Prognosis of Uncorrected Biliary Atresia: An Update By Susan Adelman • In order to provide a baseline for comparison with the results of the Kasai hepatic portoenterostomy, follow-up information was obtained for 89 infants who underwent surgical exploration alone for biliary atresia from 1956 through 1975. Of these patients, one is apparently cured. one is alive with liver failure. three are lost to follow-up and 84 are dead. The rate of apparent cure among patients with follow-up was 1.1 %. The average age at death was 12 rna, the mean 10 mo. During this same period. nine patients were operated upon for neonatal biliary obstructions other than biliary atresia. and five are apparently cured. Reported apparent cure rates after the Kasai procedure or one of its variations. while not good. still compare favorably with the cure rate of unoperated patients.
INDEX WORDS: Biliary atresia; hepatic portoenterostomy.
T
HE PREVIOUSLY accepted operative approach to biliary atresia is now challenged by the Kasai hepatic portoenterostomy. The standard approach in the past was to perform an exploratory laparotomy and an operative cholangiogram in all cases and then proceed with a biliary-enteric anastomosis only if a localized cystic dilatation of the biliary tree was found. In contrast, Kasai I and others" have advocated resection of the atretic common duct followed by construction of a Roux-en-Y anastomosis between the jejunum and transected porta hepatis in the absence of any localized cystic dilatation. Reported apparent cure rates for the Kasai hepatic portoenterostomy have ranged from 0%;\ to 36%." Survival rates of patients after traditional exploration and cholangiogram without anastomosis are not as well documented in the literature. Discussions of this topic frequently include reports of patients who seemed to have spontaneous remissions of their biliary obstruction following exploratory laparotomy alone. It is in part because of these patients that surgeons have been reluctant to perform the Kasai en bloc resection of the atretic common bile duct, thus rendering spontaneous remissions impossible. A desire to document whether or not these patients with remissions actually exist prompted the present study.
Journal of Pediatric Surgery. Vol. 13, No.4 (August). 1978
MATERIALS AND METHODS The files of the Children's Hospital of Michigan's Department of Pathology were searched for infants who had undergone liver biopsy for obstructive jaundice from 1956 through 1975. Mortality statistics on patients with mechanical obstruction of the biliary tract were obtained from hospital charts, autopsy reports, office records of attending pediatricians, and death certificates from the Michigan Department of Public Heal tho Only three patients were lost to follow-up.
RESULTS
Of all the patients who underwent liver biopsy during this time, 89 were diagnosed as having biliary atresia. An additional 6 patients had choledochal cysts, 2 had hypoplastic biliary ducts, I had bile duct plug syndrome," 2 had atypical obstructive jaundice, 84 had neonatal hepatitis, 3 had alpha-I-antitrypsin deficiency, and 3 had other nonobstructive liver disease. Of the 89 patients with extrahepatic biliary atresia, 84 patien ts are dead, 2 patients are alive, and 3 patients are lost to follow-up (Table 1). The age at death ranged from 2 mo to 4 yr, with an average of 12 mo and a mean of 10 mo. Sixteen children underwent surgical exploration after 12 wk of age, and the average survival of these children was 14.5 mo, including the longest survivor, who was explored at 10 mo of age and died at the age of 4 yr. Of the living patients, one has jaundice and cirrhosis at 3 yr of age and is not expected to survive. The other patient had a liver biopsy that was originally interpreted as consistent with an extrahepatic obstruction and an operative cholangiogram that filled a small gallbladder but no biliary ducts. At 6 mo of age, jaundice had inexplicably cleared and he is now anicteric at 11 yr of age. Although it is tempting to call him a diagnostic error, we have included him in this report as a biliary atresia, since nothing that was seen at
From the Department of Pediatric Surgery. Children's Hospital of Michigan and Wayne State University. Detroit, Mich. Address reprint requests to Susan Adelman, M.D., 3800 Woodward, Suite /016, Detroit, Mich. 48201. © 1978 by Grune & Stratton, Inc. 0022-3468/78/1304-0010$01.00/0
389
390
SUSAN ADELMAN
Table 1. Patients Who Underwent Exploration Without Corrective Procedure for Biliary Atresia From 1956 Through 1976· Total patients Alive Icteric Anicteric Dead Lost to follow-up
89 2
84 3
• At the Children's Hospital of Michigan.
laparotomy or on liver biopsy could have prevented the surgeon or pathologist from making that diagnosis. Two atypical patients with obstructive jaundice have been excluded from our series of patients with biliary atresia, but they still remain diagnostic dilemmas. One child, a microcephalic, had a preoperative duodenal aspirate that contained bile. Laparotomy was performed at I mo of age, and a cholangiogram showed a normal gallbladder, cystic duct, and common duct, with reflux into the pancreatic duct. The gallbaldder contained bile, but all visible proximal biliary ducts were atretic. He is alive and free ofjaundice 12 yr later. The second patient, after four exchange transfusions in the neonatal period, had a percutaneous liver biopsy at 3 wk of age that showed an obstructive pattern. However, within I wk after the biopsy, the jaundice began to resolve, and he was discharged without exploration. He remained anticteric and was apparently normal when last seen at 6 yr of age. DISCUSSION
After a complete history and physical examination, any infant over 2 wk of age with an increased conjugated bilirubinemia has laboratory determinations of liver enzymes, urinary reducing substances, viral titers for toxoplasmosis, rubella, cytomegalovirus and hepatitis, and alpha-I-antitrypsin levels. If the diagnosis of biliary atresia is still entertained, the patient has a liver biopsy, usually done percutaneously, We do not use rose bengal or other ancillary diagnostic techniques since the rate of diagnostic error in interpretation of the liver biopsy at this institution has been only 6.3%:' In the past, if the biopsy was read as consistent with extrahepatic biliary obstruction, the patient was explored in the standard fashion, and a liver biopsy and an operative
cholangiogram were obtained. Patients who underwent hepatic portoenterostomies since 1976 have been excluded from this report. It is interesting to note that among the patients with hepatitis, 57 were male and 27 female. Most series show a more striking predominance of females among the infants with atresia and males among those with hepatitis. We know of no particular reason why our series should differ, unless perhaps in the past the apparent sex difference between the two groups had been overemphasized. Out of 89 patients who were found to have biliary atresia at laparotomy, only the one unusual patient and the three patients who were lost to follow-up could possibly have been cured. In the th ree lost cases, though, no aspect of either the hospital course or operative findings has suggested that they might have done unusually well. Thus, of the biliary atresia patients alone, survival among patients with adequate followup was 1.1%. The patients who had been remembered as cases of spontaneous resolution included the one true long-term survivor previously mentioned, the patients with the atypical findings at laparotomy, the patient whose jaundice cleared after percutaneous liver biopsy alone, and several actually discharged with diagnoses other than biliary atresia, including infants with alpha-I-antitrypsin deficiency, hypoplastic ducts, bile duct plug syndrome, and several whose diagnoses were finally confirmed as neonatal hepatitis after remaining in doubt in the immediate postoperative period. Two previous reports have presented longterm follow-up of patients explored for biliary atresia. Hays and Synder" reported an average survival of 19 mo for 39 patients. Three of these patients lived to 4, 5, and 8 yr of age, respectively. It must be remembered, however, that in 1963, alpha-I-antitrypsin deficiency liver disease had not yet been recognized, so that one or several of these long-term survivors might have had the deficiency instead of biliary atresia. Danks et al." explored 48 of 50 patients and had one cure. In the same paper they presented a contrasting group of eight other patients who underwent Kasai's hepatic portoenterostomy, of whom four were alive and well at 4-6 yr postoperatively." Campbell et al." reported 100% mortality
391
UNCORRECTED BILIARY ATRESIA
among 9 patients after a Kasai hepatic portoenterostomy, with an average survival of 15.3 mo from the time of surgery. They emphasized the fact that their average survival was even shorter than that achieved by Hays and Snyder.' Compared to the 12-mo average survival reported in this paper, it was actually a modest improvement. This may reflect the absence in Hays and Snyder's report of longterm patients, any of thom could have had alpha-I-antitrypsin disease. For a valid comparison of surgical exploration with the results of the Kasai procedure, only the 89 patients in this series who were thought to have had biliary atresia at laparotomy should be considered. Ninety-three patients diagnosed by liver biopsy to have alpha-I-antitrypsin deficiency, neonatal hepatitis, or other nonobstructive liver disease, as well as 6 with choledochal cysts, I with bile plug syndrome, and 2 with hypoplastic biliary ducts have been rigorously excluded from this report. Only one infant could
have been potentially harmed by sacrifice of the atretic common duct as is necessary in the Kasai procedure. On the other hand, the apparent cure rate among patients found to have biliary atresia at the time of exploration, excluding the 3 lost patients and the I who is now terminal, was 1.1 %. In contrast, the best preliminary reports of apparent cure rates for the Kasai procedure are 14 %, I 15 %,4 23 %,2 and 36% .:1 Further follow-up will be necessary to clarify these figures and to establish this comparison. ACKNOWLEDGMENTS I am indebted to all the members of the Department of Surgery, Children's Hospital of Michigan, whose cases were included in this study; to A. Joseph Brough, M.D., Chief of Laboratory Medicine, CHM, and Associate Professor of Pathology, WSU, both for his assistance and for the use of the Pathology Department records, and to Ronald L. Poland, M.D., Associate Professor of Pediatrics, WSU, and Director of Newborn Services, CHM, for his helpful suggestions.
REFERENCES I. Kasai M: Treatment of biliary atresia with special
reference to hepatic portoenterostomy and its modifications. Prog Pediatr Surg 6:5, 1974 2. Lilly JR, Altman RP. Hepatic portoenterostomy (the Kasai operation) for biliary atresia. Surgery 78:76, 1975 3, Campbell DP, Smith EI, Bhatia M, et al: Hepatic portoenterostorny: An assessment of its value in the treatment of biliary atresia. Ann Surg 181:591, 1975 4. Hays OM: Biliary atresia: The current state of confusion. Surg Clin North Am 53:1257,1973
5. Brough AJ, Bernstein J: Conjugated hyperbilirubinemia in early infancy: A reassessment of liver biopsy. Human Pathol 5:507, 1974 6. Bernstein J, Braylan R, Brough AJ: Bile-plug syndrome: A correctable cause of obstructive jaundice in infants. Pediatrics 43:272, 1969 7. Hays OM, Snyder WH: Life-span in untreated biliary atresia, Surgery 54:373, 1963 8. Danks OM, Campbell PE, Clarke AM, et al: Extrahepatic biliary atresia, Am J Dis Child 128:684, 1974 9. Danks OM: Personal communication
INDEX WORDS: Biliary atresia; hepatic portoenterostomy.
T
HE PREVIOUSLY accepted operative approach to biliary atresia is now challenged by the Kasai hepatic portoenterostomy. The standard approach in the past was to perform an exploratory laparotomy and an operative cholangiogram in all cases and then proceed with a biliary-enteric anastomosis only if a localized cystic dilatation of the biliary tree was found. In contrast, Kasai I and others" have advocated resection of the atretic common duct followed by construction of a Roux-en-Y anastomosis between the jejunum and transected porta hepatis in the absence of any localized cystic dilatation. Reported apparent cure rates for the Kasai hepatic portoenterostomy have ranged from 0%;\ to 36%." Survival rates of patients after traditional exploration and cholangiogram without anastomosis are not as well documented in the literature. Discussions of this topic frequently include reports of patients who seemed to have spontaneous remissions of their biliary obstruction following exploratory laparotomy alone. It is in part because of these patients that surgeons have been reluctant to perform the Kasai en bloc resection of the atretic common bile duct, thus rendering spontaneous remissions impossible. A desire to document whether or not these patients with remissions actually exist prompted the present study.
Journal of Pediatric Surgery. Vol. 13, No.4 (August). 1978
MATERIALS AND METHODS The files of the Children's Hospital of Michigan's Department of Pathology were searched for infants who had undergone liver biopsy for obstructive jaundice from 1956 through 1975. Mortality statistics on patients with mechanical obstruction of the biliary tract were obtained from hospital charts, autopsy reports, office records of attending pediatricians, and death certificates from the Michigan Department of Public Heal tho Only three patients were lost to follow-up.
RESULTS
Of all the patients who underwent liver biopsy during this time, 89 were diagnosed as having biliary atresia. An additional 6 patients had choledochal cysts, 2 had hypoplastic biliary ducts, I had bile duct plug syndrome," 2 had atypical obstructive jaundice, 84 had neonatal hepatitis, 3 had alpha-I-antitrypsin deficiency, and 3 had other nonobstructive liver disease. Of the 89 patients with extrahepatic biliary atresia, 84 patien ts are dead, 2 patients are alive, and 3 patients are lost to follow-up (Table 1). The age at death ranged from 2 mo to 4 yr, with an average of 12 mo and a mean of 10 mo. Sixteen children underwent surgical exploration after 12 wk of age, and the average survival of these children was 14.5 mo, including the longest survivor, who was explored at 10 mo of age and died at the age of 4 yr. Of the living patients, one has jaundice and cirrhosis at 3 yr of age and is not expected to survive. The other patient had a liver biopsy that was originally interpreted as consistent with an extrahepatic obstruction and an operative cholangiogram that filled a small gallbladder but no biliary ducts. At 6 mo of age, jaundice had inexplicably cleared and he is now anicteric at 11 yr of age. Although it is tempting to call him a diagnostic error, we have included him in this report as a biliary atresia, since nothing that was seen at
From the Department of Pediatric Surgery. Children's Hospital of Michigan and Wayne State University. Detroit, Mich. Address reprint requests to Susan Adelman, M.D., 3800 Woodward, Suite /016, Detroit, Mich. 48201. © 1978 by Grune & Stratton, Inc. 0022-3468/78/1304-0010$01.00/0
389
390
SUSAN ADELMAN
Table 1. Patients Who Underwent Exploration Without Corrective Procedure for Biliary Atresia From 1956 Through 1976· Total patients Alive Icteric Anicteric Dead Lost to follow-up
89 2
84 3
• At the Children's Hospital of Michigan.
laparotomy or on liver biopsy could have prevented the surgeon or pathologist from making that diagnosis. Two atypical patients with obstructive jaundice have been excluded from our series of patients with biliary atresia, but they still remain diagnostic dilemmas. One child, a microcephalic, had a preoperative duodenal aspirate that contained bile. Laparotomy was performed at I mo of age, and a cholangiogram showed a normal gallbladder, cystic duct, and common duct, with reflux into the pancreatic duct. The gallbaldder contained bile, but all visible proximal biliary ducts were atretic. He is alive and free ofjaundice 12 yr later. The second patient, after four exchange transfusions in the neonatal period, had a percutaneous liver biopsy at 3 wk of age that showed an obstructive pattern. However, within I wk after the biopsy, the jaundice began to resolve, and he was discharged without exploration. He remained anticteric and was apparently normal when last seen at 6 yr of age. DISCUSSION
After a complete history and physical examination, any infant over 2 wk of age with an increased conjugated bilirubinemia has laboratory determinations of liver enzymes, urinary reducing substances, viral titers for toxoplasmosis, rubella, cytomegalovirus and hepatitis, and alpha-I-antitrypsin levels. If the diagnosis of biliary atresia is still entertained, the patient has a liver biopsy, usually done percutaneously, We do not use rose bengal or other ancillary diagnostic techniques since the rate of diagnostic error in interpretation of the liver biopsy at this institution has been only 6.3%:' In the past, if the biopsy was read as consistent with extrahepatic biliary obstruction, the patient was explored in the standard fashion, and a liver biopsy and an operative
cholangiogram were obtained. Patients who underwent hepatic portoenterostomies since 1976 have been excluded from this report. It is interesting to note that among the patients with hepatitis, 57 were male and 27 female. Most series show a more striking predominance of females among the infants with atresia and males among those with hepatitis. We know of no particular reason why our series should differ, unless perhaps in the past the apparent sex difference between the two groups had been overemphasized. Out of 89 patients who were found to have biliary atresia at laparotomy, only the one unusual patient and the three patients who were lost to follow-up could possibly have been cured. In the th ree lost cases, though, no aspect of either the hospital course or operative findings has suggested that they might have done unusually well. Thus, of the biliary atresia patients alone, survival among patients with adequate followup was 1.1%. The patients who had been remembered as cases of spontaneous resolution included the one true long-term survivor previously mentioned, the patients with the atypical findings at laparotomy, the patient whose jaundice cleared after percutaneous liver biopsy alone, and several actually discharged with diagnoses other than biliary atresia, including infants with alpha-I-antitrypsin deficiency, hypoplastic ducts, bile duct plug syndrome, and several whose diagnoses were finally confirmed as neonatal hepatitis after remaining in doubt in the immediate postoperative period. Two previous reports have presented longterm follow-up of patients explored for biliary atresia. Hays and Synder" reported an average survival of 19 mo for 39 patients. Three of these patients lived to 4, 5, and 8 yr of age, respectively. It must be remembered, however, that in 1963, alpha-I-antitrypsin deficiency liver disease had not yet been recognized, so that one or several of these long-term survivors might have had the deficiency instead of biliary atresia. Danks et al." explored 48 of 50 patients and had one cure. In the same paper they presented a contrasting group of eight other patients who underwent Kasai's hepatic portoenterostomy, of whom four were alive and well at 4-6 yr postoperatively." Campbell et al." reported 100% mortality
391
UNCORRECTED BILIARY ATRESIA
among 9 patients after a Kasai hepatic portoenterostomy, with an average survival of 15.3 mo from the time of surgery. They emphasized the fact that their average survival was even shorter than that achieved by Hays and Snyder.' Compared to the 12-mo average survival reported in this paper, it was actually a modest improvement. This may reflect the absence in Hays and Snyder's report of longterm patients, any of thom could have had alpha-I-antitrypsin disease. For a valid comparison of surgical exploration with the results of the Kasai procedure, only the 89 patients in this series who were thought to have had biliary atresia at laparotomy should be considered. Ninety-three patients diagnosed by liver biopsy to have alpha-I-antitrypsin deficiency, neonatal hepatitis, or other nonobstructive liver disease, as well as 6 with choledochal cysts, I with bile plug syndrome, and 2 with hypoplastic biliary ducts have been rigorously excluded from this report. Only one infant could
have been potentially harmed by sacrifice of the atretic common duct as is necessary in the Kasai procedure. On the other hand, the apparent cure rate among patients found to have biliary atresia at the time of exploration, excluding the 3 lost patients and the I who is now terminal, was 1.1 %. In contrast, the best preliminary reports of apparent cure rates for the Kasai procedure are 14 %, I 15 %,4 23 %,2 and 36% .:1 Further follow-up will be necessary to clarify these figures and to establish this comparison. ACKNOWLEDGMENTS I am indebted to all the members of the Department of Surgery, Children's Hospital of Michigan, whose cases were included in this study; to A. Joseph Brough, M.D., Chief of Laboratory Medicine, CHM, and Associate Professor of Pathology, WSU, both for his assistance and for the use of the Pathology Department records, and to Ronald L. Poland, M.D., Associate Professor of Pediatrics, WSU, and Director of Newborn Services, CHM, for his helpful suggestions.
REFERENCES I. Kasai M: Treatment of biliary atresia with special
reference to hepatic portoenterostomy and its modifications. Prog Pediatr Surg 6:5, 1974 2. Lilly JR, Altman RP. Hepatic portoenterostomy (the Kasai operation) for biliary atresia. Surgery 78:76, 1975 3, Campbell DP, Smith EI, Bhatia M, et al: Hepatic portoenterostorny: An assessment of its value in the treatment of biliary atresia. Ann Surg 181:591, 1975 4. Hays OM: Biliary atresia: The current state of confusion. Surg Clin North Am 53:1257,1973
5. Brough AJ, Bernstein J: Conjugated hyperbilirubinemia in early infancy: A reassessment of liver biopsy. Human Pathol 5:507, 1974 6. Bernstein J, Braylan R, Brough AJ: Bile-plug syndrome: A correctable cause of obstructive jaundice in infants. Pediatrics 43:272, 1969 7. Hays OM, Snyder WH: Life-span in untreated biliary atresia, Surgery 54:373, 1963 8. Danks OM, Campbell PE, Clarke AM, et al: Extrahepatic biliary atresia, Am J Dis Child 128:684, 1974 9. Danks OM: Personal communication
