Comparison and Evaluation of CTGF and P2/MS as Noninvasive Markers in Fibrosis Evaluation in Chronic Liver Diseases

Serpil Çiftel; Naciye Özlem Saygılı Yönem; Hilmi Ataseven; Sedat Çiftel; Ahmet Altun

doi:10.7197/cmj.1212431

Research Article

Comparison and Evaluation of CTGF and P2/MS as Noninvasive Markers in Fibrosis Evaluation in Chronic Liver Diseases

Year 2022, , 443 - 448, 31.12.2022

Serpil Çiftel , Naciye Özlem Saygılı Yönem Hilmi Ataseven , Sedat Çiftel , Ahmet Altun

https://doi.org/10.7197/cmj.1212431

Abstract

Background/Aims: To compare CTGF (connective tissue growth factor) and P2/MS [platelet count (109 / L)] 2 / [monocyte fraction (%) x segment neutrophil fraction (%)] ratio as non-invasive tests with liver biopsy in the detection of liver fibrosis. Thus, to determine whether CTGF and P2/MS index results can be used as a noninvasive marker, in the diagnosis of chronic liver disease
Materials and Methods: A total of 52 chronic hepatitis patients with concurrent liver biopsy (27 female, 25 male) were included in the study group. The subjects' ages ranged between 18 and 70, and none of the subjects had undergone liver disease-related treatment. The control group was made up of a total of 31 healthy individuals without liver disease (18 female, 13 male) from similar age groups. Liver biopsy results of patients were reported at 7 stages according to Modified Knodell Scoring (ISHAK).
Results: CTGF levels were higher in patients with chronic hepatitis (1.06±0.70 ng/ml) than the control group (0,72±0,32 ng/ml) (P<0,05). When the P2/MS indexes were compared according to the liver biopsy results of the patients in the study group, the difference was found to be significant. As the degree of fibrosis increased, P2/MS index decreased.
Conclusions: As a noninvasive test, it was seen that CTGF and P2/MS is parallel to liver biopsy in reflecting liver fibrosis. These noninvasive markers can be used where liver biopsies cannot be performed or where repetition is necessary, and in the follow-up of patients for early detection of fibrosis.

Keywords

Fibrosis, Liver, CTGF

Supporting Institution

Unit of the Cumhuriyet University Scientific Research Projects (CÜBAP)

Project Number

T533 numbered project

References

1.Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol. 2019; 70: 151– 71.
2.Bork P. The modular architecture of a new family of growth regulators related to connective tissue growth factor. FEBS Letters. 1993;327 (2): 125–30.
3.Z. Chen, N. Zhang, H.Y. Chu, Y. Yu, Z.K. Zhang, G. Zhang, Zhang BT. Connective tissue growth factor: from molecular understandings to drug discovery. Front Cell Dev Biol, 2020; 29: 8:593269.
4.Huang G, Brigstock DR. Regulation of hepatic stellate cellsby connective tissuegrowth factor. Frontiers in Bioscience.2012;17: 2495-507.
5.Makino Y, Hikita H, Kodama T, Shigekawa M, Yamada R, Sakamori R, Eguchi H, Morii E, Yokoi H, Mukoyama M, Hiroshi S, Tatsumi T, Takehara T. CTGF Mediates Tumor-Stroma Interactions between Hepatoma Cells and Hepatic Stellate Cells to Accelerate HCC Progression. Cancer Res. 2018; 78, 4902-914.
6.Wu Y, Wang W, Peng XM, He Y, Xiong YX, Liang HF, Chu L, Zhang BX, Ding ZY, Chen XP. Rapamycin Upregulates Connective Tissue Growth Factor Expression in Hepatic Progenitor Cells Through TGF-β-Smad2 Dependent Signaling. Front Pharmacol. 2018; 8; 9: 877.
7. Alatas FS, Matsuura T, Pudjiadi AH, Wijaya S, Taguchi T. Peroxisome Proliferator-Activated Receptor Gamma Agonist Attenuates Liver Fibrosis by Several Fibrogenic Pathways in an Animal Model of Cholestatic Fibrosis. Pediatr Gastroenterol Hepatol Nutr. 2020; 23(4):346-55.
8.Hao C, Xie Y, Peng M, Ma L, Zhou Y, Zhang Y, Kang W, Wang J, Bai X, Wang P, Jia Z. Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo. Clin Exp Med. 2014; 14(2):141-50.
9.Yu SJ, Kim DH, Lee JH, Chung GE, Yim JY, Park MJ, Kim YJ, Yoon JH, Jang JJ, Lee HS. Validation of P2/MS and other noninvasive fibrosis scoring systems in the Korean population with nonalcoholic fatty liver disease. Korean J Gastroenterol. 2011; 57(1): 19-27.
10.Lee JH, Yoon JH, Lee CH, Myung SJ, Keam B, Kim BH, Chung GE, Kim W, Kim YJ, Jang JJ, Lee HS. Complete blood count reflects the degree of oesophageal varices and liver fibrosis in virus-related chronic liver disease patients. J Viral Hepat. 2009 ;16(6): 444-52.
11.Kim BK, Han KH, Park JY, Ahn SH, Chon CY, Kim JK, Paik YH, Lee KS, Park YN, Kim DY. External validation of P2/MS and comparison with other simple non-invasive indices for predicting liver fibrosis in HBV-infected patients. Dig Dis Sci. 2010 ;55(9): 2636-43
12.Kim BK, Han KH, Park JY, Ahn SH, Kim JK, Paik YH, Lee KS, Chon CY, Kim DY. Prospective validation of P2/MS noninvasive index using complete blood counts for detecting oesophageal varices in B-viral cirrhosis. Liver Int. 2010; 30(6): 860-66.
13.Kennedy P, Wagner M, Castéra L, Hong CW, Johnson CL, Sirlin CB, Taouli B. Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions. Radiology. 2018 ;286(3): 738-63.
14.Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, Cosgrove D, Ferraioli G, Friedrich-Rust M, Gilja OH, Goertz RS, Karlas T, de Knegt R, de Ledinghen V, Piscaglia F, Procopet B, Saftoiu A, Sidhu PS, Sporea I, Thiele M. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall Med. 2017 ;38(4): e16-e47
15.Thomaides-Brears HB, Alkhouri N, Allende D, Harisinghani M, Noureddin M, Reau NS, French M, Pantoja C, Mouchti S, Cryer DRH. Incidence of Complications from Percutaneous Biopsy in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2022 ;67(7):3366-394
16.Karlsen TH, Sheron N, Zelber-Sagi S, Carrieri P, Dusheiko G, Bugianesi E, Pryke R, Hutchinson SJ, Sangro B, Martin NK, Cecchini M, Dirac MA, Belloni A, Serra-Burriel M, Ponsioen CY, Sheena B, Lerouge A, Devaux M, Scott N, Hellard M, Verkade HJ, Sturm E, Marchesini G, Yki-Järvinen H, Byrne CD, Targher G, Tur-Sinai A, Barrett D, Ninburg M, Reic T, Taylor A, Rhodes T, Treloar C, Petersen C, Schramm C, Flisiak R, Simonova MY, Pares A, Johnson P, Cucchetti A, Graupera I, Lionis C, Pose E, Fabrellas N, Ma AT, Mendive JM, Mazzaferro V, Rutter H, Cortez-Pinto H, Kelly D, Burton R, Lazarus JV, Ginès P, Buti M, Newsome PN, Burra P, Manns MP. The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet. 2022; 1;399 (10319): 61-116
17.Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004; 7;351(15): 1521-31.
18.Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T; LIDO Study Group. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005 ;128(7): 1898-906.
19.Gressner AM, Yagmur E, Lahme B, Gressner O, Stanzel S. Connective tissue growth factor in serum as a new candidate test for assessment of hepatic fibrosis. Clin Chem. 2006 ;52(9): 1815-17.
20.Sonnylal S, Shi-Wen X, Leoni P, Naff K, Van Pelt CS, Nakamura H, Leask A, Abraham D, Bou-Gharios G, de Crombrugghe B. Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis. Arthritis Rheum. 2010 ;62(5): 1523-32.
21.Zhang D, Wang NY, Yang CB, Fang GX, Liu W, Wen J, Luo C. The clinical value of serum connective tissue growth factor in the assessment of liver fibrosis. Dig Dis Sci. 2010 ;55(3):767-74.
22.Kovalenko E, Tacke F, Gressner OA, Zimmermann HW, Lahme B, Janetzko A, Wiederholt T, Berg T, Müller T, Trautwein C, Gressner AM, Weiskirchen R. Validation of connective tissue growth factor (CTGF/CCN2) and its gene polymorphisms as noninvasive biomarkers for the assessment of liver fibrosis. J Viral Hepat. 2009 ;16(9): 612-20.