icon_folder.gif   Conference Reports for NATAP  
  AASLD ( American Association for the Study of Liver Diseases)
November 9-13, 2001, Dallas
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More on the HALT-C Trial: 4-year study of Maintenance Therapy in 1350 patients
Written for NATAP by Mark Sulkowski, MD, Johns Hopkins University School of Medicine
  Abstract 279. Retreatment of Interferon And Interferon-Ribavirin Non-Responders with Peginterferon-alpha-2a (Pegasys) And Ribavirin: Initial Results from the Lead-In Phase of the Halt-C Trial
The HALT-C trial was designed to determine if long term maintenance interferon therapy, administered over 4 years, could prevent histologic progression, reduce the development of hepatocellular carcinoma and the need for hepatic transplantation in patients with chronic HCV and advanced fibrosis or cirrhosis who remain HCV-RNA (+) despite therapy. Since peginterferon plus ribavirin is more effective than standard interferon/ribavirin for treatment of chronic HCV all patients enrolled in the HALT-C trial were first treated with peginterferon plus ribavirin during the lead-in phase of this trial.
This study is enrolling 1350 patients with advanced liver disease (bridging fibrosis/cirrhosis, Ishak Fibrosis stage > 3) and no evidence of hepatic decompensation. All patients had previously failed to respond to interferon-based therapy administered for at least 12 weeks. After screening, all patients received pegylated interferon alfa-2a (180 mcg weekly) plus ribavirin (1 - 1.2 grams/day). Patients who are HCV-RNA (-) at week 20 continue therapy for 48 weeks total. Patients who are HCV-RNA (+) either stop treatment or receive a maintenance dose of Pegasys 90ug/week for 3.5 years.
Dr. Adrian Di Bisceglie presented on-treatment virologic response data on the first 268 patients who completed at least 20 weeks of therapy within this ongoing study. For the purpose of this presentation, viral response was defined as an undetectable HCV-RNA level at treatment week 20. 15 (5.6%) patients discontinued therapy prior to week 20. At week 20, 107 of 268 patients (42%) (based on an intention-to-treat analysis) had an undetectable HCV RNA level. These patients will continue therapy for an additional 28 weeks and, per protocol, will not enter the "maintenance" phase of the study. There were several important "sub-group" analysis presented. Persons who had only failed prior interferon monotherapy were much more likely to achieve a response than those who failed prior interferon/ribavirin combination therapy (53% > 31%) and African-Americans were significantly less likely to respond than others (10% < 43%).
In addition, a large number of patients had dose reductions of the PEG-interferon (53%), ribavirin (44%) or both (47%). Thus, while the discontinuation rate was quite low (~5%), it remains uncertain if such dose reductions will impair the overall effectiveness of the therapy. Nonetheless, these results are encouraging and suggest that persons with advanced liver disease who failed to respond virologically to prior therapy may benefit from a course of pegylated interferon/ribavirin.
Editorial note: Baseline data for 268 patients-- 41% of patients in study had cirrhosis at baseline. 84% were genotype 1. Mean ALT was 124. 88% were Caucasian. 63% had received IFN+RBV. Mean HCV-RNA was 3.5 million IU/mL. Mean age 50. The degree of fibrosis was associated with response (44% Ishak 3-4 [bridgng fibrosis] vs 31% Ishak 5-6 [cirrhosis], p=0.03). Gender was not associated with response (40 vs male vs 36% female, NS). Genotype was a factor in response Genotype 2b: 88%; genotype 3a: 93%, genotype 1a: 30%; genotype 1b: 39%; genotype 2a: 35%. Baseline HCV-RNA did not appear to influence response. Mean reduction in HCV-RNA was 3.7 log; 45% had a 3+ log reduction, while 15% had a 2-log reduction, 21% had a 1-log reduction, and 18% had <1-log reduction. It will be interesting to see if the patients with little viral load reduction demonstrate improved, stopped, or slowed fibrosis.
The long-term goals or outcomes from HALT-C will take several years to achieve. These interim results are similar to those seen in several other smaller studies reported at the conference.