medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2013, Number 2

<< Back Next >>

Ann Hepatol 2013; 12 (2)

Prediction of minimal residual viremia in HCV type 1 infected patients receiving interferon-based therapy

Knop V, Teuber G, Klinker H, Möller B, Rasenack J, Hinrichsen H, Gerlach T, Spengler U, Buggisch P, Neumann K, Sarrazin C, Zeuzem S, Berg T

Language: English
References: 30
Page: 190-198
PDF size: 158.60 Kb.


ABSTRACT

Introduction. Complete suppression of viral replication is crucial in chronic HCV treatment in order to prevent relapse and resistance development. We wanted to find out which factors influence the period from being already HCV RNA negative by bDNA assay (‹ 615 IU/mL) to become undetectable by the more sensitive TMA test (‹ 5.3 IU/mL). Material and methods. Evaluated were 433 HCV type 1-infected patients. All of them received 1.5 ug/kg Peg-IFNα-2b plus ribavirin for 18-48 weeks. bDNA was performed weekly during the first 8 weeks and thereafter at weeks 12, 24, and 48. Patients who became bDNA undetectable were additionally analysed by TMA. Results. Of the 309 patients with on-treatment response (‹ 615 IU/mL), 289 also reached undetectable HCV RNA levels by TMA. Multivariate analysis revealed that viremia ≤ 400,000 IU/mL (p = 0.001), fast initial virologic decline (p = 0.004) and absence of fibrosis (p = 0.035) were independent predictors of an accelerated on-treatment response by TMA assay in already bDNA negative patients. bDNA negative patients becoming HCV RNA undetectable by TMA within the following 3 weeks had a frequency of relapse of 21%, whereas those showing TMA negativity after 3 weeks relapsed in 38% (p = 0.001). In RVR patients (bDNA ‹ 615 IU/mL at week 4) the corresponding relapse rates were 15.3% vs. 37.5%, respectively (p = 0.003). Conclusion. Early viral kinetics, baseline viremia and fibrosis stage are important tools to predict persistent minimal viremia during interferon-based therapy. The data have implications for designing a more refined treatment strategy in HCV infection, even in the setting of protease inhibitor-based triple treatment.


REFERENCES

  1. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349: 825-32.

  2. Di Bisceglie AM. Hepatitis C. Lancet 1998; 351: 351-5.

  3. Lauer GM, Walker BD. Hepatitis C virus infection. N Eng J Med 2001; 345: 41-52.

  4. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005; 5: 558-67.

  5. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-206.

  6. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364: 2405-16.

  7. Berg T, Andreone P, Pol S, et al. Predictors of virological response with telaprevir-based combination treatment in HCV genotype 1-infected patients with prior peginterferon/ribavirin treatment failure: Post-hoc analysis of the phase III realize study. Hepatology 2011; 54(Suppl.): 375A.

  8. Sulkowski MS, Asselah T, Ferrenci P, et al. Treatment with the second generation HCV protease inhibitor BI201335 results in high and consistent SVR rates – results from SILEN-C1 in treatment-naïve patients across different baseline factors. Hepatology 2011; 54(Suppl.): 473A.

  9. Barbeau JM, Goforth J, Caliendo AM, Nolte FS. Performance characteristics of a quantitative TaqMan hepatitis C virus RNA analyte-specific reagent. J Clin Microbiol 2004; 42: 3739-46.

  10. Forman MS, Valsamakis A. Verification of an assay for quantification of hepatitis C virus RNA by use of an analyte- specific reagent and two different extraction methods. J Clin Microbiol 2004; 42: 3581-8.

  11. Sarrazin C, Hendricks DA, Sedarati F, Zeuzem S. Assessment, by transcription-mediated amplification, of virologic response in patients with chronic hepatitis C virus treated with peginterferon alpha-2a. J Clin Microbiol 2001; 39: 2850-5.

  12. Hendricks DA, Friesenhahn M, Tanimoto L, Goergen B, Dodge D, Comanor L. Multicenter evaluation of the VERSANT HCV RNA qualitative assay for detection of hepatitis C RNA. J Clin Microbiol 2003; 41: 651-6.

  13. Harrington PR, Zeng W, Naeger LK. Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment. Hepatology 2011. Epub.

  14. Morishima C, Morgan TR, Everhart JE, Wright EC, Shiffman ML, Everson GT, Lindsay KL, et al. HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial. Hepatology 2006; 44: 360-7.

  15. Berg T, Weich V, Teuber G, Klinker H, Möller B, Rasenack J, Hinrichsen H, et al. Individualized treatment strategy according to early viral kinetics in hepatitis C virus type 1-infected patients. Hepatology 2009; 50: 369-77.

  16. Wiegand J, Neumann K, Böhm S, Weich V, Teuber G, Klinker H, Möller B, et al. Importance of minimal residual viremia for relapse prediction in patients with chronic hepatitis C genotype 1 infection. Clin Infect Dis 2011; 53: 1111-4.

  17. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: 1513-20.

  18. Foster GR, Fried MW, Hadziyannis SJ, Messinger D, Freivogel K, Weiland O. Prediction of sustained virological response in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) and ribavirin. Scand J Gastroenterol 2007; 42: 247-55.

  19. Shirakawa H, Matsumoto A, Joshita S, Komatsu M, Tanaka N, Umemura T, Ichijo T, et al. Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology 2008; 48: 1753-60.

  20. Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, Wiedenmann B, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology 2003; 37: 600-9.

  21. Zeuzem S, Herrmann E, Lee J-H, Fricke J, Neumann AU, Modi M, Colucci G, et al. Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon α2a. Gastroenterology 2001; 120: 1438-47.

  22. Layden JE, Layden TJ, Reddy KR, Levy-Drummer RS, Poulakos J, Neumann AU. First phase viral kinetic parameters as predictors of treatment response and their influence on the second phase viral decline. J Viral Hepatitis 2002; 9: 340-5.

  23. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy. Science 1998; 282: 103-7.

  24. Zeuzem S, Schmidt JM, Lee J-H, Rüster B, Roth WK. Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo. Hepatology 1996; 42: 1915-23.

  25. Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibranyi E, et al. Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol 2006; 44: 97-103.

  26. Jensen DM, Morgan TR, Marcellin P, Pockros PJ, Reddy KR, Hadziyannis SJ, Ferenci P, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy. Hepatology 2006; 43: 954-60.

  27. Ferenci P, Laferl H, Scherzer TM, Gschwantler M, Maieron A, Brunner H, Stauber R, et al. Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response. Gastroenterology 2008; 135: 451-8.

  28. Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, Lee LP, et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology 2008; 47: 1884-93.

  29. Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, et al. Extended treatment duration for hepatitis C virus type 1: Comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 2006; 130: 1086-97.

  30. Gerotto M, Dal Pero F, Bortoletto G, Ferarri A, Pisitis R, Sebastiani G, Fagiuoli S, et al. Hepatitis C minimal residual viremia (MRV) detected by TMA at the end of Peg-IFN plus ribavirin therapy predicts post-treatment relapse. J Hepatol 2006; 44: 83-7.




2020     |     www.medigraphic.com