Influence of interleukin-6 gene polymorphism on the efficacy of antiviral treatment in patients with chronic hepatitis C

Authors

  • Yu. Yu. Riabokon Zaporizhzhia State Medical University, Ukraine,
  • K. V. Kalashnyk Zaporizhzhia State Medical University, Ukraine,
  • O. V. Riabokon Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2019.1.155826

Keywords:

chronic hepatitis C, interleukin-6, genetic polymorphism, antiviral agents

Abstract

Aim. The aim of the work was to determine the influence of interleukin-6 gene polymorphism on the effectiveness of antiviral therapy in patients with chronic hepatitis C.

Materials and methods. A total of 83 patients with chronic hepatitis C (CHC). were included in the study. The efficacy of therapy with the peg-IFNα + SOF + RBV was analyzed depending on the polymorphism of interleukin-6 gene (rs1800795).

Results. All CHC patients with the CC genotype (14 – 100 %) responded to antiviral therapy with the peg-IFNα + RBV + SOF, but only 85.5 % of the patients with CG/GG genotypes responded (59 of the 69). In CHC patients with CG/GG genotypes, who responded to the therapy by SVR 24 formation, the HCV-RNA negativization was slower, in contrast to patients with the CC genotype, who showed a persistent absence of the virus in the blood from the 4th week of treatment. All patients with the CC genotype of IL-6 gene polymorphism presented complete normalization of ALT activity at this time if SVR 24 had been achieved. In the vast majority of CHC patients with SVR 24 and the CG/GG genotype after the therapy cessation, ALT activity continued to decrease and normalized after 24 weeks of observation in 94.9 % (56 of the 59). However, 20.0 % of patients with the CG/GG genotype who did not respond with the formation of SVR 24, had elevated serum ALT activity at the time of SVR 24 evaluation.

Kendall’s rank correlation was performed to determine the factors, which statistically significantly affect the results of peg-IFNα + RBV + SOF therapy. IL-6 gene polymorphism had an effect on the efficacy of therapy, both on the HCV-RNA negativization in the blood at the end of treatment (P = 0.04) and on the achievement of SVR 24 (P = 0.03). The lack of response as well as the lack of SVR 12 and SVR 24 formation at the time of therapy completion were associated with the IL-6 gene CG/GG polymorphism presence and a higher index of ALT activity at the beginning of treatment (τ = -0,18, P < 0.01).

Conclusions. In CHC patients, the CC genotype of IL-6 gene (rs1800795) is a favorable prognostic factor for the formation of SVR24 in the treatment of peg-IFNα + RBV + SOF. Patients who did not respond to the treatment by SVR 24 formation had only the IL-6 gene CG/GG polymorphism. Even in HCV patients with CG/GG genotypes who responded to the treatment by SVR 24 formation, the negativization of HCV-RNA in the blood was slower, unlike the patients with CC genotype. The absence of response at the time of therapy completion, as well as the absence of SVR 12 and SVR 24, were associated with the presence of the IL-6 gene CG/GG polymorphism and a higher level of ALT activity at the beginning of therapy (τ = -0,18, P < 0.01).

 

References

Golubovska, O. (2016). Primenenie kombinacij lekarstvennykh sredstv dlya lecheniya pacientov s khronicheskim gepatitom C: obzor klinicheskikh issledovanij i osobennosti nacional'nykh standartov terapii [Combination of drugs for treatment of patients with chronic hepatitis C: a review of clinical trials and features of the national treatment standards]. Klinicheskaya infektologiya i parazitologiya, 3(18), 304–312. [in Russian].

Mohammed, A., Auckle, R., Li, H., Xu, S., Liu, L., Zhao, D., & Che, W. (2018). Pegylated Interferon-α Plus Ribavirin Therapy Improves Left Ventricular Diastolic Dysfunction in Patients With Chronic Hepatitis C Attaining Sustained Virological Response. The American Journal Of The Medical Sciences, 355(6), 566–572. doi: 10.1016/j.amjms.2018.02.001.

Kozielewicz, D., Grabińska, A., Madej, G., & Wietlicka-Piszcz, M. (2018). Efficacy and safety of pegylated interferon α and ribavirin in patients monoinfected with HCV genotype 4. Gastroenterology Review, 13(1), 22–29. doi: 10.5114/pg.2018.74558.

(2016) AASLD/IDSA/IAS-USA. HCV Guidance: Recommendations for Testing, Managing and Treating Hepatitis C. Retrieved from http://www.hcvguidelines.org/

Ministerstvo okhorony zdorovia (2016) Nakaz MOZ Ukrainy «Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry virusnomu hepatyti С» vid 18.07.2016 r. №729 [Order of the Ministry of Health of Ukraine «On Approval and Implementation of Medical-Technological Documents for the Standardization of Medical Aid in the Case of Hepatitis C» from July 18, 2016 №729]. [in Ukrainian].

Evon, D., Esserman, D., Bonner, J., Rao, T., Fried, M., & Golin, C. (2013). Adherence to PEG/ribavirin treatment for chronic hepatitis C: prevalence, patterns, and predictors of missed doses and nonpersistence. Journal Of Viral Hepatitis, 20(8), 536–549. doi: 10.1111/jvh.12079.

Milara, J., Outeda-Macias, M., Aumente-Rubio, M. D., Más-Serrano, P., Aldaz, A., Calvo, M. V., et al. (2015). PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study. Farm Hosp., 39(1), 29–43. doi: 10.7399/fh.2015.39.1.8547.

Mechie, N., Röver, Ch., Cameron, S., & Amanzada, A. (2014). Predictability of IL-28B-polymorphism on protease-inhibitor-based triple-therapy in chronic HCV-genotype-1 patients: A meta-analysis. World Journal Of Hepatology, 6(10), 759–765. doi: 10.4254/wjh.v6.i10.759.

Suppiah, V., Moldovan, M., Ahlenstiel, G., Berg, T., Weltman, M., Abate, M., et al. (2009). IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nature Genetics, 41(10), 1100–1104. doi: 10.1038/ng.447.

Guo, P., Li, G., Sun, X., & Wu, D. (2016). Influence of IL10 Gene polymorphisms on the sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy. Infection, Genetics And Evolution, 45, 48–55. doi: 10.1016/j.meegid.2016.08.016.

Sadeghi, S., Davari, M., Asli, E., Gharibzadeh, S., Vaziri, F., Jamnani, F. et al. (2017). Effect of IL15 rs10833 and SCARB1 rs10846744 on virologic responses in chronic hepatitis C patients treated with pegylated interferon-α and ribavirin. Gene, 630, 28–34. doi: 10.1016/j.gene.2017.08.005.

Vince, A., Duvnjak, M. & Kurelac, I. (2013). Treatment guidelines for patients with genotype 1 chronic hepatitis C infection. Acta Medica Croatica, 67(4), 329–38.

Coppola, N., Pisaturo, M., Sagnelli, C., Sagnelli, E., & Angelillo, I. (2014). Peg-Interferon Plus Ribavirin with or without Boceprevir or Telaprevir for HCV Genotype 1: A Meta-Analysis on the Role of Response Predictors. Plos ONE, 9(4), e94542. doi: 10.1371/journal.pone.0094542.

Gower, E., Estes, C., Blach, S., Razavi-Shearer, K., & Razavi, H. (2014). Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal Of Hepatology, 61(1), S45–S57. doi: 10.1016/j.jhep.2014.07.027.

European Association for the Study of the Liver (2017). EASL Recommendations on Treatment of Hepatitis C 2016. J. Hepatology, 66(1), 153–194. doi: 10.1016/j.jhep.2016.09.001.

Koff, R. (2014). Review article: the efficacy and safety of sofosbuvir, a novel, oral nucleotide NS5B polymerase inhibitor, in the treatment of chronic hepatitis C virus infection. Alimentary Pharmacology & Therapeutics, 39(5), 478–487. doi: 10.1111/apt.12601.

Donaldson, E. F., Harrington, P. R., O'Rear, J. J., & Naeger, L. K. (2014). Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology, 61(1), 56–65. doi: 10.1002/hep.27375.

Keating, G. M. (2015). Ledipasvir/Sofosbuvir: A Review of Its Use in Chronic Hepatitis C. Drugs, 75(6), 675–685. doi: 10.1007/s40265-015-0381-2.

Petta, S., Cabibbo, G., Enea, M., Macaluso, F., Plaia, A., Bruno, R. et al. (2014). Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C. Hepatology, 59(5), 1692–1705. doi: 10.1002/hep.27010.

Giannitrapani, L., Soresi, M., Balasus, D., Licata, A., & Montalto, G. (2013). Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma. World Journal Of Gastroenterology, 19(16), 2449–55. doi: 10.3748/wjg.v19.i16.2449.

Cussigh, A., Falleti, E., Fabris, C., Bitetto, D., Cmet, S., Fontanini, E., et al. (2011). Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics, 63(1), 33–41. doi: 10.1007/s00251-010-0491-7.

Yee, L. J., Im, K., Borg, B., Yang, H., & Liang, T. (2009). Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection. Genes & Immunity, 10(4), 365–372. doi: 10.1038/gene.2009.26.

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Riabokon YY, Kalashnyk KV, Riabokon OV. Influence of interleukin-6 gene polymorphism on the efficacy of antiviral treatment in patients with chronic hepatitis C. Zaporozhye medical journal [Internet]. 2019Feb.8 [cited 2024Feb.24];(1). Available from: http://zmj.zsmu.edu.ua/article/view/155826

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