoing Kasai operation. Median age at surgery was 79 days. BA patients with TB7/TB0 ratio of <0.8 were found in 38 %. Outcome at 6-month post-op could be evaluated in 126 patients (good: poor = 68:58). The 1-, 3- and 5-year survival rates with native livers were 85, 70 and 65 %, respectively. The median overall survival with native livers was 164 months. Median follow-up time was 87 months. Logistic regression showed that gender and age at operation were not significant factors impacting on early outcome (p > 0.05). However, TB7/TB0 ratio of <0.8 was an independent factor for good outcome (Odds ratio = 3.0, p = 0.006). Cox regression analysis demonstrated that 5-year survival rate was significantly correlated with TB7/TB0 ratio of <0.8 (HR = 0.46, 95 % CI 0.23-0.91, p = 0.025) and outcome at 6th month post-op (HR = 0.05, 95 % CI 0.01-0.15, p < 0.001). CONCLUSIONS: The >20 % decrease in serum TB at 7th day post-Kasai is a predictor for good outcome. BA patients with TB7/TB0 of <0.8 had 5-year survival with native livers significantly higher than those with the ratio of >0.8.

Elevated serum periostin is associated with liver stiffness and clinical outcome in biliary atresia.

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.

Soluble receptor for advanced glycation end products and liver stiffness in postoperative biliary atresia.

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.

Bleeding tendency in an adolescent with chronic small bowel obstruction.

We report a case of fat-soluble vitamin deficiency in a 14-year old boy who had chronic duodenal obstruction. He presented with periodic unexplained bleeding tendency. The laboratory results showed positive fat globules in stool and prolonged prothrombin time. His further investigation revealed low plasma vitamin A and undetectable plasma vitamin E. After parenteral vitamin K and oral vitamin A and E supplement, these abnormalities resolved although he still had absent knee jerk. We propose that fat malabsorption and fat-soluble vitamin deficiency can occur after prolonged duodenal obstruction that induce bacterial overgrowth following by bile acid deconjugation. Despite very few case reports, screening for fat malabsorption and fat-soluble vitamin deficiency might be warranted in patients with chronic small bowel obstruction.

Transient elastography for predicting esophageal/gastric varices in children with biliary atresia.

BACKGROUND: Transient elastography (TE) is an innovative, noninvasive technique to assess liver fibrosis by measuring liver stiffness in patients with chronic liver diseases. The purpose of this study has been to explore the accuracy of TE and clinical parameters in predicting the presence of esophageal/gastric varices in children with biliary atresia (BA) following portoenterostomy. METHODS: Patients with BA status post portoenterostomy and normal children were recruited. Splenomegaly and presence of EV/GV were determined by physical examination and endoscopy, respectively. Aspartate transaminase to platelet ratio index (APRI) was used as a serum fibrosis marker. TE was performed by using FibroScan. Data was expressed as mean ± SD. RESULTS: Seventy-three BA patients (male:female = 32:41; age 9.11 ± 5.64 years) and 50 normal controls (male:female = 19:31; age 11.00 ± 3.31 years) were enrolled. The liver stiffness score of BA patients was significantly higher than that of normal controls (27.37 ± 22.48 and 4.69 ± 1.03 kPa; p < 0.001). Patients with EV/GV had significantly higher liver stiffness score and APRI than those without EV/GV. As for EV/GV diagnosis, the areas under the receiver operating characteristic curve were 0.89 (95% CI 0.80 to 0.98) for TE and 0.87 (95% CI 0.78 to 0.96) for APRI, respectively. The sensitivity (and specificity) of TE (using a cut-off value of 12.7 kPa) and APRI (using a cut-off value of 1.92) in predicting EV/GV were 84% (77%) and 84% (83%), respectively, whereas the sensitivity (and specificity) of splenomegaly in predicting EV/GV were 92% (85%). CONCLUSIONS: Transient elastography is a useful tool for predicting the presence of EV/GV. In addition, basic physical examination, routine biochemical and hematological tests, are still worthwhile and correlate well with the presence of EV/GV in patients with BA post portoenterostomy.

Serum adiponectin and transient elastography as non-invasive markers for postoperative biliary atresia.

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.

High serum matrix metalloproteinase-3 and liver stiffness in postoperative biliary atresia.

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.

Association of circulating osteopontin levels with clinical outcomes in postoperative biliary atresia.

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.

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia.

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.

Novel mutations in the STK11 gene in Thai patients with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS), a rare autosomal dominant inherited disorder, is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. Patients with this syndrome have a predisposition to a variety of cancers in multiple organs. Mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a major cause of PJS. Here we present the clinical and molecular findings of two unrelated Thai individuals with PJS. Mutation analysis by Polymerase Chain Reaction-sequencing of the entire coding region of STK11 revealed two potentially pathogenic mutations. One harbored a single nucleotide deletion (c.182delG) in exon 1 resulting in a frameshift leading to premature termination at codon 63 (p.Gly61AlafsX63). The other carried an in-frame 9-base-pair (bp) deletion in exon 7, c.907_915del9 (p.Ile303_Gln305del). Both deletions were de novo and have never been previously described. This study has expanded the genotypic spectrum of the STK11 gene.

Elevated serum macrophage migration inhibitory factor levels in post-operative biliary atresia.

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.