Generic placeholder image

Current Chemical Biology

Editor-in-Chief

ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Mini-Review Article

Serum Biomarkers for Noninvasive Diagnosis of Liver Diseases: How Laudable are These Tools?

Author(s): Ankita Singh, Vipul Ranjan, Rina Das*, Karun Bhatti, Dinesh Kumar Mehta and Ram Mohan Chidurala

Volume 15, Issue 2, 2021

Published on: 11 November, 2020

Page: [128 - 138] Pages: 11

DOI: 10.2174/2212796814999201111204639

Price: $65

Abstract

Innumerable reasons have been reported that affect and infect the liver and cause liver diseases. The evaluation and follow-up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, it has become evident that this once defined as “gold-standard” is now not the best method as it involves many limitations. Attempts to reveal non-invasive diagnostic tools have generated serum biomarkers, multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and are less expensive than a liver biopsy. Biomarkers have various advantages like minimally invasive, easy to apply with great availability and easier reproducibility, useful for monitoring therapy and less expensive. But then, direct biomarkers involved in extracellular matrix turnover need further validation in different geographic population and indirect biomarkers may not predict early pathophysiological changes in liver parenchyma. The accuracy and diagnostic value of most, if not all, of these biomarkers remain controversial. Hence, there is a need for a biomarker that is specific for the liver and can identify the magnitude of the clinical outcome of the disease.

In this review, we discuss the clinical utility, limitations, and development of noninvasive biomarkers in their use as diagnostic and prognostic tests and analyze whether the present known serum biomarkers are laudable and accurate tools for the diagnosis of liver diseases.

Keywords: Biomarkers, direct biomarkers, indirect biomarkers, liver diseases, non-invasive, liver diseases.

Graphical Abstract

[1]
Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371(9615): 838-51.
[http://dx.doi.org/10.1016/S0140-6736(08)60383-9] [PMID: 18328931]
[2]
Marcellin P, Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int 2018; 38(12)(Suppl. 1): 2-6.
[http://dx.doi.org/10.1111/liv.13682] [PMID: 29427496]
[3]
Dolganiuc A. Alcohol and viral hepatitis: Role of lipid rafts. Alcohol Res 2015; 37(2): 299-309.
[PMID: 26695752]
[4]
Osna NA, Donohue TM Jr, Kharbanda KK. Alcoholic liver disease: Pathogenesis and current management. Alcohol Res 2017; 38(2): 147-61.
[PMID: 28988570]
[5]
Li S, Sun X, Chen M, et al. Liver fibrosis conventional and molecular imaging diagnosis update. J Liver 2019; 8(1): 1-21.
[PMID: 31341723]
[6]
Guan YS, He Q. A current update on the rule of alternative and complementary medicine in the treatment of liver diseases. Evid Based Complement Alternat Med 2013; 2013: 321234.
[http://dx.doi.org/10.1155/2013/321234] [PMID: 24109491]
[7]
Gowda S, Desai PB, Hull VV, Math AAK, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J 2009; 3(11): 17.
[PMID: 21532726]
[8]
Sharma S, Khalili K, Nguyen GC. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol 2014; 20(45): 16820-30.
[http://dx.doi.org/10.3748/wjg.v20.i45.16820] [PMID: 25492996]
[9]
Graig LA, Phillips JK, Moses HL. Biomarker tests for molecularly targeted therapies: key to unlocking precision medicine Washington (DC): National Academies Press (US). 2016.
[http://dx.doi.org/10.17226/21860]
[10]
Lyman GH, Moses HL. Biomarker tests for molecularly targeted therapies: laying the foundation and fulfilling the dream. J Clin Oncol 2016; 34(17): 2061-6.
[http://dx.doi.org/10.1200/JCO.2016.67.3160] [PMID: 27069080]
[11]
Mayeux R. Biomarkers: potential uses and limitations. NeuroRx 2004; 1(2): 182-8.
[http://dx.doi.org/10.1602/neurorx.1.2.182] [PMID: 15717018]
[12]
Yamamoto S, Hayasaka F, Deguchi K, Okudera T, Furusawa T, Sakai Y. Absorption and plasma kinetics of collagen tripeptide after peroral or intraperitoneal administration in rats. Biosci Biotechnol Biochem 2015; 79(12): 2026-33.
[http://dx.doi.org/10.1080/09168451.2015.1062711] [PMID: 26155906]
[13]
Zhang YZ, Ran LY, Li CY, Chen XL. Diversity, structures, and collagen-degrading mechanisms of bacterial collagenolytic proteases. Appl Environ Microbiol 2015; 81(18): 6098-107.
[http://dx.doi.org/10.1128/AEM.00883-15] [PMID: 26150451]
[14]
Hasturk H, Kantarci A. Activation and resolution of periodontal inflammation and its systemic impact. HHS public access 2015; 69(1): 255-73.
[http://dx.doi.org/10.1111/prd.12105]
[15]
Rek A, Krenn E, Kungl AJ. Therapeutically targeting protein-glycan interactions. Br J Pharmacol 2009; 157(5): 686-94.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00226.x] [PMID: 19371327]
[16]
Hwang h-j, Han JW, Kim GH, et al. Functional expression and characterization of the recombinant N- Acetyl-glucosamine / N- acetyl- galactosamine – specific marine algal lectin BPL3. Mar drugs 2018; 16(6): 1-17.
[17]
Duarte S, Baber J, Fujii T, Coito AJ. Liver fibrosis: A complication on the biomarkers status and there significances during diseases progression. Future Sci 2009; 45(2): 2-5.
[18]
Connor JCO, Mccusker RH, Strle K, Johnson RW, Dantzer R, Kelley KW. Absorption and plasma kinetics of collagen tripeptide after peroral or intraperitoneal administration in rats. Biosci Biotechnol Biochem 2009; 252(217): 91-110.
[19]
Seo WY, Kim JH, Baek DS, et al. Production of recombinant human procollagen type I C-terminal propeptide and establishment of a sandwich ELISA for quantification. Sci Rep 2017; 7(1): 15946.
[http://dx.doi.org/10.1038/s41598-017-16290-9] [PMID: 29162919]
[20]
Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. BioMed Res Int 2013; 2013(s81): 284873.
[http://dx.doi.org/10.1155/2013/284873] [PMID: 24069595]
[21]
Nishimura M. Circulating aminoterminal propeptide of type procollagen as a biomarker of cardiovascular events in patients undergoing periodontol. Atheroscler thromb 2019; 26(1): 340-50.
[22]
Khan S, Subedi D, Chowdhury MM. Use of amino terminal type III procollagen peptide (P3NP) assay in methotrexate therapy for psoriasis. Postgrad Med J 2006; 82(967): 353-4.
[http://dx.doi.org/10.1136/pgmj.2005.041533] [PMID: 16679477]
[23]
Tanjore H, Kalluri R, Membranes B. The role of type IV collagen and basement membranes in cancer progression and metastasis. Am J Pathol 2006; 168(3): 715-7.
[http://dx.doi.org/10.2353/ajpath.2006.051321] [PMID: 16507886]
[24]
Hohenester E, Yurchenco PD. Laminins in basement membrane assembly. Cell Adhes Migr 2013; 7(1): 56-63.
[http://dx.doi.org/10.4161/cam.21831] [PMID: 23076216]
[25]
Nallagangula KS, Nagaraj SK. Liver fibrosis: A complication on the biomarkers status and there significances during diseases progression metrix metalloproteinases in liver injury. Repair and fibrosis 2015; 45(2): 147-51.
[26]
Hasanov H, Mammadova K, Guliyeva F, Azizova U, Mikailova N. The role of matrix metalloproteinases in human body biology and medicne. Int Anesthesiol Clin 2018; 10(6): 10-2.
[27]
Sankari SL, Krupaa RJ, Kumar GMK, Balachander N. MMP- Matrix metalloproteinase. Biomed Pharmacol J 2016; 9(2): 885.
[http://dx.doi.org/10.13005/bpj/1025]
[28]
Bischoff TKR. Physiology and pathophysiology of matrix metalloproteases. Amino acid 2011; 41: 271-90.
[29]
Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000; 1477(1-2): 267-83.
[http://dx.doi.org/10.1016/S0167-4838(99)00279-4] [PMID: 10708863]
[30]
Cui N, Hu M, Khalil RA, Surgery V, Surgery E. Production of recombinant human procollagen type I C-terminalpropeptide and establishment of a sandwich ELISA for quantification. J Proteome Res 2018; 617: 1-60.
[31]
Gao Y, Liu S, Huang J, et al. The ecm-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int 2014; 648459: 8.
[http://dx.doi.org/10.1155/2014/648459]
[32]
Necas J, Bartosikova L, Brauner P, Kolar J. Hyaluronic acid (hyaluronan). Veterinarni medicin 2008; 53(8): 397-411.
[33]
Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health 2009; 1(6): 461-8.
[http://dx.doi.org/10.1177/1941738109350438] [PMID: 23015907]
[34]
Iorio V, Troughton LD, Hamill KJ. Laminins: Roles and utility in wound repair. Adv Wound Care (New Rochelle) 2015; 4(4): 250-63.
[http://dx.doi.org/10.1089/wound.2014.0533] [PMID: 25945287]
[35]
Sasaki T, Fässler R, Hohenester E. Laminin: the crux of basement membrane assembly. J Cell Biol 2004; 164(7): 959-63.
[http://dx.doi.org/10.1083/jcb.200401058] [PMID: 15037599]
[36]
Chen ZL, Strickland S. Laminin gamma1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve. J Cell Biol 2003; 163(4): 889-99.
[http://dx.doi.org/10.1083/jcb.200307068] [PMID: 14638863]
[37]
Shao R, Atlantic F. YKL-40 acts as an angiogenic factor to promote tumor angiogenesis. Front Physiol 2013; 4(5): 122.
[http://dx.doi.org/10.3389/fphys.2013.00122] [PMID: 23755018]
[38]
Coffman FD. Chitinase 3-Like-1 (CHI3L1): a putative disease marker at the interface of proteomics and glycomics. Crit Rev Clin Lab Sci 2008; 45(6): 531-62.
[http://dx.doi.org/10.1080/10408360802334743] [PMID: 19003601]
[39]
Schultz NA, Johansen JS. YKL-40—A protein in the field of translational medicine: a role as a biomarker in cancer patients? Cancer wound 2010; 2: 1453-91.
[http://dx.doi.org/10.3390/cancers2031453]
[40]
Cruz-Munoz W, Khokha R. The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci 2008; 45(3): 291-338.
[http://dx.doi.org/10.1080/10408360801973244] [PMID: 18568853]
[41]
Bowen-Pope DF, Raines EW. History of discovery: platelet-derived growth factor. Arterioscler Thromb Vasc Biol 2011; 31(11): 2397-401.
[http://dx.doi.org/10.1161/ATVBAHA.108.179556] [PMID: 22011752]
[42]
Raica M, Cimpean AM. Platelet-derived growth factor (pdgf)/pdgf receptor (pdgfr) axis as target for antitumor and antiangiogenic therapy. Pharmaceuticals (Basel) 2010; 3(3): 572-99.
[http://dx.doi.org/10.3390/ph3030572] [PMID: 27713269]
[43]
Blum M, Waldner M, Gisi U. A single point mutation in the novel PvCesA3 gene confers resistance to the carboxylic acid amide fungicide mandipropamid in Plasmopara viticola. Fungal Genet Biol 2010; 47(6): 499-510.
[http://dx.doi.org/10.1016/j.fgb.2010.02.009] [PMID: 20226261]
[44]
Sækmose SG, Mössner B, Christensen PB, et al. Microfibrillar-associated protein 4: a potential biomarker for screening for liver fibrosis in a mixed patient cohort. PLoS One 2015; 10(10): e0140418.
[http://dx.doi.org/10.1371/journal.pone.0140418] [PMID: 26460565]
[45]
Nelson DR, Gonzalez-Peralta RP, Qian K, et al. Transforming growth factor-β 1 in chronic hepatitis C. J Viral Hepat 1997; 4(1): 29-35.
[http://dx.doi.org/10.1046/j.1365-2893.1997.00124.x] [PMID: 9031062]
[46]
Kanzler S, Bumann M, Schirmacher P, et al. Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue level of transforming growth factor -β. Viral hepat 2001; 8(6): 430-7.
[http://dx.doi.org/10.1046/j.1365-2893.2001.00314.x]
[47]
Yilmaz Y, Dolar E, Ulukaya E, et al. Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis. World J Gastroenterol 2007; 13(6): 837-44.
[http://dx.doi.org/10.3748/wjg.v13.i6.837] [PMID: 17352011]
[48]
Yang M, Xu D, Liu Y, et al. Combind serum biomarkers in non invasive diagnosis of non- alcoholic steatohepatitis. PLoS One 2015; 10(6): e0131664.
[http://dx.doi.org/10.1371/journal.pone.0131664] [PMID: 26121037]
[49]
Kamitori S, Okamoto A, Hirotsu K, et al. Three-dimensional structures of aspartate aminotransferase from Escherichia coli and its mutant enzyme at 2.5 A resolution. J Biochem 1990; 108(2): 175-84.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a123178] [PMID: 2121725]
[50]
Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008; 47(4): 1363-70.
[http://dx.doi.org/10.1002/hep.22109] [PMID: 18366115]
[51]
Chinnaraj M, Chen Z, Pelc LA, et al. Structure of prothrombin in the closed form reveals new details on the mechanism of activation. Sci Rep 2018; 8(1): 2945.
[http://dx.doi.org/10.1038/s41598-018-21304-1] [PMID: 29440720]
[52]
Spinella R, Sawhney R, Jalan R. Albumin in chronic liver disease: structure, functions and therapeutic implications. Hepatol Int 2016; 10(1): 124-32.
[http://dx.doi.org/10.1007/s12072-015-9665-6] [PMID: 26420218]
[53]
Mendez-Sanchez N, Vitek L. Biomarkers in disease:methods, discoveries and applications. Bilirubin as a biomarker in liver disease 2017; 1(6): 281-304.
[54]
Verma VV, Gupta R, Goel M. “Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies”. Biol Direct 2015; 10(1): 49.
[http://dx.doi.org/10.1186/s13062-015-0080-7] [PMID: 26370226]
[55]
Parra M, Stahl S, Hellmann H. Vitamin B 6 and its role in cell metabolism and physiology. Cell 2018; 7(84): 461.
[56]
Li Y, Fang D, Bao Z, et al. High aspartate transaminase/alanine transaminase ratio predicts poor prognosis in patients with localized upper tract urothelial cancer: a propensity score-matched study in a large Chinese center. OncoTargets Ther 2019; 12: 2635-48.
[http://dx.doi.org/10.2147/OTT.S193771] [PMID: 31114222]
[57]
Arciola JM, Horenstein NA. Characterization of the PLP-dependent transaminase initiating azasugar biosynthesis. Biochem J 2018; 475(13): 2241-56.
[http://dx.doi.org/10.1042/BCJ20180340] [PMID: 29907615]
[58]
Kim EE, Wyckoff HW. Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. J Mol Biol 1991; 218(2): 449-64.
[http://dx.doi.org/10.1016/0022-2836(91)90724-K] [PMID: 2010919]
[59]
Millán JL, Whyte MP. Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int 2016; 98(4): 398-416.
[http://dx.doi.org/10.1007/s00223-015-0079-1] [PMID: 26590809]
[60]
Sharma U, Pal D, Prasad R. Alkaline phosphatase: an overview. Indian J Clin Biochem 2014; 29(3): 269-78.
[http://dx.doi.org/10.1007/s12291-013-0408-y] [PMID: 24966474]
[61]
Mohammadi Aria M, Erten A, Yalcin O. Technology advancements in blood coagulation measurements for point-of-care diagnostic testing. Front Bioeng Biotechnol 2019; 7(12): 395.
[http://dx.doi.org/10.3389/fbioe.2019.00395] [PMID: 31921804]
[62]
Quick AJ. The development and use of the prothrombin tests. Circulation 1959; 19(1): 92-6.
[http://dx.doi.org/10.1161/01.CIR.19.1.92] [PMID: 13619026]
[63]
Contreras M, Landt CL, Harrison SA. Clinical advances in liver, pancreas, steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy : a prospective study. YGAST 2011; 140(1): 124-31.
[http://dx.doi.org/10.1053/j.gastro.2010.09.038]
[64]
Report C, Belousov A. Albumin and its application. Mathews J Case Rep 2019; 4: 1-6.
[http://dx.doi.org/10.30654/MJCR.10046]
[65]
Wade NJ, Ono H, Mapp AP, Lillakas L. The singular vision of William Charles wells (1757-1817). J Hist Neurosci 2011; 20(1): 1-15.
[http://dx.doi.org/10.1080/09647040903552764] [PMID: 21253934]
[66]
Belousov A. Concept to the problems of transfusion of albumin. Biomed J Sci Tech Res 2019; 18: 13765-9.
[http://dx.doi.org/10.26717/BJSTR.2019.18.003186]
[67]
Li Y, Fang D, Bao Z, et al. High aspartate transaminase/alanine transaminase ratio predicts poor prognosis in patients with localized upper tract urothelial cancer: a propensity score-matched study in a large Chinese center. OncoTargets Ther 2019; 12: 2635-48.
[http://dx.doi.org/10.2147/OTT.S193771] [PMID: 31114222]
[68]
Čvorović J, Passamonti S. Membrane transporters for bilirubin and its conjugates. Front Pharmacol 2017; 8(12): 887.
[http://dx.doi.org/10.3389/fphar.2017.00887] [PMID: 29259555]
[69]
Bosma PJ. Inherited disorders of bilirubin metabolism. J Hepatol 2003; 38(1): 107-17.
[http://dx.doi.org/10.1016/S0168-8278(02)00359-8] [PMID: 12480568]
[70]
Levitt DG, Levitt MD, Gastroenterology E. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease. Clin Exp Gastroenterol 2014; 7(7): 307-28.
[http://dx.doi.org/10.2147/CEG.S64283] [PMID: 25214800]
[71]
Kim EE, Wyckoff HW, West MB, et al. Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. J Mol Biol 1991; 218(2): 449-64.
[http://dx.doi.org/10.1016/0022-2836(91)90724-K] [PMID: 2010919]
[72]
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J 2016; 15(1): 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[73]
Akaydın SY. Correlation between gamma-glutamyl transferase activity and glutathione levels in molecular subgroups of breast cancer. Breast health 2020; 16(1): 72-6.
[http://dx.doi.org/10.5152%2Fejbh.2019.5147]
[74]
Chen H, Zhang Y, Li S, et al. Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma. Cancer Manag Res 2018; 10: 1947-58.
[http://dx.doi.org/10.2147/CMAR.S167036] [PMID: 30022853]
[75]
Soresi M, Giannitrapani L, Cervello M, Licata A, Montalto G. Non invasive tools for the diagnosis of liver cirrhosis. World J Gastroenterol 2014; 20(48): 18131-50.
[http://dx.doi.org/10.3748/wjg.v20.i48.18131] [PMID: 25561782]
[76]
Nallagangula KS, Nagaraj SK, Venkataswamy L, Chandrappa M. Liver fibrosis: a compilation on the biomarkers status and their significance during disease progression. Future Sci OA 2017; 4(1): FSO250.
[http://dx.doi.org/10.4155/fsoa-2017-0083] [PMID: 29255622]
[77]
Rosenberg WMC, Voelker M, Thiel R, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004; 127(6): 1704-13.
[http://dx.doi.org/10.1053/j.gastro.2004.08.052] [PMID: 15578508]
[78]
Murawaki Y, Ikuta Y, Okamoto K, Koda M, Kawasaki H. Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C. J Gastroenterol 2001; 36(6): 399-406.
[http://dx.doi.org/10.1007/s005350170084] [PMID: 11428586]
[79]
Patel K, Gordon SC, Jacobson I, et al. Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients. J Hepatol 2004; 41(6): 935-42.
[http://dx.doi.org/10.1016/j.jhep.2004.08.008] [PMID: 15582126]
[80]
Hind IF. non-invasive biomarker of liver fibrosis: an overview. Hepatol 2014; 15(4): 1-15.
[http://dx.doi.org/10.1155/2014/357287]
[81]
Grigorescu M. Noninvasive biochemical markers of liver fibrosis. J Gastrointestin Liver Dis 2006; 15(2): 149-59.
[PMID: 16802010]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy