We report the clinicopathologic findings of a patient with biliary atresia associated with vesicoureteral reflux who underwent a liver transplant and nephroureterectomy simultaneously. The patient was a 22-month-old female infant born of a nonconsanguineous marriage, who was reported to be icteric from first day of life. Her antenatal history was significant for bilateral hydronephrosis. The results of a liver biopsy showed findings of biliary atresia, and the results of a radiograph showed bilateral vesicoureteral reflux. Therefore, the patient underwent a liver transplant and a right nephroureterectomy simultaneously. In the days after the operation, the patient died because of extrahepatic hematoma. In conclusion, a child having biliary atresia must remain for investigation of associated anomalies including vesicoureteral reflux.

Key words : Urinary tract infection, Urogenital anomaly

Introduction

Biliary atresia is a well-known entity with an incidence of 0.8 to 1 per 10 000 live births.¹ It is a panbiliary disease affecting the intrahepatic and extrahepatic biliary tree, probably as an end result of a destructive inflammatory process leading to fibrosis and obliteration of the biliary tree, with development of secondary biliary cirrhosis.^2,3 When left untreated in early childhood, the condition leads to death from liver insufficiency, with an average survival of 12 to 19 months. Fewer than 10% of patients survive beyond 3 years of age.^4,5 Also, biliary atresia may present with multiple congenital anomalies in about 20% cases such as polysplenia, situs inversus, intestinal atresias, and cardiovascular anomalies.⁶ However, the co-occurrence of vesicoureteral reflux and biliary atresia is uncommon. We report the clinicopathologic findings of a patient with biliary atresia associated with vesicoureteral reflux who underwent a liver transplant and nephroureterectomy simultaneously.

Case Report

A 22-month-old female infant born of nonconsan-guineous marriage was reported as being icteric from the first day of life. Her antenatal history was significant for bilateral hydronephrosis. The results of hepatobiliary scintigraphy showed that there was no passage to the intestine. The results of liver biopsy showed findings of biliary atresia. Accordingly, she underwent a Kasai operation.

She had been referred to our hospital when she was 19 months old, owing to complaints of jaundice, itching, and increased abdominal distension. On examination, the child had icterus, clubbing, abdominal distention, hepatomegaly, splenomegaly, and ascites. The results of her laboratory analyses showed anemia, thrombocytopenia, direct hyper-bilirubinemia, raised liver transaminases, hypo-albuminemia, and prolonged prothrombin time. The results of a renal scintigraphy showed decreased cortical uptake, and the findings of vesicoureteral reflux for both sides of the ureter (grade 5 vesicoureteral reflux at right side, and grade 4 at left side). The dimension of the left kidney was bigger than normal limits while the right kidney was in atrophic limits. At 22 months, the patient underwent a liver transplant and a right nephroureterectomy simultaneously. A histopathologic examination of the native liver showed cirrhosis with diffuse hepatocanalicular cholestasis. The atrophic right kidney (6 g) of the patient showed multiple parenchymal cysts and chronic pyelonephritis, such as diffuse interstitial inflammation, tubular atrophy, interstitial fibrosis, and granulomas, which we considered as developing secondary to the opaque material, which was likely Tamm–Horsfall protein. In addition to chronic inflammation of the pelvicaliceal system, an ureteropelvic dilatation also was seen. A few days after the liver transplant, the patient died owing to extrahepatic hematoma probably caused by persistent thrombocytopenia.

Discussion

Congenital biliary atresia is a rare condition characterized by idiopathic dysgenesis of the bile ducts. If left untreated, biliary atresia leads to liver cirrhosis, liver failure, and premature death. Liver transplant is the only cure.

At our hospital, between September 2001 and December 2012, there were 334 liver transplants, in which 160 cases were younger than 17 years old, and 32 of these 160 cases underwent transplant owing to biliary atresia. Among 32 recipients of biliary atresia, 26 of them survived (81, 25%) and 6 died (18, 75%) owing to early postoperative complications (3 sepsis, 1 renal failure, 1 pulmonary aspiration, and 1 hemorrhage). These data show that with advances in surgical techniques and management, children with biliary atresia after a liver transplant can achieve satisfactory survival rates. In United States and Europe, liver transplant in children is also a well-established procedure, and the 5-year survival rate of transplanted children with biliary atresia is 83% to 87%.7,8 The early mortality of our patient could be explained by her undergoing a liver transplant and nephroureterectomy simultaneously.

Vesicoureteral reflux is the abnormal flow of urine from the bladder to the upper urinary tract. In general population, approximately 10% of children are reported to show vesicoureteral reflux.⁹ Cohort studies estimate that vesicoureteral reflux occurs in about 32% of siblings of an affected child.10 This rate may be as low as 7% in older siblings and as high as 100% in identical twins.¹⁰ These findings indicate that vesicoureteral reflux is an inherited condition.¹⁰ When a child with vesicoureteral reflux gets a urinary tract infection, bacteria can move into the kidney and lead to scarring. Scarring of the kidney can be associated with progressive kidney failure, which finally leads to end-stage renal disease.

To the best of our knowledge, this is the third case in the English literature of vesicoureteral reflux with no other associated urogenital and/or anorectal anomaly and simultaneous biliary atresia. Similar to our present case, the other 2 cases with biliary atresia and vesicoureteral reflux co-occurrence were reported from our institution by Baskin and associates.¹¹ In their study, the authors reviewed 26 pediatric patients for the presence of urinary tract infection in pediatric liver transplant candidates, and they concluded that urinary tract infection occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease.¹¹ The risk of urinary tract infection in patients with biliary atresia was found 14.9 times higher than it is in children with other types of chronic liver disease.¹¹ Embryonic or fetal biliary atresia is associated with other congenital anomalies, and may be the result of mutations in the general controlling of normal bile duct formation or differentiations that secondarily induce an inflammatory/immune response within the common bile duct and liver after the initiation of bile flow at approximately 11 to 13 weeks’ gestation.¹²

A review of the English literature indicates that a few cases of biliary atresia are associated with urogenital and anorectal anomalies, which may cause a tendency toward urinary tract infection.¹³ The tendency toward urinary tract infection in patients with biliary atresia can explained by the co-occurrence of vesicoureteral reflux in both our case and in the other 2 cases, which were reported previously by Baskin and associates.¹¹ In addition, other urogenital and anorectal anomalies also can shown an increased risk of urinary tract infection in cases with biliary atresia such as Amae and associates who reported an infant with biliary atresia who showed urinary tract infection, probably secondary to the anorectal agenesia and complicated urogenital anomaly (right hydronephrosis and hydroureter and high vaginal atresia, bladder hypogenesis, and atresia of the left kidney, ureter, and urethral orifice).¹³ In addition, other biliary atresia cases with various urogenital and anorectal anomalies have been reported, and most of them showed an increased risk of urinary tract infections during follow-up.

In conclusion, urinary tract infection is common in children with biliary atresia and in such cases, we must not forget the tendency of the presence of urogenital and anorectal anomalies. A child having biliary atresia must be remain under investigation for associated anomalies including vesicoureteral reflux that must be treated as soon as possible because of its ability to rapidly progress to chronic pyelonephritis and end-stage renal failure.

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