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Study Description

Reprinted from


The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial is a randomized controlled trial designed to evaluate the safety and efficacy of long-term use of pegylated interferon for the treatment of chronic hepatitis C in patients who failed to respond to previous interferon therapy. The HALT-C Trial was developed to determine whether prolonged interferon therapy altered histological and clinical outcomes in a group of patients who had failed to eradicate hepatitis C virus with previous interferon treatment.

Study Hypotheses

  1. In patients with chronic hepatitis C and bridging fibrosis who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can prevent progression to cirrhosis.
  2. In patients with cirrhosis secondary to chronic hepatitis C who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can reduce the risks of hepatic decompensation or of hepatocellular carcinoma.

Study Design

1145 patients with chronic HCV and advanced hepatic fibrosis (Ishak stage 3-6) who failed to respond to previous treatment with interferon were enrolled at 10 clinical centers and entered into a Lead-in phase. They were treated with a combination of pegylated interferon (Pegasys®, Hoffmann-La Roche) 180 µg/week and ribavirin (1000-1200 mg/day) for 24 weeks. Patients who had no detectable HCV-RNA at week 20 continued on combination therapy until week 48.

662 patients who did not clear virus were randomly assigned at week 24 to either continue treatment with pegylated interferon alone (90 µg/week) for an additional 42 months, or to have treatment discontinued. All patients were followed at 3-month intervals following randomization. Liver biopsy was performed at baseline and after 1.5 and 3.5 years of treatment.

Because of slower than expected enrollment and the approval by the FDA of peginterferon alfa-2b after the start of the trial, we modified the study protocol in three ways. First, criteria for admission to the trial were liberalized to allow patients to enter the trial with lower platelet and white blood cell counts than had been initially considered safe or tolerable. Second, 151 Lead-in patients and those continuing on therapy after 24 weeks who demonstrated return of viremia during or after their 48-week treatment period (called "Breakthrough" or "Relapse" patients, respectively) were allowed to return to enter the randomized trial. Third, 237 patients treated with peginterferon alfa-2b (or with peginterferon alfa-2a in licensing trials) outside the HALT-C Trial who in other respects met all study criteria, having received the equivalent of Trial Lead-in period therapy, were allowed to enter the long-term trial as "Express" patients.

A total 1050 patients were randomized.

Those patients who completed Month 48 were offered an "extended follow-up (observation only)" until October 2009. These visits will primarily be to identify outcome events, and to provide information to patients concerning the current status of the trial. Some questionnaires, blood tests, and an ultrasonogram will be performed.

Quarterly (every 3 months)

  • Interval history of complications, adverse events
  • Current medications
  • Brief physical examination
  • Laboratory tests: liver panel, CBC, INR, AFP
  • Child-Pugh Score
  • Stored serum


  • Complete physical examination
  • Ultrasound of liver

1.5 years (M24 visit, middle of study)

  • Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)

3.5 years (M48, end of study)

  • Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)
  • Endoscopy: evaluate esophageal varices and portal hypertension

After Month 48

  • Observation only (no treatment) to determine clinical outcomes
  • Clinic visit every 6 months with current medications, brief PE, liver panel, CBC, AFP, stored
  • Serum
  • Ultrasound of liver every 6 months

Outcome Variables

Primary outcome variables to be assessed in the two groups of patients include:

  • Development of cirrhosis on liver biopsy (progression of Ishak fibrosis score by 2 points or more)
  • Development of hepatic decompensation, as shown by:
    • Sustained increase in the Child-Turcotte-Pugh score to 7 points or higher
    • Variceal hemorrhage
    • Ascites
    • Spontaneous bacterial peritonitis
    • Hepatic encephalopathy
    • Development of hepatocellular carcinoma
    • Death
Secondary outcomes include quality of life, serious adverse events, events requiring dose reductions, and development of presumed hepatocellular carcinoma.

  • Study Weblink: HALT-C
  • Study Type: Randomized Controlled Clinical Trial
  • Number of study subjects that have individual level data available through Authorized Access: 966

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

The following eligibility criteria were evaluated during screening.


  • A history of chronic HCV
  • Failure to achieve a virologic or biochemical response during previous interferon therapy (with or without ribavirin)
  • An elevation in serum AST or ALT within 6 months of enrollment
  • At least stage 3 fibrosis on liver biopsy by the Ishak scoring system
  • An age of 18 years or greater
  • Willingness to utilize adequate contraception when being treated with ribavirin


  • Any other co-existent liver disease
  • A Child-Turcotte-Pugh Score of 7 points or greater
  • A history of ascites, hepatic encephalopathy or variceal hemorrhage
  • A platelet count < 75,000, PMN count < 1,500 or Hct < 33%
  • An AFP > 200 ng/ml or the presence of a hepatic mass suggestive of HCC
  • A bilirubin > 2.5 mg/dl (except for patients with Gilbert's syndrome)
  • A serum creatinine > 1.5 mg/dl
  • Co-infection with HIV
  • Poorly controlled diabetes mellitus
  • Another serious medical disorder
  • A serious psychiatric disorder
  • A history of alcohol abuse within the past year
  • The use of illicit drugs within the past two years
  • Intolerance to previous interferon treatment
  • Inability to provide informed consent
  • Pregnancy, breast feeding, or the male partner of a pregnant woman
  • Inability or unwillingness to undergo liver biopsy

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina Human610_Quadv1_B 601273 1048904
Study History

  • Screening visits for the HALT-C trial were held between June 2000 and May 2003.
  • Enrollment into the Lead-in phase began in August 2000. Enrollment concluded in January 2003 for Lead-in patients and in April 2003 for Express patients. The first patient was randomized in January 2001 and the last patient was randomized in August 2004.
  • As stated in the protocol, all treatment ended in January 2007.
  • Extension phase consisting of surveillance follow-up through October 2009.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution
  • Principal Investigators
    • Gyongyi Szabo, MD. University of Massachusetts, Worcester, MA, USA
    • Herbert Bonkovsky, MD. University of Connecticut, Farmington, Connecticut, USA
    • Adrian M. Di Bisceglie, MD. Saint Louis University School of Medicine, Saint Louis, Missouri, USA
    • Jules Dienstag, MD. Massachusetts General Hospital, Boston, MA, USA
    • Gregory T. Everson, MD. University of Colorado Health, Sciences Center, Denver, CO, USA
    • Mark Ghany, MD. Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA
    • Timothy R. Morgan, MD. University of California, Irvine, Orange, CA, USA
    • William Lee, MD. University of Texas Southwestern, Dallas, TX, USA
    • Karen L. Lindsay, MD. University of Southern California, Los Angeles, CA, USA
    • Anna Lok, MD. University of Michigan, Ann Arbor, MI, USA
    • Richard K. Sterling, MD. Virginia Commonwealth University, Richmond, VA, USA
    • David Gretch, MD PhD. University of Washington, Seattle, WA, USA
    • Anne M. Stoddard, ScD. New England Research Institutes, Watertown, MA, USA
  • Principal Investigator (Genetics)
    • Gonzalo Laje, MD MHSc. National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA