Implication of early‐onset biliary atresia and extrahepatic congenital anomalies

Background: The aim of the present study was to determine the rate of early‐onset biliary atresia (BA) and its implications, for embryonic‐type BA in Taiwan, a high‐prevalence area for BA. The relationship between the timing of disease onset and congenital extrahepatic anomalies was also identified. Methods: Medical records of 130 infants born in Taiwan with biliary atresia between January 1996 and December 2005 were reviewed retrospectively. The gold standard for the diagnosis of biliary atresia was intraoperative cholangiography. As well as medical records review, abdominal imaging and echocardiograms were performed to determine other structural anomalies. Early‐onset BA was defined as acholic stool and cholestatic jaundice observed before 2 weeks of age. Results: On review of onset of acholic stool and cholestatic jaundice before 2 weeks of age, 31 patients (23.8%) were defined as having early‐onset BA. Twenty patients (15.4%) had major congenital extrahepatic anomalies. One (0.7%) had biliary atresia splenic malformation syndrome (BASM). Both early‐onset and late‐onset BA may be associated with other structural anomalies. Patients with early‐onset BA had a higher probability of having major extrahepatic anomaly (9/31 vs 11/99, P= 0.046). Situs anomalies accompanying major gastrointestinal (GI) tract anomalies occurred only in early‐onset BA patients. Conclusions: After comprehensively investigating the timing of onset and associated congenital extrahepatic anomalies in BA patients in Taiwan, only one BASM with double spleen was detected. A total of 23.8% of patients had early‐onset BA, and this group of patients is prone to extrahepatic anomalies. Situs anomalies accompanying major GI tract anomaly may be indicative of embryonic‐type early‐onset BA.     

Impaired T-lymphocyte proliferation function in biliary atresia patients with chronic cholestatic jaundice after a Kasai operation

To investigate the association between chronic cholestatic jaundice, systemic immunity, and various infectious complications in patients with biliary atresia (BA), we performed a survey of the systemic immune function in 30 children with BA. Patients were divided into a jaundice group (total serum bilirubin > or = 2 mg/dL for >6 mo) and control group (total serum bilirubin <2 mg/dL for >6 mo) with comparable age. Patients were tested for serum immunoglobulin and complement levels, mitogen response, interleukin (IL)-4, IL-5, and interferon-gamma production after phytohemagglutinin (PHA) stimulation, blood cell and lymphocyte subpopulation counts, phagocytic function, and leukocyte adhesion complex. They were then followed prospectively for 6 mo, and severe infectious complications requiring hospitalization were recorded. Compared with jaundice-free patients, T-lymphocyte proliferation function, determined by PHA mitogen test was significantly lower (p = 0.02) in BA patients with chronic cholestatic jaundice after a Kasai operation. During the study period, patients with chronic cholestatic jaundice had a higher risk of severe infectious complications than their jaundice-free counterparts (risk ratio = 5.87; p = 0.001). In conclusion, BA patients with chronic cholestatic jaundice are associated with impairment of T-lymphocyte proliferation and increased incidence of severe infectious complications.     

Use of gamma-glutamyl transpeptidase in the diagnosis of biliary atresia

A simple, nonsurgical means of differentiating biliary atresia (BA) from neonatal hepatitis has remained elusive. To determine its diagnostic usefulness, serum gamma-glutamyl transpeptidase (GGTP) levels were measured prospectively in 17 infants (aged 5 to 16 weeks) admitted consecutively to rule out BA. Seven patients were found to have BA, seven had neonatal hepatitis (NH), and three had alpha 1-antitrypsin (A1A) deficiency. The mean maximal GGTP level in those patients with NH (183 +/- 54 IU/L) was significantly lower than that found in patients with BA (760 +/- 492 IU/L) or A1A deficiency (1,725 +/- 921 IU/L). In the 14 patients without A1A deficiency, a serum GGTP level greater than 300 IU/L correctly identified six of seven patients with BA, while a GGTP level less than 300 IU/L correctly identified seven of seven patients with NH, although including one false-negative finding, in a patient with choledochal cyst and BA.     

Diagnostic utility of hepatobiliary scintigraphy with 99mTc-DISIDA in neonatal cholestasis

We retrospectively evaluated the utility of hepatobiliary scintigraphy and various clinical factors in differentiating intrahepatic cholestasis from biliary atresia in 28 consecutive infants with neonatal cholestasis. One millicurie of technetium-labeled diisopropyliminodiacetic acid (DISIDA) was administered intravenously, and images were obtained for up to 24 hours or until gastrointestinal excretion was noted. Nine separate studies in seven infants with biliary atresia were correctly interpreted as showing no gastrointestinal excretion of radionuclide. Of the 21 patients with intrahepatic cholestasis, only nine had gastrointestinal excretion on the first study; in eight without excretion, a second study was done, and five of these showed gut excretion. All infants with either neonatal hepatitis (six) or inspissated bile syndrome (three) had demonstrable gastrointestinal excretion either on the first or second DISIDA study. However, five of six infants with paucity of intrahepatic bile ducts, two of six infants with cholestasis secondary to total parenteral nutrition, and one infant with cholangiolitis did not show evidence of gastrointestinal excretion. The mean birth weight, mean gestational age, and mean weight at study were significantly greater (P less than 0.005) for infants with biliary atresia without excretion than for infants with intrahepatic cholestasis without excretion. The mean direct bilirubin concentration was 6.0 mg/dL for both infants with biliary atresia and infants with intrahepatic cholestasis without excretion; however, infants with excretion had a significantly lower (P less than 0.02) mean direct bilirubin value of 3.4 mg/dL. Excretion was noted in four infants with total bilirubin values greater than 10.0 mg/dL. The absence of gut excretion on the first DISIDA study was 100% sensitive but only 43% specific for biliary atresia. In infants without gut excretion of DISIDA, birth weight greater than 2200 g was 100% sensitive and 92% specific for biliary atresia. We conclude that DISIDA scanning, together with clinical data, is useful in differentiating extrahepatic from intrahepatic cholestasis. The absence of gut excretion on the first DISIDA study does not necessarily indicate extrahepatic obstruction; the study should be repeated if the diagnosis is not clear.     

Significance of serum lipoprotein-X and gammaglutamyltranspeptidase in the diagnosis of biliary atresia. A preliminary study in 27 cholestatic young infants

As simple and nonsurgical means of differentiating biliary atresia (BA) from intrahepatic cholestasis of unknown origin (IC), liver function tests including serum lipoprotein-X (LP-X) and -glutamyltranspeptidase (GGTP) were done and evaluated for their usefulness in the diagnosis of 27 cholestatic Japanese young infants. Except for LP-X and GGTP levels (P<0.01, P<0.001), there were no significant differences between the BA (n=11) and IC (n=13) groups. When values of mean plus 4 standard deviations were used to differentiate BA from IC (89 mg/100 ml for LP-X and 194 IU/l for GGTP), all BA patients gave positive results for either the crtical LP-X of GGTP values. On the other hand, all IC patients gave negative results for both levels, although patients with a paucity of intrahepatic biliary ducts (n=3) were also positive for either the critical LP-X or GGTP values. The combination test with serum LP-X and GGTP is recommended for helping to differntiate BA from IC in cholestatic young infants.Abbreviations BA biliary atresia - IC intrahepatic cholestasis of unknown origin - LP-X lipoprotein-X - GGTP -glutamyltranspeptidase - PIBD paucity of the intrahepatic bile duct     

Multicenter randomized trial of postoperative corticosteroid therapy for biliary atresia

Purpose

We aimed to evaluate early response to two different corticosteroids doses after Kasai portoenterostomy for biliary atresia (BA).

Methods

A prospective, randomized trial was performed in infants from the nationwide BA registry with type 3 BA. Sixty-nine infants were randomized to receive either 4 mg/kg/day (group A, n = 35) or 2 mg/kg/day prednisolone (group B, n = 34). The corticosteroids were started on postoperative day 7, and the dose was tapered toward day 30. Results of liver function tests on days 31 and 60 were compared between the groups.

Results

Mean bilirubin, AST, ALT, and GGT levels did not significantly differ between the groups. However, the levels of total and direct bilirubin of infants <70 days old at surgery significantly differed between the groups. Four patients from group A and five from group B, dropped out of the study. Complications during the first month after PE were comparable between the groups.

Conclusions

An initial 4 mg/kg/day dose did not significantly improve liver function, except that bilirubin levels were lower in the subgroup of infants <70 days old at surgery. There were no significant complications with either dose of corticosteroids.     

Survival after first esophageal variceal hemorrhage in patients with biliary atresia

OBJECTIVE: To determine the influence of the new onset of esophageal variceal hemorrhage (EVH) on transplant-free survival in children with biliary atresia and to examine variables that predicted survival after the onset of EVH. METHODS: Retrospective chart review of 134 patients with biliary atresia who underwent portoenterostomy between 1973 and 1992 at a single institution; 29% had EVH. RESULTS: The risk of death or need for liver transplantation was 50% at 6 years after the initial episode of EVH. Patients with a serum bilirubin concentration < or =4 mg/dL at the first episode of EVH had transplant-free survival of >80% for 4 years after this episode, those with bilirubin levels >4 to 10 mg/dL had 50% survival at 1 year, and those with bilirubin levels >10 mg/dL had 50% survival at 4 months. The risk of death or transplant for a child with EVH and total serum bilirubin levels >10 mg/dL was 12.0 (95% CI: 6.0, 24.1), 4 to 10 mg/dL was 7.2 (3.1, 16.7), and < or =4 mg/dL was 0.6 (0.1, 3.1) times the risk of a same-aged child who did not have EVH. CONCLUSIONS: Children with biliary atresia and first EVH episode have a variable prognosis related to total serum bilirubin concentration at the time of the episode.     

Improvement in accuracy of gamma-glutamyl transferase for differential diagnosis of biliary atresia by correlation with age

In order to determine the accuracy of serum gamma-glutamyl transferase (GGT) as a test for biliary atresia, we reviewed the charts of 29 infants with cholestatic jaundice less than one year of age. All patients underwent liver biopsy or laparotomy with cholangiogram to establish neonatal hepatitis (NH) or extrahepatic biliary atresia (EHBA). We also gathered information from 176 patients from published studies. Sensitivity, specificity, and likelihood ratios (LR) were calculated with 95% confidence interval (95% CI). GGT levels of the EHBA group were higher than those from the NH group. For diagnosis of EHBA at a cut-off level >250 U/L, sensitivity was 83.3% (95% CI, 55.2- 95.3%); specificity, 70.6% (95 CI, 46.9-86.7%); and negative LR, <2.0. When we added data from other studies considering age (<4 weeks, 4-8 weeks, and >8 weeks), GGT performance increased, especially for the first age group: with cut-off of 150 U/L, sensitivity was 91.7%; specificity, 88%; and positive LR, 7.8. Thus, for improving reliability of GGT levels for EHBA diagnosis, they need to be correlated to infant age.     

Usefulness of magnetic resonance cholangiopancreatography in biliary structures in infants: a four-case report

In this paper, we report the usefulness of magnetic resonance cholangiopancreatography (MRCP) in excluding biliary atresia (BA) as the cause of neonatal cholestasis. MRCP with a 1.5-T magnetic resonance (MR) imaging unit was performed on four jaundiced neonates and infants aged from 38 days to 106 days. The diagnosis of BA (n=2) was confirmed with surgery, liver biopsy and surgical cholangiography. Diagnosis of neonatal hepatitis (NH, n=2) was confirmed with clinical follow-up until jaundice resolved, while one of them was diagnosed with surgical cholangiography. In all discoloured acholic stools, increased direct bilirubin (4.4–11.3 mg/dl) with positive lipoprotein X prompted technetium ^99mTc disofenin scanning, which showed no excretion. Computed tomography (CT) showed a gallbladder in one with hepatitis but no intrahepatic bile duct in two with BA. The Kasai operation was performed in two patients with BA. In two patients with BA, neither the common bile duct nor the common hepatic ducts were visible at MRCP. In two patients with NH, MRCP clearly depicted both the common hepatic and the common bile ducts. MRCP was accurate in excluding BA as the cause of neonatal cholestasis, while ^99mTc disofenin cholescintigraphic findings were false-positive in two patients with non-obstructive cholestasis. We conclude that MRCP can be used to depict the major biliary structures of neonates and small infants and to exclude BA as the cause of neonatal cholestasis by allowing visualisation of the biliary tract.     

Bone density and 25-hydroxyvitamin D level in extrahepatic biliary atresia

Biliary atresia (BA) represents a common cholestatic affliction of the gastrointestinal tract affecting infants and children. The objective of the present study was to evaluate 42 patients (20 with and 22 without jaundice) diagnosed with extrahepatic BA for bone mineral content and serum 25-hydroxyvitamin D (HVD) levels. Physical examination and anthropometric nutritional assessment were performed. The investigation included liver function tests and serum calcium (Ca), phosphate (P), magnesium (Mg), and 25-HVD levels. Dual-energy X-ray absorptiometry was used to measure the bone mineral density (BMD) of the lumbar spine (L₁–L₄). Our results showed that 16 jaundiced␣patients (80%) and only 3 nonjaundiced patients (13.6%) showed osteoporosis (P< 0.05). All patients had normal serum Ca and P levels. Only 1 nonjaundiced patient had a low serum Mg level. Serum 25-HVD levels (mean ± SD) were 20.71 ± 8.24, 16.12 ± 4.3, and 9.18 ± 5.84 ng/ml, respectively, in subjects with normal bone density (n=7), osteopenia (n=3), and osteoporosis (n=11). Bone disease represents a well-known complication among long-term survivors of BA. To date, the pathogenesis has remained unexplained. Since, as demonstrated in the present study, jaundiced patients develop osteoporosis more frequently than nonjaundiced patients, hyperbilirubinemia may have an influence. Bone-mineral deficiency can be detected earlier by means of BMD measurement (non-invasive method) than by measuring serum Ca, P, and Mg levels in these patients. Accepted: 27 November 2000     

Urinary sulfated bile acid analysis for the early detection of biliary atresia in infants

Background: Measurement of urinary sulfated bile acid (USBA) is a non‐invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). Methods: We determined the USBA‐to‐creatinine ratio (USBA/cr) in 1148 infants at 10–40 days after birth. All infants were followed until the 3‐ to 4‐month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. Results: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow‐up period. Conclusion: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false‐positive rate is decreased by improving the methods for sample collection and urine storage.     

Elevated serum nitric oxide metabolites in biliary atresia

Biliary atresia (BA) remains one of the most intractable liver diseases in children. The aim of this study was to investigate the possible roles of nitric oxide (NO) in BA. Serum levels of nitrite and nitrate (NO production) were determined using a colorimetric method from 65 post-operative BA patients and 12 healthy children. The patients were categorized into two groups according to their jaundice status, and serum alanine aminotransferase (ALT, a marker for liver injury). Unpaired t tests were used. Data are expressed as mean and SD in terms of μmol/l. Age and gender between BA patients and controls were comparable. Serum NO metabolites of BA patients was higher than the controls (79.77±21.22 vs. 65.75±9.44, P=0.001). Subgroup analysis revealed that there was no difference in serum nitrate/nitrite levels of BA patients without jaundice compared to those with jaundice (78.85±23.23 vs. 80.90±18.76, P=0.70). However, patients with serum ALT≥100 IU/l had higher levels of serum NO metabolites compared to those with serum ALT<100 IU/l. In conclusion, NO production was elevated in BA patients compared to normal controls. Serum NO was associated with serum ALT levels, but not with jaundice status, in BA patients. These suggest that NO plays a role in the pathophysiology of liver injury in post-operative BA.     

Retinal neurodevelopmental assessment with electroretinogram in patients with biliary atresia

BACKGROUND: To evaluate the effect of n-3 polyunsaturated fatty acid (PUFA) deficiency on the development of retinal function in children with biliary atresia (BA), we examined serum fatty acid levels and performed electororetinogram (ERG) in patients with BA. METHODS: The study group was composed of one male and four female BA patients (8-14 years) with serum bilirubin levels ranging from 0.40 to 1.48 mg/dL. All of the subjects were born as full-term infants. The fatty acid composition of total lipids in serum was analyzed by gas chromatography before the Kasai operation, approximately 10 months after the Kasai operation, and at the time of the ERG study. The ERG was recorded using corneal contact lens electrodes. RESULTS: Two of the five patients showed decreased levels of arachidonic acid and docosahexaenoic acid (DHA) before and after the operation, but no abnormal findings on ERG were detected in these patients. The other three patients had decreased levels of alpha-linolenic acid or DHA after the operation, but again, no abnormalities were found on ERG. CONCLUSION: These results suggest that insufficiencies of DHA and other n-3 PUFA in full-term infants might not have an influence on later ERG results.     

Antenatal presentation of biliary atresia

OBJECTIVES: To investigate the incidence, presence of associated anomalies, type of malformation, and natural history of children with biliary atresia (BA) who presented antenatally.Study design The database of 194 infants diagnosed with BA at our tertiary referral unit between 1991 and 2002 was reviewed for infants in whom routine antenatal ultrasound had revealed biliary cystic malformations (BCMs). A retrospective analysis of their medical records was undertaken. RESULTS: Nine infants (six girls) with BCM were identified (4.6% of total referred patients with BA); all were born after 37 weeks' gestational age and presented to us at a median age of 4 weeks (range, 1-14 weeks). The presence of the BCM was confirmed on postnatal ultrasonography. Median age at corrective surgery was 5 weeks (range, 2-16 weeks). At surgery, six patients had type III BA, including one with the biliary atresia-splenic malformation syndrome; two had type II BA; and one had type I BA. Postoperatively, the infants were followed for a median of 2 years (range, 6 months to 11 years). All infants successfully cleared their jaundice. CONCLUSIONS: Improved techniques in routine antenatal ultrasonography can allow early recognition of BCM. This study suggests that BCM noted antenatally may represent early presentation of both biliary atresia-splenic malformation and nonsyndromic BA.     

Expression of osteopontin correlates with portal biliary proliferation and fibrosis in biliary atresia

The acquired or perinatal form of biliary atresia is a Th1 fibro-inflammatory disease affecting both the extrahepatic and intrahepatic bile ducts. Osteopontin (OPN) is a Th1 cytokine implicated in several fibro-inflammatory and autoimmune diseases. We examined the expression of OPN in acquired biliary atresia in comparison to normal liver and several pediatric cholestatic liver diseases. We also assessed OPN expression by cultured human bile duct epithelial cells. We found that liver OPN mRNA and protein expression were significantly increased in biliary atresia versus normal and other cholestatic diseases. OPN expression in biliary atresia was localized to epithelium of proliferating biliary structures (ductules and/or ducts) and bile plugs contained therein. No portal biliary OPN expression could be demonstrated in normal liver, syndromic biliary atresia, biliary obstruction not due to biliary atresia, and idiopathic neonatal hepatitis. OPN expression by human bile duct epithelial cells in culture was responsive to IL-2 and TNF-alpha. Our results demonstrate an up-regulation of OPN expression by interlobular biliary epithelium in biliary atresia, which correlates with biliary proliferation and portal fibrosis. These findings suggest a role for OPN in the pathogenesis of biliary atresia.     

胆道闭锁Kasai手术后综合管理

胆道闭锁(biliary atresia,BA)是婴儿期肝内外胆管进行性炎症及肝纤维化的疾病,其病因及疾病进展机制尚不清楚.Kasai手术(Kasai portoenterostomy,KPE)是治疗胆道闭锁的首选术式,成功的Kasai手术能够重建胆汁引流,但Kasai手术后长期自体肝生存(native liver s...     

Making the diagnosis of biliary atresia using the triangular cord sign and gallbladder length

Background. To evaluate the accuracy and utility of the triangular cord sign and gallbladder length in diagnosing biliary atresia by sonography.?Materials and methods. Sixty fasted infants with cholestatic jaundice aged 2–12 weeks were examined sonographically using a 5–10 MHz linear array transducer, focusing on the triangular cord sign (as described by Choi et al. [1]), the gallbladder, and ducts. The triangular cord is defined as a triangular or tubular echogenic density seen immediately cranial to the portal vein bifurcation; it represents the fibrotic remnant of the obliterated cord in biliary atresia. The findings were blinded to blood chemistry, ^{99 m}Tc-DISIDA hepatobiliary scintigraphy, and liver biopsy. Diagnosis of biliary atresia was confirmed at surgery and histology. Non-biliary atresia infants resolved medically. Comparative charges of the various investigations was made.?Results. Twelve infants had biliary atresia, and ten demonstrated a definite triangular cord. The two false-negatives had small or nonvisualized gallbladders. No false-positives were recorded. Gallbladder length ranged from 0–1.45 cm with a mean of 0.52 cm in biliary atresia compared to a mean of 2.39 cm in nonbiliary atresia infants. ^{99 m}Tc-DISIDA hepatobiliary scintigraphy showed no excretion (false-positive) in 23 % of nonbiliary atresia cases. Scintigraphy and liver biopsy charges were 2 and 6 times that of sonography, respectively.?Conclusion. The triangular cord sign and gallbladder length together are noninvasive, inexpensive, and very useful markers for biliary atresia. Received: 26 May 1999/Accepted: 28 July 1999     

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??Abstract?? Objective??To evaluate the value of biochemical markers in the diagnosis of biliary atresia ??BA?? and neonatal intrahepatic cholestasis caused by citrin deficiency ??NICCD??. Methods??Totally 77 infants in hospital with infantile hepatitis syndrome ??IHS?? were enrolled from December 1?? 2008 to March 31?? 2009. Totally 27 patients were diagnosed as having BA and 11 with NICCD. Biochemical markers were compared between groups including alanine transaminase ALT?? aspartate transaminase AST ?? alkaline phosphatase ALP?? γ-glutamyl transpeptidase γ-GT?? total bilirubin TB?? direct bilirubin DB?? total bile acid TBA?? total cholesterol TC??to compute ALT/AST??ALP/γ-GT and glucose GLU?? lactic acid LAC?? total protein TP?? albumin ALB in the NICCD group. The data were analyzed by T test and ROC curve with SPSS10.0. Results??γ-GT was significantly elevated in the infants with BA when compared to non-BA group ??P = 0.003???? cut-off point was 332.5U/L. ALP/γ-GT was significantly lower in the patients with BA??and cut-off point was 1.93. The infants with NICCD had significantly different biochemical markers including GLU?? LAC?? TP?? ALB?? ALT/AST and γ-GT. Conclusion??Biochemical markers could be considered as complementary diagnosis of BA and NICCD for differentiating infants with IHS.     

Newborn screening for biliary atresia in the United States

Despite advances in our understanding of the pathogenesis of biliary atresia (BA), BA remains the most common cause of end-stage liver disease in children and the leading indication for pediatric liver transplantation. Age at time of Kasai portoenterostomy (KPE), performed to provide bile drainage, strongly correlates with transplant-free survival, mostly due to progression of intrahepatic fibrosis to cirrhosis. Unfortunately, challenges remain in recognizing that a jaundiced infant may have BA. To better diagnose infants with BA at an earlier age, population-based screening programs in countries such as Taiwan, Japan, and China have utilized stool color cards. Early results have been promising demonstrating earlier diagnosis, earlier KPE, and, hence, improved outcomes. Cost-effectiveness studies focused on stool color card screening in North America where the incidence of BA is much lower also project improved transplant-free survival rate with a savings in terms of healthcare expenditure. There is also evidence that postnatal serum bilirubin levels may also be effective as a screening tool given that all infants with BA exhibit hyperbilirubinemia at birth. The American Academy of Pediatrics (AAP) recently advocated studying the implementation of newborn screening for BA in the United States. Further efforts and analyses within the United States are ongoing, but current evidence is supportive of screening for BA even in low incidence countries.     

Type-I but not type-II interferon receptor knockout mice are susceptible to biliary atresia

The etiology of biliary atresia (BA) is not yet understood, but recent studies have shown inflammation with an up-regulated interferon (IFN) activity in the intra- and extrahepatic bile ducts of patients with BA. These findings support an inflammatory/infectious cause of BA as mimicked in our infective murine model. To study the role of the IFN receptors in our model, we used mice with inactivated INF-alpha/beta receptor A129, with inactivated IFN-gamma receptor G129, or inactivation of both interferon receptors AG129 as well as the wild type controls W129. Mice were infected with rotavirus within 48h of birth and 7 d postpartum. The incidence of BA in each group was determined during a 3 wk period. In the second week the virus load was measured. BA incidence was 76% in A129 and 67% in AG129 animals, whereas in the G129 group only 33% of the pups developed BA. The wild type presented with a BA-incidence of 15%, while 7 d old mice failed to develop BA. There was no significant difference in the virus load of the livers between the groups independent of clinical symptoms. In conclusion, inactivation of type I INF-receptor significantly increases the incidence of BA following postpartal rotavirus infection. This effect is independent of the presence of type II-INF-receptors. Thus, in our model a type I IFN-linked deregulation of the innate immune system appears to be crucial for the induction of biliary atresia.