Roberta J. Hall

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.

Biliary atresia and the polysplenia syndrome

There is a widely held but unsubstantiated belief that in infants with biliary atresia and coexisting polysplenia syndrome, the Kasai operation fails. An equally poor prognosis has been forecast for patients with this complex treated by liver transplantation. From 1975 to 1989, 16 of 131 infants with biliary atresia (12%) had one or more components of the polysplenia syndrome: polysplenia (8), intestinal malrotation (12), preduodenal portal vein (6), absent inferior vena cava (6), aberrant hepatic artery (4), or abdominal heterotaxia (4). Although technically more demanding, 12 of the 15 polysplenia patients achieved biliary drainage after operation. (One patient had exploration only, because of parental preference). Four children are alive; two are anicteric and well at ages 5 and 8 following Kasais operation, and two by virtue of liver transplantation done at ages 4 and 7. Three of the five patients who had liver transplantation died. Acturial survival was 44% at 5 years, not significantly different from that of the 115 nonpolysplenia patients (48%). When associated with the constellation of anomalies known as the polysplenia syndrome, biliary atresia is most likely caused by an early (at approximately the fifth week) embryonic insult. The anomalies do not preclude successful biliary reconstruction using the Kasai procedure or successful liver transplantation.

Biliary atresia: Early determination of prognosis*

Analyses of bile bilirubin during the first month after Kasai operations, and of the liver biopsies obtained at the time of initial surgery, were done in 67 patients with biliary atresia. Bilirubin excretion (milligrams per day) was determined as the product of the bile volume and its concentration. Operative liver biopsies were evaluated for fibrosis, bile duct proliferation, bile stasis, giant cell transformation, and parenchymal degeneration; the severity of each abnormality was graded on a scale of 0 to 4. A forward stepwise regression procedure using the Cox proportional hazards model identified the relationship between survival and covariants. Thirty-nine of 67 patients died. Of these, 38 excreted less than 6 mg of bilirubin per day during the first postoperative month. The other patient died of a coexisting anomaly. Nine other patients who excreted less than 6 mg of bilirubin per day are alive but are either jaundiced or awaiting transplantation. Nineteen patients who excreted greater than or equal to 6 mg of bilirubin per day are alive (mean follow-up, 61 months) with normal or near-normal liver function. The severity of liver fibrosis, bile duct proliferation, and bile stasis did not correlate with survival, whereas giant cell transformation and parenchymal degeneration were highly significant (P less than or equal to .000 and P less than or equal to .0003, respectively). Twenty-six infants with grade 1-4 giant cell transformation or grade 2-4 parenchymal degeneration had a mean survival of 11 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary atresia in the newborn

A prenatal sonographic diagnosis of extrahepatic biliary atresia was made and, 76 hours after birth, operatively confirmed. A standard Kasai operation was performed, with the exception of the use of an ancillary appendiceal conduit to provide biliary drainage of an independent bile duct draining the right anterior hepatic segment. Hepatic and ductal histology were identical to those usually found in biliary atresia in a 6- to 8-week-old infant. The child is well at 16 months.

Surgical implications of bronchopulmonary dysplasia

Twenty of 30 patients with bronchopulmonary dysplasia (BPD) had major tracheobronchial abnormalities, which in 18 could be incriminated as contributing to their symptoms. There were 15 examples of tracheobronchial stenosis, 13 of tracheomalacia, nine of bronchomalacia, and one of tracheal web. Sixteen patients had operations. Tracheostomy was successful as a temporizing measure in ten patients although there was significant morbidity. Balloon dilatation of tracheobronchial stenosis produced temporary (2) or long-term (2) improvement in four patients. Electroresection of tracheobronchial stenosis was successful in the three instances it was employed. Lobectomy for lobar emphysema was curative in both patients. Aortopexy for tracheomalacia improved all three patients. We conclude that (1) symptomatic major airway lesions are not uncommon manifestations of BPD, (2) many of the lesions are amenable to surgical therapy, and (3) bronchoscopic evaluation should be considered early in the course of infants with BPD.

Endoscopic esophageal varix ligation: Technique and preliminary results in children

A technique for treating esophageal variceal hemorrhage in children using endoscopically placed rubber ligatures was evaluated in six children. The method offers a major advantage over chemical obliteration of varices by sclerosants in the absence of systemic, local, or distant organ reactions and, perhaps, in the avoidance of esophageal motor dysfunction.

Esophageal Endosclerosis in Children

During the past 6 years, 25 consecutive patients with esophageal variceal hemorrhage were treated by esophageal endosclerosis (direct injection of varices with a sclerosing agent). The primary disease in the 25 children was portal vein thrombosis (11 patients), biliary atresia (nine patients), and hepatic cirrhosis from cystic fibrosis (three patients), alpha 1-antitrypsin deficiency (one patient), and neonatal hepatitis (one patient). Thirteen patients were treated during acute, major variceal hemorrhage. Esophageal endosclerosis was repeated at regular intervals until all esophageal varices were obliterated. Twenty-one patients completed therapy. Four patients died: one of a complication of therapy and three of the primary disease. Other than the one death, complications were minor. Recurrent esophageal variceal hemorrhage has not been encountered in follow-up from 9 months to 6 years after completion of therapy.

Portal Venous Velocity in Biliary Atresia

From December 1986 to April 1989, 38 patients with biliary atresia (eight newly diagnosed) were evaluated with doppler ultrasound of the portal venous system. Peak and mean velocities were computer derived from the spectral waveform. Good velocity was greater than 15 cm/s, intermediate velocity was 8 to 14 cm/s, abnormal velocity was less than 7 cm/s or hepatofugal. Patients were grouped according to clinical status: group 1 (n = 14), normal liver function; group 2 (n = 15), recurrent cholangitis; group 3 (n = 2), established bile drainage but complicated cirrhosis; group 4 (n = 7), failed portoenterostomy. All patients with normal liver function (group 1) had good or intermediate velocities. Thirteen of 15 patients with recurrent cholangitis (group 2) had good or intermediate velocities. Both patients in this group with abnormal velocities required transplantation. In group 3 the patient with abnormal velocity is on the transplant waiting list. In group 4, abnormal velocities preceded or coincided with deterioration of liver function in five of seven patients. Doppler ultrasound provides useful anatomic information, determines direction of flow, quantitates velocity of flow, and, when performed serially, provides adjunctive information on liver status in children with biliary atresia. These preliminary results suggest that patients with abnormal or significantly decreasing velocity are destined for transplantation. Patients with good portal venous velocity warrant ongoing, aggressive surgical management.

Long-term survival after Kasai's operation for biliary atresia

Long-term survival of biliary atresia patients after Kasai hepaticoportoenterostomy is being increasingly reported. Prognostic factors indicative of a favorable long-term outcome consist of: (1) early age at operation; (2) bilirubin excretion of at least 6 mg daily 1 month after operation; (3) favorable hepatic histology at the time of operation; and (4) low incidence of postoperative cholangitis. Jaundice-free long-term survival is now attained in from one-fourth to one-third of patients undergoing Kasai hepaticoportoenterostomy by experienced surgeons in the Western hemisphere. In many long-term survivors there is normalization of liver function, improvement in hepatic histology, and resolution of the complications of portal hypertension. Most patients in this category have made a normal adjustment to their disease and lead active adolescent and adult lives.

Biliary atresia: perspective on transplantation

In North America, long-term, jaundice-free survival following Kasais operation for biliary atresia is 25%–35%; thus, the majority of patients require liver transplantation for salvage. The timing of organ replacement is crucial. Patients without bile drainage because of either surgical election or operative failure should be referred immediately. Patients with ongoing but inadequate biliary drainage should be referred at a time that coincides with a plateau of the growth curve or if cholangitis is recalcitrant. Portal hypertension itself is not an indication for transplantation irrespective of its manifestations. Ascites, however, when primarily due to hypoalbuminemia, is a solid indication for transplantation. Other tests of liver function are generally unreliable. Factors found to be unimportant or of questionable adverse impact on transplant outcome include previous operation, coexisting infection limited to the liver, nonpatent portal vein, and/or abnormal liver function tests. The only factor that was found to significantly influence outcome was patient size and age. Thus, bile drainage after Kasai portoenterostomy, by permitting growth, improves the chances for a favorable outcome. Transplant 1-year survival is from 60% to 88%. Liver replacement is not without complications, namely technical errors, infection, and rejection. Nonetheless, in a majority of cases hepatic transplantation provides the only opportunity for high-quality long-term survival.