CD14 and TIMP-1 as predictive biomarkers of extensive liver fibrosis in Egyptian HCV-patients
By: Eman M. Abd El Azeem, Magda Kamal El Din Ezz, Dr. Amin M. Abdel Baki, Asmaa Abd ElFattah Deghedy
Key Words: HCV, Fibrosis, S-CD14, TIMP-1, TGF-β1
Int. J. Biosci. 10(4), 66-80, April 2017Certificate
HCV infection is closely associated with liver ﬁbrosis, a major risk factor related to liver cirrhosis and hepatocellular carcinoma. Therefore, the aim of this study was to analyze the association of serum s-CD14 and TIMP-1 level with the stages of fibrosis in hepatic tissue of HCV infected patients as an alternative non-invasive method to avoid using liver biopsy. This study included seventy HCV patients with liver fibrosis classified into four subgroups according to the degree of fibrosis: group 1 (with liver fibrosis F4), group 2 (with liver fibrosis F3), group 3 (with liver fibrosis F2) and group 4 (with liver fibrosis F1). Normal subjects were conserved as group 5 (control group). Direct biomarkers, serum s-CD14, TGF-β1and TIMP-1 levels were determined by the quantitative sandwich enzyme immunoassay (ELISA) technique. Serum ALT, AST, albumin, total bilirubin, prothrombin time and concentration, complete blood count were detected. Indirect biomarkers, ALT/AST Ratio (AAR) and Fib4 were also calculated. Serum sCD14, TGF-β1 and TIMP-1 levels showed a highly significant increase, also serum level of AFP increased significantly in all groups compared to normal control. This increment was parallel to the degree of fibrosis. The diagnostic accuracy of all direct blood markers rose with increasing stage of fibrosis, while the accuracy of indirect markers (AAR and Fib 4) increased in the early stage of fibrosis. Performance of sCD14 in our study was the best direct blood marker for diagnosis of extensive fibrosis (F3 and F4).In conclusion, sCD14 may be a more relevant biomarker of disease progression.
CD14 and TIMP-1 as predictive biomarkers of extensive liver fibrosis in Egyptian HCV-patients
Ahram Online. Fact box: 15 facts about Hepatitis C in Egypt and the latest approved drugs. 15th Annual Congress of the Egyptian Society of Hepatology, Gastroenterology and Infectious Diseases. Ahram Online used the recommendations of the panel, along with information from the Egyptian Ministry of Health and World Health Organization (WHO) Ingy Deif, Cairo, Thursday 29 May 2014.
Benyon R, Arthur M. 2001. Extracellular matrix degradation andthe role of hepatic stellate cells. Seminars in Liver Disease 21, 373-384.
Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, Bonkovsky HL. 2005. Serum alpha fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. Journal of Hepatology. 43, 434–441.
Doumas BT, Perry BW, Sasse EA, Straumfjord JV. 1973.Standardization in bilirubin assays: evaluation of selected methods and stability of bilirubin solutions. Clinical Chemistry. 19, 984–993.
Duffield JS, Forbes SJ, Constandinou CM. 2005.Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. Journal of Clinical Investigation. 115, 56–65.
European Association for Study of Liver. 2015. EASL recommendations on treatment of hepatitis C 2015. Journal of Hepatology 63, 199–236.
Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, Rapaccini G, Del Poggio P, Di Nolfo MA, Benvegnù L. 2006.Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? American Journal of Gastroenterology 101, 524–532.
Flores A, Marrero JA. 2014. Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics. Clinicl Medecine Insights: Oncology 8, 71-76.
Gella FJ, Olivella T, Cruz PM, Arenas J, Moreno R, Durban R, Gomez JA. 1985. A simple procedure for routine determination of aspartate aminotransferase and alanine aminotransferase with pyridoxal phosphate. Clinical Chimica Acta 153, 241-247.
Giannini E, Risso D, Botta F, Chiarbonello B, Fasoli A, Malfatti F, Romagnoli P, Testa E, Ceppa P, Testa R. 2003.Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease. Archives of Internal Medecine 163, 218-224.
Gioannini TL, Weiss JP. 2007.Regulation of interactions of Gram-negative bacterial endotoxins with mammalian cells. Immunologic Research. 39, 249–260.
Han DW. 2002. Intestinal endotoxemia as a pathogenetic mechanism in liver failure. World Journal of Gastroenterology 8, 961–965
Hernandez-Gea V, Friedman SL. 2011. Pathogenesis of accelerated fibrosis in HIV/HCV co-infection. Annual Review of Pathology: Mechanisms of Disease.6, 425–456.
Hoofnagle JH. 2002. Course and outcome of hepatitis C. Hepatology 36, 21–29.
Iagoda AB, Koroĭ PV, Geĭvandova NI, Nikitina OA, Kastornaia IV. 2006.Growth factors and the hystologic picture of the liver in chronic viral hepatitis and hepatic cirrhosis. Klinicheskaia Meditsina. 84, 44-7.
Imajo K, Fuhita K, Yoneda M, Nozaki Y, Ogawa Y. 2012. Hyperresponsivity to low-dose endotoxin durin progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metabolism 16, 44-54.
Inagaki Y, Okazaki I. 2007. Emerging insights into transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut 56, 284-292.
Irvine KM, Wockner LF, Shanker M, Fagan KJ, Horsfall LU, Fletcher LM. 2016. The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease. Liver International. 36, 370–377.
Kakisaka K, Kataoka K, Onodera M, Suzuki A, Endo K, Tatemichi Y. 2015.Alpha-fetoprotein: A biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure. Hepatology Research. 45, 12–20.
Katharine M, Irvine Leesa F, Wockner, Isabell
Hoffmann, Leigh U, Horsfall1, Kevin J, Fagan, Veonice Bijin, Bernett Lee, Andrew D, Clouston, Guy Lampe, John E, Connolly, Elizabeth E, Powell. 2016. Multiplex serum protein analysis identifies novel biomarkers of advanced fibrosis in patients with chronic liver disease with the potential to improve diagnostic accuracy of established biomarkers. PLoS ONE 11, 1-13.
Kitchens RL, Thompson PA.2005.Modulatory effects of sCD14 and LBP on LPS-host cell interactions. Journal of Endotoxin Research. 11, 225–229.
Lee HC, Sung SS, Krueger PD, Jo YA, Rosen HR, Ziegler SF, Hahn YS. 2013. Hepatitis C virus promotesT- helper (Th)17responses through thymicstromal lymphopoietin production by infected hepatocytes. Hepatology 57,1314–1324.
Li S, Vriend LE, Nasser IA, Popov Y, Afdhal NH, Koziel MJ, Schuppan D, Exley MA, Alatrakchi N. 2012. Hepatitis C virus-speciﬁc T-cell derived transforming growth factor beta is associated with slow hepatic ﬁbrogenesis. Hepatology 56, 2094–2105.
Liu YR, Lin BB, Zeng DW, Zhu YY, Chen J, Zheng Q, et al.2014.Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross-sectional study of 619 consecutive patients with chronic hepatitis B. BMC Gastroenterology 14, 145-153.
Luo R, Yang S, Xie J, Zhao Z, He Y, Yao J. 2001.Diagnostic value of five serum markers for liver fibrosis. Chinese Journal of Hepatology. 9, 148-150.
Mahmoud YA, Mumtaz GR, Riome S, Miller D, Abu-Raddad LJ. 2013. The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis. BMC Infectious Disease. 13, 288. http://dx.doi.org/10.1186/1471-2334-13-151.
Manning D, Afdhal N. 2008. Diagnosis and quantitation of fibrosis. Gastroenterology 134, 1670-1681.
Marzena Ciechomska, Christiaan A, Huigens, Thomas Hügle, Tess Stanly, Andreas Gessner, Bridget Grifﬁths, Timothy RDJ, Radstake, Sophie Hambleton, Steven O’Reilly, Jacob M, Van Laar. 2012. Toll-like receptor-mediated, enhanced production of proﬁbrotic TIMP-1 in monocytes from patients with systemic sclerosis: role of serum factors. Annals of Rheumatic Diseases 72, 1382–1389.
Matsuzaki K. 2009. Modulation of TGF-β signaling during progression of chronic liver diseases. Frontiers in Bioscience. 14, 2923–2934.
Ministry of Health, Egypt, El-Zanaty, Associates, Egypt, ICF International. 2015. Egypt Health Issues Survey2015. Cairo, Egypt and Rockville, MD: Ministry of Healthand ICF International.
Nassef YE, Shady MM, Galal EM, Hamed MA. 2013.Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children.Memorias do Instituto Oswaldo Cruz. 10, 887-93.
Nawar EA, Abul-fadl AM, Hassanin BE, Abd El Haie OM, EL-Tokhy M. 2011.Clinical value of transforming growth factor beta as a marker of fibrosis in adolescents with chronic liver diseases. Journal of American Science. 7, 464-71.
Netanya G, Sandler, Christopher Koh, Annelys
Roque, Jason L, Eccleston, Rebecca B. Siegel, Mary DeMino, David E, Kleiner, Steven G. Deeks T, Jake Liang, Theo Heller, Daniel C, Douek. 2011. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 141, 1220–1230.
Neuman MG, Benhamou JP, Bourliere M, Ibrahim A, Malkiewicz I, Asselah T, 2002.Serum tumor necrosis factor-alpha and transforming growth factor-beta levels in chronic hepatitis C patients are immunomodulated by therapy. Cytokine. 17, 108-17.
Patrick Schmid, Andrea Bregenzer, Milo Huber, Andri Rauch, Wolfram Jochum, Beat Müllhaupt, Pietro Vernazza, Milos Opravil, Rainer Weber, Swiss HIV Cohort Study. 2015. Progression of liver fibrosis in HIV/HCV co-infection: A comparison between non Invasive assessment methods and liver biopsy. PLoS ONE 10, 1-18. http://dx.doi.org/10.1371/journal.pone.0138838
Pereira Tde A, Witek RP, Syn WK, Choi SS, Bradrick S, Karaca GF, Agboola KM, Jung Y, Omenetti A, Moylan CA, Yang L, FernandezZapico ME, Jhaveri R, Shah VH, Pereira FE, Diehl AM. 2010. Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma. Laboratory Investigation 90, 1690–1703.
Richardson P, Duan Z, Kramer J, Davila JA, Tyson GL, El-Serag HB. 2011. Determinants of serum alphafeto protein levels in hepatitis C- infected patients. Clinical Gastroenterology and Hepatology. 10, 428–433.
Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, Watanabe Y, Koi S, Onji M, Ohta Y, Choo QL, Houghton M, Kuo G. 1990. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proceedings of the National Acadamy of Sciences of the United States of America 87, 6547–6549.
Tachi Y, Hirai T, Ishizu Y, Honda T, Kuzuya T, Hayashi K. 2015. Alpha-fetoprotein levels after interferon therapy predict regression of liver fibrosis in patients with sustained virological response. Journal of Gastroenterology and Hepatology. 31, 1001–8.
Theise ND, HC Bodenheimer, LD Ferrell. 2007. Acute and chronic viral hepatitis. In: AD Burt, BC Portman, and LD Ferrell (Eds.), Macsween’s pathology of the liver. PP,399-441. Churchill livingstone Elsevier.
Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S. 2007.FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibro test. Hepatology 46, 32-36. http://dx.doi.org/10.1002/hep.21669.
Yoshioka K, Fujita A, Kondo S, Miyake T, Sakaki Y, Shiba T. 1992. Production of a unique multi-lamella structure in the nuclei of yeast expressing Drosophila copia gag precursor. FEBS letters 302, 5-7.
Yung-Yu Hsieh, Shui-Yi Tung, Kamfai Lee, Cheng-Shyong Wu, Kuo-Liang Wei, Chien-Heng Shen, Te-Sheng Chang, Yi-Hsiung Lin. 2012. Routine blood tests to predict liver fibrosis in chronic hepatitis C. World Journal of Gastroenterology 18, 746-753.
Zavadil J, Bottinger EP. 2005. TGF-β and epithelial-to-mesenchymal transitions. Oncogene.24, 5764–5774.
Zeremski M, Petrovic LM, Talal AH. 2007. The
role of chemokines as inﬂammatory mediators in chronic hepatitis C virus infection. Journal of Viral Hepatitis 14, 675–687.
CD14 and TIMP-1 as predictive biomarkers of extensive liver fibrosis in Egyptian HCV-patients.
Int. J. Biosci. 10(4), 66-80, April 2017
By Authors and International Network for
Natural Sciences (INNSPUB)