Skip to main content
NCBI home page
Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 1999 Jan;14(1):59–90. doi: 10.1007/BF02869152

Biochemical diagnosis of liver disease

Paul L Wolf 1,✉
PMCID: PMC3453559  PMID: 23105203

Abstract

It is important that clinicians and laboratorians, including clinical chemists and pathologists, recognize and understand the clinical significance of abnormal liver function tests. The liver regulates many important metabolic functions. Hepatic injury is associated with distortion of these metabolic functions. Hepatic disease can be evaluated and diagnosed by determining serum concentrations of a number of serum analytes. Many serum analytes exist to assist in the biochemical diagnosis of liver disease. The focus of this paper is on the analytes which are associated with hepatic necrosis, cholestasis, defects in excretion and end stage hepatic disease which results in decreased synthetic function. The abnormalities of these serum analytes will be correlated with the important types of liver disease.

Key words: Liver function tests, albumin, bilirubin, alkaline phosphatase and transaminases

Full Text

The Full Text of this article is available as a PDF (2.2 MB).

References

  • 1.Tygstrup N. Assessment of liver function: Principles and practice. J. Gastroenterol. Hepatol. 1990;5:468–682. doi: 10.1111/j.1440-1746.1990.tb01426.x. [DOI] [PubMed] [Google Scholar]
  • 2.Corless J.K., Middleton H.M. Normal liver function: A basis for understanding hepatic disease. Arch. Intern. Med. 1983;143:2291–2294. doi: 10.1001/archinte.143.12.2291. [DOI] [PubMed] [Google Scholar]
  • 3.Skrede S., Solberg H.E., Ritland S., Blomhoff J.P., Schrumpf E., Elgjo K., Gjone E. Diagnostic and prognostic value of laboratory tests assessed in a follow-up study of 200 patients with liver disease. Clin. Chem. 1982;28:1177–1181. [PubMed] [Google Scholar]
  • 4.Reichling J.J., Kaplan M.M. Clinical use of serum enzymes in liver disease. Dig. Dis. Sci. 1988;33:1601–1614. doi: 10.1007/BF01535953. [DOI] [PubMed] [Google Scholar]
  • 5.Killingsworth L.M. Plasma protein patterns in health and disease. Crit. Rev. Clin. Lab. Sci. 1979;11:1–30. doi: 10.3109/10408367909105852. [DOI] [PubMed] [Google Scholar]
  • 6.Peters T. Serum albumin. In: Putman F., editor. The-plasma proteins. 2nd. New Delhi, USA: Academic Press; 1975. pp. 133–133. [Google Scholar]
  • 7.Pinnel A.E., Northam B.E. New automated dye-binding method for serum albumin determination with bromcresol purple. Clin. Chem. 1978;24:80–86. [PubMed] [Google Scholar]
  • 8.Blanchaert M. Analysis of bilirubin and bilirubin mono-and di-conjugates. Biochem. J. 1980;185:115–128. doi: 10.1042/bj1850115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Doumas B.T., Perry B.W., Sasse E.A, Straumfjord J.V. Standardization in bilirubin assays: Evaluation of selected methods and stability of bilirubin solutions. Clin. Chem. 1973;19:984–993. [PubMed] [Google Scholar]
  • 10.Lott, J.A. and Wolf, P.L. Alanine and aspartate aminotransferase (ALT and AST). In: Clin. Enzymol. Eds. Lott, J.A., Wolf, P.L., Yearbook Medical Publishers, Chicago, USA. 111–157.
  • 11.Pantenghini M., Malechiodi A., Calarco M., Bonora R. Clinical and diagnostic significance of aspartate aminotransferase isoenzymes in sera of patients with liver diseases. J. Clin. Chem. Clin. Biochem. 1984;22:153–158. doi: 10.1515/cclm.1984.22.2.153. [DOI] [PubMed] [Google Scholar]
  • 12.DeRitis F., Cacciatora L. Clin. Hepatol. Eds. Csomos, G., Thaler, H. Berlin, Germany: Springer India; 1983. Differential diagnosis of liver diseases; pp. 16–28. [Google Scholar]
  • 13.Nalpas B., Vassault A., LeGuilon A. Serum activity of mitochondrial aspartate aminotransferase; a sensitive marker of alocoholism with or without alcoholic hepatitis. Hepatology. 1984;4:893–896. doi: 10.1002/hep.1840040517. [DOI] [PubMed] [Google Scholar]
  • 14.Schmidt E., Schmidt F.W. Progress in the enzyme diagnosis of liver disease; reality or illusion? Clin. Biochem. 1990;23:375–382. doi: 10.1016/0009-9120(90)90085-9. [DOI] [PubMed] [Google Scholar]
  • 15.Lott J.A., Landesman P.W. The enzymology of skeletal muscle disorders. Crit. Rev. Clin. Lab. Sci. 1984;20:153–190. doi: 10.3109/10408368409165773. [DOI] [PubMed] [Google Scholar]
  • 16.Rosalki S.B. Serum enzymes in disease of skeletal muscle. Clin. Lab. Med. 1989;9:767–781. [PubMed] [Google Scholar]
  • 17.Wolf P.L., Lott J.A., Nitti G.J., Bookstein R. Changes in serum enzymes, lactate and haptoglobin following acute physical stress in international class athletes. Clin. Biochem. 1987;20:73–77. doi: 10.1016/S0009-9120(87)80102-9. [DOI] [PubMed] [Google Scholar]
  • 18.Wolf P.L. Clinical significance of serum high-molecular-mass alkaline phosphatase, alkaline phosphatase-lipoprotein-x complex, and intestinal variant alkaline phosphatase. Jour. Clin. Lab. Anal. 1994;81:172–176. doi: 10.1002/jcla.1860080311. [DOI] [PubMed] [Google Scholar]
  • 19.Wolf P.L. High-molecular-weight alkaline phosphatase and alkaline phosphatase lipoprotein x complex in cholestasis and hepatic malignancy. Arch. Pathol. Lab. Med. 1990;114:577–579. [PubMed] [Google Scholar]
  • 20.Hoof V., DeBroe M.E. Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit. Rev. Clin. Lab. Sci. 1994;31(3):197–293. doi: 10.3109/10408369409084677. [DOI] [PubMed] [Google Scholar]
  • 21.Wolf P.L. Clinical significance of an increased or decreased serum alkaline phosphatase. Arch. Pathol. Lab. Med. 1978;102:497–501. [PubMed] [Google Scholar]
  • 22.Birkett D.J., Done J., Neale F.C., Posen S. Serum alkaline phosphatase in pregnancy; an immunological study. Br. Med. J. 1966;1:1210–1212. doi: 10.1136/bmj.1.5497.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Siraganian P.A., Mulvihill J.J., Mulivor R.A., Miller R.W. Benign familial hyperphosphatasemia. J. Am. Med. Assoc. 1989;261:1310–1312. doi: 10.1001/jama.261.9.1310. [DOI] [PubMed] [Google Scholar]
  • 24.Wolf P.L. The significance of transient hyperphosphatasemia of infancy and childhood to the clinician and clinical pathologist. Arch. Pathol. Lab. Med. 1995;119:774–775. [PubMed] [Google Scholar]
  • 25.Moss D.W. Alkaline phosphatase isoenzymes. Clin. Chem. 1982;28:2007–2016. [PubMed] [Google Scholar]
  • 26.Hoof V.O., Lepoutre L.G., Hoylaerts M.F., Chevigne R., DeBroe M.E. Improved agarose electrophoretic method for separating alkaline phosphatase isoenzymes in serum. Clin. Chem. 1988;34:1857–1862. [PubMed] [Google Scholar]
  • 27.Rosalki S.B., Foo A.Y., Burlina A., Prellwitz W., Stieber P., Neumeier D., Klein G., Poppe W.A., Bodenmuller H. Multicentric evaluation of Iso-ALP test kit for measurement of bone alkaline phosphatase in serum and plasma. Clin. Chem. 1993;39:648–652. [PubMed] [Google Scholar]
  • 28.Hill C.S., Wolfert R.L. The preparation of monoclonal antibodies which react preferentially with human bone alkaline phosphatase and not liver alkaline phosphatase. Clin. Chim. Acta. 1989;186:315–320. doi: 10.1016/0009-8981(90)90050-3. [DOI] [PubMed] [Google Scholar]
  • 29.Bradbeer J.N., Zanelli J.M., Lindsay P.C., Pearson J., Reeve J. Relationship between the location of osteoblastic alkaline phosphatase activity and bone formation in human iliac crest bone. J. Bone Min. Res. 1992;7:905–912. doi: 10.1002/jbmr.5650070807. [DOI] [PubMed] [Google Scholar]
  • 30.Moss D.W. Changes in enzyme expression related to differentiation and regulatory factors: the acid phosphatase of osteoclasts and other macrophages. Clin. Chim. Acta. 1992;209:131–138. doi: 10.1016/0009-8981(92)90344-P. [DOI] [PubMed] [Google Scholar]
  • 31.Hoof V.O., Oosterom A.T., Lepoutre L.G., DeBroe M.E. Alkaline phosphatase isoenzyme patterns in malignant disease. Clin. Chem. 1992;38:2546–2551. [PubMed] [Google Scholar]
  • 32.Fishman W.H., Inglis N.R., Stolbach L.L., Krant M.J. A serum alkaline phosphatase isoenzymes of human neoplastic cell origin. Cancer Res. 1968;28:150–154. [PubMed] [Google Scholar]
  • 33.Nathanson L., Fishman W. New observations on the Regan isoenzyme of alkaline phosphatase in cancer patients. Cancer. 1971;27:1388–1397. doi: 10.1002/1097-0142(197106)27:6<1388::AID-CNCR2820270619>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  • 34.Stolbach L., Krant M., Fishman W. Ectopic production of alkaline phosphatase isoenzyme in patients with cancer. New Engl. J. Med. 1969;281:757–762. doi: 10.1056/NEJM196910022811403. [DOI] [PubMed] [Google Scholar]
  • 35.Hada T., Higashino K., Okochi T., Yamamura Y. Kasahara-variant alkaline phosphatase in renal cell carcinoma. Clin. Chim. Acta. 1978;89:311–316. doi: 10.1016/0009-8981(78)90330-3. [DOI] [PubMed] [Google Scholar]
  • 36.Tietz N.W., Burtis C.A., Duncan P., Erwin K., Petitclerc C.J., Rinker A.D., Shuey D., Zygowic E.R. A reference m of gamma-glutamyl transferase. CRC Crit. Rev. Clin. Lab. Sci. 1983;12:1–58. [Google Scholar]
  • 47.Burlina A. Improved method of fractionating gamma-glutamyl transferase by electrophoresis on cellulose acetate. Clin. Chem. 1978;24:502–504. [PubMed] [Google Scholar]
  • 48.Rosalki S.B., Rau D. Serum gamma-glutamyl transpeptidase activity in alcoholism. Clin. Chim. Acta. 1972;39:41–47. doi: 10.1016/0009-8981(72)90297-5. [DOI] [PubMed] [Google Scholar]
  • 49.Nemesanszky E., Lott J.A., Arato M. Changes in serum enzymes in moderate drinkers after an alcohol challenge. Clin. Chem. 1988;34:525–527. [PubMed] [Google Scholar]
  • 50.Sacchetti L., Castaldo G., Salvatore F. The γ-glutamyltransferase isoenzyme pattern in serum as a signal discriminating between hepatobiliary diseases, including neoplasias. Clin. Chem. 1988;34:352–355. [PubMed] [Google Scholar]
  • 51.Eriksen J., Olsen P.S., Thomsen A.C. Gamma-glutamyl-transpeptidase, aspartate aminotransferase, and erythrocyte mean corpuscular volume as indicators of alcohol consumption in liver disease. Scand. J. Gastroenterol. 1984;19:813–819. [PubMed] [Google Scholar]
  • 52.Acheampong-Mensah D. Activity of gamma-glutamyl-transpeptidase in serum of patients receiving anticonvulsant or anticoagulant therapy. Clim. Biochem. 1976;9:67–70. doi: 10.1016/S0009-9120(76)80019-7. [DOI] [PubMed] [Google Scholar]
  • 53.Rosalki S.B., Tarlow D., Rau D. Plasma gamma-glutamyl-transpeptidase elevation in patients receiving enzyme-inducing drugs. Lancet. 1971;ii:376–377. doi: 10.1016/S0140-6736(71)90093-6. [DOI] [PubMed] [Google Scholar]
  • 54.Cullen D.R., Goldberg D.M. The association between serum triglycerides and GGT activity in diabetes mellitus. Clin. Biochem. 1976;9:208–211. doi: 10.1016/S0009-9120(76)80059-8. [DOI] [PubMed] [Google Scholar]
  • 55.Humphries B.A., Melnychuk M., Donegan E.J., Snee R.D. Automated enzymatic assay for plasma ammonia. Clin. Chem. 1979;25:26–30. [PubMed] [Google Scholar]
  • 56.Mitchell R.A., Partin J.C., Partin J.S., Ram M.L. Hepatic and encephalopathic components of Reye's syndrome: Factor analysis of admission data from 209 patients. Neurology. 1985;35:1236–1239. doi: 10.1212/wnl.35.8.1236. [DOI] [PubMed] [Google Scholar]
  • 57.Mondzac A., Ehrlich G.E., Seegmiller J.E. An enzymatic determination of ammonia in biological fluids. J. Lab. Clin. Med. 1965;66:526–531. [PubMed] [Google Scholar]
  • 58.Shahangian S., Ash K.O., Wahlstrom N.O., Warden J.D., Saffle J.R., Taylor A., Green L.S. Creatine kinase and lactate dehydrogenase isoenzymes in serum of patients suffering burns, blunt trauma, or myocardial infarction. Clin. Chem. 1984;30:1332–1338. [PubMed] [Google Scholar]
  • 59.Bruns D.E., Savory J., Wills M.R. More on “flipped” lactate dehydrogenase patterns in myocardial infarction. Clin. Chem. 1984;30:1881–1882. [PubMed] [Google Scholar]
  • 60.Ketchum C.H., Robinson C.A., Hall L.M., Grizzle W.E. Clinical significance and partial biochemical characterization of lactate dehydrogenase isoenzyme 6. Clin. Chem. 1984;30:46–49. [PubMed] [Google Scholar]
  • 61.Wolf P.L. Lactate dehydrogenase-6: A biochemical sign of serious hepatic circulatory disturbance. Arch. Intern. Med. 1985;145:1396–1397. doi: 10.1001/archinte.145.8.1396. [DOI] [PubMed] [Google Scholar]
  • 62.Kato S., Ishii H., Kano S., Horii K., Tsuchiya M. Evidence that “lactate dehydrogenase isoenzyme 6” is in fact alcohol dehydrogenase. Clin. Chem. 1984;30:1585–1586. [PubMed] [Google Scholar]
  • 63.Gambino, R. (1980) Wilson's disease, an early diagnosis is essential. Lab. Rep. Physic. 51–54.
  • 64.Wolf P.L., Ray G., Kaplan H. Evaluation of copper oxidase (ceruloplasmin) and related tests in Hodgkin's disease. Clin. Biochem. 1979;12:202–204. doi: 10.1016/S0009-9120(79)80095-8. [DOI] [PubMed] [Google Scholar]
  • 65.Wolf P.L. Ceruloplasmin: Methods and clinical use. CRC Crit. Rev. Lab. Sci. 1982;17:229–245. doi: 10.3109/10408368209107037. [DOI] [PubMed] [Google Scholar]
  • 66.Wolf P.L., Enlander D., Dalziel J., Swanson J. Green plasma in blood donors. New Eng. Jour. Med. 1969;281:205–206. doi: 10.1056/NEJM196907242810407. [DOI] [PubMed] [Google Scholar]
  • 67.Wald N.J., Cuckle H.S. Nomogram for estimating an individual's risk of having a fetus with open spina bifida. Br. J. Obstet. Gynaecol. 1982;89:598–604. doi: 10.1111/j.1471-0528.1982.tb04711.x. [DOI] [PubMed] [Google Scholar]
  • 68.Wolf P.L. In: Enzyme tests in body fluids other than blood and urine. Moss D.W., Rosalki S.B., editors. London, U.K.: Edwards Arnold Publisher; 1996. pp. 270–271. [Google Scholar]
  • 69.Balistreri W.F., Suchy F.J., Farrell M.K., Heubi J.E. Pathologic versus physiologic cholestasis: Elevated serum concentration of a secondary bile acid in the presence of hepatobiliary disease. J. Pediatr. 1981;98:399–402. doi: 10.1016/S0022-3476(81)80702-0. [DOI] [PubMed] [Google Scholar]
  • 70.Danielsson H., Sjovall J. Bile acid metabolism. Ann. Rev. Biochem. 1975;44:233–253. doi: 10.1146/annurev.bi.44.070175.001313. [DOI] [PubMed] [Google Scholar]
  • 71.Bean P., Liegmann K., Lovli T., Westby C., Sundrehagen E. Semiautomated procedures for evaluation of carbohydrate-deficient transferrin in the diagnosis of alcohol abuse. Clin. Chem. 1997;43:6983–6989. [PubMed] [Google Scholar]
  • 72.Stibler H. Carbohydrate-deficient transferrin in serum; a new marker of potentially harmful alcohol consumption reviewed. Clin. Chem. 1991;37:2029–2037. [PubMed] [Google Scholar]
  • 73.Anton R., Bean P. Two methods for measuring carbohydrate-deficient transferrin in inpatient alcoholics and healthy controls compared. Clin. Chem. 1994;40:364–368. [PubMed] [Google Scholar]
  • 74.Doyle K.M., Cluette-Brown J.E., Dube O.M., Bernhardt T.G., Morse C.R., Laposata M. J. Am. Med. Assoc. 1996;176:1152–1156. doi: 10.1001/jama.276.14.1152. [DOI] [PubMed] [Google Scholar]
  • 75.Doyle K.M., Bird D.A., al-Salihi S., Hallag Y., Cluete-Brown J.E., Goss K.A., Laposata M. Fatty acid ethyl esters are present in human serum after ethanol ingestion. J Lipid Res. 1994;35:428–437. [PubMed] [Google Scholar]
  • 76.Betro M.G. Significance of increased alkaline phosphatase and lactate dehydrogenase activities coincident with normal serum bilirubin. Clin. Chem. 1972;18:1429–1429. [PubMed] [Google Scholar]

Articles from Indian Journal of Clinical Biochemistry are provided here courtesy of Springer

RESOURCES