The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical implication of serum uric acid level in pegylated interferon and ribavirin combination therapy for chronic hepatitis C infection

  • Oh, In Soo (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Won, Joung Won (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Kim, Hyung Joon (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Lee, Hyun Woong (Department of Internal Medicine, Chung-Ang University College of Medicine)
  • Received : 2016.12.06
  • Accepted : 2017.05.22
  • Published : 2017.11.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Combined treatment of pegylated $interferon-{\alpha}$ (PEG-IFN) and ribavirin (RBV) has long been accepted as the standard treatment for chronic hepatitis C virus (HCV) infection. Many predictive factors for treatment response have been identified. The aim of this study was to evaluate the efficacy and safety of combined PEG-IFN plus RBV and to examine the value of serum uric acid as a predictive factor in the treatment of chronic hepatitis C. Methods: A total of 74 patients chronically infected with HCV were enrolled between December 2004 and June 2009. Patients received subcutaneous PEG-IFN (${\alpha}-2a$: $180{\mu}g$ once a week) in combination with RBV (1,000 to 1,200 mg daily depending on body weight). We evaluated treatment responses represented by early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and relapse, as well as diverse adverse events. Various viral and host features were also assessed to clarify factors associated with treatment response. Results: During treatment, EVR was achieved in 26 patients (26/33, 78.8%) with HCV genotype 1. ETR and SVR were achieved in 59 (77.6%) and 56 patients (73.6%), respectively, across all genotypes. Genotype 2/3, lower HCV RNA, and lower uric acid were associated with higher SVR. Conclusions: The treatment response to combination therapy with PEG-IFN plus RBV was effective, especially in genotype 2/3. Uric acid might be useful as a predictive factor for response to therapy for chronic hepatitis.

Keywords

References

  1. Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat 1999;6:35-47. https://doi.org/10.1046/j.1365-2893.1999.6120139.x
  2. Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002;36(5 Suppl 1):S35-S46.
  3. Romero-Gomez M, Del Mar Viloria M, Andrade RJ, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 2005;128:636-641. https://doi.org/10.1053/j.gastro.2004.12.049
  4. Poynard T, McHutchison J, Davis GL, et al. Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C. Hepatology 2000;32:1131-1137. https://doi.org/10.1053/jhep.2000.19347
  5. Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004;39:1147-1171. https://doi.org/10.1002/hep.20119
  6. European Association for the Study of the Liver. EASL International Consensus Conference on hepatitis C. Paris, 26-28, February 1999, Consensus Statement. J Hepatol 1999;30:956-961. https://doi.org/10.1016/S0168-8278(99)80154-8
  7. Tsoi KK, Ma TK, Sung JJ. Endoscopy for upper gastrointestinal bleeding: how urgent is it? Nat Rev Gastroenterol Hepatol 2009;6:463-469. https://doi.org/10.1038/nrgastro.2009.108
  8. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon- alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346-355. https://doi.org/10.7326/0003-4819-140-5-200403020-00010
  9. McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009;361:580-593. https://doi.org/10.1056/NEJMoa0808010
  10. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-982. https://doi.org/10.1056/NEJMoa020047
  11. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-965. https://doi.org/10.1016/S0140-6736(01)06102-5
  12. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003;38:645-652.
  13. Ferenci P, Fried MW, Shiffman ML, et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol 2005;43:425-433. https://doi.org/10.1016/j.jhep.2005.04.009
  14. Davis GL, Lau JY. Factors predictive of a beneficial response to therapy of hepatitis C. Hepatology 1997;26(3 Suppl 1):122S-127S. https://doi.org/10.1002/hep.510260721
  15. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399-401. https://doi.org/10.1038/nature08309
  16. Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin- 28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139:120-129. https://doi.org/10.1053/j.gastro.2010.04.013
  17. Dai CY, Huang JF, Hsieh MY, et al. Insulin resistance predicts response to peginterferon-alpha/ribavirin combination therapy in chronic hepatitis C patients. J Hepatol 2009;50:712-718. https://doi.org/10.1016/j.jhep.2008.12.017
  18. Hung CH, Lee CM, Lu SN. Hepatitis C virus-associated insulin resistance: pathogenic mechanisms and clinical implications. Expert Rev Anti Infect Ther 2011;9:525-533. https://doi.org/10.1586/eri.11.33
  19. Lopez-Suarez A, Elvira-Gonzalez J, Bascunana-Quirell A, et al. Serum urate levels and urinary uric acid excretion in subjects with metabolic syndrome. Med Clin (Barc) 2006;126:321-324. https://doi.org/10.1157/13085753
  20. Puoti C, Bellis L, Castellacci R, Montagnese F, Bergami N, Petrone De Luca P. HCV carriers with persistently normal aminotransferase levels. Hepatology 2004;40:266-267.
  21. Cavalcante LN, Lyra AC. Predictive factors associated with hepatitis C antiviral therapy response. World J Hepatol 2015;7:1617-1631. https://doi.org/10.4254/wjh.v7.i12.1617
  22. Pellicano R, Puglisi G, Ciancio A, et al. Is serum uric acid a predictive factor of response to IFN-treatment in patients with chronic hepatitis C infection? J Med Virol 2008;80:628-631. https://doi.org/10.1002/jmv.21123
  23. Civantos Modino S, Guijarro de Armas MG, Monereo Mejias S, et al. Hyperuricemia and metabolic syndrome in children with overweight and obesity. Endocrinol Nutr 2012;59:533-538. https://doi.org/10.1016/j.endonu.2012.06.010
  24. Abreu E, Fonseca MJ, Santos AC. Association between hyperuricemia and insulin resistance. Acta Med Port 2011;24 Suppl 2:565-574.
  25. Miyanari Y, Atsuzawa K, Usuda N, et al. The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 2007;9:1089-1097. https://doi.org/10.1038/ncb1631
  26. Lanaspa MA, Sanchez-Lozada LG, Choi YJ, et al. Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem 2012;287:40732-40744. https://doi.org/10.1074/jbc.M112.399899
  27. Choi YJ, Shin HS, Choi HS, et al. Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab Invest 2014;94:1114-1125. https://doi.org/10.1038/labinvest.2014.98
  28. Zhu Y, Hu Y, Huang T, et al. High uric acid directly inhibits insulin signalling and induces insulin resistance. Biochem Biophys Res Commun 2014;447:707-714. https://doi.org/10.1016/j.bbrc.2014.04.080
  29. Szanto P, Grigorescu M, Dumitru I, Serban A. Steatosis in hepatitis C virus infection: response to anti-viral therapy. J Gastrointestin Liver Dis 2006;15:117-124.

Cited by

  1. Occult hepatitis C virus infection in patients with beta‐thalassemia major: Is it a neglected and unexplained phenomenon? vol.120, pp.7, 2017, https://doi.org/10.1002/jcb.28472
  2. Predicting Metabolite-Disease Associations Based on Spy Strategy and ABC Algorithm vol.7, pp.None, 2020, https://doi.org/10.3389/fmolb.2020.603121