Atorvastatin in Combination with Pegylated Interferon and Ribavirin Provided High Rate of Sustained Virological Response in Patients with Genotype 3 Hepatitis C Virus
DOI:
https://doi.org/10.3889/oamjms.2019.459Keywords:
Hepatitis C virus infection, Statins, Pegylated interferon alpha, Ribavirin, Sustained virological responseAbstract
BACKGROUND: Chronic hepatitis C virus infection represents a more frequent cause of liver cirrhosis and hepatocellular carcinoma. Statins, inhibit HCV replication in vitro, enhance the antiviral effect of the already known antiviral drugs and reduce their resistance.
AIM: To determine the impact of additional therapy (treatment with Atorvastatin 20 mg) to the standard antiviral therapy (pegylated interferon alpha-peg-IFN α and ribavirin) on achieving sustained virological response (SVR).
MATERIAL AND METHODS: In the study which is comparative, open-label, prospective-retrospective, 70 patients diagnosed with chronic hepatitis C virus infection who met criteria for treatment with standard antiviral therapy combined with anti-lipemic therapy (Atorvastatin 20 mg) were included. Patients in the study were divided into two groups: one group of 35 patients receiving combination therapy (Atorvastatin + peg-IFN α + Ribavirin) and another group of 35 patients received only standard antiviral therapy. Those parameters were followed in all patients: genotyping, quantification of the virus, histological assessment of liver inflammation and fibrosis degree (before starting treatment), the presence of steatosis, laboratory analysis: hematology, liver, lipid and carbohydrate status, insulin blood level (the calculation of HOMA-IR) and body mass index (BMI) calculation. The overall treatment of the patients depends from the virus genotype, thus, patients with genotype 1 and 4 received 48 weeks standard antiviral therapy, but patients with genotypes 2 and 3 received 24 weeks of antiviral therapy. SVR was considered an undetectable level of HCV RNA levels 24 weeks after completion of antiviral therapy. The results were statistically analysed, and all results for p < 0.05 were considered statistically significant.
RESULTS: Combination therapy leads to a slightly higher percentage of SVR (85.71%) in patients with chronic hepatitis C versus standard therapy (74.29%), but in a group of patients with genotype 3 this rate of SVR amounting to 95.83%. Combination therapy leads to significant improvement of lipid and glucose status after treatment, and in terms of side effects, there was no appearance of serious adverse events that would be a reason for discontinuation of the therapy.
CONCLUSION: Combination therapy Atorvastatin + pegylated interferon alpha + Ribavirin leads to high rate of SVR of 95.83% in patients with chronic hepatitis C, genotype 3. Statins can be used safely in patients with chronic hepatitis C.
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References
Civan J, Hann HW. Hepatitis C Virus Mediated Hepatocellular Carcinoma: A Focused Review for a Time of Changing Therapeutic Options. N A J Med Sci. 2014; 7(1):8-16. https://doi.org/10.7156/najms.2014.0701008
Tsoulfas G, Goulis I, Giakoustidis D, et al. Hepatitis C and liver transplantation. Hippokratia. 2009; 13(4):211-215.
Aizawa Y, Seki N, Nagano T, Abe H. Chronic hepatitis C virus infection and lipoprotein metabolism. World Journal of Gastroenterology. 2015; 21(36):10299-1031. https://doi.org/10.3748/wjg.v21.i36.10299 PMid:26420957 PMCid:PMC4579877
Kim CW and Chang KM. HCV virology and life cycle. Clin Mol Hepatol. 2013; 19:17-25. https://doi.org/10.3350/cmh.2013.19.1.17 PMid:23593605 PMCid:PMC3622851
McLauchlan J. Lipid droplets and hepatitis C virus infection. Biochim Biophys Acta. 2009; 1791:552-559. https://doi.org/10.1016/j.bbalip.2008.12.012 PMid:19167518
Zhu Y-Z, Qian X-J, Zhao P, Qi Z-T. How hepatitis C virus invades hepatocytes: The mystery of viral entry. World Journal of Gastroenterology. 2014; 20(13):3457-3467. https://doi.org/10.3748/wjg.v20.i13.3457 PMid:24707128 PMCid:PMC3974512
Felmlee DJ, Hafirassou ML, Lefevre M, Baumert TF, Schuster C. Hepatitis C Virus, Cholesterol and Lipoproteins - Impact for the Viral Life Cycle and Pathogenesis of Liver Disease. Viruses. 2013; 5(5):1292-1324. https://doi.org/10.3390/v5051292 PMid:23698400 PMCid:PMC3712309
Enjoji M, Kohjima M, Kotoh K, Nakamuta M. Metabolic disorders and steatosis in patients with chronic hepatitis C: Metabolic strategies for antiviral treatments. International journal of hepatology. 2012;2012. https://doi.org/10.1155/2012/264017 PMid:22701799 PMCid:PMC3373124
Kapadia SB, Chisari FV. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(7):2561-2566. https://doi.org/10.1073/pnas.0409834102 PMid:15699349 PMCid:PMC549027
Lambert J, Bain V, et al. Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to haelthy humans. Hepatology 2013; 57:1697-1704. https://doi.org/10.1002/hep.25990 PMid:23417775
Davies JT, Delfino SF, Feinberg CE, et al. Current and Emerging Uses of Statins in Clinical Therapeutics: A Review. Lipid insights. 2016; 9:13-29. https://doi.org/10.4137/LPI.S37450 PMid:27867302 PMCid:PMC5110224
Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45:89-118. https://doi.org/10.1146/annurev.pharmtox.45.120403.095748 PMid:15822172 PMCid:PMC2694580
Janicko M, Drazilova S, Pella D, Fedacko J, Jarcuska P. Pleiotropic effects of statins in the diseases of the liver. World Journal of Gastroenterology. 2016; 22(27):6201-6213. https://doi.org/10.3748/wjg.v22.i27.6201 PMid:27468210 PMCid:PMC4945979
Simon TG, Butt AA. Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon clinical outcomes. World Journal of Gastroenterology. 2015; 21(27):8293-8303. https://doi.org/10.3748/wjg.v21.i27.8293 PMid:26217081 PMCid:PMC4507099
Wang C, Gale M, Keller BC, Huang H, Brown MS, Goldstein JL, Ye J. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 2005; 18:425-434. https://doi.org/10.1016/j.molcel.2005.04.004 PMid:15893726
Bader T, Fazili J, Madhoun M, Aston C, Hughes D, Rizvi S, et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008; 103:1383-1389. https://doi.org/10.1111/j.1572-0241.2008.01876.x PMid:18410471
Shavakhi A, Minakari M, Bighamian A, Sadeghian S, et al. Statin efficiacy in the treatment of hepatitis C genotip I. J Res Med Sci. 2014; 19(Suppl 1):S1-S4.
Vere CC, Streba CT, Streba L, Rogoveanu I. Statins in the Treatment of Hepatitis C. Hepatitis Monthly. 2012; 12:369-71. https://doi.org/10.5812/hepatmon.5998 PMid:22879825 PMCid:PMC3412552
Delang L, Paeshuyse J et al. Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development. Hepatology. 2009; 50:6-16. https://doi.org/10.1002/hep.22916 PMid:19437494
Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N: Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology. 2006; 44:117-125. https://doi.org/10.1002/hep.21232 PMid:16799963
O'Leary JG, Chan JL, McMahon CM, Chung RT. Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: A pilot clinical trial. Hepatology. 2007; 45:895-8. https://doi.org/10.1002/hep.21554 PMid:17393518
Butt AA, Yan P, Bonilla H, Abou-Samra AB, Shaikh OS, Simon TG, et al. Effect of addition of statins to antiviral therapy in hepatitis C virus-infected persons: Results from ERCHIVES. Hepatology. 2015; 62(2):365-74. https://doi.org/10.1002/hep.27835 PMid:25847403
Mihaila RG. Statins in Chronic Hepatitis C: Stage result. Biomed Res. 2014; 25 (4):463-469.
Rao GA, Pandya PK. Statin therapy improves sustained virologic response among diabetic patients with chronic hepatitis C. Gastroenterology. 2011; 140:144-152. https://doi.org/10.1053/j.gastro.2010.08.055 PMid:20833169
Simon TG, King LY, Zheng H, Chung RT. Statin Use is Associated with a Reduced Risk of Fibrosis Progression in Chronic Hepatitis C. Journal of hepatology. 2015; 62(1):18-23. https://doi.org/10.1016/j.jhep.2014.08.013 PMid:25135867 PMCid:PMC4272642
Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N: Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology. 2006; 44:117-125. https://doi.org/10.1002/hep.21232 PMid:16799963
Aizaki H, Lee KJ, Sung VM, Ishiko H, Lai MM. Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts. Virology. 2004; 324(2):450-61. https://doi.org/10.1016/j.virol.2004.03.034 PMid:15207630
Ikeda M, Kato N. Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon. J Pharmacol Sci. 2007; 105(2):145-50. https://doi.org/10.1254/jphs.FM0070050 PMid:17928739
O'Leary JG, Chan JL, McMahon CM, Chung RT. Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: A pilot clinical trial. Hepatology. 2007; 45:895-8. https://doi.org/10.1002/hep.21554 PMid:17393518
Forde KA, Law C, O'Flynn R, Kaplan DE. Do statins reduce hepatitis C RNA titers during routine clinical use? World J Gastroenterol. 2009; 15(40):5020-7. https://doi.org/10.3748/wjg.15.5020 PMid:19859994 PMCid:PMC2768880
Selic Kurincic T, Lesnicar G, Poljak M, Meglic Volkar J, Rajter M, Prah J, et al. Impact of added fluvastatin to standard-of-care treatment on sustained virological response in naïve chronic hepatitis C Patients infected with genotypes 1 and 3. Intervirology. 2014; 57(1):23-3. https://doi.org/10.1159/000354541 PMid:24080608
Atsukawa M, Tsubota A, Kondo C, Itokawa N, Narahara Y, Nakatsuka K, et al. Combination of fluvastatin with pegylated interferon/ribavirin therapy reduces viral relapse in chronic hepatitis C infected with HCV genotype 1b. J Gastroenterol Hepatol. 2013; 28(1):51-6. https://doi.org/10.1111/j.1440-1746.2012.07267.x PMid:22989264
Georgescu EF, Streba L, Teodorescu R, Mateescu G, Abagiu MT. 10 potential enhancement of both early (evr) and sustained (svr) virological response by fluvastatin in chronic hepatitis c treated with standard pegifn-ribavirin therapy. A pilot study. Journal of Hepatology. 2011; 54:S5. https://doi.org/10.1016/S0168-8278(11)60012-3
Sezaki H, Suzuki F, Akuta N, Yatsuji H, et al. An open pilot study exploring the efficacy of fluvastatin, pegylated interferon and ribavirin in patients with hepatitis C virus genotype 1b in high viral loads. Intervirology. 2009; 52(1):43-8. https://doi.org/10.1159/000213504 PMid:19372703
Kondo C, Atsukawa M, Tsubota A, Itokawa N, Fukuda T, Matsushita Y, et al. An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin. J Viral Hepat. 2012; 19:615-622. https://doi.org/10.1111/j.1365-2893.2011.01584.x PMid:22863265
Shavakhi A, Minakari M, Bighamian A, et al. Statin efficacy in the treatment of hepatitis C genotype I. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2014; 19(Suppl 1):S1-S4.
Malaguarnera M, Vacante M, Russo C, et al. Rosuvastatin reduces nonalcoholic fatty liver disease in patients with chronic hepatitis C treated with α-interferon and ribavirin: Rosuvastatin reduces NAFLD in HCV patients. Hepatitis Monthly. 2011; 11(2):92-98.
Zhu Q, Li N, Han Q, Zhang P, Yang C, Zeng X, et al. Statin therapy improves response to interferon alfa and ribavirin in chronic hepatitis C: A systematic review and meta-analysis. Antiviral Res. 2013; 98:373-9. https://doi.org/10.1016/j.antiviral.2013.04.009 PMid:23603497
Lai Wei, Seng Gee Lim, Qing Xie, KÃnh Nguyen Văn, Teerha Piratvisuth, Yan Huang, et al. Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial. Lancet Gastroenterol Hepatol. 2018; 4(2):127-134. https://doi.org/10.1016/S2468-1253(18)30343-1
Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015; 373: 2608-2617. https://doi.org/10.1056/NEJMoa1512612 PMid:26575258
Cheinquer H, Sette H Jr., Wolff FH, de Araujo A, Coelho-Borges S, Soares SRP, et al. Treatment of Chronic HCV Infection with the New Direct Acting Antivirals (DAA): First Report of a Real World Experience in Southern Brazil. Annals of hepatology. 2017; 16(5):727-33. https://doi.org/10.5604/01.3001.0010.2717 PMid:28809742
Ganda OP. Statin-induced diabetes: incidence, mechanisms, and implications. F1000Research. 2016; 5. https://doi.org/10.12688/f1000research.8629.1 PMid:27408693 PMCid:PMC4926726
Delgado-Borrego A, Jordan SH, Negre B, et al. Reduction of Insulin Resistance with Effective Clearance of Hepatitis C Infection: Results from The Halt-C Trial. Clin Gastroenterol Hepatol. 2010; 8(5):458-462. https://doi.org/10.1016/j.cgh.2010.01.022 PMid:20156586 PMCid:PMC2856733
Romero-Gómez M, Fernández-RodrÃguez CM, Andrade RJ, et al. Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C. J Hepatol. 2008; 48(5):721-727. https://doi.org/10.1016/j.jhep.2007.11.022 PMid:18308416
Verpaalen B, Neyts J, Delang L. Are statins a viable option for the treatment of infections with the hepatitis C virus? Antiviral Res. 2014; 105:92-9. https://doi.org/10.1016/j.antiviral.2014.02.020 PMid:24613180
Simon TG, Bonilla H, Yan P, Chung RT, Butt AA. Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. Hepatology. 2016; 64(1):47-57. https://doi.org/10.1002/hep.28506 PMid:26891205 PMCid:PMC4917438
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Copyright (c) 2019 Beti Todorovska, Viktorija Caloska-Ivanova, Magdalena Dimitrova-Genadieva, Meri Trajkovska, Rozalinda Popova-Jovanovska, Kalina Grivceva-Stardelova, Fana Licoska-Josifovic, Vladimir Andreevski, Elena Curakova-Ristovska, Nenad Joksimovic
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