Abstract
To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-α. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5′-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P<0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P<0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.
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References
Hoofnagle JH, Mullen KD, Jones, DB, Rustgi V, Di Bisceglie AM, Peters M, Waggoner JG, Park Y, Jones EA. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. N Engl J Med 315:1575–1578, 1986
Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Perrillo RP, Carey W, Jacobson IM, Payne J, Dienstag JL, Van Thiel DH, Tamburo C, Lefkowitch J, Albrecht J, Meschievitz C, Ortego TJ, Gibas A. Hepatitis Interventional Therapy Group: Treatment of chronic hepatitis C with recombinant interferon alpha. N Engl J Med 321:1501–1506, 1989
Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner JG, Goodman Z, Banks SM, Hoofnagle JH. Recombinant interferon alpha therapy for chronic hepatitis C: A randomized, double-blind, placebo-controlled trial. N Engl J Med 321:1506–1510, 1989
Shindo M, Di Bisceglie AM, Cheung L, Shih JW, Cristiano K, Feinstone SM, Hoofnagle JH: Decrease in serum hepatitis C viral RNA during alpha-interferon therapy for chronic hepatitis C. Ann Internal Med 115:700–704, 1991
Hagiwara H, Hayashi N, Mita E, Ueda K, Takehara T, Kasahara A, Fusamoto H, Kamada T: Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-α. Hepatology 15:37–41, 1992
Balart LA, Perrillo R, Roddenberry J, Regenstein F, Shim KS, Shieh YSC, Taylor B, Dash S, Gerber MA: Hepatitis C RNA in liver of chronic hepatitis C patients before and after interferon alfa treatment. Gastroenterology 104:1472–1477, 1993
Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Itoh Y, Takayanagi M, Higashi Y, Shibata M, Morishita T: Detection of hepatitis C virus by polymerase chain reaction and response to interferon-α therapy: Relationship to genotype of hepatitis C virus. Hepatology 16:293–299, 1992
International Group: Acute and chronic hepatitis revisited. Lancet 2:914–919, 1977
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol chloroform extraction. Anal Biochem 162:156–159, 1987
Kanai K, Iwata K, Nakao M, Okamoto H: Suppression of hepatitis C virus RNA by interferon-α. Lancet 336:245, 1990
Okamoto H, Okada S, Sugiyama Y, Tanaka T, Sugai Y, Akahane Y, Machida A, Mishiro S, Yoshizawa H, Miyakawa Y, Mayumi M: Detection of hepatitis C virus by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5′-noncoding region. Jpn J Exp Med 60:215–222, 1990
Kwok S, Higuchi R: Avoiding false positives with PCR. Nature 339:237–238, 1989
Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane, Y, Sugai Y, Tanaka T, Sato K, Tsuda F, Miyakawa Y, Mayumi M: 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
Kato N, Yokosuka O, Hosoda K, Ito Y, Ohto M, Omata M: Quantification of hepatitis C virus by competitive reverse transcription-polymerase chain reaction: Increase of the virus in advanced liver disease. Hepatology 18:16–20, 1993
Higuchi R: Recombinant PCR.In PCR Protocols. MA Innis, DH Gelfand, JJ Sninsky, and TJ White (eds). San Diego, Academic Press, 1990, pp 177–183
Garson JA, Brillanti S, Ring C, Perini P, Miglioli M, Barbara L: Hepatitis C viremia rebound after “successful” interferon therapy in patients with chronic non-A, non-B hepatitis. J Gen Virol 37:210–214, 1992
Okada S, Akahane Y, Suzuki H, Okamoto H, Mishiro S: The degree of variability in the amino terminal region of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremic patients. Hepatology 16:619–624, 1992
Okuda M: HCV-RNA assay in peripheral blood mononuclear cells in relation to IFN therapy. Gastroenterol Jpn 28:535–540, 1993
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Hino, K., Okuda, M., Konishi, T. et al. Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-α therapy. Digest Dis Sci 40, 14–20 (1995). https://doi.org/10.1007/BF02063935
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DOI: https://doi.org/10.1007/BF02063935