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Traditional Markers in Liver Disease

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Biomarkers in Liver Disease

Abstract

Liver diseases are many and can often be difficult to diagnose, because symptoms can be vague and easily confused with other health problems. However, physicians can be helped by specific markers used to diagnose and follow up liver diseases. In fact some of the enzymes and the end products of the metabolic pathway occurring in the liver are very sensitive for the abnormality occurred and, for this reason, may be considered as biochemical markers of liver dysfunction. In this chapter, we will examine the main markers of liver diseases, dividing them as markers of hepatic necrosis, markers of hepatic obstruction, markers of liver’s biosynthetic capacity, markers of hepatic steatosis, markers of hepatic fibrosis, and markers of hepatic tumor.

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Abbreviations

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

LDH:

Lactate dehydrogenase

γ-GT:

Gamma glutamyl transferase

PT:

Prothrombin time

INR:

International normalized ratio

PICP:

Procollagen type I carboxy-terminal peptide

PIIINP:

Procollagen type III amino-terminal peptide

TGF-β1:

Transforming growth factor-β1

AFP:

α-Fetoprotein

NTP:

5′ Nucleotidase

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

References

  • Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.

    Article  CAS  PubMed  Google Scholar 

  • Asmaa IG, Shahid AK, Edward LS. Diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2009;15:1301–14.

    Article  Google Scholar 

  • Badra G, Lotfy M, El-Refaie A, Obada M, Abdelmonem E, Kandeel S, et al. Significance of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in chronic hepatitis C patients. Acta Microbiol Immunol Hung. 2010;57(1):29–42.

    Article  CAS  PubMed  Google Scholar 

  • Beckingham IJ, Ryder SD. Clinical review ABC of diseases of liver, pancreas, and biliary system investigation of liver and biliary disease. BMJ. 2001;322:33–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495–500.

    Article  CAS  PubMed  Google Scholar 

  • Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21:3–16.

    Article  CAS  PubMed  Google Scholar 

  • Chan DF, Li AM, Chu WC, Chan MH, Wong EM, Liu EK, et al. Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord. 2004;28(10):1257–63.

    Article  CAS  PubMed  Google Scholar 

  • Cheung BM, Ong KL, Wong LY. Elevated serum alkaline phosphatase and peripheral arterial disease in the United States national health and nutrition examination survey 1999–2004. Int J Cardiol. 2009;135:156–61.

    Article  PubMed  Google Scholar 

  • Cortez-Pinto H, Camilo ME, Baptista A, De Oliveira AG, De Moura MC. Non-alcoholic fatty liver: another feature of the metabolic syndrome? Clin Nutr. 1999;18:353–8.

    Article  CAS  PubMed  Google Scholar 

  • Daniel SP, Marshal MP. In: Eugene RS, Michel FS, Willis CM, editors. Schiff’s diseases of the liver, vol. 1. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2007. p. 19–54. Laboratory test.

    Google Scholar 

  • Day CP. Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol. 2002;16:663–78.

    Article  CAS  PubMed  Google Scholar 

  • Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865–73.

    Article  CAS  PubMed  Google Scholar 

  • Fairbanks KD, Tavill AS. Liver disease in alpha 1-antitrypsin deficiency: a review. Am J Gastroenterol. 2008;103(8):2136–41.

    Article  CAS  PubMed  Google Scholar 

  • Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol. 2001;96:2448–55.

    Article  CAS  PubMed  Google Scholar 

  • Friedman SF, Martin P, Munoz JS. Laboratory evaluation of the patient with liver disease. Hepatology, a textbook of liver disease. Philedelphia: Saunders; 2003. p. 661–709.

    Google Scholar 

  • Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134(4):960–74.

    Article  PubMed  Google Scholar 

  • Giannini E, Botta F, Fasoli A, Romagnoli P, Mastracci L, Ceppa P. Increased levels of gamma GGT suggest the presence of bile duct lesions in patients with chronic hepatitis C: absence of influence of HCV genotype, HCV-RNA serum levels, and HGV infection on this histological damage. Dig Dis Sci. 2001;46:524–9.

    Article  CAS  PubMed  Google Scholar 

  • Giboney PT. Mildly elevated liver transaminase levels in the asymptomatic patient. Am Fam Physician. 2005;71(6):1105–10.

    PubMed  Google Scholar 

  • Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J. 2009;3:17.

    PubMed  PubMed Central  Google Scholar 

  • Hagiwara S, Kudo M, Kawasaki T, Nagashima M, Minami Y, Chung H, et al. Prognostic factors for portal venous invasion in patients with hepatocellular carcinoma. J Gastroenterol. 2006;41:1214–9.

    Article  PubMed  Google Scholar 

  • Hayasaka A, Suzuki N, Fujimoto N, Iwama S, Fukuyama E, Kanda Y, et al. Elevated plasma levels of matrix metalloproteinase-9 (92-kd type IV collagenase/gelatinase B) in hepatocellular carcinoma. Hepatology. 1996;24:1058–62.

    Article  CAS  PubMed  Google Scholar 

  • Jadhao SB, Yang RZ, Lin Q, Hu H, Anania FA, Shuldiner AR, Gong DW. Murine alanine aminotransferase: cDNA cloning, functional expression, and differential gene regulation in mouse fatty liver. Hepatology. 2004;39:1297–302.

    Article  PubMed  Google Scholar 

  • Joy D, Thava VR, Scott BB. Diagnosis of fatty liver disease: is biopsy necessary? Eur J Gastroenterol Hepatol. 2003;15:539–43.

    PubMed  Google Scholar 

  • Kanzler S, Baumann M, Schirmacher P, Dries V, Bayer E, Gerken G, et al. Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor beta. J Viral Hepat. 2001;8(6):430–7.

    Article  CAS  PubMed  Google Scholar 

  • LaRusso NF, Summerskill WH, McCall JT. Abnormalities of chemical tests for copper metabolism in chronic active liver disease: differentiation from Wilson’s disease. Gastroenterology. 1976;70:653–5.

    CAS  PubMed  Google Scholar 

  • Lieber CS, Weiss DG, Paronetto F, Veterans Affairs Cooperative Study 391 Group. Value of fibrosis markers for staging liver fibrosis in patients with precirrhotic alcoholic liver disease. Alcohol Clin Exp Res. 2008;32(6):1031–9.

    Article  CAS  PubMed  Google Scholar 

  • Lindqvist U, Laurent TC. Serum hyaluronan and aminoterminal propeptide of type III procollagen: variation with age. Scand J Clin Lab Invest. 1992;52(7):613–21.

    Article  CAS  PubMed  Google Scholar 

  • Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50:1844–50.

    Article  CAS  PubMed  Google Scholar 

  • Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–9.

    Article  CAS  PubMed  Google Scholar 

  • Mauro P, Renze B, Wouter W. Enzymes. In: Carl AB, Edward R, David EB, editors. Tietz textbook of clinical chemistry and molecular diagnostics. 4th ed. St. Louis: Elsevier; 2006. p. 604–16.

    Google Scholar 

  • McCullough AJ. Update on nonalcoholic fatty liver disease. J Clin Gastroenterol. 2002;34:255–62.

    Article  PubMed  Google Scholar 

  • Nalpas B, Vassault A, Charpin S, Lacour B, Berthelot P. Serum mitochondrial aspartate aminotransferase as a marker of chronic alcoholism: diagnostic value and interpretation in a liver unit. Hepatology. 1986;6(4):608–14.

    Article  CAS  PubMed  Google Scholar 

  • Nanji AA, French SW, Freeman JB. Serum alanine aminotransferase to aspartate aminotransferase ratio and degree of fatty liver in morbidly obese patients. Enzyme. 1986;36:266–9.

    CAS  PubMed  Google Scholar 

  • Nicoll DC. In: Stephen JM, Maxine AP, editors. Current medical diagnosis and treatment. 46th ed. Columbos: Mc Graw hill; 2007. p. 1767–75. Appendix: Therapeutic drug monitoring and laboratory reference ranges.

    Google Scholar 

  • Nimni ME. Fibrillar collagens: their biosynthesis, molecular structure, and mode of assembly. In: Zern MA, Reid LM, editors. Extracellular matrix. New York: Marcel Dekker; 1993. p. 121–48.

    Google Scholar 

  • Pratibha K, Usha A, Rajni A. Serum adenosine deaminase, 5′ nucleotidase and malondialdehyde in acute infective hepatitis. Indian J Clin Biochem. 2004;19:128–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rej R. Measurement of aminotransferases, aspartate aminotransferases. CRC Crit Rev Clin Lab Sci. 1985;21:99–103.

    Article  Google Scholar 

  • Rosalki SB, Mcintyre N. Biochemical investigations in the management of liver disease, vol. 2. New York: Oxford university press; 1999. p. 503–21. Oxford textbook of clinical hepatology.

    Google Scholar 

  • Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, Mullen KD, Cooper JN, Sheridan MJ. The utility of radiological imaging in non-alcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.

    Article  PubMed  Google Scholar 

  • Sakugawa H, Nakayoshi T, Kobashigawa K, Yamashiro T, Maeshiro T, Miyagi S, et al. Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2005;11:255–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherlock S. Assessment of liver function disease of liver and biliary system: Sheila Sherlock. 10th ed. London: Blackwell science ltd; 1997. p. 17–32.

    Google Scholar 

  • Siegelman ES, Rosen MA. Imaging of hepatic steatosis. Semin Liver Dis. 2001;21:71–80.

    Article  CAS  PubMed  Google Scholar 

  • Simko V. Alkaline phosphatases in biology and medicine. Dig Dis. 1991;9:189–93.

    Article  CAS  PubMed  Google Scholar 

  • Smith K, Varon HH, Race GJ, et al. Serum 5′-nucleotidase in patients with tumour in the liver. Cancer. 1966;17:1281–5.

    Article  Google Scholar 

  • Sohocki MM, Sullivan LS, Harrison WR, Sodergren EJ, Elder FF, Weinstock G. Human glutamate pyruvate transaminase (GPT): localization to 8q24.3, cDNA and genomic sequences, and polymorphic sites. Genomics. 1997;40:247–52.

    Article  CAS  PubMed  Google Scholar 

  • Soliday FK, Conley YP, Henker R. Pseudocholinesterase deficiency: a comprehensive review of genetic, acquired, and drug influences. AANA J. 2010;78(4):313–20.

    Google Scholar 

  • Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR. 2007;189(6):W320–3.

    Article  PubMed  Google Scholar 

  • Sugiura M, Nakamura M, Ikoma Y, Yano M, Ogawa K, Matsumoto H, et al. High serum carotenoids are inversely associated with serum gamma-glutamyl transferase in alcohol drinkers within normal liver function. J Epidemiol. 2005;15:180–6.

    Article  PubMed  Google Scholar 

  • Sun J. Matrix metalloproteinases and tissue inhibitor of metalloproteinases are essential for the inflammatory response in cancer cells. J Signal Transduct. 2010;2010:1–7.

    Google Scholar 

  • Takahara T, Furui K, Yata Y, Jin B, Zhang LP, Nambu S, et al. Dual expression of matrix protease-2 and membrane type I-matrix proteinase in fibrotic human livers. Hepatology. 1997;26:1521–9.

    Article  CAS  PubMed  Google Scholar 

  • Thapa BR, Anuj W. Liver function tests and their interpretation. Indian J Pediatr. 2007;74:663–71.

    Article  CAS  PubMed  Google Scholar 

  • Tiribelli C, Ostrow JD. New concepts in bilirubin and jaundice: report of the third international bilirubin workshop, April 6–8, 1995, Trieste, Italy. Hepatology. 1996;24:1296–311.

    Article  CAS  PubMed  Google Scholar 

  • Veidal SS, Vassiliadis E, Bay-Jensen AC, Tougas G, Vainer B, Karsdal MA. Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats. Fibrogenesis Tissue Repair. 2010;3(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Walsh KM, Timms P, Campbell S, MacSween RN, Morris AJ. Plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) as noninvasive markers of liver disease in chronic hepatitis C: comparison using ROC analysis. Dig Dis Sci. 1999;44:624–30.

    Article  CAS  PubMed  Google Scholar 

  • Wong HY, Tan JYL, Lim CC. Abnormal liver function test in symptomatic pregnant patient: the local experience in Singapore. Ann Acad Med. 2004;33:204–8.

    CAS  Google Scholar 

  • Wu A, Slavin G, Levi AJ. Elevated serum gamma-glutamyl-transferase (transpeptidase) and histological liver damage in alcoholism. Am J Gastroenterol. 1976;65:318–23.

    CAS  PubMed  Google Scholar 

  • Yang RZ, Blaileanu G, Hansen BC, Shuldiner AR, Gong DW. cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase. Genomics. 2002;79:445–50.

    Article  CAS  PubMed  Google Scholar 

  • Yoneda M, Mawatari H, Fujita K, Yonemitsu K, Kato S, Takahashi H, Kirikoshi H, Inamori M, Nozaki Y, Abe Y, Kubota K, Saito S, Iwasaki T, Terauchi Y, Togo S, Maeyama S, Nakajima A. Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage. J Gastroenterol. 2007;42(5):375–81.

    Article  CAS  PubMed  Google Scholar 

  • Yoneda M, Nozaki Y, Endo H, Mawatari H, Iida H, Fujita K, et al. Serum ferritin is a clinical biomarker in Japanese patients with nonalcoholic steatohepatitis (NASH) independent of HFE gene mutation. Dig Dis Sci. 2010;55:808–14.

    Article  CAS  PubMed  Google Scholar 

  • Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41(1):48–54.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, PAVIA, P.le C. Golgi, 2 – 27100, Pavia, Italy

    Giuseppe Derosa & Pamela Maffioli

  2. Center for the Study of Endocrine-Metabolic Pathophysiology and Clinical Research, University of Pavia, Pavia, Italy

    Giuseppe Derosa

  3. Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy

    Giuseppe Derosa

  4. Center for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Giuseppe Derosa & Pamela Maffioli

  5. PhD School in Experimental Medicine, University of Pavia, Pavia, Italy

    Pamela Maffioli

Authors
  1. Giuseppe Derosa
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  2. Pamela Maffioli
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Correspondence to Giuseppe Derosa .

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Editors and Affiliations

  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Derosa, G., Maffioli, P. (2016). Traditional Markers in Liver Disease. In: Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7742-2_13-1

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  • DOI: https://doi.org/10.1007/978-94-007-7742-2_13-1

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  • Online ISBN: 978-94-007-7742-2

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