The use of ultrasonography in the diagnosis of biliary atresia

Preoperative upper abdominal ultrasonograms of babies with biliary atresia were reviewed in order to determine the efficacy of this technique in the differential diagnosis of biliary atresia and neonatal hepatitis. In 4 patients with neonatal hepatitis and 8 normal controls, ultrasonograms showed echoes of the gallbladder. In 14 patients with biliary atresia, echoes of the gallbladder were not apparent. It is concluded that preoperative ultrasonograms provide an efficient diagnostic method for differentiating biliary atresia from neonatal hepatitis.Offprint requests to: T. Okasora     

Diagnostic laparoscopy-assisted cholangiography in infants with prolonged jaundice

Cholangiography is often crucial for establishing the definitive cause of neonatal jaundice. We present our protocol for using laparoscopy-assisted cholangiography in infants with prolonged jaundice and discuss its benefits. Firstly, a 5 mm supra-umbilical trocar is introduced to create a port for a 0° laparoscope. A 5 mm trocar is then inserted through a right subcostal incision to allow the liver and gallbladder to be visualized. If the gallbladder is of good size, the fundus is exteriorized through the right subcostal trocar site and a catheter is inserted into the gallbladder for cholangiography. If the gallbladder is atretic, the fundus is not exteriorized and a laparotomy is performed for open intraoperative cholangiography because the lumen of an atretic gallbladder is usually not fully patent and cholangiography through its exteriorized fundus often fails. We reviewed 18 jaundiced infants thought to have biliary atresia (BA) who had laparoscopy-assisted cholangiography. At laparoscopy, four patients had good sized gallbladders and minimal to mild liver fibrosis. They underwent cholangiography via the exteriorized fundus, and BA in two cases and biliary hypoplasia in two cases were identified. The remaining 14 had atretic gallbladders and varying degrees of liver fibrosis. Cholangiography via the exteriorized fundus was performed in one patient, but failed and converted to open cholangiography. Open intraoperative cholangiography identified BA in all 14 cases. All BA cases progressed to Kasai portoenterostomy directly after diagnosis. Laparoscopy is used to determine the type of cholangiography to be performed based on the appearance of the gallbladder and this simple, accurate, and safe protocol allows the anatomical structure of the biliary tree to be obtained accurately with minimal surgical intervention.     

Definitive exclusion of biliary atresia in infants with cholestatic jaundice: the role of percutaneous cholecysto-cholangiography

Definitive exclusion of biliary atresia in the infant with cholestatic jaundice usually requires operative cholangiography. This approach suffers from the disadvantage that sick infants are subjected to a time-consuming and potentially negative surgical exploration. The purpose of this study was to determine if percutaneous cholecystocholangiography (PCC) prevents unnecessary laparotomy in infants whose cholestasis is caused by diseases other than biliary atresia. This study is a 10 year retrospective review of all infants with persistent direct hyperbilirubinemia and inconclusive biliary nuclear scans who underwent further evaluation for suspected biliary atresia. A gallbladder ultrasound (US) was obtained in all patients. When the gallbladder was visualized, further imaging by PCC was done under intravenous sedation; otherwise, the standard operative cholangiogram (OCG) was performed, with liver biopsy as indicated. The primary outcome was the diagnostic accuracy of PCC, especially with respect to preventing a laparotomy. There were 35 infants with suspected biliary atresia, with a mean age of 8 weeks (range 1-14 weeks). Nine infants whose gallbladder was visualized by ultrasound underwent PCC that definitively excluded biliary atresia. Of this group, the most frequent diagnosis (five patients) was total parenteral nutrition-associated cholestasis. The other 26 infants with absent or decompressed gallbladder had laparotomy and OCG, which identified biliary atresia in 16 patients (61%). Laparotomy was avoided in all 9 patients who underwent PCC, thus reducing the negative laparotomy rate by 47%. There were no complications associated with PCC. Several alternative techniques to operative cholangiogram have been described for the definitive exclusion of biliary atresia, but many of these have distinct drawbacks. Advances in interventional radiology techniques have permitted safe percutaneous contrast evaluation of the biliary tree. Identification of a normal gall bladder on sonogram is highly predictive of the absence of biliary atresia. Further confirmation can be accurately obtained by a combination of PCC and percutaneous liver biopsy.     

Apparent gut excretion of Tc-99m-DISIDA in a case of extrahepatic biliary atresia

Our patient had DISIDA scan at 39 days of age to exclude biliary atresia. Gut excretion was seen 18h after injection and the diagnosis of neonatal hepatitis was made. Because of continued elevated liver function values, liver biopsy was performed and demonstrated findings consistent with biliary atresia. Exploratory laparotomy performed 8 days after the scan showed patent cystic duct, bile duct, and gall-bladder, but an atretic common hepatic duct. This case is an example of documented biliary atresia demonstrating gut excretion on the DISIDA scan.     

Alpha1-fetoprotein in neonatal hepatobiliary disease.

It has been suggested that the quantitative estimation of serum alpha-1-fetoprotein may help in distinguishing the neonatal hepatitis syndrome from biliary atresia. We measured the serum AFP concentration in 52 neonates and infants with various hepatobiliary disorders, including neonatal hepatitis syndrome (group I), biliary atresia (group II), and other hepatopathies such as choledochal cyst (group III). The mean serum AFP concentration in patients with neonatal hepatitis was significantly greater than the mean concentration in the other two groups. There was no significant difference between the mean serum AFP concentrations in patients with biliary atresia and in group III patients. Patient age was noted to be an important factor: Serum AFP levels greater than 35 microgram/ml in infants one to four months of age suggpst the diagnosis of neonatal hepatitis syndrome. Serum AFP levels below 10 microgram/ml in infants less than four months of age suggest the diagnosis of biliary atresia or hepatopathies other than neonatal hepatitis. However, the variable and significant overlapping of serum AFP values between 10 and 35 microgram/ml limit the diagnostic value of this test.     

Hitching the gallbladder in laparoscopic-assisted cholecysto-cholangiography: a simple technique

Neonatal cholestatic disorder in the late neonatal period requires often cholangiography to differentiate between biliary atresia and other causes of prolonged neonatal jaundice. A simplified method of a laparoscopic-assisted cholecysto-cholangiography is presented. Retrospective chart review was conducted of all patients who from May 2002 to April 2012 underwent a laparoscopic-assisted cholecysto-cholangiography with routine fixation of the fundus of the gallbladder to the lateral aspect of the abdominal wall. A total of 18 infants (8 boys) aged 41–104 (median 64) days underwent laparoscopic-assisted cholecysto-cholangiography for prolonged jaundice. The technique identified ten cases of a patent bile duct system and eight biliary atresias. (Thirty-two cases of suspected biliary atresia were confirmed by laparoscopy alone.) Two cases required suturing of a bile leak at the puncture site. Hitching the gallbladder to the lateral abdominal wall is a simple method allowing an optimal radiographic assessment of the extra- and intra-hepatic bile duct anatomy.     

Serial ultrasonic examination to differentiate biliary atresia from neonatal hepatitis — special reference to changes in size of the gallbladder

We performed serial ultrasonic examinations to differentiate biliary atresia from neonatal hepatitis. The subjects studied were 144 children (100 normal neonates and infants, 31 patients with neonatal hepatitis and 13 patients with biliary atresia). They were examined by ultrasound before, during and after feeding. In 97 out of 100 normal children and all patients with neonatal hepatitis, the gallbladder was identified, and the change in size following oral feeding was observed. In four children with severe neonatal hepatitis which could not be differentiated from biliary atresia by clinical and laboratory data, we readily identified the gallbladder and observed the change in the size following oral feeding. In 8 of 13 patients with biliary atresia, we identified a small gallbladder whose size was not affected by oral feeding. In the other patients the gallbladder was not identified before, during or after oral feeding. On the basis of these results, we consider that serial ultrasonic examination with oral feeding aids in a differential diagnosis of biliary atresia and neonatal hepatits.     

Polysplenia syndrome associated to neonatal hepatitis

OBJECTIVE: To report the unusual association between neonatal hepatitis and polysplenia syndrome.METHODS: Clinical, biochemical, histopathological, surgical and image analysis methods were used.RESULTS: The 36 days old patient presented hyperbilirubinemia with increase of direct reacting bilirubin and high alkaline phosphatase. The physical examination evidenced jaundice and hepatomegaly. The chest X-ray showed situs inversus and dextrocardia. Abdominal ultrasonography presented an increase in liver volume, mainly at the right lobe. There were two cystic lesions at the liver with absence of intrahepatic biliary tract dilatation. Absence of splenomegaly. Biliary scintigraphy didn't show any excretion of radioisotope to the duodenum while transoperative cholangiography presented contrast medium flowing to the duodenum lumen. During laparotomy it was possible to observe polysplenia, abdominal aorta to the right of the lower vena cava, gallbladder at the left lobe of the liver, appendix on the left side of the abdomen and sigmoid colon on the right side. The hepatic wedge biopsy was compatible with idiopathic neonatal hepatitis.CONCLUSION: The finding of polysplenia syndrome in patients with neonatal cholestasis doesn't necessarily indicate the recurrent presence of extrahepatic biliary atresia.     

Extrahepatic biliary atresia versus neonatal hepatitis. Review of 137 prospectively investigated infants.

In a prospective regional survey of neonatal hepatitis syndrome 32 infants had extrahepatic biliary atresia (EHBA) and 103 had hepatitis. No cause for the lesion was found in infants with extrahepatic biliary atresia, but in 32 with hepatitis a specific cause was identified, 24 having genetic deficiency of the serum protein alpha1-antitrypsin. No differences were observed in parental age, mother's health in pregnancy, month of birth, birth order, or sex of the infants. Familial idiopathic hepatitis occurred in 3 of 67 sibs of patients with idiopathic hepatitis, but the 33 sibs of EHBA patients had no liver disease. Of the infants with hepatitis, 36 were of low birthweight, less than 2.5 kg, and 23 were born prematurely. Infants with biliary atresia were all of normal birthweight and only one was born prematurely. Consideration of clinical and biochemical abnormalities in the first 2 months of life showed no differences between the two groups except that infants with EHBA were more commonly jaundiced from birth (80%) and had more frequently acholic stools (83%). The frequency of these features in patients with hepatitis being 68% and 52%. Standard tests of liver function were not discriminatory. Percutaneous liver biopsies were diagnostic in 75% of those with EHBA and in 92% of those with hepatitis. The I131 Rose Bengal faecal excretion was less than 10% in 26 of 28 infants with EHBA and in only 5 of 18 with hepatitis. These latter two investigations together allowed a correct preoperativer diagnosis of EHBA in all instances. Bile drainage was achieved surgically in only 3 cases. A major reason for these poor results may have been the late referral of cases for diagnosis and laparotomy, which should be performed as soon as the diagnosis is suspected and always by 70 days of age.     

The diagnostic significance of cholescintigraphy and ultrasound examination in cholestatic syndromes in infancy

Thirty-three neonates and infants with cholestatic syndromes of various etiologies were evaluated by cholescintigraphy and ultrasound examinations. The results of these two diagnostic procedures were compared with the final diagnosis as confirmed by liver biopsy and/or laparotomy and the clinica follow-up of the infants. Fourteen patients had an obstructive cholangiopathy (11 biliary atresia, 2 choledochal cysts, 1 congenital choledochal stenosis), 13 had neonatal hepatitis, and 6 had cholestasis of another etiology. Typical ultrasonic and/or scintigraphic findings confirmed or excluded the need for surgical exploration in 28 patients. Thus, for must infants with cholestatic syndromes it is possible to differentiate the cause without invasive diagnostic techniques such as liver biopsy or exploratory laparotomy.     

Lack of correlation between infection with reovirus 3 and extrahepatic biliary atresia or neonatal hepatitis

Infection with reovirus 3 (Reo-3) has been suggested as the cause of extrahepatic biliary atresia and idiopathic neonatal hepatitis, but confirmation has been lacking. Therefore we have searched for a specific anti-Reo-3 antibody response in the sera of patients with biliary atresia or neonatal hepatitis and for Reo-3 antigens in their hepatobiliary tissues. Sera from 23 infants with extrahepatic biliary atresia, 12 with neonatal hepatitis, 30 age-matched control patients with other liver diseases, and 55 control patients without liver disease were tested by an enzyme-linked immunosorbent assay for total (IgA, IgG, and IgM) anti-Reo-3 antibodies; sera of infants younger than 6 months of age were tested also for IgM anti-Reo-3 antibodies alone. There was no difference between either total or IgM anti-Reo-3 antibody levels in infants with extrahepatic biliary atresia or neonatal hepatitis and levels in control infants. Reo-3 antigens were not detected in the hepatobiliary tissues of 19 infants (18 with biliary atresia, one with neonatal hepatitis) by an immunoperoxidase method that readily demonstrated Reo-3 in control infected HEp-G2 cells. Our data do not support a relationship between neonatal liver diseases and infection with Reo-3.     

Serum 25-hydroxy-vitamin D in hepatobiliary disease in infancy.

Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin.     

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.     

IMMUNE RESPONSES IN PATIENTS WITH OBSTRUCTIVE JAUNDICE OF INFANCY

ABSTRACT. To investigate possible involvement of immune responses in the pathogenesis of obstructive jaundice in infancy we measured antibody to liver specific lipoprotein (LSP) by radio immunoassay and immune complexes by their ability to bind Clq in sera from 16 patients with extrahepatic biliary atresia and 16 with neonatal hepatitis and 13 age matched controls. Anti-LSP was present in 6 of 16 with preoperative biliary atresia and 6 of 16 with hepatitis. Mean percentage Clq bound was higher in hepatitis (22 SD 15 %) than preoperative biliary atresia (11.1 SD 2.3 %). Nine of 16 hepatitis patients had elevated Clq binding as compared with 1 of 16 with biliary atresia. The highest value for anti-LSP and Clq binding were found in sera from patients with histologically severe hepatitis and hepotitis associated with specific viral or bacterial causes. Anti-LSP was significantly raised 5 months post-operatively in all of 6 patients with biliary atresia and poor biliary drainage but only 2 of 5 survivors. Elevated Clq binding was detected in 6 of 7 with poor drainage and 1 of 7 survivors at the same stage. Anti-LSP and Clq binding fell in 4 patients with neonatal hepatitis on recovery. These findings suggest that immunological mechanisms, possibly involving antibody to hepatocyte membrane components and immune complexes, may be involved in the pathogenesis of progressive liver disease in biliary atresia.     

Hepatobiliary scintigraphy and the string test in the evaluation of neonatal cholestasis

We evaluated [99mTc]diisopropylphenyl-carbamoylmethylimidodiacetic acid ([99mTc]DISIDA) cholescintigraphy with measurement of duodenal fluid radioactivity collected by the string test in patients with neonatal cholestasis. Twenty-six infants with prolonged jaundice and acholic stools were studied prospectively. Twelve patients had neonatal hepatitis, 12 biliary atresia, and one each Alagille syndrome and alpha 1-antitrypsin deficiency liver disease. All infants except the biliary atresia patients and four of the neonatal hepatitis patients revealed bowel activity on scan 6 h after tracer administration. At 24 h, three of these latter patients with neonatal hepatitis and two of the patients with biliary atresia revealed bowel activity. String radioactive counts for neonatal hepatitis ranged from 99,574 to 967,205 cpm (374,504 +/- 232,210 cpm; mean +/- SD) and for biliary atresia from 8,342 to 370,346 cpm (117,149 +/- 98,698 cpm; mean +/- SD). While neither test alone was capable of correctly differentiating among all patients, those patients with biliary atresia had either a negative hepatobiliary scan at 24 h or string radioactive count below 197,007 cpm. Disparity between the hepatobiliary scan and the string radioactive counts mandates further diagnostic investigation. These data suggest that simultaneous administration of the string test with hepatobiliary scintigraphy is advantageous in the evaluation of infants with cholestatic jaundice.     

Value of sonography in prolonged neonatal jaundice. Findings in 13 cases]

BACKGROUND: Different conditions are associated with a prolonged cholestatic jaundice in the neonatal period: viral hepatitis, biliary atresia and choledocal cyst are the most frequent causes. Laboratory findings are necessary, although they do not permit an etiologic diagnosis in all cases. Serial ultrasonographic study could be proposed for the evaluation of biliary excretion before and after feeding, in order to differentiate between these three conditions. PATIENTS AND METHODS: Between February 1993 and January 1997, 13 newborns (seven girls and six boys) aged from 30 to 186 days, presented with jaundice and conjugated hyperbilirubinemia. They were evaluated by laboratory tests; serial ultrasonographic examinations were performed after 4 hours fasting then 1 and 2 hours after meal. RESULTS: The gallbladder (GB) was visualized in nine patients. In five of these patients, it contracted after feeding suggesting the diagnosis of neonatal hepatitis, that was confirmed by the clinical evolution. In three patients, the GB did not change in size and the diagnosis of biliary atresia was surgically proven. In one patient, a choledocal cyst was visualized and confirmed by surgery. The GB was not identified after 4 hours of fasting in four patients; biliary atresia was suspected and confirmed by surgery. CONCLUSION: Serial ultrasound of the GB is an easy and non-invasive method. It was useful in identifying those conditions requiring surgery in eight patients. We recommend its use as the initial method in the evaluation of neonatal jaundice before the other invasive methods.     

Comparison of radionuclear scintigraphy and liver biopsy in the evaluation of neonatal cholestasis

Twenty-eight patients with neonatal cholestasis were given appropriate tests to arrive at a definitive diagnosis. Comparison of the results showing total obstruction on scintigraphy but not on liver biopsy is presented. It is suggested that liver biopsy be performed to confirm the diagnosis prior to undertaking exploratory laparotomy when radionuclear scan suggests extrahepatic biliary atresia.     

Endoscopic retrograde cholangiopancreatography in infantile cholestasis.

The difficulty of distinguishing surgically correctable causes of conjugated hyperbilirubinaemia in infants from other causes means that some infants may undergo laparotomy and intraoperative cholangiography unnecessarily, and others may be referred for surgery too late. In an attempt to improve the diagnostic accuracy in infants with conjugated hyperbilirubinaemia when standard methods produced equivocal results, we have been using prototype paediatric duodenoscopes (PJF 7.5 and XPJF 8.0; Olympus) to perform endoscopic retrograde cholangiopancreatography (ERCP). From 159 infants with conjugated hyperbilirubinaemia, 11 were referred for ERCP, which was performed in nine. In four in whom bile ducts were definitely visualised laparotomy was avoided. Operative cholangiography confirmed patent bile ducts in one in whom visualisation had been uncertain. Three of four in whom bile ducts were not seen had extrahepatic biliary atresia. Visible bile drainage in the fourth excluded atresia. No major complications ensued but there was radiological evidence of gall bladder perforation in one (common hepatic duct block) and overinflation with air was a problem until finer cannulae (Wilson-Cook) were introduced. In appropriately selected patients with conjugated hyperbilirubinaemia, ERCP with paediatric duodenoscopes in experienced hands may provide useful diagnostic information.     

Hyperparathyroidism in hepatobiliary disease in infancy

Metabolism of calcium and magnesium may be disturbed in hepatobiliary disease because of deficient or absent bile flow into the gut, since bile is important for the intestinal absorption of these elements. In the present paper the tubular reabsorption of phosphate (TRP), calcium (TRCa), and magnesium (TRMg) were determined in an attempt to evaluate the parathyroid function of infants and children with hepatobiliary disease. In unrepaired biliary atresia TRP was conspicuously reduced (mean 49.8%, SD 15.1). In successfully repaired biliary atresia the value was increased near the normal range (mean 80.7%, SD 8.1). In neonatal hepatitis the value was variable in individual cases, but significantly lower than the normal (mean 47.6%, SD 19.9). TRCa was reduced in one third of the patients with unrepaired biliary atresia and in one fifth of the cases of neonatal hepatitis. The value was within the normal range in repaired biliary atresia. TRMg was decreased in both unrepaired and repaired biliary atresia and in neonatal hepatitis. The effect of intravenous calcium infusion on TRP, TRCa and TRMg was evaluated in 3 patients with unrepaired biliary atresia. TRP was conspicuously enhanced after infusion. TRCa was decreased in 3 to a variable extent. TRMg was moderately increased in 2 and greatly decreased in 1. These results indicate that infants with hepatobiliary disease are in a state of secondary hyperparathyroidism because of deficient or absent bile flow into the intestines.     

Serum alpha-fetoprotein levels in extrahepatic biliary atresia, idiopathic neonatal hepatitis and alpha-1-antitrypsin deficiency (PiZ).

Serum alpha-fetoprotein levels were measured using a sensitive radioimmunoassay in 77 infants presenting with persistent conjugated hyperbilirubinaemia. A breed range of alpha-fetoprotein concentrations occurred in both the 23 infants with extrahepatic biliary atresia and the 35 with idiopathic neonatal hepatitis but the 13 with alpha-1-antitrypsin deficiency had uniformly low levels. High alpha-fetoprotein concentrations (above 10 000 mug/1) favoured the diagnosis of neonatal hepatitis especially in the first ten weeks of life, but the overlap between neonatal hepatitis and extrahepatic biliary atresia was large and alpha-fetoprotein determination cannot be recommended as a reliable method for distinguishing the two conditions. Serial alpha-fetoprotein values showed no consistent relationship with standard liver function tests and gave no guide to prognosis. There was an association between alpha-fetoprotein production and needle biopsy evidence of hepatic giant cell transformation. The uniformly low alpha-fetoprotein levels in alpha-1-antitrypsin deficient infants with neonatal hepatitis is a new observation and possible mechanisms for disordered glycoprotein release are discussed.