Abstract
We carried out a retrospective study of 71 patients with congenital non-hemolytic hyperbilirubinemia who had been treated at our institution over the 25 years from 1965 to 1990. Twenty patients had Gilbert's syndrome, 1 had Crigler-Najjar syndrome, 1 had new type unconjugated hyperbilirubinemia, 21 had Dubin-Johnson syndrome, and 28 had Rotor's syndrome. We also reviewed 20 patients with constitutional indocyanine green (ICG) excretory defect. The study focused on the hepatic transport of serum bilirubin, bromsulfophthalein (BSP), and ICG. In Dubin-Johnson syndrome, a defect appeared in late-stage transport, while uptake and storage capacity were normal. In Rotor's syndrome, defects were found in the early stage, and storage capacity was reduced, while excretion into bile was slightly suppressed. A secondary rise in serum ICG was seen in 5 of the 10 patients with Dubin-Johnson syndrome. The transport defect in Gilbert's syndrome was unclear. It could not be considered to be homogeneous, but it may exist at multiple sites, from the conjugation with serum proteins to excretion into bile. Following phenobarbital administration, the ICG secondary rise in the 5 patients with Dubin-Johnson syndrome disappeared, and ICG was rapidly cleared from blood. However, in patients with Dubin-Johnson syndrome, BSP clearance in serum did not show any change before and after phenobarbital administration. ICG excretion in patients with constitutional ICG excretory defect was due only to the impairment o ICG transport, and the defect was suggested to be hepatic uptake. These results indicate that studies of the hepatic transport of bilirubin, BSP, and ICG are useful for determining the etiological factors involved in congenital hyperbilirubinemia and constitutional ICG excretory defect.
Similar content being viewed by others
References
Rotor AB, Manahan L, Florentin A. Familial non-hemolytic jaundice with direct van den Bergh reaction. Acta Med Philip 1948; 5:37–49.
Dubin IN, Johnson FB. Chronic idiopathic jaundice with unidentified pigment in liver cells; new clinicopathologic entity with report of 12 cases. Medicine 1954;33:155–197.
Schiff L, Billing BH, Oikawa Y. Familial non-hemolytic jaundice with conjugated bilirubin in the serum. A case study. N Engl J Med 1959;260:1315–1318.
Wolf RL, Pizette M, Richman A, et al. Chronic idiopathic jaundice. A study of two afficted families. Am J Med 1960;28:32–41.
Arias IM. Studies of chronic familial non-hemolytic jaundice with conjugated bilirubin in the serum with and without an unidentified pigment in the liver cells. Am J Med 1961;31:510–518.
Wolkoff AW, Wolpert E, Pascasio FM, et al. Rotor's syndrome: A distinct inheritable pathophysiologic entity (abstract). Gastroenterology 1974;67:838.
Gilbert A, Lereboullet P, Hersher M. Les trois cholémies congénitales. Bull Soc Med Hosp Paris 1907;24:1203.
Nambu M, Yamashiro U, Oikawa Y, et al. A case with chronic nonhemolytic unconjugated hyperbilirubinemia (Crigler-Najjar syndrome tuype II) with special reference to pathogenesis and classification of unconjugated hyperbilirubinemia (in Japanese). Acta Hepatol Jpn 1978;19:22–32.
Nambu M, Ueda C, Yoshimura K, et al. A new type of constitutional hyperbilirubinemia with unconjugated bilirubin: A case of non-hemolytic hyperbilirubinemia with marked retention on sulfobromophthalein test (in Japanese). Acta Hepatol Jpn 1980; 21:1690–1697.
Namihisa T, Nambu M, Kobayashi N, et al. Nine cases with marked retention of indocyanine green test and normal sulfobromophthalein test without abnormal liver histology: Constitutional indocyanine green excretory defect. Hepato-Gastroenterol 1981;28:6–12.
Barber-Riley G, Goetzee AE, Richards TG, et al. The transfer of bromsulphthalein from the plasma to the bile in man. Clin Sci 1961;20:149–159.
Kanai T. Compartment analysis of transport and tolerance test of indocyanine green in normal subjects and in patients with hepatic dysfunction (in Japanese). Jpn J Gastroenterol. 1972;69:228–243.
Richards TG, Tindall VR, Young A. A modification of the bromsulphthalein liver function test to predict the dye content of the liver and bile. Clin Sci 1959;18:499–511.
Namihisa T, Nambu M, Kanai T, et al Compartmental analysis of indocyanine green transport in normal subjects and patients with hepatic dysfunction. Gastrenterol Jpn 1974;9:287–292.
Wheeler HO, Meltzer JI, Bradley SE. Biliary transport and hepatic storage of sulfobromophthalein sodium in the unanesthetized dog, in normal man, and in patients with hepatic disease. J Clin Invest 1960;39:1131–1141.
Nambu M. Hepatic clearance of indocyanine green in patients with liver diseases (in Japanese). Jpn J Gastroenterol 1966;63: 777–794.
Bailey A, Robinson D, Dawson AM. Does Gilbert's disease exist. Lancet 1977;30:931–933.
Portman OW, Chowdhury JR, Chowdhury NR, et al. A nonhuman primate model of Gilbert's syndrome. Hepatology 1984;4: 175–179.
Rodes J, Zubinarreta A, Bruguer M. Metabolism of bromsulphalein in Dubin-Johnson syndrome. Dig Dis 1972;17:545–552.
Yamamuro W, Nakagawa K, Mizuyoshi H et al. Studies on the metabolism of three BSP fractions in patients with constitutional jaundice (in Japanese). Acta Hepatol Jpn 1985;12:1646–1653
Erlinger S, Dhumeaux D, Desjeux JF, et al. Hepatic handling of unconjugated dyes in the Dubin-Johnson syndrome. Gastroenterology 1973;64:106–110.
Watanabe S, Nishioka M, Kodama T, et al. Clincopathological studies of the Dubin-Johnson syndrome complicated with chronic hepatitis. Gastroenterol Jpn 1982;17:576–584.
Dhumeaux D, Berthelot P. Chronic hyperbilirubinemia associated with hepatic uptake and storage impairment. A new syndrome resembling that of the mutant Southdown sheep. Gastroenterology 1975;69:988–993.
Namihisa T, Nambu M. Rotor's and Dubin-Johnson syndrome (correspondence). N Engl J Med 1977;297:560.
Berk PD, Bloomer JR, Howe RB, et al. Constitutional hepatic dysfunction (Gilbert's syndrome). A new definition based on kinetic studies with conjugated radiobilirubin. Am J Med 1970; 49:296–305.
Gentile S, Persico M, Tiribelli C. Abnormal hepatic uptake of low doses of sulfobromophthalein in Gilbert's syndrome: The role of reduced affinity of plasma membrane carrier of organic anions. Hepatology 1990;12:213–217.
Okuda K, Ohkubo H, Musa H, et al. Marked delay in indocyanine green plasma clearance with a near-normal bromsulfophthalein retention test: A constitutional abnormality? Gut 1979;17:588–594.
Namihisa T, Nambu M, Kobayashi N, et al. A case with apparent discrepancy between ICG test and BSP test (constitutional ICG excretory defect). Characteristic change in plasma disappearance curve. Jpn J Gastroenterol 1974;71:168–173.
Medler C, Burke M, Shani M, et al. The effect of phenobarbital on patients with Dubin-Johnson syndrome. Digestion 1976;14:394–399.
Shani M, Seligsohn U, Ben-Ezzer J. Effect of phenobarbital on liver functions in patients with Dubin-Johnson syndrome. Gastroenterology 1974;67:303–308.
Namihisa T, Nambu M. The chemical examination of blood and urine. ICG and BSP. How shall we judge the result (in Japanese)? Jpn J Clin Med 1980;38:701–715.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nambu, M., Namihisa, T. Hepatic transport of serum bilirubin, bromsulfophthalein, and indocyanine green in patients with congenital non-hemolytic hyperbilirubinemia and patients with constitutional indocyanine green excretory defect. J Gastroenterol 31, 228–236 (1996). https://doi.org/10.1007/BF02389522
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02389522