Hong Koh

Assessment of liver fibrosis and cirrhosis by aspartate aminotransferase-to-platelet ratio index in children with biliary atresia

Background: In patients with biliary atresia (BA), liver fibrosis and cirrhosis commonly occur even after Kasai hepatoportoenterostomy. Although liver biopsy is the gold standard to evaluate liver fibrosis, it is invasive and may result in life-threatening complications. The aspartate aminotransferase-to-platelet ratio index (APRI) is a safe and simple method to assess liver fibrosis in patients with chronic liver diseases. To use APRI as a postoperative follow-up tool, we validated the diagnostic power of APRI for the degree of liver fibrosis in postoperative patients with BA. Patients and Methods: Patients with newly diagnosed BA who underwent the Kasai procedure between March 2006 and May 2009 were analyzed. Several laboratory tests including APRI were performed. Liver wedge biopsy specimens were obtained during the surgical procedure, and histopathologic analyses were performed using the Metavir classification. Results: Thirty-five patients (12 boys, median age of 1.9 months) were enrolled. Metavir scores were F1 in 0, F2 in 11, F3 in 11, and F4 in 13 patients. The areas under the receiver operating characteristics curves for F ≥ 3 and F = 4 were 0.92 and 0.91, respectively. Distinct optimal cutoff values of APRI for F ≥ 3 and F = 4 were obtained (1.01 and 1.41, respectively). Clinical outcomes of patients were significantly different between 2 groups (noncirrhosis vs cirrhosis) based on APRI before and 3 months after the Kasai procedure. Conclusion: APRI may be used as a simple and readily available tool for assessing liver fibrosis without additional risks in patients with BA during postoperative follow-up care.

Hepatic Fibrosis Scan for Liver Stiffness Score Measurement: A Useful Preendoscopic Screening Test for the Detection of Varices in Postoperative Patients With Biliary Atresia

Objective:Even after successful Kasai portoenterostomy, progressive hepatic fibrosis in postoperative patients with biliary atresia (BA) can be associated with portal hypertension and esophageal or gastric varices. Therefore, early diagnosis and close follow-up of varices are important. We investigated the correlation between the liver stiffness scores measured by FibroScan and the presence of esophageal or gastric varices to examine the usefulness of FibroScan as a preendoscopic screening test for varices. Patients and Methods:A total of 49 of 81 children with BA following successful Kasai operations were enrolled in this study. FibroScan and endoscopic examination were performed prospectively. Results:There were 22 males (44.9%) and the mean age of the patients was 3.8 ± 2.7 years. Esophageal or gastric varices were present in 30 patients (Vx group) and absent in 19 (nVx group). The mean liver stiffness score was significantly higher in the Vx group (21.35 ± 10.31 kPa in the Vx group versus 9.75 ± 8.61 kPa in the nVx group, P < 0.001). The optimal cutoff value of the liver stiffness score for the prediction of a varix was 9.7 kPa with a sensitivity of 0.97 and a specificity of 0.80. Conclusions:Liver stiffness scores measured by FibroScan correlate well with the presence of esophageal or gastric varices. FibroScan is a novel, noninvasive, and useful screening method for the preendoscopic detection of varices in postoperative patients with BA.

Transient elastography and sonography for prediction of liver fibrosis in infants with biliary atresia.

The purpose of this study was to assess the diagnostic performance of transient elastography and sonography for noninvasive evaluation of liver fibrosis in infants with biliary atresia.

Agranular platelets as a cardinal feature of ARC syndrome.

We aimed to describe abnormal platelet morphology and its clinical significance in infants who were diagnosed with arthrogryposis renal dysfunction and cholestasis (ARC) syndrome. We collected all of the cases of ARC syndrome referred to a single pediatric referral center. In all patients, platelet counts and analysis of platelet morphology were performed with peripheral blood smear specimens. Electron microscopy images were obtained to examine the ultrastructure of the platelets. Over the 12-year period, 12 cases of ARC syndrome were identified. The sex ratio (male:female) was 1:1. The median birth weight was 3.15u2009kg (range, 2.3 to 3.8u2009kg). Failure to thrive was observed in all the patients. The major cause of death was recurrent febrile illness and pneumonia. The median age at death was 8.9 months (range, 2.6 to 28.8u2009kg). Their median body weight at death was 3.1u2009kg (range, 2.6 to 6.0u2009kg). Close examination of their peripheral blood smear (n=11) specimens showed large, pale, agranular platelets similar to those seen in gray platelet syndrome. Electron microscopic images of the platelets (n=7) revealed a lack of α; granules. Agranular platelets are a common finding in ARC syndrome. Agranular platelets should be considered as a cardinal feature of ARC syndrome and can be useful as a noninvasive diagnostic marker for ARC syndrome.

Gadopentetate dimeglumine-enhanced MR cholangiopancreatography in infants with cholestasis

BackgroundBiliary atresia (BA) is a progressive, obliterative cholangiopathy that occurs in neonates with hepatic portoenterostomy the treatment of choice, but early surgery is important for optimum outcomes. MRI, including MR cholangiopancreatography (MRCP) may be a diagnostically useful alternative to US, but the heavily T2-weighted sequences used include not only bile duct signals, but also other heterogeneously high signal intensities from surrounding structures.ObjectiveTo evaluate the effects of gadolinium when used to decrease background signal intensity on T2-weighted MR cholangiopancreatography (MRCP) in infants and to evaluate the qualitative improvement of the depiction of the common bile duct (CBD) for evaluating neonatal cholestasis.Materials and methodsOur Institutional Review Board approved this prospective study. MRCP was performed with gadopentetate dimeglumine injection using a 1.5-T scanner. Pre- and postcontrast MRCP images were compared. Forty-nine infants (male:femaleu2009=u200921:28; age 0–12xa0months, mean 2.3) were included. The final diagnoses were biliary atresia (BA) in 28 cases and non-BA in 21. Quantitative analysis was conducted using region-of-interest measurements of mean signal intensities of the liver, pancreatic head and gallbladder (if defined). Qualitative analysis was performed by four radiologists who subjectively scored image confidence in the presence of CBD on a 4-point scale (0 for definitely absent, 1 for probably absent, 2 for probably present, and 3 for definitely present).ResultsThe signal-to-noise ratios were significantly decreased in the liver and pancreatic head after contrast medium enhancement (mean 5.7→4.0 in liver and mean 44.9→12.7 in the pancreatic head; Pu2009<u20090.0001), and this finding was constant in both the BA and the non-BA group. The mean confidence score in the presence of CBD decreased in the BA group (0.9→0.5; Pu2009<u20090.0001), but did not change significantly in the non-BA group (2.0→2.1; Pu2009=u20090.459) after contrast medium enhancement. Both intra- and interobserver agreement was higher after contrast medium enhancement (Pu2009=u20090.046).ConclusionGadopentetate dimeglumine-enhanced MRCP increased the diagnostic confidence of absence of the CBD in cholestatic infants with increased intra- and interobserver agreement.

Points to be considered when applying FibroScan s probe in children with biliary atresia

Objectives: With the introduction of smaller probes (S1, S2), the use of transient elastography has been expanded to children. Accordingly, we aimed to address points of consideration in probe choice and interpretation of measured liver stiffness by applying and comparing FibroScan S and M probes in biliary atresia. Methods: Using S1, S2, and M probes, 3 liver stiffness measurements, success rates, and interquartile ranges were obtained from 100 patients. Patients were assigned to 2 groups according to thoracic perimeter (⩽45u200acm vs >45u200acm). In both groups, obtained values were compared and the relation between liver stiffness measurement and aspartate aminotransferase-to-platelet ratio index was analyzed. Results: In the small-thorax group, the success rate was highest with the S1 probe and the intraclass correlation coefficient (ICC) was highest for S1 versus S2 (0.98), compared with that for S1 versus M (0.69) and S2 versus M (0.77). In the large-thorax group, ICC was the highest for S2 versus M (0.88), compared with that for S1 versus S2 (0.69) and S1 versus M (0.51). In the small-thorax group, correlations between aspartate aminotransferase-to-platelet ratio index and liver stiffness measurement were stronger for S1 (0.65) and S2 (0.64) than for M (0.49). In the large-thorax group, all probes showed good correlation, S1 (0.68), S2 (0.62), and M (0.62). Conclusions: We recommend that the S1 probe is more appropriate for use in small children, especially those with a thorax perimeter of <45u200acm. If no S probe is available, the M probe may be acceptable in children whose thorax perimeter is >45u200acm.

Clinical benefit of liver stiffness measurement at 3 months after Kasai hepatoportoenterostomy to predict the liver related events in biliary atresia

Background The progression of hepatic fibrosis may result in decompensated hepatic failure with cirrhosis, liver related events (LRE) such as ascites, variceal bleeding, and death after successful and timely Kasai hepatoportoenterostomy (HPE) in biliary atresia. The aim of this study is to suggest clinical benefit of the liver stiffness measurement (LSM) using transient elastography at 3 months after the Kasai operation to predict LRE. Methods Between January 2007 and December 2011, 69 eligible biliary atresia patients who underwent Kasai HPE and performed transient elastography before and 3 months after HPE were included. The occurrences of LRE were analyzed for all patients. All patients were divided into 2 groups (with and without LRE) for comparison. Multivariate analysis was used to detect the independent risk factors of LRE. The area under the receiver operation characteristics curve (AUROC) was used to establish the LSM optimal cutoff value of 3 months after Kasai operation in predicting LRE. Results LSM value, aminotransferase, albumin, bilirubin, and PT-INR significantly differed among the two groups. Multivariate analysis demonstrated LSM value as the most powerful independent factor of the development of LRE. The cut-off value of 19.9 kPa was calculated to be optimal for predicting LRE development with total sensitivity and specificity of 1.804. AUROC resulted in 0.943, with sensitivity of 85.3% and specificity of 95.2%. Conclusions The LSM value of 3 months after Kasai HPE can be a useful predictor of LRE development.

The efficacy of aspartate aminotransferase-to-platelet ratio index for assessing hepatic fibrosis in childhood nonalcoholic steatohepatitis for medical practice.

Purpose Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.

Ultrasonographic findings of type IIIa biliary atresia

Purpose: To describe the ultrasonographic (US) findings of type IIIa biliary atresia. Methods: We retrospectively reviewed a medical database of patients pathologically confirmed to have biliary atresia, Kasai type IIIa, between January 2002 and May 2013 (n=18). We evaluated US findings including the visible common bile duct (CBD), triangular cord thickness, gallbladder size and shape, and subcapsular flow on color Doppler US; laboratory data; and pathological hepatic fibrosis grades. We divided them into two groups-those with visible (group A) and invisible (group B) CBD on US-and compared all parameters between the two groups. Results: CBD was visible on US in five cases (27.8%; group A) and invisible in 13 cases (72.2%; group B). US was performed at an earlier age in group A than in group B (median, 27 days vs. 60 days; P=0.027) with the maximal age of 51 days. A comparison of the US findings revealed that the triangular cord thickness was smaller (4.1 mm vs. 4.9 mm; P=0.004) and the gallbladder length was larger (20.0 mm vs. 11.7 mm; P=0.021) in group A. The gallbladder shape did not differ between the two groups, and the subcapsular flow was positive in all cases of both groups. There was no significant difference in the laboratory data between the two groups. Upon pathological analysis, group A showed low-grade and group B showed low- to high-grade hepatic fibrosis. Conclusion: When CBD is visible on US in patients diagnosed with type IIIa biliary atresia, other US features could have a false negative status. A subcapsular flow on the color Doppler US would be noted in the type IIIa biliary atresia patients.

MRI-based decision tree model for diagnosis of biliary atresia

ObjectivesTo evaluate MRI findings and to generate a decision tree model for diagnosis of biliary atresia (BA) in infants with jaundice.MethodsWe retrospectively reviewed features of MRI and ultrasonography (US) performed in infants with jaundice between January 2009 and June 2016 under approval of the institutional review board, including the maximum diameter of periportal signal change on MRI (MR triangular cord thickness, MR-TCT) or US (US-TCT), visibility of common bile duct (CBD) and abnormality of gallbladder (GB). Hepatic subcapsular flow was reviewed on Doppler US. We performed conditional inference tree analysis using MRI findings to generate a decision tree model.ResultsA total of 208 infants were included, 112 in the BA group and 96 in the non-BA group. Mean age at the time of MRI was 58.7 ± 36.6 days. Visibility of CBD, abnormality of GB and MR-TCT were good discriminators for the diagnosis of BA and the MRI-based decision tree using these findings with MR-TCT cut-off 5.1 mm showed 97.3 % sensitivity, 94.8 % specificity and 96.2 % accuracy.ConclusionsMRI-based decision tree model reliably differentiates BA in infants with jaundice. MRI can be an objective imaging modality for the diagnosis of BA.Key Points• MRI-based decision tree model reliably differentiates biliary atresia in neonatal cholestasis.• Common bile duct, gallbladder and periportal signal changes are the discriminators.• MRI has comparable performance to ultrasonography for diagnosis of biliary atresia.