Portoenterostomy For Biliary Atresia Research Articles

Correlation between Histological Changes of Liver and Early Surgical Outcome of Kasai Portoenterostomy in Biliary Atresia

Background: Biliary atresia (BA) is a progressive fibrosing obstructive cholangiopathy involving both resulting in the intrahepatic and extrahepatic bile ducts. Hepatic portoenterostomy was first described by Kasai and Suzuki in 1959 to re-establish bile flow in biliary atresia patients. Currently, the accepted management of infants with biliary atresia is to re-establish bile flow by Kasai portoenterostomy followed by liver transplantation when indicated. Purpose: The purpose of this study is to correlate the surgical outcome following Kasai portoenterostomy with liver histology at the time of extended Kasai Portoenterostomy for biliary atresia who are operated in this institution. Methods: This prospective study was done in the department of Pediatric Surgery, BSMMU, with study period from October 2017 to march 2020.Wedge biopsies of liver was taken at the time of Extended Kasai portoenterostomy. Liver biopsies were graded as mild (grade-1), moderate (grade-2) and severe (grade-3) degree of fibrosis by single pathologist. Serial measurement of serum bilirubin were made preoperative and postoperatively to assess the degree of bile drainage in relation to degree of liver fibrosis. Results: A total of thirty infants underwent Extended KPE during study period. The mean age at the time of surgery was 89.7 (±23.4SD) days ranging from 57days to 140 days. 16 infants were operated before 90 days and rest 14 were operated beyond 90 days of life. Out of 30 infants, 3 cases were grade -1 fibrosis, 15 cases were grade- 2 and 12 cases were grade-3 fibrosis. 12(40%) infants cleared jaundice at three months after surgery, of which only 2 patients belonged to grade-3 fibrosis. 9(30%) infants were jaundice free at 6 months, among them 8 infants belonged to lower degree of fibrosis (grade-1 and grade-2). Only 1infant belonged to higher degree of fibrosis (grade-3). Conclusion: Currently, the concept for management of infants with biliary atresia considers successful establishment ..

The clinical impact of macrophage polarity after Kasai portoenterostomy in biliary atresia.

Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called "macrophage polarity." The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course. Thirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed. The M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high (n = 19) and non-high (n = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0-2), the M2 non-high group had a significantly lower native liver survival rate than the high group (p = 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE. Non-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis.

Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia.

Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19 , and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61pg/mL, p <0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145pg/mL, p =0.047), and those subsequently underwent liver transplantation (410 vs. 99pg/mL, p =0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109pg/mL predicted native liver survival (HR: 4.31, p <0.001) also among patients operated <60 days of age (HR: 8.77, p =0.004) or after successful KPE (HR: 6.76, p =0.01). Serum FGF19 correlated positively with increased serum primary bile acids ( R =0.41, p =0.004) and ductular reaction ( R =0.39, p =0.004). Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction.

Biochemical markers to predict the development of gastrointestinal bleeding and esophageal varices after portoenterostomy in biliary atresia

Gastrointestinal bleeding (GIB) due to esophageal varices (EV) is one of the factors that negatively impact native liver survival of patients with biliary atresia (BA). Gastrointestinal fibroscopy (GIF) is usually used to determine the presence of EVs; however, it requires general anesthesia. The aim of this study is to search for markers in blood tests obtained during routine check-ups that can predict the development of GIB. Data of patients with BA who underwent portoenterostomy at our hospital from 2014 to 2020 were retrospectively reviewed. The patients' data were assigned to three groups according to specific time points: Group B, which included data at GIB; Group NB-T, which included data at GIF and EV treatment; and Group NB-NT, which included data at GIF without treatment. The data in Group B were compared to those of other groups. In our study, GIB occurred in 11 patients, and 12 cases and 8 cases were classified into Groups NB-NT and NB-T, respectively. Compared with the other groups, only ChE and M2BPGi in Group B showed statistically significant differences. ChE and M2BPGi are useful for predicting GIB.

Outcomes of late Kasai portoenterostomy in biliary atresia: a single-center experience.

ObjectivesTo describe the clinical, histopathologic, and outcomes data for a cohort of patients with biliary atresia (BA), and to identify the factors affecting survival.MethodsThis was a cross-sectional study of all BA patients diagnosed between 1999 and 2017. Clinical, biochemical, imaging, and histopathologic data were analyzed, and Kaplan–Meier survival rates were compared to identify potential prognostic factors.ResultsWe evaluated 23 patients. The median age at the Kasai procedure was 77 ± 34 days, and the median overall survival was 12.5 ± 65 months. Thirteen (56%) patients survived with their native livers, 3 (13%) received a transplant, and 6 died (26%) while awaiting a transplant. Cholangitis and the use of ursodeoxycholic acid were associated with longer survival, while impaired synthetic function was associated with shorter survival.ConclusionsMost patients presented late for the Kasai procedure. The survival rate with the native liver was comparable to other cohorts. Therefore, clinicians are encouraged to refer for the Kasai procedure even with late presentation (between 60 and 90 days), provided there is no hepatic decompensation.

Hepatic glypican-3 and alpha-smooth muscle actin overexpressions reflect severity of liver fibrosis and predict outcome after successful portoenterostomy in biliary atresia

BackgroundGlypican-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. MethodsLiver 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. ResultsUp-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. ConclusionHepatic overexpressions of glypican-3 and alpha-smooth muscle actin were associated with hepatic dysfunction and the degree of liver fibrosis in biliary atresia.

Divergent expression of liver transforming growth factor superfamily cytokines after successful portoenterostomy in biliary atresia

Pathogenesis of progressive liver fibrosis in biliary atresia after successful portoenterostomy remains unclear. We related hepatic expression of transforming growth factor beta (TGF-β) superfamily cytokines to histologic liver injury after successful portoenterostomy. Enrolled in our study were 28 patients with biliary atresia who had liver biopsies obtained during and after successful portoenterostomy, which normalized serum bilirubin (<20 µmol/l). Biopsies were evaluated for cholestasis, inflammation, ductal reaction, and fibrosis and were stained immunohistochemically for transforming growth factor beta 1, transforming growth factor beta 2, connective tissue growth factor, and decorin. Respective gene expression (TGFB1, TGFB2, TGFB3, CTGF, DCN) was analyzed at follow-up using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results were compared with fibrotic and healthy control livers. After median follow-up of 3.0 years, histologic cholestasis resolved, whereas fibrosis had progressed only in isolated biliary atresia. Liver protein expression of transforming growth factor beta 1 and connective tissue growth factor (P < .001 for both), but not that of transforming growth factor beta 2 or decorin, decreased after successful portoenterostomy, although expression of all four cytokines remained elevated. In accordance with postportoenterostomy changes in protein expression, follow-up ribonucleic acid expression of TGFB2 and DCN, but not that of TGFB1 and CTGF, was upregulated when compared with the controls. Both protein and gene expression of transforming growth factor beta 1 and protein expression of transforming growth factor beta 2, connective tissue growth factor and decorin correlated with METAVIR fibrosis stage. Syndromic patients (n = 12) showed milder fibrosis and lower transforming growth factor beta 1 expression than patients with isolated biliary atresia. These findings support a central role of transforming growth factor beta superfamily in mediating continuing liver fibrogenesis after successful portoenterostomy. Transforming growth factor beta pathway cytokines responded divergently to clearance of jaundice, which was reflected by differential progression of fibrosis between syndromic and isolated patients.

α-Smooth muscle actin expression predicts the outcome of Kasai portoenterostomy in biliary atresia.

Background/Aims:Biliary atresia (BA) is a cholangio-destructive disease of the infant liver presenting with features of obstructive cholangiopathy. The Kasai portoenterostomy (KPE) is the first line of management. The aim of our study was to identify the characteristic features of liver histology in BA that impact the outcome of KPE.Patients and Methods:Data from 30 consecutive children was retrieved from our prospectively maintained database of children undergoing KPE. This included basic demographics, laboratory values and histopathological data from liver biopsy. The stages of fibrosis, presence of ductal plate malformation (DPM), giant cell transformation, extramedullary hematopoiesis and area percentage of α-SMA (α-smooth muscle actin) expression was correlated with jaundice clearance after KPE using standard statistical tests. Native liver survival was computed.Results:Overall, 13 (43%) children cleared jaundice in this series and 10 (33%) are alive with native liver. Lower area percent expression of α-SMA correlated with increased probability of jaundice clearance after KPE (P < 0.001). There was no correlation between stage of fibrosis and jaundice clearance (P = 0.52). DPM, giant cell transformation and extramedullary hematopoiesis did not correlate with outcome. All children who are alive with native liver had lower expression of α-SMA.Conclusion:α-SMA expression may be a potential predictor of jaundice clearance and native liver survival after KPE.

Learning curve of laparoscopic Kasai portoenterostomy for biliary atresia: report of 100 cases

BackgroundLaparoscopic Kasai portoenterostomy (LKPE) is performed for biliary atresia (BA). As LKPE is a technically demanding operation, a learning curve should be defined to guide training. The aim of this study was to identify the learning curve of LKPE for BA.MethodsMetrics of perioperative safety and efficiency for 100 cases of LKPE were evaluated. Outcomes were followed to 67.2 ± 12.1 months. Cumulative sum (CUSUM) analysis was used to identify inflexion point corresponding to the learning curve. Outcome measures included operative time (ORT), rate of clearance of jaundice (CJ) and survival with native liver (SNL).ResultsBetween May 2009 and May 2013, 100 consecutive patients with BA underwent LKPE. The rate of conversion from LKPE to open Kasai portoenterostomy (OKPE), intraoperative transfusion and any perioperative complications was 11, 26 and 16%, respectively. There was no perioperative mortality. The CUSUM analysis revealed a learning curve of 50 for LKPE. Precipitous ORT reductions from an initial mean operative time of 316.3 min that was observed in the first 50 to 232.2 min of the late 50 cases (P < 0.01). Subsequently, cases 1 to 50 were considered ‘early experience’, whereas cases 51 and higher were considered as ‘late experience’ for statistical analysis. The rate of CJ and SNL was significantly higher after the early 50 cases (P < 0.05). In contrast, the rate of intraoperative transfusion, the median time of oral feeding initiated after operation, and the length of hospital stay was not different between the both groups (P > 0.05).ConclusionsIn this experience, improved perioperative and postoperative parameters for LKPE were observed in the last 50 patients when compared with the first 50 patients. The dedicated training is likely to contribute to significantly shorter learning curves in future adopters.

Intravenous immunoglobulin for the treatment of intractable cholangitis after Kasai portoenterostomy in biliary atresia patients.

To assess the efficacy of intravenous immunoglobulin (IVIG) as add-on treatment for intractable cholangitis (IC) after Kasai portoenterostomy (KPE) in biliary atresia (BA) patients. 113 BA patients who had one or more episodes of cholangitis after KPE were recruited in this study. According to whether response to routine conservative treatment, all patients were divided into IC group and simple cholangitis (SC) group. Meanwhile, patients with IC subdivided into IVIG group and control group according to whether application of IVIG. The IC group had higher serum procalcitonin (PCT) (P = 0.014), C-reactive protein (CRP) (P = 0.023), and γ-Gltamyltranspeptidase (γ-GGT) (P = 0.031) level than the SC group. The IVIG group had shorter duration of fever after treatment (P = 0.011) and length of hospital stay (P = 0.018) than the control group. The time until recurrent episode of cholangitis was significant longer in IVIG group than in control group (P = 0.019). IVIG as add-on treatment may be an effective treatment for the cholangitis acute episode, and we conclude by calling for more prospective studies to attest to the role of IVIG in the treatment of cholangitis.

Liver transplantation for deterioration in native liver function after portoenterostomy for biliary atresia in Japan: Short- versus long-term survivors

PurposeWe reviewed our post-Kasai portoenterostomy biliary atresia (BA) patients who required liver transplantation (LTx) for deterioration in native liver (NL) function to investigate mortality in relation to age at LTx. MethodsBA patients indicated for LTx when less than 18years old (U18; n=17) and when 18 or older (18+; n=13) were compared. All achieved jaundice clearance postoperatively (TBil ≤1.2mg/dL (≈20μmol/L)). ResultsIn U18, living-donor (LD) LTxs were performed at a median of 6.1years (range: 0.5–16.7; n=14) and cadaveric (CD) LTxs at a median of 1.3years (1.1–1.5; n=3). In 18+, LDLTxs were performed at a median of 28years (18–37; n=8), and 1 case died from graft versus host disease. CDLTxs were indicated in 5, but 4 died at a median of 30years (26–32), a mean of 1.4years (0.7–1.8) after NL deterioration commenced. One case is awaiting CDLTx. At the time of review, all U18 and 7 LDLTx cases in 18+ were clinically stable. Mortality rates were 0% in U18 and 38% in 18+ (P=.006). ConclusionOur results highlight the extremely grave prognosis for long-term BA patients requiring LTx when 18 or older because of poor donor availability in Japan. Level of evidenceLevel III.

Review of redo-Kasai portoenterostomy for biliary atresia in the transition to the liver transplantation era.

ABSTRACTPortoenterostomy (PE) is the standard therapy for biliary atresia (BA). PE offers the chance of survival to children with BA. PE was the ultimate therapeutic modality for BA before liver transplantation (LT) was available. Failure of biliary drainage with PE was almost invariably fatal in children with BA. In such cases, redo-PE was performed to salvage patients following PE failure. PE remains the standard first treatment for BA despite the availability of LT. Further, redo-PE is also performed in a limited number of cases despite the development of LT as an alternative means of PE. However, there is concern that redo-PE increases morbidity at the time of subsequent LT. Laparoscopic redo-PE has recently been described. Laparoscopic redo-PE is expected to reduce complications of LT by preventing abdominal adhesion associated with repetitive surgery. In the present article, the future utility of redo-PE and the history of its changing roles are reviewed.

Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia.

The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow‐up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme‐linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real‐time reverse‐transcription PCR. Liver expression of MMP‐7 and cytokeratin‐7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP‐7 (29‐fold, p < 0.001), MMP‐2 (3.1‐fold, p < 0.001), MMP‐14 (1.7‐fold, p = 0.007), and TIMP‐1 (1.8‐fold, p < 0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin‐7, expression of MMP‐7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p < 0.001) in relation to controls. BA patients had 6‐fold higher serum levels of MMP‐7 (p < 0.001), which correlated positively with hepatic MMP‐7 gene (r = 0.548, p = 0.007) and protein (r = 0.532, p = 0.007) expression. Patients showed a positive correlation between biliary MMP‐7 expression and Metavir fibrosis stage (r = 0.605, p = 0.001) and portal fibrosis grade (r = 0.606, p = 0.001). Neither similarly increased MMP‐7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure‐associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered hepatic expression of MMP‐7 in the progression of liver fibrosis after successful PE and introduce a potential therapeutic target to pharmacologically extend native liver survival by inhibiting MMP‐7 hyperactivity. Serum MMP‐7 may be a valuable postoperative prognostic tool in BA.

APRi predicts native liver survival by reflecting portal fibrogenesis and hepatic neovascularization at the time of portoenterostomy in biliary atresia

BackgroundAspartate aminotransferase-to-platelet ratio index (APRi) may be useful noninvasive prognostic tool in biliary atresia (BA). We studied whether APRi predicts native liver survival and parallels biochemical and immunohistological signs of liver injury and fibrogenesis at the time of Kasai portoenterostomy (PE). MethodsSerum and liver specimens were obtained at PE from 29 BA patients for liver biochemistry including APRi, histology and immunohistochemical analysis of collagen 1, α-SMA and CD34. APRi values were related to native liver survival and other clinical data as well as serum liver biochemistry, liver histology and immunohistochemistry at PE. ResultsMedian age at PE was 63 (range 7–141) days and median APRi was 0.92 (0.13–6.39). APRi had strong positive correlations with patient age (r=0.684, p<0.001) and biochemical signs of hepatocyte injury and cholestasis. APRi showed no significant correlations with Metavir (r=0.336, p=0.223) or Ishak (r=0.289, p=0.262) global fibrosis scores nor with liver collagen 1 expression (r=0.260, p=0.222). In contrast, portal fibrosis score (r=0.515, p=0.013), predominantly portal α-SMA expression (r=0.519, p=0.015) and amount CD34-positive microvessels in the centrizonal region (r=0.604, p=0.004) correlated positively with APRi. Patients (n=10) who underwent liver transplantation had significantly higher APRi at presentation (1.34 vs. 0.77, p=0.017) compared to those who survived with native liver (n=19). ConclusionsAPRi correlates with portal fibrosis, expression of α-SMA and the amount of CD34-positive microvessels, suggesting that APRi predicts native liver survival by reflecting portal myofibroblastic cell activation, fibrogenesis and associated neovascularization.

Native Liver Histology After Successful Portoenterostomy in Biliary Atresia

Biliary atresia is the most common indication for childhood liver transplantation. The effects of successful portoenterostomy (PE) on native liver histology remain unclear. We assessed changes in native liver histology after a successful PE in relation to liver function and clinical outcomes. In total, 70 native liver biopsies of 44 biliary atresia patients were obtained at PE (n=30), 4.2 years after successful PE (n=23) and 1.1 years after failed PE (n=17), and reviewed for cholestasis, fibrosis, inflammation, and cytokeratin 7 (CK7) immunopositivity (chronic cholestasis). Ten transplant donor livers served as controls. After a successful PE [serum bilirubin 11 (2 to 35) μmol/L at biopsy], histologic native liver cholestasis completely resolved in 83% of the patients and portal inflammation significantly decreased. Nevertheless, enhanced fibrosis [Metavir stage 2 (1-4) vs. 4 (1-4)], bile duct proliferation [grade 2 (1-2) vs. 1 (0-2)], and periportal CK7 immunostaining [grade 1 (0-2) vs. 1 (0-4)] persisted in 100%, 87%, and 61% of subjects, respectively. Metavir fibrosis stage corresponded cirrhosis (stage 4) in 52% of the patients, associated with the presence of portal hypertension, and correlated with serum-conjugated bilirubin (r=0.601, P=0.002), bile duct proliferation (r=0.657, P=0.001), and CK7 positivity (r=0.657, P=0.001). Aspartate transferase to platelet ratio index predicted native liver fibrosis and development of esophageal varices. The degree of fibrosis and portal inflammation at PE were unrelated to native liver survival. Despite resolution of cholestasis and decreasing inflammation, bile duct proliferation, periportal CK7 immunostaining, and fibrosis persist after successful PE. Fibrosis is associated with biochemical cholestasis, bile duct proliferation, CK7 immunopositivity (chronic cholestasis), and development of portal hypertension.

Serial ultrasound findings associated with early liver transplantation after Kasai portoenterostomy in biliary atresia

To investigate the ultrasound findings associated with early liver transplantation (LT) after Kasai portoenterostomy (Kasai) in children with biliary atresia (BA). Children with BA (n = 30) who underwent Kasai were classified into early LT group (n = 17, LT within 1 year after Kasai) and Kasai alone group (n = 13, alive with their native livers). Serial ultrasound (baseline and follow-up before LT or post-Kasai 1 year) images were reviewed to investigate significant ultrasound findings related to early LT using both univariate and multivariate models. Images were reviewed focusing on the hepatic artery diameter, portal vein diameter, and signs of portal hypertension. The hepatic artery diameters in the early LT group were significantly larger than those in the Kasai alone group both at baseline (p = 0.007) and follow-up ultrasound (p < 0.001). The portal vein diameters on follow-up ultrasound were smaller in the early LT group than the Kasai alone group (p < 0.001). On multivariate analysis, baseline hepatic artery diameter (hazard ratio, 20.4; 95% confidence interval, 3.7-110.6; p < 0.001) and the presence of splenomegaly at follow-up ultrasound (17.7; 2.6-121.8; p = 0.004) were significant predictors associated with early LT. The optimal cut-off value of the baseline hepatic artery diameter was 1.9 mm (82% sensitivity and 77% specificity). Enlarged hepatic artery at baseline ultrasound and the presence of splenomegaly at follow-up ultrasound were associated with early LT after Kasai in children with BA.

A rare complication in an adult patient after Kasai portoenterostomy for biliary atresia

Kasai portoenterostomy has significantly prolonged the survival of patients with biliary atresia not undergoing liver transplantation. However, patients develop complications at some point during their life. The development of hepatocellular carcinoma is a very rare complication and has never been reported till date in the adult population. We report a case of development of hepatocellular carcinoma in a patient who had the Kasai procedure done for biliary atresia. It can pose a diagnostic and therapeutic challenge to physicians and delay in diagnosis is common in such patients, which can lead to grave consequences. We suggest that strict recommendations be made to avoid delays in the diagnosis of hepatocellular carcinoma, by intensifying screening in this group of patients by optimum use of magnetic resonance imaging (MRI).

Reappraising the portoenterostomy procedure according to sound physiologic/anatomic principles enhances postoperative jaundice clearance in biliary atresia

The portoenterostomy (PE) procedure for treating biliary atresia (BA) has been so repeatedly modified that it currently hardly resembles Kasai's original PE (KOPE). Now PE involves an extended lateral dissection and a wide anastomosis (extended PE: EPE). We reappraised KOPE and created our-KOPE (OKOPE) by adhering strictly to its principles and techniques. We compared outcome of EPE and OKOPE. We reviewed 24 consecutive cases of PE for BA performed at our institution from 2005 to 2011. Thirteen had EPE, and 11 had OKOPE. Body weight, serum total bilirubin, age at PE, total steroid dosage required for jaundice clearance (JC: total bilirubin ≤1.2 mg/dL), JC ratio, time taken for JC, survival rate with the native liver (SNL), and SNL after JC (SNL + JC) were compared at 16 months (shortest mean follow-up). Postoperative management protocols were identical for both groups. The JC ratio was significantly higher for OKOPE (90.9%) than EPE (46.2%) (p = 0.02). Both SNL and SNL + JC were significantly higher for OKOPE (90.9 and 72.7%) than EPE (30.8 and 30.8%) (p = 0.003 and p = 0.04, respectively). All other variables were similar for both groups. Jaundice clearance following OKOPE would appear to be better than after EPE.

The outcome of laparoscopic portoenterostomy for biliary atresia in children

There were only a few reports on laparoscopic portoenterostomy for biliary atresia in children. We report our experience on laparoscopic Kasai operation for biliary atresia. A retrospective review of all children who had biliary atresia underwent laparoscopic portoenterostomy from January 2002 to September 2006 were included and analyzed. Sixteen children (five boys and eleven girls) with a mean age of 66 days (range 47-106 days) at operation were included in this study. All patients had type III biliary atresia. There was no conversion to open procedure. The operative time ranged from 193 to 435 min (mean 292 min). At a median follow-up of 72 months (range 33-89 months), eight patients were free of jaundice with bilirubin level <20 μmol/L and did not require liver transplantation. Seven patients underwent liver transplantation. One patient who had persistent elevated bilirubin defaulted follow-up. One patient complicated with volvulus of intestine post-operatively. All patients survived except one patient who had combined liver and intestine transplantation. Laparoscopic portoenterostomy in children with biliary atresia is technically feasible. 50% of children who had type III biliary atresia were free of jaundice and did not require liver transplantation. A longer follow-up is required to assess the long-term outcome.

Surrogate markers of cholesterol metabolism in children with native liver after successful portoenterostomy for biliary atresia

Purpose Cholestasis gradually ensues after portoenterostomy for biliary atresia (BA) and may deteriorate liver function. Cholesterol metabolism and its relationships with serum markers of liver function were evaluated in children living with native liver after successful portoenterostomy for BA. Subjects and methods Serum lipids, noncholesterol sterol ratios to cholesterol, that is, surrogate markers of cholesterol metabolism, and liver function were cross-sectionally studied in 17 consecutive children after successful (postoperative bilirubin <20 μmol/L) portoenterostomy for BA with native liver and a mean age of 5.2 years. The results were compared with healthy age-matched controls. Results Mean serum total and low-density lipoprotein cholesterol and campesterol ratio were 18%, 43%, and 26% less than those of controls, respectively ( P < .01 for all). Despite low serum cholesterol and campesterol (marker of cholesterol absorption) levels, serum lathosterol (marker of cholesterol synthesis) was decreased by 34% ( P < .0001) from control levels and reflected serum prealbumin ( r = 0.666) and cholestanol ( r = −0.515, P < .05 for both). Cholestanol, twice higher than those of controls ( P < .0001), reflected abnormally high serum alkaline phosphatase, glutamyl transferase, and bile acids ( r = 0.558-0.711, P < .05). Serum campesterol was inversely related with lathosterol ( r = −0.238, P < .05) in controls, but not in patients ( r = −0.039). Conclusion Children living with native liver after portoenterostomy for BA are inclined to low serum concentration and absorption of cholesterol. Cholesterol homeostasis was disturbed so that low cholesterol absorption was not associated with compensatory increase in cholesterol synthesis that decreased together with worsening of cholestasis.