Early Hepatitis C Virus-Rna Responses Predict Interferon... : Hepatology (original) (raw)

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Early Hepatitis C Virus-Rna Responses Predict Interferon Treatment Outcomes in Chronic Hepatitis C

Lee, William M. M.D.*,1; Reddy, Rajender K.2; Tong, Myron J.3; Black, Martin4; van Leeuwen, Dirk J.5; Hollinger, Blaine F.6; Mullen, Kevin D.7; Pimstone, Neville8; Albert, Donald9; Gardner, Sheila9

1_University of Texas Southwestern Medical Center at Dallas, Dallas, TX_

2_University of Miami, Miami, FL_

3_Huntington Memorial Hospital, Pasadena, CA_

4_Temple University Hospital, Philadelphia, PA_

5_University of Alabama at Birmingham, Birmingham, AL_

6_Baylor College of Medicine, Houston, TX_

7_MetroHealth Medical Center, Cleveland, OH_

8_University of California, Davis, Sacramento, CA_

9_Amgen, Boulder, CO_

10_Other investigators in the Consensus Interferon Study Group: R. Bailey, HYS Centre, Edmonton, Alberta, Canada; V. G. Bain, University of Alberta, Edmonton, Alberta, Canada; K. Bala, St. Bernardine Liver Disease Center, San Bernardino, CA; L. A. Balart, Louisiana State University School of Medicine, New Orleans, LA; H. Bonkovsky, University of Massachusetts Medical Center, Worcester, MA; W. M. Cassidy, Louisiana State University, Baton Rouge, LA; J. Donovan, University of Nebraska Medical Center, Omaha, NE; M. Ehrinpreis, Harper Hospital, Detroit, MI; G. T. Everson, University of Colorado Health Science Center, Denver, CO; S. V. Feinman, University of Toronto, Toronto, Ontario, Canada; R. T. Foust, Medical University of South Carolina, Charleston, SC; H. Fromm, George Washington University, Washington, DC; S. D. Hauser, Brigham and Women's Hospital, Boston, MA; E. J. L. Heathcote, University of Toronto, Toronto, Ontario, Canada; J. C. Hoefs, University of CA Medical Center, Orange, CA; S. James, University of Maryland at Baltimore, Baltimore, MD; D. M. Jensen, Rush–Presbyterian St. Luke's Medical Center, Chicago, IL; E. B. Keeffe, Stanford University, Palo Alto, CA; P. G. Killenberg, Duke University Medical Center, Durham, NC; E. L. Krawitt, University of Vermont Health Center, Burlington, VT; S. S. Lee, Health Science Center, Calgary, Alberta, Canada; H. R. Lesesne, General Clinical Research Center, Chapel Hill, NC; K. D. Lyche, University of California, San Diego, San Diego, CA; G. Y. Minuk, University of Manitoba, Winnipeg, Manitoba, Canada; K. M. Payne, University of Kansas Medical Center, Kansas City, KS; P. J. Pockros, Scripps Clinic, La Jolla, CA; H. Rosenblate, Rush North Shore Medical Center, Skokie, IL; D. A. Shafritz, Albert Einstein College of Medicine, Bronx, NY; C. I. Smith, Minnesota Clinical Research Center, St. Paul, MN; B. E. Willems, Hospital St. Luc, Montreal, Quebec, Canada; and J. Willis, Washington University School of Medicine, St. Louis, MO_

* University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235–9151. Fax: (214) 648–3715.

Received: 8 December 1997; Accepted: 18 June 1998

Abstract

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)–RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse–transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN–naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2–week intervals in the naive study and 8–week intervals in the retreatment study. Patients received initial CIFN (9 μg) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN–treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV–RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 μg CIFN. Ninety–five percent of the sustained responders were HCV–RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.