DIAGNOSTIC PROBLEMS IN HEPATOLOGY

CASE REPORT

A 4-month-old former 30-week premature infant presented with jaundice. Upon discharge from the newborn intensive care unit at 6 weeks of age, his direct bilirubin was 0.5 mg/dL (normal = < 0.3 mg/dL). Evaluation at 4 months of age included standard biochemical screening assays and an abdominal ultrasound, which demonstrated hepatosplenomegaly, ascites, and reversal of blood flow in the portal vein. A percutaneous liver biopsy revealed cirrhosis, cholestasis, and bile ductular proliferation. Given his advanced age and the presence of cirrhosis, a portoenterostomy was not performed. Supportive care, including fat soluble vitamins and a medium chain triglyceride containing formula, was administered.

He failed to thrive and was referred for possible liver transplant evaluation at 7 months of age. External examination was remarkable for jaundice and normal facial features. The liver was firm, nodular and palpable 8 cm below the right costal margin, and the spleen was palpable 2 cm below the left costal margin. No cardiac murmur was appreciated. There were ascites, and diminished muscle mass and subcutaneous adipose tissue. Laboratory evaluations revealed a total bilirubin of 12.7 mg/dL (normal ≤ 1.0 mg/dL), an albumin of 3.1 g/dL (normal = 3.9-5.0 g/dL), alkaline phosphatase of 724 U/L (normal = 145-420 U/L), gamma-glutamyl transpeptidase of 643 U/L (normal = 5-32 U/L), and a prothrombin time of 13 seconds (control = 11-15 seconds). Magnetic resonance cholangiopancreatography (MRCP) demonstrated focal areas of cystic dilatation, as well as some beading of the intrahepatic biliary system. The entire extrahepatic biliary system was massively dilated. The gallbladder was normal (Fig. [1]). There was no evidence of renal disease, including normal creatinine, urine analysis, renal ultrasonography, and renal magnetic resonance imaging. Living-related left lateral segment orthotopic liver transplantation was performed 3 weeks after initial evaluation for indications including intractable ascites, failure to thrive, and cholangitis. Post-operative chylous ascites was treated conservatively and the patient was discharged 23 days after the transplant. Follow-up at 6 months has been unremarkable with tacrolimus- based primary immunosuppression.

REFERENCES

• 1 Suchy F J, Shneider B L. Neonatal jaundice and cholestasis. In: Kaplowitz N, ed. Liver and Biliary Diseases Philadelphia: Williams & Wilkins 1996: 495-510
• 2 Balistreri W, Grand R, Hoofnagle J. Biliary atresia: Current concepts and research directions.  Hepatology . 1996;  23 1682-1692
• 3 Smith F EM, Miller V, Doughty I M, Patel L, David T J. Severe jaundice in two infants with cystic fibrosis.  J Royal Soc Med . 1996;  89 289P-290P
• 4 Nebbia G, Hadchouel M, Odievre M, Alagille D. Early assessment of evolution of liver disease associated with a1-antitrypsin deficiency in childhood.  J Pediatr . 1983;  102 661-665
• 5 De V ree, Jacquemin E, Sturm E. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis.  Proc Natl Acad Sci USA . 1998;  95 282-287
• 6 Amedee-Manesme O, Bernard O, Brunelle F. Sclerosing cholangitis with neonatal onset.  J Pediatr . 1987;  111 225-229
• 7 Crittenden S L, McKinley M J. Choledochal cyst-clinical features and classification.  Am J Gastroenterol. . 1985;  80 643-647
• 8 Forbes A, Murray-Lyon I M. Cystic disease of the liver and biliary tract.  Gut . 1991;  S116-S122 (S116-S122)
• 9 Miyano T, Yamataka A. Choledochal cysts.  Curr Opin Pediatr . 1997;  9 283-288
• 10 Chapman R W. Risk factors for biliary tract carcinogenesis.  Ann Oncol . 1999;  S308-S311 (S308-S311)
• 11 Savader S J, Benenati J F, Venbrux A C. Choledochal cysts: Classification and cholangiographic appearance.  AJR Am J Roentgenol . 1991;  156 327-331
• 12 Caroli J. Diseases of the intrahepatic biliary tree.  Clin Gastroenterol . 1973;  2 147-161
• 13 Desmet V J. Congenital diseases of intrahepatic bile ducts: Variations on the theme ``ductal plate malformation''.  Hepatology . 1992;  16 1069-1083
• 14 Summerfield J A, Nagafuchi Y, Sherlock S, Cadafalch J, Scheuer P J. Hepatobiliary fibropolycystic diseases.  A clinical and histological review of 51 patients. J Hepatol . 1986;  2 141-156
• 15 Theise N D, Miller F, Worman H J. Bilary cystadenocarcinoma arising in a liver with fibropolycystic disease.  Arch Pathol Lab Med . 1993;  117 163-165
• 16 Taylor A C, Palmer K R. Caroli's disease.  Eur J Gastroenterol Hepatol . 1998;  10 105-108
• 17 Desmet V J. What is congenital hepatic fibrosis?.  Histopathology . 1992;  20 465-477
• 18 Sherlock S, Dooley J. Diseases of the Liver and Biliary System.  Oxford: Blackwell Scientific, 1993: 548-555
• 19 Oldham K T, Hart M J, White T T. Choledochal cysts presenting in late childhood and adulthood.  Am J Surg . 1981;  141 568-571
• 20 Tandon R K, Grewal H, Anand A C, Vashisht S. Caroli's syndrome: A heterogeneous entity.  Am J Gastroenterol . 1990;  85 170-173
• 21 Rao P LNG, Pathak I C, Datta D V. Choledochal cyst associated with intra hepatic cysts (Caroli's disease).  Indian Pediatr . 1978;  15 965-967
• 22 Pinto R B, Lima J P, da Silveira TR, et a l. Caroli's disease: Report of 10 cases in children and adolescents in southern Brazil.  J Pediatr Surg . 1998;  33 1531-1535
• 23 Lilly J R. Surgery of coexisting biliary malformations in choledochal cyst.  J Pediatr Surg . 1979;  14 643-647
• 24 Barros J L, Polo J R, Sanabia J, Garcia-Sabrido J L, Gomez-Lorenzo F J. Congenital cystic dilatation of the intrahepatic bile ducts (Caroli's disease): Report of a case and review of the literature.  Surgery . 1979;  85 589-592
• 25 Gupta R, Pruthi H S, Baijal S S, Saraswat V A. An unusual choledochal cyst.  J Gastroenterol Hepatol . 1997;  12 771-774
• 26 Kim M H, Ryu J S, Yang S K. Three cases of congenital hepatic fibrosis with Caroli's disease in three siblings.  Korean J Intern Med . 1990;  5 101-107
• 27 Lake D N, Smith P M, Wheeler M H. Congenital hepatic fibrosis and choledochus cyst.  Br Med J . 1977;  2 1259-1260
• 28 Nakanuma Y, Terada T, Ohta G, Kurachi M, Matsubara F. Caroli's disease in congenital hepatic fibrosis and infantile polycystic disease.  Liver . 1982;  2 346-354
• 29 Evans-Jones G, Cudmore R. Choledochal cyst and congenital hepatic fibrosis.  J Pediatr Surg . 1990;  25 1259-1260
• 30 Fujiwara Y, Ohizumi T, Kakizaki G, Fujiwara T. Congenital dilatation of intrahepatic and common bile ducts with congenital hepatic fibrosis.  J Pediatr Surg . 1976;  11 273-274
• 31 Todani T, Watanabe Y, Narusue M, Tabuchi K, Okajima K. Congenital bile duct cysts: Classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst.  Am J Surg . 1977;  134 263-269
• 32 Todani T, Narusue M, Watanabe Y, Tabuchi K, Okajima K. Management of congenital choledochal cyst with intrahepatic involvement.  Ann Surg . 1978;  187 272-280
• 33 O'Neill Jr J A. Choledochal cyst.  Curr Probl Surg . 1992;  29 363-410
• 34 D'Agata I D, Jonas M M, Perez-Atayde A R, Guay-Woodford L M. Combined cystic disease of the liver and kidney.  Semin Liver Dis . 1994;  14 215-228
• 35 Lilly J R. The surgical treatment of choledochal cyst.  Surg Gynecol Obstet . 1979;  149 36-42
• 36 Moore K C. Persaud TVN.  The Developing Human. Philadelphia: W.B. Saunders 1993: 243
• 37 Desmet V J. Ludwig symposium on biliary disorders-part I. Pathogenesis of ductal plate abnormalities.  Mayo Clin Proc . 1998;  73 80-89
• 38 Blankenberg T A, Lund J K, Ruebner B H. Normal and abnormal development of human intrahepatic bile ducts. An immunohistochemical perspective.  Perspect Pediatr Pathol . 1991;  14 143-167
• 39 Jorgensen M J. The ductal plate malformation.  Acta Pathol Microbiol Scand Suppl . 1977;  257 1-87
• 40 Babbitt D P, Starshak R J, Clemett A R. Choledochal cyst: A concept of etiology.  Am J Roentgenol Radium Ther Nucl Med . 1973;  119 57-62
• 41 Yamashiro Y, Miyano T, Suruga K, Shimomura H, Suda K, Matsumoto M, Nittono H. Experimental study of the pathogenesis of choledochal cyst and pancreatitis, with special reference to the role of bile acids and pancreatic enzymes in the anomalous choledocho-pancreatico ductal junction.  J Pediatr Gastroenterol Nutr . 1984;  3 721-727
• 42 Martinez J R, Grantham J J. Polycystic kidney disease: Etiology, pathogenesis, and treatment.  Disease-a-Month . 1995;  61 695-765
• 43 Watnick T, Germino G G. Molecular basis of autosomal dominant polycystic kidney disease.  Semin Nephrol . 1999;  19 327-343