Histologic oddities at the porta hepatis in biliary atresia

Purpose

Highly unusual histologic findings at the porta hepatis in 3 infants who underwent Kasai portoenterostomy for biliary atresia are reported.

Methods

Portoenterostomy was performed using a standard operative technique. Serial transverse sections of the excised portal plate were examined by light microscopy along with sections from the distal extrahepatic biliary remnants, gallbladder, and liver biopsy.

Results

Of 61 consecutive infants who underwent Kasai portoenterostomy for biliary atresia, 3 were found to have highly unusual histologic features at the porta hepatis. All had type 3 biliary atresia. Two had hilar biliary ductules lined in part by squamous epithelium, and the third had a focus of mature hyaline cartilage surrounded by perichondrium adjacent to biliary ductules. In each case, these unusual histologic features were localized to the porta hepatis in the region of the transected portal plate.

Conclusions

The presence of hyaline cartilage at the portal plate is likely to be an expression of defective morphogenesis, thus supporting the concept of disordered embryogenesis in the etiology of biliary atresia. Squamous epithelium within biliary ductules might also reflect a similar mechanism but could alternatively be an unusual metaplastic response to inflammation at this site.     

Significance of ductal plate malformation in the postoperative clinical course of biliary atresia

Purpose

Ductal plate malformation (DPM) is one of the etiologic theories for the development of biliary atresia (BA). In this study, we investigated the significance of DPM in the postoperative clinical course of BA, especially as a predictive factor of jaundice clearance.

Methods

Between 1988 and 2005, 31 patients with uncorrectable BA underwent hepatoportoenterostomy and steroid therapy. Immunohistochemistry was used to characterize biliary structures using cytokeratin 19. Specimens were defined as DPM-positive if a concentric cellular arrangement was detected. This retrospective study included comparisons of preoperative characteristics, the postoperative jaundice period, and cumulative steroid doses between patients with and without DPM.

Results

Of the 31 patients with uncorrectable BA, 25 (80.6%) became jaundice-free. Ductal plate malformation was detected in 11 (35.5%) of the 31. Between the 2 groups, there were no differences in preoperative characteristics or in the postoperative jaundice-free rate. Among those who became anicteric, the postoperative jaundice period was 145.3 ± 69.9 days in the DPM-positive group (n = 9) and 81.8 ± 44.7 days in the DPM-negative group (n = 16) (P < .05). The total administered steroids were 149.7 ± 78.2 and 95.0 ± 60.2 mg/kg, respectively (P = .09).

Conclusion

Ductal plate malformation may disturb bile flow and require more steroid to improve bile drainage. Therefore, the presence of DPM in the liver predicts poor bile flow after hepatoportoenterostomy in infants with BA.     

The spectrum of surgical jaundice in infancy

Background

Conjugated jaundice arising during infancy may be caused by a number of different surgical conditions. The aim of this study was to compare clinical features, management, and outcome of all types of surgical jaundice presenting in the first year of life.

Methods

A retrospective review was conducted of all infants born in the United Kingdom with jaundice caused by a surgical cause referred to the authors’ institution from January 1992 to December 1999.

Results

There were 171 infants who could be separated into 3 specific groups: biliary atresia (BA, n = 137), inspissated bile syndrome (IBS; n = 14), and choledochal malformation (CM; n = 12) together with a group containing various miscellaneous conditions (n = 8). Infants with BA had higher bilirubin (P < .01) and aspartate aminotransferase levels (P < .001) and came to surgery earlier (P < .01) than infants with either IBS or CM. Infants with IBS and CM were more likely to be premature and have other malformations, respectively. Ultrasound scan was the principal investigation in the differentiation of BA from other causes of jaundice. Accurate prelaparotomy diagnosis was made by percutaneous liver biopsy in 87% of cases later shown to be BA. Currently, 88 (64%) of children with BA are alive with their native liver postportoenterostomy, 4 have died, and 45 have undergone liver transplantation (with 1 death postoperatively). A policy of primary portoenterostomy for BA followed by transplantation, if necessary, resulted in a survival rate of over 95%. All children in the other diagnostic groups are alive and anicteric after appropriate surgical intervention.

Conclusions

Approximately 80% of infants presenting with surgical jaundice have biliary atresia, whereas those with inspissated bile syndrome and choledochal malformations make up most of the remainder. Mortality in this age-group is confined to infants with BA, but even on these infants an overall survival rate of greater than 95% is currently expected.     

Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease

Purpose

Gallstone formation is a common problem in neonates on prolonged courses of total parenteral nutrition (TPN). The authors hypothesized that the use of cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would prevent gallstone formation in a high-risk group of patients with TPN.

Methods

A prospective, randomized, blinded, controlled trial of neonates who were on a prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to receive CCK vs placebo. Patients remained on the study until taking more than 50% of energy enterally. Children were recalled between 2 and 4 years after completing TPN for ultrasonographic examination of their hepatobiliary tree.

Results

Neonates (38 studied) required a mean (±SD) of 33 ± 16 days of TPN. Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was not effective in preventing the formation of gallstones (3 stones in infants receiving CCK, P = .51). Diagnosis (P = .56), birth weight (P = .54), gestational age (P = .18), and duration of TPN (P = .53) did not correlate with gallstone formation. To address the management of these stones, all 4 were placed on a prolonged course of ursodeoxycholic acid (mean duration, 11.6 ± 5.4 months). Two additional infants (not in the original study) with TPN-associated gallstone disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were performed every 6 months. No patient achieved any degree of stone dissolution. One patient underwent cholecystectomy for symptomatology.

Conclusions

Total parenteral nutrition-associated gallstones were detected in 10% of children, and most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not effective in preventing TPN-associated gallstones. In addition, the use of ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods will be needed to address the prevention and treatment of these stones.     

Cystic biliary atresia: an etiologic and prognostic subgroup

Introduction

Cystic biliary atresia (CBA) is an uncommon variant of biliary atresia (BA) in which prognosis may be relatively favorable but liable to misdiagnosis as choledochal cyst, and potentially offers insights into the etiology of BA. Because some cases can be detected antenatally, CBA in general may have its origins in utero life. We assessed our experience with CBA.

Methods

Single-center retrospective review of infants with CBA over a 13-year period (January 1994 to December 2006) was done. Data are given as medians (range).

Results

Of 270 infants with BA, 29 (9 male) were identified as CBA. Antenatal ultrasonography had detected an abnormality in 12 (41%) infants at a median of 22 weeks (17-34 weeks) of gestation. All infants underwent postnatal excision and Kasai portoenterostomy (KP). Those with antenatally detected CBA came to surgery younger (36 [14-67] vs 48 days [35-147 days], P = .004). Twenty cysts (69%) had a fibroinflammatory wall with no biliary epithelial lining and 6 (26%) contained bile. Age at KP was significantly and positively correlated (r = 0.46, P = .01) with liver fibrosis, as assessed in liver biopsy materials obtained at KP, but not with grade of “hepatocyte disarray” (P = .74). Twenty infants (69%) cleared their jaundice (bilirubin <20 μmol/L) within 6 months after KP. Age at KP markedly affected outcome.

Conclusion

Cystic BA is a clinically distinct variant of BA. Despite onset in prenatal life, earlier than presumed for isolated BA, it has a better prognosis, particularly with early surgery.     

Glucocorticoid receptor alpha expression in the intrahepatic biliary epithelium and adjuvant steroid therapy in infants with biliary atresia

Background/Purpose

In patients with cirrhosis, proinflammatory cytokines increase progressively in relation to the severity of liver dysfunction. Proinflammatory cytokines regulate the expression of glucocorticoid receptors (GcRs). On the other hand, GcRs mediate the effects of glucocorticoid steroids on bile excretion in the biliary epithelium. Glucocorticoid receptors have 2 isoforms: a cytoplasmic glucocorticoid receptor α (GcRα) mediates thier physiological effects, whereas a nuclear localized glucocorticoid receptor β (GcRβ) acts as a dominant negative inhibitor of GcRα activity. We examined the histology features of liver biopsy and the expression of GcRα in the intrahepatic biliary epithelium in infants with biliary atresia.

Patients/Methods

The patients were divided into 2 groups: patients in group 1 (n = 17) had a total bilirubin level below 1.0 mg/dL at least once after surgery, whereas patients in group 2 (n = 14) has never had bilirubin level below 1.0 mg/dL postoperatively. Liver biopsies taken from 31 infants with biliary atresia at the time of hepatic portoenterostomy between 1988 and 2002 were examined for immunohistochemistry and histology with H&E staining. The degree of GcRα expression in the biliary epithelium was semiquantitatively analyzed using staining scores. The histology features of the liver biopsy were also semiquantitatively analyzed by using the same scores to evaluate the liver injury. Intravenous prednisolone dosage was started with 4 mg/kg per day and tapered by a half dose every 2 days. The protocol was orally repeated during admission until the stool became constantly cholic. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient by rank. Significance is set at a 95% confidence interval (P < .05).

Results

There was a significant positive correlation between the liver histology and the GcRα scores in all patients with biliary atresia (P = .0128; r = 0.429). In group 1, there was a significant positive correlation between the GcRα expression scores and the total dose of prednisolone administered (P = .0063; r = 0.767).

Conclusions

The increase and degree of GcRα expression were associated with the severity of liver injury and may correlate with the dose of prednisolone required to sustain bile flow after successful hepatic portoenterostomy.     

Congenital biliary atresia: liver injury begins at birth

Background

The timing of onset of liver injury in biliary atresia (BA) is not known, although in approximately 10% of cases, biliary pathologic condition associated with the biliary atresia splenic malformation syndrome must begin well before birth.

Methods

The study involved retrospective case-note review for infants with definite BA who underwent laparotomy within first week of life.

Results

Three infants were identified who had occlusive BA evident on the first day of life. In all cases, their liver was grossly normal, and histologic changes were trivial.

Conclusion

This suggests that the detrimental cholestatic liver injury, later characteristic of BA, only begins from the time of birth despite a prenatal occlusive biliary pathology. It may be that tissue injury only occurs with the onset of the perinatal bile surge initiating periductal bile leakage and the triggering of an inflammatory and ultimately fibrotic response.     

Kasai portoenterostomy: 12-year experience with a novel adjuvant therapy regimen

Aim

The role of adjuvant therapy with corticosteroids and choleretics after Kasai portoenterostomy for biliary atresia (BA) remains uncertain. Experience with a novel postoperative adjuvant therapy regimen is reported.

Methods

Between 1994 and 2006, 71 infants with BA were referred. Four died from uncorrectable congenital heart disease/cardiorespiratory failure without undergoing portoenterostomy, 7 underwent primary liver transplantation (3 referred ≥19 weeks of age), and 60 underwent portoenterostomy at a median of 51 (10-104) days. Of these, 55 (92%) had type 3 BA and 6 had the BA splenic malformation syndrome. Fifty (83%) received the following adjuvant therapy beginning on postoperative day 5: oral dexamethasone 0.3 mg/kg bd for 5 days, 0.2 mg/kg bd for 5 days, and 0.1 mg/kg bd for 5 days together with oral ursodeoxycholic acid 5 mg/kg bd and phenobarbitone 5 mg/kg nocte, both of which were continued for 1 year. All infants received routine perioperative prophylactic antibiotics.

Results

Overall, 42 of 60 (70%) infants cleared their jaundice (bilirubin <20 μmol/L): 38 of 50 (76%) with the dexamethasone/ursodeoxycholic acid regimen compared with 4 of 10 (40%) not receiving this adjuvant treatment. There were 4 late deaths after portoenterostomy: 2 from associated congenital disorders and 2 after liver transplantation. Of the remaining 56 children, 39 (70%) are currently alive with their native liver at a median follow-up of 3.3 years and 17 are alive after liver transplantation. Surgical complications occurred in 3 after portoenterostomy: adhesive bowel obstruction (2) and an anastomotic leak. One infant had gastrointestinal bleeding that may have been related to dexamethasone, but this resolved with ranitidine. There were no perioperative septic complications.

Conclusion

In this series, adjuvant postoperative treatment with a short course of oral dexamethasone and longer-term ursodeoxycholic acid significantly improved the outcome after Kasai portoenterostomy.     

Hepatobiliary scintigraphy after Kasai procedure for biliary atresia: clinical correlation and prognostic value

Background/Purpose

Kasai portoenterostomy (KP) is regarded as first-line treatment for biliary atresia, although its postoperative course is often unpredictable. Hepatobiliary scintigraphy using technetium-labeled iminodiacetic acid derivatives offers a dynamic, objective assessment both of parenchymal liver function and restored biliary excretion. The value of postoperative radionuclide scans was assessed prospectively in a large population of post-KP infants.

Methods

Radionuclide scans consisted of an intravenous dose of 20 MBq of ^99mTc mebrofenin iminodiacetic acid and subsequent gamma camera imaging. Four scan variables were evaluated: the hepatic extraction fraction (HEF; ie, initial liver uptake divided by the peak vascular uptake), the half-life of tracer excretion (TEX), the shape of the excretion curve, and the presence of activity in the Roux loop at 4 hours postinjection. All infants had type 3 biliary atresia with a median age at KP of 59 days (24-120 days). To assess predictive value, outcome (clearance of jaundice and need for transplant) was assessed at 6 months (for 1-week scan) and 2 years (for 6-month scan).

Results

Eighty-seven infants underwent a radionuclide scan at 1 week post-KP. The median HEF was 34% (10%-90%). No relationship could be identified between HEF (P = .2) or excretion curve shape (P = .9) and outcome (at 6 months), and there were too few examples of a measurable TEX to allow meaningful comparison. The only predictive element at this time point was Roux loop activity (positive predictive value, 79%; negative predictive value, 53%; for “good” isotope bowel activity).Forty-four infants completed a second scan at 6 months. Median HEF increased from a baseline of 37% (11%-90%) to 64% (8%-100%) (P < .0001), although there was no significant intercorrelation (P = .12). The most predictive variables (of outcome at 2 years) were curve shape (positive predictive value, = 95%, negative predictive value, 82%) and TEX, and the least predictive was now Roux loop activity.

Conclusions

Early (at 7 days) hepatic scintigraphy is not predictive of poor outcome in general, although Roux loop activity does indicate later success. Later hepatic scintigraphy (at 6 months) allows a detailed assessment of dynamic liver function with biliary excretion variables predictive of outcome in the medium term.     

A population-based study of the outcome after small bowel atresia/stenosis in New South Wales and the Australian Capital Territory, Australia, 1992-2003

Purpose

The purpose of the study was to describe the incidence, epidemiology, and survival of infants with small bowel atresia/stenosis in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia.

Methods

A population-based cohort study was conducted of infants diagnosed with small bowel atresia/stenosis in NSW and the ACT from 1992 to 2003. Data were obtained from the prospectively collated NSW and ACT Neonatal Intensive Care Units' data collection. Individual risk factors for mortality were assessed using the χ² test.

Results

The incidence of small bowel atresia/stenosis in NSW and the ACT was 2.9 per 10,000 births. Of 299 infants identified with small bowel atresia, 13 were stillborn. Of the 286 live born infants, most (52%) were delivered preterm (<37 weeks' gestation) with an 87% survival, whereas 48% were term with a 98% survival. More than half the infants (54%) had an associated birth defect. The overall mortality was 8%. Prematurity and low birth weight were identified as independent risk factors for mortality (P < .001).

Conclusions

This study of small bowel atresia/stenosis provides population-based outcomes for clinicians and families. It is important to investigate infants with small bowel atresia for associated birth defects. Although the mortality rate has decreased over the last 50 years, it remains substantial at 8% and is higher in premature and low birth weight infants.     

Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach

Introduction

Staging systems have been developed to predict survival after resection of hilar cholangiocarcinoma. Notably, they have not been validated nor compared for relative predictive ability.

Methods

Forty-two patients underwent resection of hilar cholangiocarcinoma and have been followed through a prospectively collected database. The tumors were staged using the Bismuth-Corlette, Blumgart, and American Joint Committee on Cancer (AJCC) systems, and a significant relationship with survival was sought.

Results

Eleven patients were treated by extrahepatic biliary resection alone, while 31 required extrahepatic biliary resections with in-continuity hepatic resections. All patients underwent adjuvant therapy. To date, 30 patients have died with a mean survival time of 30 months ± 35.0 (SD). Twelve patients are alive with a mean survival of 90 months ± 61.8. By regression analysis, none of the staging systems had a significant relationship with survival (Bismuth: P = .64; Blumgart: P = .66; AJCC: P = .31).

Conclusions

Most patients with hilar cholangiocarcinoma require in-continuity hepatic resections. Survival after resection promotes an aggressive approach, with cure in as many as 30%. Staging systems should not impact the decision to operate or postoperative management, as all tumors should be aggressively resected and all patients should receive adjuvant treatment.     

Analysis of donor risk factors associated with graft outcomes in orthotopic liver transplantation

Background

In orthotopic liver transplantation (OLT), the critical shortage of organ donors is the reason for accepting marginal donors. Although the outcome of OLT does not entirely seem to have been affected by the use of such donors identification of predictive risk factors is challenging. This study sought to identify significant risk factors associated with graft outcomes in our institute.

Methods

We retrospectively analyzed donor-associated factors for recipients who underwent liver transplantation from January 2002 to December 2009 for displaying primary dysfunction (PDF) as primary nonfunction (PNF) and initial poor function (IPF).

Results

We examined 97 post-liver transplant patients (male:female 70:27) whose average age was 52.74 years. The majority of indications for OLT were hepatitis B and/or C cirrhosis, alcoholic cirrhosis, and hepatocellular carcinoma. The incidence of PDF was 31.9% (31/97) including 7.2% PNF (7/97) and 24.7% IPF (24/97), versus 68.1% (66/97) with immediate function. The donors last serum alanine aminotransferase value being more than 65 IU/L was the only risk factor for poor graft function (P = .034). Donor peak and last serum sodium were potential risk factors.

Conclusion

Although many factors including a high serum sodium level are associated with a marginal liver graft, Last donor alanine aminotransferase level was the only significant factor that predicted the PDF.     

Enteral granulocyte colony-stimulating factor for the treatment of mild (stage I) necrotizing enterocolitis: a placebo-controlled pilot study

Background/Purpose

The presence of granulocyte colony-stimulating factor (G-CSF) in human milk and the expression of G-CSF receptors on intestinal villous enterocytes of neonates suggest that G-CSF has a role in the development and integrity of the gastrointestinal tract. We hypothesized that enteral recombinant human G-CSF (rhG-CSF) given to preterm infants with necrotizing enterocolitis (NEC) in the earlier stages could protect against disease progression and complications.

Methods

Preterm infants with mild (stage I) NEC (n = 18) were assigned to receive enteral rhG-CSF (n = 8) or placebo (n = 10) for 5 days from the first day of the diagnosis. Clinical and gastrointestinal parameters were followed during the whole period of hospitalization.

Results

In the study group, none of the infants with stage I NEC had a clinical progression to stage II or III, whereas in the control group, 5 (50%) infants with stage I NEC had a disease progression to stage II or III (P < .05). In the study group, the time required for the resolution of clinical and radiological findings of NEC and the total duration of systemic therapy and hospitalization were significantly shorter than the control group (P < .001).

Conclusion

Enteral rhG-CSF treatment could prevent the progression of mild (stage I) NEC to further stages and decrease the time required for the resolution of clinical and radiological signs of the disease.     

Comparison of drainage techniques for biliary atresia

Purpose

Traditional Kasai portoenterostomy and porto-appendiceal duodenostomy have been utilized for biliary atresia. Differences in outcome between patients who underwent either Kasai portoenterostomy or porto-appendiceal duodenostomy were compared.

Methods

A review of all children who underwent a drainage procedure for biliary atresia from 1986 to 2000 (n = 30) was performed. Age at drainage procedure, subsequent liver transplantation, and outcomes were evaluated. Outcome variables included success rates (total bilirubin < 2.0 mg/dL) and survival rate. Statistical analysis was done with χ² and Student’s t test.

Results

Long-term follow-up was available on 28 of 30 patients. Age at biliary drainage was insignificant. Success rates between porto-appendiceal duodenostomy (31%) and Kasai portoenterostomy (82%) were statistically significant. Survival rate for patients who underwent a Kasai portoenterostomy was 10 of 11 patients. Survival rate for patients who underwent porto-appendiceal duodenostomy was 14 of 16 patients. Overall survival rate was comparable between porto-appendiceal duodenostomy (88%) and Kasai portoenterostomy (91%).

Conclusions

Although overall survival rate was comparable, patients who underwent porto-appendiceal duodenostomy were less successful in alleviating hyperbilirubinemia compared with Kasai portoenterostomy. This is shown further by the greater incidence of subsequent liver transplantation in infants with prior porto-appendiceal duodenostomy. Although the appendix may serve as an alternative biliary conduit, traditional Kasai portoenterostomy appears to achieve better biliary drainage.     

Biliary atresia--a fifteen-year review of clinical and pathologic factors associated with liver transplantation

Purpose

The aim of this study was to identify clinical and pathologic factors associated with liver transplantation in infants with biliary atresia initially treated with Kasai hepatic portoenterostomy (KHPE).

Methods

Institutional Review Board approval was obtained. Records of patients with biliary atresia diagnosed between January 1986 and December 2000 were reviewed. Patients were divided into those who never required transplantation, those who underwent transplant in the first year after KHPE, and those who required transplantation later in childhood. Analysis of variance (ANOVA) compared multiple factors among the 3 groups. Proportional analysis compared those who required transplantation against those who did not. Statistical significance was considered achieved if P was less than .05.

Results

Forty-five patients were identified. Survival after KHPE was 96% (43 of 45). Sixteen (37%) never required transplantation, 13 (30%) underwent transplant within 1 year after KHPE, and 14 (33%) underwent transplant more than 1 year after KHPE. ANOVA comparison showed that the duration of jaundice before KHPE as a predictor for liver transplantation approached significance (P = .082). Proportional analysis found that a longer initial duration of jaundice before KHPE (P = .016) and failure to establish biliary flow (P = .033) were also significant predictive factors. An initial requirement for phototherapy (P = .057) and ductules less than 200 μm in diameter (P = .060) showed a trend toward predictor of liver transplantation.

Conclusions

A longer duration of jaundice before KHPE, failure to establish bile flow, requirement for phototherapy in the neonatal period, and ductules smaller than 200 μm are associated with liver transplant after KHPE.     

Antenatal diagnosis of bowel dilatation in gastroschisis is predictive of poor postnatal outcome

Purpose

Although gastroschisis infants usually have a good outcome, there remains a cohort of babies who fare poorly. We inquired whether the presence of bowel dilatation in utero is predictive of postnatal course in infants with gastroschisis.

Methods

We compared the clinical course of infants who had bowel dilatation with those who did not. Bowel dilatation was defined as more than 20 mm in cross-sectional diameter on ultrasound at any gestational age. Outcome measures used were length of time of parenteral nutrition, death, and surgery for intestinal failure.

Results

A review of 170 infants with gastroschisis identified 74 who had dilatation of more than 20 mm (43.5%). There was no significant difference in the incidence of intestinal atresia in those with bowel dilatation and those without (P = .07). Those with bowel dilatation spent a longer period on parenteral nutrition. There were significantly more deaths in the group with bowel dilatation (P = .01). There was no significant difference in the number of infants requiring surgery for intestinal failure between the 2 groups (P = .47).

Conclusions

We found that sonographically detected bowel dilatation more than 20 mm in utero in fetuses with gastroschisis may have value in predicting clinically significant adverse postnatal outcomes.     

The extent of biliary proliferation in liver biopsies from patients with biliary atresia at portoenterostomy is associated with the postoperative prognosis

Background/Purpose

In biliary atresia (BA), a derangement in the biliary system remains, despite portoenterostomy performance. Many factors can influence the disease progression rate. This study aimed to analyze the association between biliary proliferation extent in biopsies from BA patients and postoperative prognosis.

Methods

Biliary proliferation was evaluated by a morphometric analysis of the cytokeratin 7 positivity percentage (PCK7) in wedge liver biopsies from 47 BA patients. The extent of fibrosis was evaluated by a fibrosis score (FS). The outcome 1-year native liver survival was correlated, using a multivariable regression analysis, with PCK7, FS, and age at portoenterostomy.

Results

The PCK7 ranged between 0.80% and 14.79% (M ± SD = 7.36% ± 4.15%). Patients who died or underwent transplantation had higher PCK7 than survivors with their native livers (P < .001). The area under the receiver operating characteristic curve for PCK7 in relation to the outcome was 0.845 (P < .001). The cutoff point of PCK7 for the maximal effect on postoperative prognosis was 10.18% (sensitivity = 0.71, specificity = 0.88). The PCK7 was the only studied variable associated with 1-year native liver survival, independently of age and FS (P = .002).

Conclusion

The extent of biliary proliferation at portoenterostomy, evaluated by PCK7, was associated with 1-year native liver survival of BA patients.     

The inv mouse as an experimental model of biliary atresia

Background/Purpose

The causation of biliary atresia (BA) remains unclear. However, ductal plate malformation (DPM), maldevelopment of the intrahepatic bile ducts, is 1 of the preferred theories. The inv homozygous mouse (inv mouse), created by insertional mutagenesis, shows situs inversus and jaundice. This study investigated whether the inv mouse could be an experimental model of human BA.

Methods

In the inv mice (n = 12) and wild-type littermates (n = 12), we examined the liver function and morphologic changes in the biliary tract through serum biochemical study and morphological study.

Results

The level of serum total and conjugated bilirubin in the inv mouse was 8.1 ± 3.8 and 4.4 ± 2.4 mg/dL, respectively, significantly higher than in the wild type. Macroscopically, 11 (92%) of 12 inv mice had situs inversus, and 3 (25%) of 12 mice had preduodenal portal vein. Histologically, the continuity of the extrahepatic bile duct was preserved. However, DPM, showing proliferative biliary epithelium around the intrahepatic portal vein, was found in the liver of the inv mouse.

Conclusion

In the inv mouse, the pathologic changes in DPM were found in the intrahepatic biliary system, which were observed in some clinical cases of BA. Therefore, the intrahepatic biliary system of the inv mouse could be an experimental model of human BA with DPM.     

Medial thickening of hepatic artery branches in biliary atresia. A morphometric study

Background/Purpose

Medial layer hypertrophy of hepatic arterial branches may be associated with biliary atresia (BA) pathogenesis. This study aimed at evaluating medial layer thickness in hepatic arterial branches at portoenterostomy and liver transplantation.

Methods

The authors evaluated 1274 arterial branches both in BA cases and in control subjects involving a total of 1108 arterioles and 166 arteries. Arterial branch characteristics were morphometrically evaluated in 47 BA patients at the time of portoenterostomy. Controls were patients with intrahepatic cholestasis (n = 3), immature neonates (n = 7), and infants (n = 7) without liver disease. Progression of medial layer thickening between the time of portoenterostomy and transplantation was evaluated in 7 BA patients. Biliary atresia patients at the time of transplantation were compared with non-BA-transplanted patients (n = 4).

Results

The arterial medial layer of BA cases at portoenterostomy was thicker than that of infants without liver disease (P = .03). The arterial medial thickness increased during the interval between portoenterostomy and transplantation (P = .05). Arterioles and arteries with thickened medial layers were found in transplanted BA patients but not in patients transplanted for other liver diseases (P = .05 and P = .01). Thickening of the medial layer of the hepatic arteries was associated with focal distribution of interlobular bile ducts in portal spaces in BA (P = .02).

Conclusions

In BA, there is a progressive thickening of the arterial medial layer, suggestive of vascular remodeling, which is associated to the disappearance of interlobular bile ducts.     

Successful liver transplantation across the ABO incompatibility barrier in 6 cases of biliary atresia

Background

The problem of ABO-incompatible liver transplantation still remains unsolved in older children. In this article, we report on our experience of 6 successful ABO-incompatible liver transplantations in patients with biliary atresia.

Material and Methods

Six patients (ABO incompatibility type A→O:1 case, B→O:2 cases, A→B:3 cases) were enrolled in this study; 3 patients were aged approximately 1 year and the other 3 ranged in age from 9 to 24 years at the time of transplantation. Each patient received perioperative plasma exchange, until the anti-donor blood-type antibody titers became less than 1:16, and also systemic multidrug immunosuppressive therapy (cyclophosphamide, prednisolone, and tacrolimus). We applied the protocol of intraportal infusion therapy (local administration of prostaglandin E₁, steroid, and gabexate mesilate via a portal vein catheter), splenectomy, and rituximab administration for the older group.

Results

Both the patient and graft survival rates remain at 100%, with the follow-up period of the patients ranging from 12 and 123 months. Acute cellular rejection occurred in 2 cases, and both were steroid sensitive. There was no incidence of humoral rejection. Although all cases developed viral infection, all recovered uneventfully with the administration of antiviral agents.

Conclusion

ABO-incompatible liver transplantation can be performed with a low risk of humoral rejection or late biliary complications using this combined antirejection strategy, even in older children.