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Hepatitis C Virus (HCV) RNA Level Determined by Second-Generation Branched-DNA Probe Assay as Predictor of Response to Interferon Treatment in Patients with Chronic HCV Viremia

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Abstract

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype 1b and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-α treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype 1b patients [5.4 × 106 HCV genome equivalent (Meq)/ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype 1b patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level ≦1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype 1b patients with level ≤1.0 Meq/ml (57.6%) than in those with level >1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level ≤1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of ≦1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment.

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REFERENCES

  1. Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, Tegtmeier GE, Bonino F, Colombo M, Lee WS, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M: An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244:362–364, 1989

    Google Scholar 

  2. Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, Dioguardi N, Houghton M: Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet 8670:1006–1008, 1989

    Google Scholar 

  3. Hayashi J, Furusyo N, Ariyama I, Sawayama Y, Etoh Y, Kashiwagi S: A relationship between the evolution of hepatitis C virus variants, liver damage, and hepatocellular carcinoma in patients with hepatitis C viremia. J Infect Dis 181:1523–1527, 2000

    Google Scholar 

  4. Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC Jr, Perrillo RP, Carey W, Jacobson IM, Payne J, Dienstag JL, VanThiel D, Tamburro C, Lefkowitch J, Albretch J, Meschievitz C, Ortego TJ, Gibas A, Hepatitis Interventional Group: Treatment of chronic hepatitis C with recombinant interferon alpha. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med 321:1501–1506, 1989

    Google Scholar 

  5. Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J, Goodman Z, Banks SM, Hoofnagle JH: Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med 321:1506–1510, 1989

    Google Scholar 

  6. Furusyo N, Hayashi J, Ueno K, Sawayama Y, Kawakami Y, Kishihara Y, Kashiwagi S: Human lymphoblastoid interferon treatment for patients with hepatitis C virus-related cirrhosis. Clin Ther 19:1352–1367, 1997

    Google Scholar 

  7. Hayashi J, Ohmiya M, Kishihara Y, Tani Y, Kinukawa N, Ikematsu H, Kashiwagi S: A statistical analysis of predictive factors of response to human lymphoblastoid interferon in patients with chronic hepatitis C. Am J Gastroenterol 89:2151–2156, 1994

    Google Scholar 

  8. Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S: Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 346:1051–1055, 1995

    Google Scholar 

  9. Hayashi J, Kishihara Y, Ueno K, Yamaji K, Kawakami Y, Furusyo N, Sawayama Y, Kashiwagi S: Age-related response to interferon alfa treatment in women vs men with chronic hepatitis C virus infection. Arch Intern Med 158:177–181, 1998

    Google Scholar 

  10. Furusyo N, Hayashi J, Ohmiya M, Sawayama Y, Kawakami Y, Ariyama I, Kinukawa N, Kashiwagi S: Differences between interferon-alpha and-beta treatment for patients with chronic hepatitis C virus infection. Dig Dis Sci 44:608–617, 1999

    Google Scholar 

  11. Pawlotsky JM, Martinot-Peignoux M, Poveda JD, Bastie A, Le Breton V, Darthuy F, Remire J, Erlinger S, Dhumeaux D, Marcellin P: Quantification of hepatitis C virus RNA in serum by branched DNA-based signal amplification assays. J Virol Methods 79:227–235, 1999

    Google Scholar 

  12. Bresters D, Cuypers HT, Reesink HW, Mauser-Bunschoten EP, van den Berg HM, Schaasberg WP, Wilber JC, Urdea MS, Neuwald P, Lelie PN: Comparison of quantitative cDNA-PCR with the branched DNA hybridization assay for monitoring plasma hepatitis C virus RNA levels in haemophilia patients participating in a controlled interferon trial. J Med Virol 43:262–268, 1994

    Google Scholar 

  13. Diodati G, Bonetti P, Noventa F, Casarin C, Rugge M, Scaccabarozzi S, Tagger A, Pollice L, Tremolada F, Davite C, Realdi G, Ruol A: Treatment of chronic hepatitis C with recombinant human interferon-alpha 2a: Results of a randomized controlled clinical trial. Hepatology 19:1–5, 1994

    Google Scholar 

  14. Mita E, Hayashi N, Hagiwara H, Ueda K, Kanazawa Y, Kasahara A, Fusamoto H, Kamada T: Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer. Dig Dis Sci 39:977–982, 1994

    Google Scholar 

  15. Hayashi J, Yoshimura E, Kishihara Y, Yamaji K, Etoh Y, Ikematsu H, Kashiwagi S: Hepatitis C virus RNA levels determined by branched DNA probe assay correlated with levels assessed using competitive PCR. Am J Gastroenterol 91:314–318, 1996

    Google Scholar 

  16. Hayashi J, Kawakami Y, Nabeshima A, Kishihara Y, Furusyo N, Sawayama Y, Kinukawa N, Kashiwagi S: Comparison of HCV RNA levels by branched DNA probe assay and by competitive polymerase chain reaction to predict effectiveness of interferon treatment for patients with chronic hepatitis C virus. Dig Dis Sci 43:384–391, 1998

    Google Scholar 

  17. Detmer J, Lagier R, Flynn J, Zayati C, Kolberg J, Collins M, Urdea M, Sanchez-Pescador R: Accurate quantification of hepatitis C virus (HCV) RNA from all HCV genotypes by using branched-DNA technology. J Clin Microbiol 34:901–907, 1996

    Google Scholar 

  18. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ: Classification of chronic hepatitis: Diagnosis, grading and staging. Hepatology 19:1513–1520, 1994

    Google Scholar 

  19. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981

    Google Scholar 

  20. Hayashi J, Nakashima K, Kishihara Y, Ohmiya M, Yoshimura E, Hirata M, Kashiwagi S: Improved detection of antibodies to hepatitis C virus by the second-generation assay in patients with chronic non-A, non-B liver disease. J Infect 26:287–294, 1993

    Google Scholar 

  21. Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Sato K, Tsuda F, Miyakawa Y, Mayumi Y: Typing hepatitis C virus by polymerase chain reaction with type-specific primers: Application to clinical surveys and tracing infectious sources. J Gen Virol 73:673–679, 1992

    Google Scholar 

  22. Simmonds P, Alberti A, Alter HJ, Bonino F, Bradley DW, Brechot C, Brouwer JT, Chan SW, Chayama K, Chen DS, Choo QL, Colombo M, Cuypers HTM, Date T, Dusheiko GM, Esteban JI, Fay O, Hadzyannis SJ, Han J, Hatzakis A, Holmes EC, Hotta H, Houghton M, Irwine B, Kohara M, Kolberg JA, Kuo G, Lau JYN, Lelie PN, Maertens G, McOmish F, Miyamura T, Mizokami M, Nomoto A, Prince AM, Reesink HW, Rice C, Roggendorf M, Schalm SW, Shikata T, Shimotohno K, Stuyver L, Trepo C Weiner A, Yap PL, Urdea MS: A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 19:1321–1324, 1994

    Google Scholar 

  23. Pawlotsky JM, Martinot-Peignoux M, Poveda JD, Bastie A. Le Breton V. Darthuy F, Remire J, Erlinger S, Dhumeaux D, Marcellin P: Quantification of hepatitis C virus RNA in serum by branched DNA-based signal amplification assays. J Virol Methods 79:227–235, 1999

    Google Scholar 

  24. Dixon WJ, Brown MB, Engelman L, Jennrich R: BMDP statistical software manual. Berkeley, University of California Press, 1990

    Google Scholar 

  25. Camma C, Giunta M, Pinzell G, Morabito A, Verderio P, Pangliaro L: Chronic hepatitis C and interferon alpha: conventional and cumulative meta-analyses of randomized controlled trials. Am J Gastroenterol 94:581–595, 1999

    Google Scholar 

  26. Hayashi J, Kishihara Y, Yoshimura E, Tani Y, Yamaji K, Ikematsu H, Ishiko H, Kashiwagi S: Relationship of genotype to level of hepatitis C viraemia determined by competitive polymerase chain reaction. J Infect 30:235–239, 1995

    Google Scholar 

  27. Hayashi J, Kishihara Y, Yamaji K, Yoshimura E, Kawakami Y, Akazawa K, Kashiwagi S: Transmission of hepatitis C virus by health care workers in a rural area of Japan. Am J Gastroenterol 90:794–799, 1995

    Google Scholar 

  28. Hawkins A, Davidson F, Simmonds P: Comparison of plasma virus loads among individuals infected with hepatitis C virus (HCV) genotypes 1, 2, and 3 by quantiplex HCV RNA assay versions 1 and 2, Roche Monitor assay, and an in-house limiting dilution method. J Clin Microbiol 35:187–192, 1997

    Google Scholar 

  29. Lau JY, Davis GL, Kniffen J, Qian KP, Urdea MS, Chan CS, Mizokami M, Neuwald PD, Wilber JC: Significance of serum hepatitis C virus RNA levels in chronic hepatitis C. Lancet 341:1501–1504, 1993

    Google Scholar 

  30. Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS: Hepatitis B genotypes and the response to interferon therapy. J Hepatol 33:998–1002, 2000

    Google Scholar 

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Authors and Affiliations

  1. Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan

    Norihiro Furusyo, Jun Hayashi, Shigeki Nabeshima, Yasunori Sawayama & Seizaburo Kashiwagi

  2. Department of Environmental Medicine and Infectious Disease, Internal Medicine, Medicine and Surgery, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Jun Hayashi, Kenichiro Kashiwagi & Hisashi Nakashima

  3. Department of Medical Informatics, Kyushu University Hospital, Fukuoka, Japan

    Naoko Kinukawa

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  1. Norihiro Furusyo
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  2. Jun Hayashi
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Furusyo, N., Hayashi, J., Kashiwagi, K. et al. Hepatitis C Virus (HCV) RNA Level Determined by Second-Generation Branched-DNA Probe Assay as Predictor of Response to Interferon Treatment in Patients with Chronic HCV Viremia. Dig Dis Sci 47, 535–542 (2002). https://doi.org/10.1023/A:1017955700585

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