TLR7 gene effect on hepatic fibrosis progression rate in HIV-infected patients with chronic hepatitis C
DOI:
https://doi.org/10.14739/2310-1210.2019.3.169093Keywords:
HIV infection, chronic hepatitis C, liver fibrosis, prognosisAbstract
The aim of the research – to optimize the prediction of hepatic fibrosis (HF) progression rate in HIV-infected patients with chronic hepatitis C (CHC) based on a comprehensive assessment of general clinical, biochemical, immunological and molecular-genetic markers.
Materials and methods. A cross-sectional cohort study was conducted, which included 104 HIV-infected patients with CHC. The examination program included: assessment of complaints and anamnestic data obtained by questioning and detailed analysis of medical records, physical examination, general clinical study of peripheral blood, determination of biochemical parameters of blood serum, characterizing the functional state of the liver, the level of СD4+ Т-lymphocytes, the stages of HF according to METAVIR and genetic studies (genotyping of TLR7 in order to determine the carriage of Leu allele).
Results. The method of discriminant analysis showed that statistically significant informative diagnostic signs of the rapid rate of HF progression in HIV-infected patients with CHC are: lymphocytosis, the levels of AST and total bilirubin exceeding the upper limit of normal, among the concomitant pathology ‒ chronic cholecystitis, chronic pancreatitis, cholelithiasis and hepatic steatosis, the baseline level of СD4+ Т-lymphocytes less than 350 cells/mm3 and a carriage of the normal genotype (Gln/Gln, Gln/-) of the TLR7 gene. In order to optimize the prognostication of the affiliation of an HIV-infected patient with CHC to the risk group of HF rapid progression there was proposed a discriminant model of 5 risk factors (the normal genotype (Gln/Gln, Gln/-) of the TLR7 gene, the levels of total bilirubin and AST exceeding the upper limit of normal, lymphocytosis, the baseline level of СD4+ Т-lymphocytes less than 350 cells/mm3), the exact prognosis of which was 75 %.
Conclusions. There was proposed an effective model that allows predicting a rapid rate of HF progression in HIV-infected patients with CHC on the basis of simple characteristics, most of which are used in routine clinical practice.
References
Kozko, V. M., Bondarenko, A. V., & Yurko, K. V. (2012) Aktualni pytannia diahnostyky, likuvannia ta profilaktyky VIL/SNIDU [Topical issues of diagnosis, treatment and prevention of HIV/AIDS]. Kharkiv: KhNMU. 250. [in Ukrainian].
Gural, A. L., Marievskiy, V. F., Sergeyeva, T. A., Shaginyan, V. R., & Ruban, O. M. (2011) Kharakteristika i tendencii razvitiya e'pidemicheskogo processa gepatita C v Ukraine [Characteristics and trends of hepatitis’ С epidemic process in Ukraine]. Profilaktychna medytsyna, 1(13), 9−18. [in Russian].
Crane, М., Visvanathan, K., & Lewin, S. R. (2012) HIV infection and TLR signalling in the liver. Gastroenterol Res Pract., 2012. doi: 10.1155/2012/473925. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296181/pdf/GRP2012-473925.pdf
Peters, L., & Klein, M. B. (2015) Epidemiology of hepatitis C virus in HIV-infected patients. Curr Opin HIV AIDS, 10(5), 297–302. doi: 10.1097/COH.0000000000000183
Mamedova, E. S., Сolubovska, O. A., & Pronyuk, Kh. O. (2014) Suchasnyi pohliad na perebih ta likuvannia ko-infektsii VIL i VHS [Current view on course and treatment of HIV and HCV co-infection]. Tuberkuloz, lehenevi khvoroby, VIL-infektsiia, 1, 77−82. [in Ukrainian].
Kawai, Т., & Akira, S. (2013) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity, 34(5), 637−50. doi: 10.1016/j.immuni.2011.05.006
Sasai, M., & Yamamoto, М. (2013) Pathogen recognition receptors: ligands and signaling pathways by Toll-like receptors. Int Rev Immunol., 3(2), 116−33. doi: 10.3109/08830185.2013.774391
Howell, J., Angus, P., Gow, P., & Visvanathan, K. (2013) Toll-like receptors in hepatitis C infection: Implications for pathogenesis and treatment. J Gastroenterol Hepatol., 28(5), 766−76. doi: 10.1111/jgh.12170
Xu, Y., & Zhong, J. (2016) Innate immunity against hepatitis C virus. Curr Opin Immunol., 42, 98−104. doi: 10.1016/j.coi.2016.06.009
Roh, Y. S., Park, S., Kim J. W., Lim, C. W., Seki, E., & Kim, B. (2014) Toll-like receptor 7-mediated type I interferon signaling prevents cholestasis- and hepatotoxin-induced liver fibrosis. Hepatology, 60(1), 237−49. doi: 10.1002/hep.26981
Dubinskaya, G. М., Sizovа, L. М., Koval, T. І., & Izyumskaya, E. M. (2016) Vplyv polimorfizmu heniv TLR4 ta TLR7 na shvydkist prohresuvannia fibrozu pechinky u khvorykh na khronichnyi hepatyt С [The influence of TLR4 and TLR7 gene polymorphisms on the rate of liver fibrosis progression in patients with chronic hepatitis C]. Hepatolohiia, 1(31), 23−32. [in Ukrainian].
Koval, T. I., Dubinskaya, G. M., & Sizova., L. M. (2017) Prognozirovanie skorosti razvitiya fibroza pecheni pri hronicheskom gepatite С u VICh-inficirovannykh pacientov [Prognosis of rapidly progressive hepatic fibrosis in HIV-infected patients with chronic hepatitis C]. Klinicheskaya infektologiya i parazitologiya, 6(3), 344−54. [in Russian].
Schott, E., Witt, H., Neumann, K., Taube, S., Oh, D. Y., Schreier, E., et al. (2007) A toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection. J Hepatol., 47(2), 203−11. doi: 10.1016/j.jhep.2007.03.021
Askar, E., Ramadori, G., & Mihm, S. (2010) Toll-like receptor 7 rs179008/Gln11Leu gene variants in chronic hepatitis C virus infection. J Med Virol., 82(11), 1859−68. doi: 10.1002/jmv.21893
Dubinskaya, G., Sizova, L., Koval, Т., Kovalyova, Е., & Kaydashev, I. (2016) Clinical and genetic predictors and prognostic model of rapidly progressive hepatic fibrosis in chronic hepatitis C. Georgian Med News, 7–8(256–257), 37−45.
Poynard, T., Bedossa, Р., & Opolon, Р. (1997) Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR and DOS-VIRC groups. Lancet, 349(9055), 825−32.
EASL Clinical Practice Guidelines: Management of hepatitis C virus infection (2014) J Hepatol., 60, 392−420.
Musin, A. G., Mutalova, E. G., Nigmatullina, A. E., Konstantinova, E. E., Musina, F. S., & Nasibullin, I. M. (2014) Sovremennye aspekty mekhanizmov fibrogeneza v pecheni [Modern aspects of liver fibrogenesis mechanisms]. Medicinskij vestnik Bashkortostana, 9(3), 95−99. [in Russian].
Puoti, M., Lorenzini, P., Cozzi-Lepri, A., Gori, A., Mastroianni, C., Rizzardini, G., et al. (2017) Incidence and progression to cirrhosis of new hepatitis C virus infections in persons living with human immunodeficiency virus. Clin Microbiol Infect., 23(4), 267.e1–267.e4. doi: 10.1016/j.cmi.2016.12.003.
Azevedo, T. C., Zwahlen, M., Rauch, A., Egger, M., & Wandeler, G. Hepatitis C in HIV-infected individuals: a systematic review and meta-analysis of estimated prevalence in Africa (2016). J Int AIDS Soc., 19(1), 20711. doi: 10.7448/IAS.19.1.20711.
Chew, K. W., & Bhattacharya, D. (2016) Virologic and immunologic aspects of HIV–hepatitis C virus coinfection. AIDS, 30(16), 2395–2404. doi: 10.1097/QAD.0000000000001203
Lui, G., Wong, V. W., Wong, G. L., Chu, W. C., Wong, C. K., Yung, I M., et al. (2016) Liver fibrosis and fatty liver in Asian HIV‐infected patients. Aliment Pharmacol Ther., 44(4), 411‒421. doi: 10.1111/apt.13702
Llewellyn, A., Simmonds, M., Irving, W. L., Brunton, G., & Sowden, A. J. (2016) Antiretroviral therapy and liver disease progression in HIV and hepatitis C co-infected patients: a systematic review and meta-analysis. Hepatology, Medicine and Policy, 1, 10. doi: 10.1186/s41124-016-0015-7.
Jones, M., & Nunez, М. (2011) HIV and hepatitis C co-infection: the role of HAART in HIV/hepatitis C virus management. Curr Opin HIV AIDS., 6(6), 546‒52. doi: 10.1097/COH.0b013e32834bcbd9
Sheptulina, A. F., Shirokova, Ye. N., & Ivashkin, V. T. (2015) Neinvazivnaya diagnostika fibroza pecheni: rol' syvorotochnyh markerov [Non-invasive of liver fibrosis diagnostics: the role of serum markers]. Ros. zhurn. Gastroehnterol., 2, 28−40. [in Russian].
Gudowska, M., Wojtowicz, E.,Cylwik, B., Gruszewska, E., & Chrostek, L. (2015) The distribution of liver steatosis, fibrosis, steatohepatitis and inflammation activity in alcoholics according to FibroMax Test. Adv Clin Exp Med., 24(5), 823−7. doi: 10.17219/acem/28485
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)