CAROLI'S DISEASE ASSOCIATED WITH CONGENITAL HEPATIC FIBROSIS AND RENAL TUBULAR ECTASIA

Transcription

1 GASTROENTEROLOGY 66: ; by The Williams & Wilkins Co. Vol. 66, No. 5 Printed in U.S.A. CAROLI'S DISEASE ASSOCIATED WITH CONGENITAL HEPATIC FIBROSIS AND RENAL TUBULAR ECTASIA A case report JAY C. MALL, M.D., GARY G. GHAHREMANI, M.D., AND J. L. BOYER, M.D. Departments of Radiology and Medicine, The University of Chicago, Pritzker School of Medicine, Chicago. Illinois A case of communicating cavernous ectasia of the intrahepatic bile ducts associated with congenital hepatic fibrosis and renal tubular ectasia is presented. Intravenous cholangiogram and rose bengal scanning permitted the diagnosis of saccular dilatation of intrahepatic bile ducts to be suspected. Pertinent clinical features of previously reported cases are also reviewed. Various types of congenital anomalies of the gallbladder and the common bile duct have been described in the medical literature Malformations of the intrahepatic biliary ductal system, however, are uncommon, and the following report concerns one of the rare examples. The disease entity first described by Caroli and associates,3 is characterized by: (1) congenital.saccular dilatation of the intrahepatic bile ducts; (2) high incidence of stone formation and cholangitis; (3) absence of hepatic cirrhosis and portal hypertension; (4) association with renal tubular ectasia or other forms of cystic disease of kidneys, and possibly, of the pancreas. Since the original description of this entity in 1958, there have been approximately 30 documented cases described in the world literature ' However, the pure form, as described above, has been uncommon. Most of the cases subsequently reported, as in our case, have had coexisting hepatic fibrosis. Other cases have probably remained unrecognized or have been mistakenly diagnosed as polycystic disease of the liver and kidneys. In none of the Received October 10, Accepted November 5, Address requests for reprints to: J. C. Mall, M.D., Department of Radiology, The University of Chicago. 950 E. 59th Street. Chicago, Illinois reported cases has the correct diagnosis been established preoperatively. In this report, we present a patient in whom the correct diagnosis was suggested by radiologic and isotope studies and was subsequently confirmed at surgery and by liver biopsy. Case Report A 20-year-old white female was admitted to the University of Chicago Hospitals in July 1965 for evaluation of recurrent abdominal pain. During the previous 2 years she had had several episodes of crampy pain in the epigastrium and the right upper abdomen. These were attributed to probable gallbladder disease because of nonvisualization on an oral cholecystogram. A hospitalization 3 months earlier was due to infectious mononucleosis and an attack of acute pancreatitis with elevation of serum amylase and lipase. Mild jaundice and low grade fever present at that time had resolved, and she was asymptomatic at the time of her fourth admission in July Physical examination revealed slight tenderness of the liver which was felt 2 cm below the right costal margin and measured 12 cm over-all by percussion. The spleen was not palpable. The examination was otherwise unremarkable. The past history indicated that she had been "sickly" all her life, often treated for "spastic colon," and had a urinary tract infection at age 6 with frequency and hematuria at that time. Significant family history included that her sister had a "kidney problem," her grandfather was found to have

2 1030 MALL ETAL. Vol. 66, No.5 "'cystic disease of kidneys" at autopsy, and her father had hypertension said to be due to "'nephritis... Laboratory data at the time of admission FIG. 1. Intravenous cholangiogram demonstrating multiple patchy collections of contrast material within the liver parenchyma. were: normal complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, and creatinine; total serum bilirubin, 0.7 mg per 100 ml; direct serum bilirubin, 0.3 mg per 100 ml; serum glutamic oxaloacetic transaminase, 34 units; serum glutamic pyruvic transaminase, 17 units; alkaline phosphatase, 3.8 Bodansky units. Plain radiographs of the abdomen did not demonstrate any opaque stones in the region of the gallbladder or kidneys. Two oral cholecystograms performed with 3 and 6 g of Telepaque (Winthrop Laboratories, New York, N. Y.) failed to opacify the gallbladder; therefore, an intravenous cholangiogram was done. This demonstrated multiple patchy collections of contrast material within the liver (fig. 1). The findings were interpreted as pooling of the contrast material in the intrahepatic biliary system due to dilatation and cholestasis. This was interpreted as being due to either a congenital abnormality or an incomplete biliary ductal obstruction and cholangitis. A 99mTc sulfur colloid scintigram of the liver demonstrated patchy distribution of the uptake. This study was repeated using rose bengal. Again, the distribution of isotope in the liver was irregular, with prolonged retention and slow drainage from the biliary ductal system (fig. 2), which retrospectively was consistent with saccular dilatation of intrahepatic ducts. Barium examinations of the gastrointestinal tract were normal. Further radiologic evaluations included a simultaneous celiac and superior mesenteric arteriogram which indicated only minimal tortuosity of the branches of hepatic arteries, and an intravenous pyelogram and bilateral selective renal arteriograms which demonstrated findings consistent with benign tubular ectasia FIG rose bengal liver scintigram. A, 10 min after injection. B, 20 hr after injection. The liver has an irregular patchy appearance with some isotope noted in the colon (arrow). This indicates decreased rate of bile drainage from dilated intrahepatic ducts.

3 May 1974 CARGUS DISEASE 1031 or so-called medullary sponge kidney (figs. 3 and 4). The patient subsequently underwent laparotomy with cholecystectomy and exploration of the common bile duct. The liver biopsy demonstrated extensive fibrosis around portal triads, FIG. 3. Intravenous pyelogram demonstrates "brushlike'.' collections of contrast material in the parenchyma adjacent to each calyx. the characteristic finding of benign tubular ectasia. many of which had developed portal-portal connections with sparing of central vein areas. However, within the portal triads there were large interlobular ducts of varying size without inflammatory infiltrate. There was marked pseudoductular transformation, particularly along the edges of the limiting plates, which were sharply demarcated from the portal triads and were striking for their lack of evidence of cell injury or inflammation. In contrast to the number and enlargement of the interlobular ducts, there was a paucity of portal veins apparent in the portal triads. These abnormalities were consistent with the diagnosis of congenital hepatic fibrosis (fig. 5). The resected gallbladder did not have any abnormality. An operative cholangiogram confirmed the preoperative findings of multiple saccular dilatations of intrahepatic biliary radicles despite patency of the hepatic and common ducts (fig. 6). Subsequent T-tube cholangiograms revealed no change in the degree of dilatation of the intrahepatic ducts even after continuous drainage of bile through the T-tube. No biliary calculi could be demonstrated on these examinations or at exploration. T-tube drainage was 200 to 400 ml per 24 hr, but stools were not acholic. No bile culture was obtained. From 1965 to 1972, the patient has been hospitalized for brief periods on six different occasions with abdominal pain, leukocytosis, fever, and abnormalities of liver function. An elevated serum amylase was also seen on one occasion. Between episodes, her liver function, including alkaline phosphatase, returned completely to normal, and she has otherwise remained well. FIG. 4. Selective renal arteriogram. A, arterial phase is normal. E, parenchymal phase demonstrating numerous small areas that do not fill with contrast material. This is consistent with the diagnosis of benign tubular ectasia.

4 1032 MALL ETAL. Vol. 66, No.5 FIG. 5. Portal area demonstrating fibrosis and dilatation of interlobular ducts consistent with congenital hepatic fibrosis m & E, x 82). Discussion Although the radiologic and pathologic features of Caroli's disease are characteristic, its clinical presentation is often nonspecific. The presence of only 30 previous cases in the world literature may not be entirely due to the rarity of the condition but may be a reflection of difficulties in clinical diagnosis and differentiation from other developmental abnormalities such as polycystic liver disease. 6, 26 The frequent finding of histologic evidence of congenital hepatic fibrosis in patients with Caroli's disease 7, 8, 26 indicates that saccular dilatation of intrahepatic ducts is not usually an isolated entity but represents only a portion of the spectrum of developmental abnormalities involving the biliary tree. Renal involvement is also common and is often manifested by renal tubular ectasia (so-called medullary sponge disease), a rather benign form of renal disease which does not result in renal failure. 9, 10, 27 The manner of inheritance of these conditions remains poorly defined since they have been observed in siblings but never in successive generations. 7 However, although overlap syndromes may occur, 28 Caroli's disease and congenital hepatic fibrosis probably differ from polycystic liver disease, which may be inherited as an autosomal dominant, 29 Polycystic disease of the liver also appears in older age groups and is usually clinically significant only because of the associated polycystic kidney disease, a severe form of renal disease frequently resulting in renal failure. The most apparent anatomical abnormality of the liver in Caroli's disease is best described by the designation "communicating cavernous ectasia of the intrahepatic bile ducts." This finding may also be associated with idiopathic dilatation of the hepatic and common bile duct In several cases, the anomalous changes were segmental and limited to one

5 May 1974 CAROLrS DISEASE 1033 FIG. 6. Operative cholangiogram demonstrating the characteristic segmental saccular dilatation of the intrahepatic ducts. The common duct is normal. lobe of the liver.4, 9, 13 In all instances, however, the areas of saccular dilatation were an integral part of the biliary ductal system and contained bile, contrasting with the findings in polycystic disease of the liver in which the cysts usually do not contain bile and do not communicate with the biliary ducts. The clinical manifestations of Caroli's disease are commonly recognized initially in children or young adults but occasionally are seen as late as the fifth decade. The nature of these manifestations depends on whether hepatic fibrosis or ectasia of the intrahepatic ducts is the predominant lesion. If it is the former, the clinical manifestations are mainly those of portal hypertension, and the most significant symptom is hematemesis. If it is the latter, the clinical manifestations are due to biliary stone formation, cholangitis, and, occasionally, liver abscess. The usual symptoms are repeated episodes of crampy upper abdominal pain with occasional fever and mild jaundice. Decreased appetite, weight loss, and tenderness of the liver without hepatomegaly are often present. Other conditions which may be confused with Caroli's disease in addition to those previously noted included sclerosing cholangitis and dilatation of the biliary ductal system due to obstructive tumors of the ampulla or head of the pancreas or to biliary tract stones. In most instances, a definitive diagnosis will require laparotomy and operative cholangiography. This rare condition should be considered in the differential diagnosis of patients with recurrent episodes of cholangitis, cholestasis, and biliary tract stones with or without evidence of portal hypertension. The diagnosis may be suggested by the demonstration of retained contrast material in the liver with a rather characteristic appearance following an intravenous cholangiogram (fig. 1). This finding has also been noted in several other cases. 13, 26 A scintigram of the liver performed with rose bengal provides corroborating evidence (fig. 2). This material is rapidly cleared by the liver and normally is excreted into the biliary tract within 1 hr and into the bowel within 2 hr. In our patient with Caroli's disease, however, the distribution of uptake was patchy, and the drainage into the bowel was significantly delayed; this latter finding only indicates that cholestasis is present and may be difficult to differentiate from incomplete obstruction of the extrahepatic ducts. Percutaneous transhepatic cholangiography

6 1034 MALL ET AL. Vol. 66,No. 5 would seem to be the ideal method for opacification of the dilated biliary ductal system of these patients. Unfortunately, none of the reported cases of Caroli's disease has had this examination. Although all the reported patients have had surgery, the limited number of patients and scarcity of follow-up data do not permit definitive conclusions regarding treatment and prognosis of Caroli's disease. Drainage of the common bile duct through a T-tube or a choledochoduodenostomy has been attempted,8. I. but only in 1 case has significant improvement been noted,6 and the procedure may actually increase the likelihood of cholangitis. Partial hepatectomy has been performed in a patient in whom the disease was limited to one lobe,9 but this procedure would obviously be of no value in patients with generalized liver involvement. Antibiotic therapy may be helpful in the acute episodes of cholangitis, but it is not known whether the ultimate clinical course will be significantly altered. Ten years of observation in this case suggests that the prognosis in Caroli's disease is not necessarily pessimistic. However, recurrent acute episodes of cholangitis, despite good medical management, are inevitable. Indeed, recurrent cholangitis, liver abscess, and septicemia have led to a fatal outcome in several previously reported cases. 3, 4, 8, Death due to sepsis, but associated with the development of cholangiocarcinoma 16 and amyloidosis, 17 has also been reported. REFERENCES 1. Braasch,]W: Congenital anomalies of the gallbladder and bile ducts. Surg Clin North Am 38: , Hayes MA, Goldenberg IS, Bishop CC: The developmental basis for bile duct anomalies. Surg Gynecol Obstet 107: , Caroli J, Soupault R, Kossakowski J, et al: La dilatation polykystique congenitale des voies biliaires intra-hepatiques: essai de classifi cation. Sem Hop Paris 34: , Caroli J, Couihaud C: Une affection nouvelle, sans doute congenitale, des voies biliaires: la dilatation kystique unilobaire des can au x hepatiques. Sem Hop Paris 34: , Caroli J, Eteve J, Emerit B: Un nouveau cas de dilatations kystiques congenitales de voies biliaires intra-hepatiques. Sem Hop Paris 36: , Guillemin G, Marcy J, Naudin E, et al: La dilatation kystique congenitale des voies biliaires intrahepatiques segmentaires. Arch Mal App Dig 54: , Hunter FM, Akdamar K, Sparks RD, et al: Congenital dilatation of the intrahepatic bile ducts. Am J Med 40: , Rosewarne MD: Cystic dilatation of the intrahepatic bile ducts. Br J Radiol 45: , Helou E, Farah M, Nasser W: Hepatectomie gauche pour dilatation congenitale des voies biliaires intra-hepatiques. Rev Int Hepatol 15: , Martin EE, Corcos V, Albano 0: La dilatation congenitale des voies biliaires intra-hepatiques segmentaires. Presse Med 73: , Esquerra-Gomez G, Riveros-Gamboa E: Case of multi-diverticular cystic dilatation of common and hepatic ducts. Am J Roentgenol Radium Ther Nucl Med 94: , Gots RE, Zuidema GD: Dilatation of the intrahepatic biliary ducts in a patient with a choledochal cyst. Am J Surg 119: , Mercadier M, Clott.]P, Melliere D, Bacourt F: Dilatation congenitale 'des voies biliaires intrahepatiques. Sem Hop Paris 44: , Lorenzo GA, Seed RW, Beal,]M: Congenital dilatation of the biliary tract. Am J Surg 121 : , Foti M, Mester Z: Durch Cholangiographie nachgewiesene Entwicklungsanomalien. Fortschr Geb Roentgenstr Nucklearmed 76: , Jones A W, Shreeve DR: Congenital dilatatioi intrahepatic biliary ducts with cholangiocarcinoma. Br Med J 2: , Fevery J, Tanghe R, Kerremans V. et al: Congenital dilatation of the intrahepatic bile ducts associated with the development of a myloidosis. Gut 13: , Halasz J, Mocsai L: Gallensteinbildung in den kongenitalen intrahepatischen Hohlraumen. Zentralbl Chir 87: , Arthur GW, Stewart JOR: Biliary cysts. Br J Surg 51: , Gilbertini G, Lode R, Torricelli A: Communicating cavernous ectasia of intrahepatic bile duct associated with mult iple cysts of the renal medulla. Panminerva Med 7: , Farah M, Helou E, Nasser W, etal: Un nouveau cas de "maladie de Caroli" avec dilatations geantes bilobaires segmentaires, compliquee de lithiase et guerie chirurgicalement. Rev Med Chil 41: , Benintendi V, Bressan G: Contributo alia conos-

7 May 1974 CARGLfS DISEASE 1035 cenza della dilatazione cistica congenita segmentaria delle vie biliaire intrahepatiche. Acta Chir Ital 29: , Turnberg LA, Jones EA, Sherlock S: Biliary secretion in a patient with cystic dilatation of the intrahepatic biliary tree. Gastroenterology 54: , Mujahed Z, Glenn F, Evans JA: Communicating cavernous ectasia of the intrahepatic ducts (Caro Ii's disease). Am J Roentgenol Radium Ther Nucl Med 113:21-26, Kelly MJ: Case of Caroli's disease. Br Med J 4:407, Caroli J, Core os V: La dilatation congenitale des voies biliaires intrahepatiques. Rev Med Chir Mal Foie 39: 1-15, Reilly BJ, Neuhauser EBD: Renal tubular ectasia in cystic disease of the kidney and liver. Am J Roentgenol Radium Ther Nucl Med 84: , Murray-Lyon 1M, Ockenden BG, Williams R: Congential hepatic fibrosis-is it a single clinical entity? Gastroenterology 64: , Foulk WT: Congenital malformations of the intrahepatic biliary tree in the adult. Gastroenterology 58: , 1970