Abstract
Although a multitude of effective liver function tests are avaiable for use in animals, a variety of modifications of currently used tests have been recently reported. In addition, newer procedures now used in human medicine may also provide unique insights into assessing and detecting acquired hepatic disorders in animals. Examples of new procedures are: assessing microsomal mixed function oxidase activity by plasma caffeine clearance; estimating the extent of active hepatic fibrogenesis through serum procollagen-III peptide levels; determining hepatic blood flow and functional mass by the galactose elimination capacity; detecting primary hepatocellular cancer through serum or urinary ligandin levels; and to estimate the liver's maximal capacity to excrete indocyanine green independent of blood flow. In evaluating drugs as to their hepatotoxicity, function tests should be included in the liver profile which measure specific metabolic alterations unique to the compound under study.
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Bass, B.D., Hoffmann, W.E. & Dorner, J.L. 1976. Normal canine lipid profiles and effects of experimentally induced pancreatitis and hepatic necrosis on lipids. American Journal of Veterinary Research, 37, 1355–1357
Bass, N.M., Kirsch, R.E., Tuff, S.A. & Saunders, S.J. 1977. Radioimmunoassay of ligandin. Biochemica et Biophysica Acta, 494, 131–143
Bass, N.M., Kirsch, R.E., Tuff, S.A. & Saunders, S.J. 1977. Radioimmunoassay of ligandin. Gastroenterology, 75, 589–594
Bass, N.M., Kirsch, R.E., Tuff, S.A., Campbell, J.A. & Saunders, S.J. 1979. Radioimmunoassay measurement of urinary ligandin in nephrotoxin treated rats. Clinical Science, 56, 419–426
Berg, P.A., Doniach, D. & Roett, I.M. 1967. Mitochodrial antibodies in primary biliary cirrhosis. Journal of Experimental Medicine, 126, 277–290
Berg, P.A., Klein, R., Lindenborn-Fotinos, J. & Klöppel, W. 1982. ATPase-associated antigen (M2): marker antigen for serological diagnosis of primary biliary cirrhosis, Lancet, (ii), 1423–1425
Berry, W. & Reichen, J. 1983. Bile acid metabolism: its relation to clinical disease. Seminars in Liver Disease, 3, 330–340
Blanckaert, N. 1980. Analysis of bilirubin and bilirubin mono- and diconjugates — determination of their relative amounts in biological samples. Biochemical Journal, 185, 115–128
Blanckaert, N., Kabra, P. & Farina, F. 1980. Measurement of bilirubin and its monoconjugates and diconjugates in human serum by alkaline methanolysis and high-performance liquid chromatography. Journal of Laboratory & Clinical Medicine 96, 198–212
Bolarin, D.M. 1984. Serum bile acid in the evaluation of colchicine treatment of carbon tetrachloride-induced liver injury. Experimental & Molecular Pathology, 41, 384–389
Bonasch, H. & Cornelius, C.E. 1964. Indocyanine green clearance — a liver function test for the dog. American Journal of Veterinary Research, 25, 254–259
Brobst, D.F. & Schall, W.D. 1972. Needle biopsy of the canine liver and correlation of laboratory data with histopathologic observations. Journal — American Veterinary Medical Association, 161, 382–388
Bruss, M.L., Gröhn, Y., Huffmann, E.M. & Lindberg, L.A. 1986. Hepatic morphology and effects of intravenous sodium propionate on plasma glucose in fed and fasted dairy cattle. American Journal of Veterinary Research, 47, 336–341
Bunch, S.E., Polak, D.M. & Hornbuckle, W.E. 1985. A modified laparoscopic approach for liver biopsy in dogs. Journal — American Veterinary Medical Association, 187, 1032–1035
Burg, A.W. 1975. Physiological disposition of caffeine. Drug Metabolism Review, 4, 199–228
Center, S.A., Baldwin, B.H., Erb, H.N. & Tennant, B.C. 1985. Bile acid concentrations in the diagnosis of hepatobiliary disease in the dog. Journal — American Veterinary Medical Assocation, 187, 935–940
Center, S.A., Bunch, S.E., Baldwin, B.H., Hornbuckle, W.E. & Tennant, B.C. 1983. Comparison of sulfobromophthalein and indocyanine green clearances in the dog. American Journal of Veterinary Research, 44, 722–726
Cooper, D., Tarrant, J., Whelan, G., Styles, C., Cook, M. & Desmond, P. 1985. Ultrasound in the diagnosis of jaundice — a review. Medical Journal of Australia, 143, 381–385
Cornelius, C.E. 1979. Biochemical evaluation of hepatic function in dogs. Journal — American Animal Hospital Association, 15, 79–88
Cornelius, C.E. 1980. Liver function. In: J.J. Kaneko (ed), Clinical biochemistry of domestic animals, (Academic Press, New York), 201–257
Cornelius, C.E., Arias, I.M. & Osburn, B.I. 1965. Hepatic pigmentation with photosensitivity: a syndrome in Corriedale sheep resembling Dubin-Johnson syndrome in man. Journal — American Veterinary Medical Association, 146, 709–713
Crowell, M.J. & Macdonald, I.A. 1980. Enzymatic determination of 3-, 7-, and 12-hydroxyl groups of fecal bile salts. Clinical Chemistry, 26, 1298–1300
Dalton, J.R.F. & Hill, F.W.G. 1972. A procedure for the examination of the liver and pancreas in dog. Journal of Small Animal Practice, 13, 527–530
DeBroe, M.E., Roels, F., Nouwen, E.J., Claeys, L. & Wieme, R.J. 1985. Liver plasma membrane: the source of high molecular weight alkaline phosphatase in human serum. Hepatology, 5, 118–128
DeNovo, R.C. & Prasse, K.W. 1983. Comparison of serum biochemical and hepatic functional alterations in dogs treated with corticosteroids and hepatic duct ligation. American Journal of Veterinary Research, 44, 1703–1709
Dodds, W.J. 1980. Hemostasis and coagulation. In: J.J. Kaneko (ed), Clinical biochemistry of domestic animals, (Academic Press, New York), 671–718
Elliot, J.M. 1980. Propionate metabolism and vitamin B12. In: Y. Ruckenbusch & P. Thivend (eds), Digestive physiology and metabolism in ruminants, (AVI Publishing Co., Westport, CT), 485–503
Engstrom-Laurent, A., Loof, L., Nyberg, A. & Schroder, T. 1985. Increased serum levels of hyaluronate in liver disease. Hepatology, 5, 638–642
Eriksson, S. & Zettervall, O. 1985. The N-terminal propeptide of collagen type III in serum as a prognostic indicator in primary biliary cirrhosis. Journal of Hepatology — Supplement, 2, 5225
Farrell, G.C., Cooksley, W.G.E., Hart, P. & Powell, L.W. 1978. Drug metabolism in liver disease — identification of patients with impaired hepatic drug metabolism. Gastroenterology, 75, 580–588
Fevery, J., Claes, J., Heirwegh, K. & DeGroote, J. 1967. Hyperbilirubinemia — significance of the ratio between direct-reacting and total bilirubin. Clinica Chimica Acta, 17, 73–79
Fevery, J. & Blanckaert, N. 1986. What can we learn from analyses of serum bilirubin? Journal of Hepatology, 2, 113–121
Fleischner, G., Kamisaka, K., Habig, W.H., Jakoby, W.B. & Arias, I.M. 1975. Human ligandin: characterization and quantitation. Gastroenterology, 69, A21/821
Fleischmajer, R., Olsen, B.R., Timpe, R., Perlish, J.S. & Lovelace, O. 1983. Collagen fibril formation during embryogenesis. Proceedings—National Academy of Sciences (USA), 80, 3354–3358
Galambos, M.R., Collins, D.C. & Galambos, J.T. 1985. A radioimmunoassay procedure for type III procollagen: its use in the detection of hepatic fibrosis. Hepatology, 5, 38–42
Gröhn, Y., 1985. Propionate loading test for liver function in spontaneously ketotic dairy cows. Research in Veterinary Science, 39, 24–28
Gröhn, Y., Bruss, M.L. & Lindberg, L.A. 1985. Propionate loading test for liver function during experimental necrosis in sheep. American Journal of Veterinary Research, 46, 952–958
Hahn, E.G. 1984. Blood analysis for liver fibrosis. Journal of Hepatology, 1, 67–73.
Hahn, E.G. & Schuppan, D. 1983. Collagen metabolism in liver disease. In: L. Bianchi (ed), Liver in metabolic diseases, (MTP Press, Lancaster, PA), 309–323
Heredia, D., Caballeria, J., Paris, A., Jimenez, W., Torres, M., Bruguera, M. & Rodes, J. 1985. Serum procollagen type III peptide does not reflect hepatic collagen content in alcoholics with inactive cirrhosis. Journal of Hepatology — Supplement, 2, S252
Himes, J.A. & Cornelius, C.E. 1973. Hepatic excretion and storage of sulfobromophthalein sodium in experimental hepatic necrosis in the dog. Cornell Veterinarian, 63, 424–431
Hobig, W.H., Pabst, M.J., Fleischner, G., Gatmaitan, G., Arias, I.M. & Jacoby, W.B. 1974. The identity of glutathione-S-transferase B with ligandin, a major binding protein of liver. Proceedings —National Academy of Sciences (USA), 71, 3879–3882
Hofmann, A.F. 1982. The aminopyrine demethylation breath test and the serum bile acid level: nominated but not yet elected to join the common liver tests. Hepatology, 2, 512–517
Hootegem, P.V., Fevery, J. & Blanckaert, N. 1985. Serum bilirubins in hepatobiliary disease: comparison with other liver function tests and changes in the postobstructive periods. Hepatology, 5, 112–117
Ito, S., Takaoka, T., Nakaya, Y., Hiasa, Y., Hiroyoshi, M., Tanaka, K. & Ichehara, A. 1982. Clinical value of the determination of serum guanase activity. Gastroenterology, 83, 1102–1108
Ito, S., Tsuji, Y., Kitagawa, N., Mizobuchi, M. & Akuaru, I. 1985. Relation between the guanase activity in donor blood and the incidence of posttransfusional non A, non B hepatitis. Hepatology, 5, 992 (abstract)
Jansen, P.L.M., Peters, W.H.M. & Janssens, A.R. 1985. Clinical value of serum bilirubin subfractionation by HPLC and conventional methods in patients with primary biliary cirrhosis. Meeting of the Dutch Gastroenterological Society and Dutch Society of Hepatology, October 4–5, 1985, Noordiaykerhout, The Netherlands
Johnson, G.F., Gilbertson, S.R., Goldfischer, S., Grushoff, P.S. & Sternlieb, I. 1984. Cytochemical detection of inherited copper toxicosis of Bedlington terriers. Veterinary Pathology, 21, 57–60
Jost, G., Gambon, R., Rossi, E. & Preisig, R. 1985. Noninvasive quantification of liver function in children using salivary caffeine clearance. Journal of Hepatology — Supplement 2, S259
Kaneko, J.J., Inouye, K. & Carlson, G.P. 1980. Serum bile acids by chemical assay and by radioimmunoassay as a test of liver function in the horse. Veterinary Clinical Pathology, 9, 39
Kaplan, M.M. 1986. Serum alkaline phosphatase — another piece is added to the puzzle. Hepatology, 6, 526–528
Kaplowitz, N., Eberle, D. & Yamada, T. 1982. Biochemical tests for liver disease In: Zakim & Boyer (eds), Hepatology: a textbook of liver disease, (W.B. Saunders Company, Philadelphia, PA), 583–612
Keiding, S. & Skak, C. 1985. Intrinsic hepatic clearance of ICG — a new quantitative measurement of liver function in man. Journal of Hepatology —Supplement 2, S262
Klein, R., Lindenborg-Fotinos, J. & Berg, P.A. 1983. Use of ATPaseassociated antigen (M2) for detection of antimitochondrial and antibodies in primary biliary cirrhosis by fluorometric immunoassay. Journal of Immunological Methods, 64, 227–238
Kobayashi, K., Sugimoto, T., Makino, H., Kumagai, M., Unoura, M., Kato, Y. & Hattori, N. 1985. Screening methods for early detection of hepatocellular carcinoma. Hepatology, 5, 1100–1105
Koike, Y., Kamijyo, K., Suzuki, Y., Kiyosawa, K., Nagata, A., Furuta, S. & Nagata, T. 1985. DNA content of hepatocytes in various stages of liver cirrhosis. Liver, 5, 156–161
Kupfer, A., Gronwall, R. & Preisig, R. 1977. Hyperbilirubinemia and slow acetylation in the horse: a parallel to Gilbert's Syndrome (GS). Digestion, 16, 353
Kurki, P., Gripenberg, M., Teppo, A. & Salaspiro, M. 1984. Profiles of antinuclear antibodies in chronic active hepatitis, primary biliary cirrhosis and alchoholic liver disease. Liver 4, 134–138
Lauff, J.J., Kasper, M.E., Wu, W. & Ambrose, R.T. 1982. Isolation and preliminary characterization of a fraction of bilirubin in serum that is firmly bound to protein. Clinical Chemistry, 28, 629–637
Lauterburg, B.H. & Bircher, J. 1976. Expiratory measurement of maximal aminopyrine demethylation in vivo: effect of phenobarbital, partial hepatectomy, portacaval shunt and bile duct ligation in the rat. Journal of Pharmacology & Experimental Therapeutics, 196, 501–509
McDonnagh, A.F. & Palma, L.A. 1984. Origin of mamalian biliprotein and rearrangement of bilirubin glucuronides in the rat. Journal of Clinical Investigation, 74, 763–770
McFarlane, I.G. & Williams, R. 1985. Liver membrane antibodies. Journal of Hepatology, 1, 313–319
Meyer, D.J., Strombeck, D.R., Stone, E.A., Zenoble, R.D. & Buss, D.D. 1978. Ammonia tolerance test in clinically normal dogs and in dogs with portasystemic shunts. Journal — American Veterinary Medical Association, 173, 377–379
Miyachi, K., Gupta, R.C., Dickson, E.R. & Tan, E.M. 1980. Precipitating antibodies to mitochondrial antigens in patients with biliary cirrhosis. Clinical & Experimental Immunology, 39, 599–606
Monzato, E., Fellin, R. & Baggeo, G. 1976. Formation of lipoprotein X. Its relation to ble compounds. Journal of Clinical Investigation, 57, 1248–1260
Muraca, M. & Blanckaert, N. 1983. Liquid-chromatographic assay and identification of mono— and diester conjugates of bilirubin in normal serum. Clinical Chemistry, 29, 1767–1771
Niemela, O., Risteli, L., Sotaniemi, E.A. & Risteli, J. 1983. Aminoterminal propeptide of type III collagen in serum in alcoholic liver disease. Gastroenterology, 85, 254–259
Nosslin, B. 1960. The direct diazo reaction of bile pigments in serum. Scandinavian Journal of Clinical & Laboratory Investigation 12: Supplementum 49, 1–176
Ohmi, N. & Arias, I.M. 1981. Ligandinemia in primary liver cell cancer in rat and man. Hepatology, 1, 316–318
Owen, C.A. & McCall, J.T. 1983. Identification of the carrier of the Bedlington terrier copper disease. American Journal of Veterinary Research 44, 694–696
Parraga, M.E. & Kaneko, J.J. 1985. The serum bile acids and the bile acid profile as tests of liver function. Veterinary Research Communications, 9, 79–88
Paumgartner, G., Probst, P., Kraines, R. & Leevy, C.D. 1970. Kinetics of indocyanine green removal from the blood. New York Academy of Sciences, 170, 134–147
Portman, O.W., Roy-Chowdhury, J., Roy-Chowdhury, N., Alexander, M., Cornelius, C.E. & Arias, I.M. 1984. A nonhuman primate model of Gilbert's syndrome. Hepatology, 4, 175–179
Poulsen, H.E. & Pilsgaard, H. 1985. Antipyrine metabolism during hepatic regeneration in the rat. Liver, 5, 196–199
Ritland, S. & Bergan, A. 1975. Plasma concentration of lipoprotein — X(LPX) in experimental bile duct obstruction. Scandinavian Journal of Gastroenterology, 10, 17–24
Rock, W.A. 1984. Laboratory assessment of coagulation disorders in liver disease. Clinics in Laboratory Medicine, 4, 419–441
Roda, A., Kricka, L.J., DeLuca, M. & Hofmann, A.F. 1982. Bioluminescense measurement of primary bile acids using immobilized 7-hydroxysteroid dehydrogenase: application to serum bile acids. Journal of Lipid Research, 23, 1354–1361
Rothuizen, J. 1985. Hyperbilirubinemia in canine hepatobiliary disease. (Proefschrift, Ryksuniversiteit, Utrecht, Netherlands), 1–168
Sabesin, S.M., 1982. Cholestatic lipoproteins — their pathogenesis and significance. Gastroenterology, 83, 704–709
Scharschmidt, B.F., Blanckaert, N. & Farina, F.A. 1982. Measurement of serum bilirubin and its mono — and diconjugates — applications to patients with hepatobiliary disease. Gut, 23, 643–649
Schlaeger, R., Haux, P. & Kattermann, P. 1982. Studies on the mechanism of the increase in serum alkaline phosphatase activity in cholestasis: significance of the hepatic bile acid concentration for the leakage of alkaline phosphatase from rat liver. Enzyme, 28, 3–13
Seetharam, S., Sussman, N.L., Komoda, T. & Alpers, D.H. 1986. The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat. Hepatology, 6, 374–380
Shafritz, D.A., Shouval, D., Sherman, H., Hadziyannis, S.J. & Kew, M.C. 1981. Integration of hepatitic B viral DNA into the genome of liver cells in chronic disease and hepatocellular carcinoma. New England Journal of Medicine, 305, 1067–1073
Sherlock, S., Dick, R. & Van Leeuwen, D.J. 1984. Liver biopsy today. Journal of Hepatology, 1, 75–85
Sherman, M., Bass, N.M., Campbell, J.A.H. & Kirsch, R.E. 1983. Radioimmunoassay of human ligandin. Hepatology, 3, 162–169
Simionatto, C.S., Anderson, K.E., Drummond, G.S. & Kappas, A. 1985. Studies on the mechanism of Sn-protoporphyrin suppression of hyperbilirubinemia. Journal of Clinical Investigation, 75, 513–521
Strombeck, D.R., Meyer, D.J. & Freedland, R.A. 1975. Hyperammonemia due to a urea cycle enzyme deficiency in two dogs. Journal-American Veterinary Medical Association, 166, 1009–1111
Strombeck, D.R. & Qualls, C. 1978. Hepatic sulfobromophthalein uptake and storage defect in a dog. Journal-American Veterinary Medical Association, 172, 1423–1426
Surrenti, C., Casini, A., Milani, S., Pasquinelli, I. & Banchetti, E. 1985. Is the determination of serum N-terminal procollagen type III peptide (s PIIIP) a reliable index of hepatic fibrosis? Journal of Hepatology, Supplement 2, S335
Trotman, B.W., Shaw, L., Roy-Chowdhury, J., Malet, P.F. & Rosato, E.F. 1983. Effect of phenobarbital on serum and biliary parameters in a patient with Crigler-Najjar syndrome, type II and acquired cholestasis. Digestive Diseases & Sciences, 28, 753–762
Tvedegaard, E., Poulsen, H.E., Vilstrup, H. & Thomsen, H.K. 1985. Functional status of the liver during chronic renal failure: an experimental study in the rabbit. Liver, 5, 183–188
Tygstrup, N. 1964. The galactose elimination capacity in control subjects and patients with cirrhosis of the liver. Acta Medica Scandinavica, 175, 281–288
Wahlländer, A., Renner, E. & Presig, R. 1985. Fasting plasma caffeine concentration. Scandinavian Journal of Gastroenterology, 20, 1133–1141
Warren, D., Cornelius, C. & Ford, B. 1984. Liver function studies on rhesus monkeys (Macaca mulatta) following the administration of hydrazine sulfate. Veterinary & Human Toxicology, 26, 295–299
Warszawski, D., Gorodischer, R., Moses, S. & Bark, H. 1977. Caffeine pharmacokinetics in young and adult dogs. Biology of the Neonate, 32, 138–142
Weiss, J.S., Gautam, A., Lauff, J.J., Sundberg, M.W., Jatlow, P., Boyer, J.L. & Seligson, D. 1983. The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. New England Journal of Medicine, 309, 147–150
Wellman, M.L., Hoffmann, W.E., Dorner, J.L. & Mock, R.E. 1982a. Comparison of the steroid-induced, intestinal, and hepatic isoenzymes of alkaline phosphatase. American Journal of Veterinary Research, 43, 1204–1207
Wellman, M.L., Hoffmann, W.E., Dorner, J.L. & Mock, R.E. 1982b. Immunoassay for the steroid-induced isoenzyme of alkaline phosphatase in the dog. American Journal of Veterinary Research, 43, 1200–1203
Wheeler, H.O., Epstein, R.M., Robinson, R.R. & Snell, E.S. 1960. Hepatic storage and excretion of sulfobromophthalein sodium in the dog. Journal of Clinical Investigation, 39, 236–247
Wu, T.W. 1984. Bilirubin analysis — the state of the art and future prospects. Clinical Biochemistry, 17, 221–229
Zaramella, M.G., Vallini, R. & Tiribelli, C. 1985. Estimation of hepatic blood flow by galactose plasma clearance in patients with liver disease. Liver, 5, 129–133
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This work was supported by USPHS-NIH grants RR00169 and AM32297.
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Cornelius, C.E. A review of new approaches to assessing hepatic function in animals. Vet Res Commun 11, 423–441 (1987). https://doi.org/10.1007/BF00380626
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DOI: https://doi.org/10.1007/BF00380626