Medical news
of the North Caucasus
Scientific journal
Mass media registration certificate dated December 7, 2006.
Series ПИ #ФС 77-26521.
Federal service for surveillance over non-violation of the legislation in the sphere of mass communications and protection of cultural heritage.
ISSN 2073-8137

Site search

Correspondence address
310 Mira Street, Stavropol, Russia, 355017

+7 8652 352524; +7 8652 353229.

+7 8652 352524.


IP-10 protein at chronic hepatitis C and its role in forecasting treatment outcomes

[Original research] [Internal diseases]
Natalya Geyvandova; Andrey Lipov; Alexandr Yagoda; Anastasia Frolova;

Clinical values were identified for serum levels of g interferon-induced protein (IP 10) to be employed in forecasting SVR to AVT for CHC, which was carried out involving 107 patients (50 females and 57 males); mean age – 43.0±11 yrs. 75 of the patients were diagnosed with genotype 1 HCV (G1), while 32 patients were identified as having non-1 genotype HCV (G2 or G3). The IP-10 levels in blood serum were detected with the ELISA method. Patients with CHC had significantly higher blood IP-10 levels compared to healthy people, and that depended on the aminotransferases’ activity as well as on the stage of hepatic fibrosis. A standard AVT with pegIFN-α medications and ribavirin given to 52 patients with G1 (SVR 54.9 %) and 27 – with G2 or G3 (SVR 75 %), showed that the patients who had reached SVR had their initial levels of IP-10 below that of non-responders. The prognostic level of IP-10 was detected, above which the likelihood of ending up at SVR in case of AVT with pegIFN-α and ribavirin was questionable: ≤ 403 pg/ml for G1 and ≤ 433 pg/ml for G2 or G3. In 18 patients who were given triple AVT – pegIFN-α + ribavirin + viral proteases inhibitors (SVR – 77.7 %) the initial levels of IP-10 at various outcomes of AVT were the same. Therefore, in case of CHC, the levels of blood IP-10 are elevated and depend on cytolysis activity and the degree of hepatic fibrosis. The levels of IP-10 protein in case of CHC may be used as a predictor regarding the standard AVT outcomes.


1. Arsentieva N. A., Semenov A. V., Tutolyan A. A. Role of polymorphism of cytokine genes in viral hepatitis C. Infekciya i immunitet – Infection & Immunity. 2012;2(4):687-698.
2. Afdhal N., Zeuzem S., Kwo P., Chojkier M., Gitlin N. et al. ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N. Engl. J. Med. 2014;370:1889-1898. doi: 10.1056/NEJMoa1402454
3. Askarieh G., Alsio A., Pugnale P., Negro F., Ferrari C. et al. Systemic and intrahepatic interferon-gammainducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C. Hepatology. 2010;51:1523-1530. doi:10.1002/hep.23509
4. Berg T., Andreoni P., Pol S., Roberts S., Younossi Z. et al. Predictors of virologic response with telaprevirbased combination treatment in HCV genotype 1-infected patients with pri or peginterferon/ribavirin treatment failure: post-hoc analysis of the phase III Realize study. Hepatology. 2011;54:375A-376A.
5. Casrouge A., Decalf J., Ahloulay M., Lababidi C., Mansour H. et al. Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV. J. Clin. Invest. 2011;121(1):308-317. doi: 10.1172/JCI40594
6. Deltenre Р. Studies on the epidemiology of hepatitis B and C virus infections are still needed. J. Hepatol. 2015;62:1225-1227. doi: 10.1016/j.jhep.2015.01.011
7. EASL Recommendations on Treatment of Hepatitis C 2015 (Guidelines). J. Hepatol. 2015;63:199-236.
8. Grebely J., Feld J. J., Applegate T., Matthews G. V., Hellard M. et al. Plasma Interferon-gamma-Inducible Protein-10 (IP-10) Levels During Acute Hepatitis C Virus Infection. Hepatology. 2013;57(6):2124-2134. doi: 10.1002/hep.26263
9. Harvey C. E., Post J. J., Palladinetti P., Freeman A. J., Ffrench R. A. et al. Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. J. Leukoc. Biol. 2003;74:360-369. doi: 10.1189/jlb.0303093
10. Hezode C., Fontaine H., Dorival C., Zoulim F., Canva V. et al. Effectiveness of telaprevir or boceprevir in treatment- experienced patients with HCV genotype 1 infection and cirrhosis. Gastroenterology. 2014;147:132- 142. doi: 10.1053/j.gastro.2014.03.051
11. Jacobson I. M., McHutchison J. G., Dusheiko G., Di Bisceglie A. M., Reddy K. R. et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N. Engl. J. Med. 2011;364:2405-2416. doi: 10.1056/ NEJMoa1012912
12. Lagging M., Romero A. I., Westin J., Norkrans G., Dhillon A. P. et al. IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection. Hepatology. 2006;44:1617- 1625. doi:10.1002/hep.21407
13. Larrubia J. R., Larrubia J. R., Calvino M., Benito S., Sanz-de-Villalobos E. et al. The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection. J. Hepatol. 2007;47(5):632-641. doi: 10.1016/j.jhep.2007.04.009
14. Lee S., Varano J., Flexman J. P., Chengc W., Watsond M. W. et al. Decreased IP-10 and elevated TGFβ1 levels are associated with viral clearance following therapy in patients with hepatitis C virus. Dis. Markers. 2010;28:273-280. doi:10.3233/DMA-2010-0699
15. McHutchison J. G., Lawitz E. J., Shiffman M. L., Muir A. J., Galler G. W. et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N. Engl. Med. 2009;361:580-593. doi: 10.1056/ NEJMoa0808010
16. Neville L. F., Mathiak G., Bagasra O. The immunobiology of interferongamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev. 1997;8:207- 219. doi: 10.1016/S1359-6101(97)00015-4
17. Pawlotsky J.-M., Feld J. J., Zeuzem S., Hoofnagle J. H. From non-A, non-B hepatitis to hepatitis C virus cure. J. Hepatol. 2015;62:S87-S99.
18. Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 2009;119(7):1745-1754. doi: 10.1172/JCI67714
19. Reiberger T., Aberle J. H., Kundi M., Kohrgruber N., Rieger A. et al. IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV/HCV coinfection. Antivir. Ther. 2008;13(8):969-976.
20. Romero A. I., Lagging M., Westin J., Dhillon A. P., Dustin L. B. et al. Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J. Infect. Dis. 2006;194:895-903. doi:10.1086/507307
21. Sisoev K. A., Chuhlovin A. B., Shachmanov D. M., Zhdanov K. V., Tutolyan A. A. The profile of cytokines and chemokines in plasma of patients with chronic hepatitis C. Infekciya i immunitet – Infection & Immunity. 2013;3(1):49-58. doi: 10.15789/2220-7619-2013-1- 49-58
22. Thomas E., Gonzalez V. D., Li Q., Modi A. A., Chen W. et al. HCV infection induces a unique hepatic innate immune response associated with robust roduction of type III interferons. Gastroenterology. 2012;142:978- 988. doi: 10.1053/j.gastro.2011.12.055
23. WHO, Hepatitis C., Fact sheet N_164, Updated April 2014. Available from . 24. You Ch. R., Park S.-H., Jeong S. W., Woo H. Y., Bae S. H. et al. Serum IP-10 Levels Correlate with the Severity of Liver Histopathology in Patients Infected with Genotype- 1 HCV. Gut and Liver. 2011;5(4):506-512. doi: 10.5009/gnl.2011.5.4.506
25. Zeremski M., Markatou M., Brown Q. B., Dorante J., Cunningham-Rundles S. et al. Interferon gamma-inducible protein 10: a predictive marker of successful treatment response in hepatitis C virus/HIV-coinfected patients. Acquir. Immune Defic. Syndr. 2007;45(3):262- 268. doi: 10.1097/QAI.0b013e3180559219
26. Zeremski M., Petrovic L. M., Chiriboga L., Brown Q. B., Yee H. T. et al. Intrahepatic levels of CXCR3-associated chemokines correlate with liver inflammation and fibrosis in chronic hepatitis C. Hepatology. 2008;48:1440-1450. doi: 10.1002/hep.22500

Keywords: chronic hepatitis C, chemokines, antiviral therapy, prognosis

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy