{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T02:05:02Z","timestamp":1768442702294,"version":"3.49.0"},"reference-count":26,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1982,8]]},"abstract":"<jats:p>A technique has recently been described by Blanckaert and his colleagues that specifically and accurately quantifies unconjugated bilirubin, diconjugated bilirubin, and the C-8 and C-12 isomers of monoconjugated bilirubin. This technique has now been used to determine the distribution pattern of bilirubin and its ester conjugates in 91 sera from 65 patients with hepatobiliary disease, and the results were compared with two conventional diazo assays. Both diazo assays yielded values for total bilirubin concentration that were markedly and unpredictably higher than those obtained by the new technique, and the direct-reacting fraction by diazo assay showed little or no agreement with the fraction of total ester conjugates determined by the new method. Previous studies using the new method had shown that bilirubin conjugates are undetectable in sera from healthy adults or individuals with Gilbert's syndrome, but they were found in 89 of the 91 present patient sera. The fraction of total serum bilirubin represented by C-8 monoconjugates, C-12 monoconjugates, diconjugates, and total ester conjugates was higher in patients with biliary obstruction than in those with parenchymal liver disease, but extensive overlap between groups prevented determination of these conjugated species from being diagnostically useful. Overall, bilirubin ester conjugates in serum consisted of 30% C-8 monoconjugates, 37% C-12 monoconjugates, and 33% diconjugates, while urine contained predominantly diconjugates.<\/jats:p>","DOI":"10.1136\/gut.23.8.643","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"643-649","source":"Crossref","is-referenced-by-count":45,"title":["Measurement of serum bilirubin and its mono- and diconjugates: application to patients with hepatobiliary disease."],"prefix":"10.1136","volume":"23","author":[{"given":"B F","family":"Scharschmidt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Blanckaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F A","family":"Farina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P M","family":"Kabra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B E","family":"Stafford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R A","family":"Weisiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1982,8,1]]},"reference":[{"issue":"77","key":"ref_1","first-page":"90","article-title":"Uber eine direkte und eine indirekte Diazo-reaktion auf Bilirubin","volume":"1916","author":"den Bergh AAH, Van; P, Muller","unstructured":"Van den Bergh AAH, Muller P. Uber eine direkte und eine indirekte Diazo-reaktion auf Bilirubin. Biochem Z 1916; 77: 90-103.","journal-title":"Biochem Z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/0002-9343(59)90310-9","article-title":"The significance of the direct-reacting fraction of serum bilirubin in hemolytic jaundice","volume":"26","author":"Tisdale, W.A.; Klatskin, G.; Kinsella, E.D.","year":"1959","unstructured":"Tisdale WA, Klatskin G, Kinsella ED. The significance of the direct-reacting fraction of serum bilirubin in hemolytic jaundice. Am J Med 1959; 26: 214-27.","journal-title":"Am J Med"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/000456327100800113","article-title":"Bilirubin standards and the determination of bilirubin by manual and technicon autoanalyzer methods","volume":"8","author":"Billing, B.; Haslam, R.; Wald, N.","year":"1971","unstructured":"Billing B, Haslam R, Wald N. Bilirubin standards and the determination of bilirubin by manual and technicon autoanalyzer methods. Ann Clin Biochem 1971; 8: 21-30.","journal-title":"Ann Clin Biochem"},{"key":"ref_4","first-page":"205","article-title":"Recent advances in the separation and analysis of diazo-positive bile pigments","volume":"22","author":"Heirwegh, K.P.M.; Fevery, J.; Meuwissen, J.A.T.P.; De Groote, J.; Compernolle, F.; Desmet, V.; Van Roy, F.P.","year":"1974","unstructured":"Heirwegh KPM, Fevery J, Meuwissen JATP, De Groote J, Compernolle F, Desmet V, Van Roy FP. Recent advances in the separation and analysis of diazo-positive bile pigments. 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Biochem J 1980; 185: 115-28.","journal-title":"Biochem J"},{"key":"ref_11","first-page":"198","article-title":"Measurement of bilirubin and its monoconjugates and diconjugates in human serum by alkaline methanolysis and high-performance liquid chromatography","volume":"96","author":"Blanckaert, N.; Kabra, P.M.; Farina, F.A.; Stafford, B.E.; Marton, L.J.; Schmid, R.","year":"1980","unstructured":"Blanckaert N, Kabra PM, Farina FA, Stafford BE, Marton LJ, Schmid R. Measurement of bilirubin and its monoconjugates and diconjugates in human serum by alkaline methanolysis and high-performance liquid chromatography. J Lab Clin Med 1980; 96: 198-212.","journal-title":"J Lab Clin Med"},{"key":"ref_12","first-page":"925","article-title":"Plasma bilirubin determination in the newborn infant","volume":"35","author":"Michaelsson, M.; Nosslin, B.; Sjolin, S.","year":"1965","unstructured":"Michaelsson M, Nosslin B, Sjolin S. Plasma bilirubin determination in the newborn infant. 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Bilirubin conjugates: formation and detection. Prog Liver Dis 1976; 5: 183-214.","journal-title":"Prog Liver Dis"},{"key":"ref_17","article-title":"Bile pigments. Chemical, biological and clinical aspects. New York and","author":"With, T.K.","year":"1968","unstructured":"With TK. Bile pigments. Chemical, biological and clinical aspects. New York and London: Academic Press, 1968."},{"key":"ref_18","first-page":"294","article-title":"The nature of four bilirubin fractions from serum and of three bilirubin fractions from bile","volume":"67","author":"Kuenzle, C.; Maier, C.; Ruttner, E.A.","year":"1966","unstructured":"Kuenzle C, Maier C, Ruttner EA. The nature of four bilirubin fractions from serum and of three bilirubin fractions from bile. J Lab Clin Med 1966; 67: 294-306.","journal-title":"J Lab Clin Med"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0378-4347(00)86073-9","article-title":"The separation of bilirubin species in serum and bile by high-performance reversed phase liquid chromatography","volume":"226","author":"Lauff, J.J.; Kasper, M.E.; Ambrose, R.T.","year":"1981","unstructured":"Lauff JJ, Kasper ME, Ambrose RT. The separation of bilirubin species in serum and bile by high-performance reversed phase liquid chromatography. J Chromatog 1981; 226: 391-402.","journal-title":"J Chromatog"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1093\/clinchem\/25.10.1761","article-title":"Spurious hyperbilirubinemia in uremic patients on propanolol therapy","volume":"25","author":"Stone, W.J.; McKinney, T.D.; Warnock, L.G.","year":"1979","unstructured":"Stone WJ, McKinney TD, Warnock LG. Spurious hyperbilirubinemia in uremic patients on propanolol therapy. 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Philadelphia and Toronto: Lippincott, 1975: 204-46."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.0954-6820.1964.tb00657.x","article-title":"Jaundice with conjugated bilirubin in hyperhemolysis","volume":"176","author":"Schalm, L.; Weber, A.P.H.","year":"1964","unstructured":"Schalm L, Weber APH. Jaundice with conjugated bilirubin in hyperhemolysis. Acta Med Scand 1964; 176: 549-53.","journal-title":"Acta Med Scand"},{"key":"ref_24","first-page":"187","article-title":"Current concepts of bilirubin metabolism and heredity hyperbilirubinemia","volume-title":"in liver disease","author":"Scharschmidt, B.F.; Gollan, J.L.","year":"1979","unstructured":"Scharschmidt BF, Gollan JL. Current concepts of bilirubin metabolism and heredity hyperbilirubinemia. In: Popper F, Schaffner F, eds. Progress in liver disease. New York: Grune and Stratton, 1979: 187-212."},{"key":"ref_25","first-page":"381","article-title":"Excretion of conjugated bilirubin in the isolated perfused rat kidney","volume":"54","author":"Gollan, J.L.; Dallinger, J.C.; Billing, B.H.","year":"1978","unstructured":"Gollan JL, Dallinger JC, Billing BH. Excretion of conjugated bilirubin in the isolated perfused rat kidney. Clin Sci Mol Med 1978; 54: 381-9.","journal-title":"Clin Sci Mol Med"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1152\/ajplegacy.1975.229.2.340","article-title":"Bilirubin UDP-glucuronyltransferase activity of Wistar rat kidney","volume":"229","author":"Foliot, A.; Christoforov, B.; Petite, J.P.; Etienne, J.P.; Housset, E.; Dubois, M.","year":"1975","unstructured":"Foliot A, Christoforov B, Petite JP, Etienne JP, Housset E, Dubois M. Bilirubin UDP-glucuronyltransferase activity of Wistar rat kidney. Am J Physiol 1975; 229: 340-3.","journal-title":"Am J Physiol"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.23.8.643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T21:57:26Z","timestamp":1757282246000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.23.8.643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1982,8]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[1982,8,1]]},"published-print":{"date-parts":[[1982,8]]}},"alternative-id":["10.1136\/gut.23.8.643"],"URL":"https:\/\/doi.org\/10.1136\/gut.23.8.643","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1982,8]]}}}