Volume 95, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Hepatitis C virus (HCV)/ coinfection is common in Egypt and other developing countries. This study aimed to investigate the influence of HCV/ coinfection on the concentration of HCV–nonstructural protein-4 (NS4) in addition to collagen III and matrix metalloproteinase-1 (MMP-1) in different hepatic fibrosis stages. We found that coinfected patients ( = 186) showed significantly ( < 0.05, Mann–Whitney test) higher concentrations of HCV-NS4, collagen III, and collagen III/MMP-1 ratio (CMR) than those with HCV monoinfection ( = 104) in different fibrosis stages. Conversely, coinfected patients showed significantly lower concentrations of MMP-1 when compared with HCV monoinfection. The elevated levels of CMR in case of HCV monoinfection yielded an estimated odds ratio of 1.8 and 2.6 for developing significant fibrosis (F2-F4) and cirrhosis (F4), respectively. HCV/ coinfection increased the risk for developing F2-F4 and F4 several fold yielding an estimated odds ratio of 11.1 and 5.2, respectively. This means that coinfected patients have a 6-fold and 2-fold increased risk of developing F2-F4 and F4, respectively, over HCV-monoinfected patients. Thus, elevated levels of HCV-NS4 and CMR in HCV/ coinfection suggest increased susceptibility of coinfected patients, compared with those with HCV monoinfection, for accelerating hepatic fibrosis progression.


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  1. European Association for Study of Liver, 2014. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 60: 392420.[Crossref]
  2. Negro F, , 2014. Curbing hepatitis C virus spread in Egypt. Lancet Glob Health 2: e495e496.[Crossref]
  3. Lavanchy D, , 2011. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 17: 107115.[Crossref]
  4. Gryseels B, , 2012. Schistosomiasis. Infect Dis Clin North Am 26: 383397.[Crossref]
  5. Colley DG, Bustinduy AL, Secor WE, King CH, , 2014. Human schistosomiasis. Lancet 383: 22532264.[Crossref]
  6. Sanghvi MM, Hotez PJ, Fenwick A, , 2013. Neglected tropical diseases as a cause of chronic liver disease: the case of schistosomiasis and hepatitis C co-infections in Egypt. Liver Int 33: 165168.[Crossref]
  7. Attallah AM, Yones E, Ismail H, El Masry SA, Tabll A, Elenein AA, El Ghawalby NA, , 1999. Immunochemical characterization and diagnostic potential of a 63-kilodalton Schistosoma antigen. Am J Trop Med Hyg 60: 493497.
  8. Strickland GT, , 2006. Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors. Hepatol 43: 915922.[Crossref]
  9. Van-Lume DS, Albuquerque M de F, Souza AI, Domingues AL, Lopes EP, Morais CN, Montenegro SM, , 2013. Association between schistosomiasis mansoni and hepatitis C: systematic review. Rev Saude Publica 47: 414424.[Crossref]
  10. Brady MT, MacDonald AJ, Rowan AG, Mills KH, , 2003. Hepatitis C virus non‐structural protein 4 suppresses Th1 responses by stimulating IL‐10 production from monocytes. Eur J Immunol 33: 34483457.[Crossref]
  11. Attallah AM, Omran MM, Nasif WA, Ghaly MF, El-Shanshoury AER, Abdalla MS, Sharada HM, Farid K, El-Shony W, Moussa ESM, El-Domany EB, Nour E, Eldosoky I, , 2012. Diagnostic performances of hepatitis C virus-NS4 antigen in patients with different liver pathologies. Arch Med Res 43: 555562.[Crossref]
  12. Chen CZ, Raghunath M, , 2009. Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis state of the art. Fibrogenesis Tissue Repair 2: 7.[Crossref]
  13. Arthur MJP, , 1994. Degradation of matrix proteins in liver fibrosis. Pathol Res Pract 190: 825833.[Crossref]
  14. Attallah AM, El-Far M, Abdel Malak CA, Omran MM, Farid K, Hussien MA, Albannan MS, Attallah AA, Elbendary MS, Elbesh DA, Elmenier NA, Abdallah MO, , 2015. Fibro-check: a combination of direct and indirect markers for liver fibrosis staging in chronic hepatitis C patients. Ann Hepatol 14: 225233.[Crossref]
  15. Poynard T, Bedossa P, Opolon P, , 1997. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 349: 825832.[Crossref]
  16. Laemmli UK, , 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680685.[Crossref]
  17. Towbin H, Staehelin T, Gordon J, , 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76: 43504354.[Crossref]
  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ, , 1951. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265275.
  19. European Association for Study of Liver, 2015. EASL recommendations on treatment of hepatitis C 2015. J Hepatol 63: 199236.[Crossref]
  20. Strader DB, Wright T, Thomas DL, Seeff LB, , 2004. Diagnosis, management, and treatment of hepatitis C. Hepatol 39: 11471171.[Crossref]
  21. Booth JC, O'Grady J, Neuberger J, , 2001. Clinical guidelines on the management of hepatitis C. Gut 49: I1I21.[Crossref]
  22. Vilstrup H, , 2003. Cirrhosis and bacterial infections. Rom J Gastroenterol 12: 297302.
  23. Mengshol JA, Golden-Mason L, Rosen HR, , 2007. Mechanisms of disease: HCV-induced liver injury. Nat Clin Pract Gastroenterol Hepatol 4: 622634.[Crossref]
  24. Bataller R, Paik YH, Lindquist JN, Lemasters JJ, Brenner DA, , 2004. Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells. Gastroenterol 126: 529540.[Crossref]
  25. Shin JY, Hur W, Wang JS, Jang JW, Kim CW, Bae SH, Jang SK, Yang SH, Sung YC, Kwon OJ, Yoon SK, , 2005. HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1. Exp Mol Med 37: 138145.[Crossref]
  26. Arthur MJ, Mann DA, Iredale JP, , 1998. Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis. J Gastroenterol Hepatol 13: S33S38.
  27. Leroy V, Monier F, Bottari S, Trocme C, Sturm N, Hilleret MN, Morel F, Zarski JP, , 2004. Circulating matrix metalloproteinases 1, 2, 9 and their inhibitors TIMP-1 and TIMP-2 as serum markers of liver fibrosis in patients with chronic hepatitis C: comparison with PIIINP and hyaluronic acid. Am J Gastroenterol 99: 271279.[Crossref]
  28. Bataller R, Brenner DA, , 2005. Liver fibrosis. J Clin Invest 115: 209218.[Crossref]
  29. Kamal SM, Turner B, He Q, Rasenack J, Bianchi L, Al Tawil A, Nooman A, Massoud M, Koziel MJ, Afdhal NH, , 2006. Progression of fibrosis in hepatitis C with and without schistosomiasis: correlation with serum markers of fibrosis. Hepatol 43: 771779.[Crossref]
  30. Inagaki Y, Okazaki I, , 2007. Emerging insights into transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut 56: 284292.[Crossref]
  31. Jarcuska P, Janicko M, Veseliny E, Jarcuska P, Skladaný L, , 2010. Circulating markers of liver fibrosis progression. Clin Chim Acta 411: 10091017.[Crossref]
  32. Knittel T, Mehde M, Kobold D, Saile B, Dinter C, Ramadori G, , 1999. Expression patterns of matrix metalloproteinases and their inhibitors in parenchymal and non-parenchymal cells of rat liver: regulation by TNF-alpha and TGF-beta1. J Hepatol 30: 4860.[Crossref]

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  • Received : 19 Feb 2016
  • Accepted : 13 Jul 2016

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