The Regression of Liver Fibrosis and Risk for Hepatocellular Carcinoma (ROLFH) Study

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by University of Arkansas
Sponsor:
Collaborators:
University of North Carolina, Chapel Hill
University of Toronto
University of Calgary
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01831037
First received: April 2, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

This study aims to demonstrate that patients with chronic hepatitis C (CHC) and B (CHB) experiencing regression of liver cirrhosis after effective antiviral therapy have decreased risk for hepatocellular carcinoma (HCC). Primary aim is to determine the incidence of HCC in patients with cirrhosis secondary to CHC and CHB, after treatment is provided, and to identify the magnitude of the decreased risk for HCC in patients experiencing regression of fibrosis. As a secondary aim, environmental risk factors for HCC development will be sought, in order to determine a subset of patients in whom it will be safe to stop surveillance.


Condition Intervention
Chronic Hepatitis C
Chronic Hepatitis B
Other: Regression of fibrosis
Other: Specific risk factors related to hepatocellular carcinoma

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Regression of Liver Fibrosis and Risk for Hepatocellular Carcinoma (ROLFH) Study

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Hepatocellular carcinoma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    According to standard imaging surveillance protocol, and confirmatory CT/MRI/biopsy


Secondary Outcome Measures:
  • Risk factors for hepatocellular carcinoma [ Time Frame: Change from baseline to 3 years ] [ Designated as safety issue: No ]
    Positive family history of liver cancer, BMI, active/previous smoking, active/previous alcohol consumption, caffeine consumption in diet, diabetes mellitus, use of drugs for chronic medical conditions

  • Profile with lowest risk for hepatocellular carcinoma [ Time Frame: Change from baseline to 3 years ] [ Designated as safety issue: No ]
    Composite of regression of fibrosis plus other specific conditions decreasing incidence of hepatocellular carcinoma to <1.5% / year


Other Outcome Measures:
  • Regression of liver fibrosis [ Time Frame: Change from baseline to 3 years ] [ Designated as safety issue: No ]
    According to Fibrotest/Fibrosure and transient elastography


Biospecimen Retention:   Samples With DNA

Serum, plasma, PBMC for DNA isolation


Estimated Enrollment: 924
Study Start Date: July 2015
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Regression of fibrosis
Group conformed by patients experiencing improvement in the noninvasive markers of fibrosis, Fibrotest/Fibrosure and transient elastography, while enrolled in the study.
Other: Regression of fibrosis
Regression of fibrosis will be defined by assessing yearly evolution of noninvasive markers in patients who received antiviral therapy before start of the study, and by comparing baseline markers before start of antiviral therapy to those on subsequent yearly visits in patients prospective recruited (>50% of cases).
Other Name: FibroTest, FibroSure, FibroScan (transient elastography)
Other: Specific risk factors related to hepatocellular carcinoma
Such as: family history of liver cancer; body mass index; alcohol, smoking and recreational drug use status; dietary habits, including use of caffeinated drinks; comorbidities such as type 2 diabetes mellitus; use of medications for other chronic diseases such as statins and angiotensin-converting enzyme inhibitors.
No regression of fibrosis
Group conformed by patients not showing the predefined improvement in the noninvasive markers of fibrosis, Fibrotest/Fibrosure and transient elastography, while enrolled in the study.

Detailed Description:

Cirrhosis is the final pathway of chronic liver disease, and up to 30% of patients develop hepatocellular carcinoma (HCC) within 5 years of diagnosis of cirrhosis. Worldwide, chronic hepatitis C (CHC) and B (CHB) account for the majority of cases of cirrhosis. Successful antiviral treatment results in regression of fibrosis in the majority of patients. Surveillance programs for early detection of HCC mandate the use of imaging (ultrasound/CT-scan) every 6 months. It has been shown in CHC and CHB that the risk of HCC is greatly reduced after viral disease is eradicated/inactive. However, the impact that regression of fibrosis and other factors could have in abating the incidence of HCC has not been systematically investigated. Currently, all patients with eradicated/inactive viral disease continue to be enrolled in HCC surveillance programs, generating anxiety in patients and very high costs to our healthcare system. Fibrotest (FT) and transient elastography (TE) are noninvasive tools proven to be useful for serial assessment of liver fibrosis.

OBJECTIVES: The proposed hypothesis is that patients with regression of liver fibrosis have decreased risk for HCC. Primary aim is to determine the incidence of HCC in patients with cirrhosis secondary to CHC and CHB, during the 3-7 years after treatment is provided, and to identify the magnitude of the decreased risk for HCC in patients experiencing regression of fibrosis. As a secondary aim, environmental risk factors for HCC development will be sought, in order to determine a subset of patients in whom it will be safe to stop surveillance.

METHODS: Patients 18-70 year-old with cirrhosis will be identified from hepatology clinics in 4 academic centers in North America. FT/TE will be obtained before the start of antivirals and yearly thereafter (prospective arm). A retrolective arm of all patients treated no earlier than Jan/2009 will also be included. In this group, baseline FT/TE will be performed off treatment (CHC) or after initial phase of therapy (CHB), and yearly thereafter. During baseline and yearly visits other factors possibly affecting HCC development will be investigated (family history, comorbidities, BMI, diet, etc.). Patients will be classified as having or having not undergone regression of fibrosis after a 3-year follow up, depending on FT and TE evolution. During follow up, all patients will undergo 6-month imaging as part of their routine HCC surveillance. Based on power calculations, enrollment should stop after 924 patients have been recruited. Kaplan-Meier and Cox regression models will be used to analyze data.

PATIENT OUTCOMES: ROLFH study uses state-of-the-art noninvasive markers of liver fibrosis to test whether reversed fibrosis decreases the risk of HCC. We believe this study will lead to a better understanding of HCC risk factors, improved patient counseling and decision making, optimized screening and allocation of health resources, and decreased healthcare costs.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with chronic hepatitis C or B, with cirrhosis, with successful antiviral treatment no earlier than January 2010 (retrospective component), or planned to start antiviral treatment by the time of recruitment

Criteria

Inclusion Criteria:

  • Age 18-70
  • Chronic liver disease due to CHC or CHB.
  • Starting of disease-specific treatment no earlier than January of 2010. Treatment could consist of:

    • combination therapy with peginterferon and ribavirin, with or without a direct-acting viral agent in CHC;
    • single or combination therapy containing peginterferon, entecavir, or tenofovir in CHB.
  • Established cirrhosis on liver biopsy (METAVIR F4) obtained before starting disease-specific treatment.
  • In patients without liver biopsy, any of the following criteria will be used as a surrogate to define cirrhosis:

    • History of spleen >13 cm, bilirubin >2, albumin <3.5, INR >1.5 (2 of 3 criteria).
    • History of APRI ([AST/ULN]/platelets x 100) >2, and esophageal varices or ascites.
    • History of Fibrotest/Fibrosure >0.74, and TE >12.5 kPa (M-probe) or >10 kPa (XL-probe).

Exclusion Criteria:

  • Known diagnosis of hepatocellular carcinoma or portal vein thrombosis
  • Conditions limiting Fibrotest/Fibrosure read: hemolysis, Gilbert's syndrome, autoimmune disease.
  • Conditions limiting TE read: ascites, heart failure with retrograde vascular congestion, extrahepatic cholestasis.
  • Pregnancy or implantable active medical device (such as pacemaker or defibrillator).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01831037

Contacts
Contact: Andres Duarte-Rojo, MD, MSc 501-686-5175 aduarterojo@uams.edu
Contact: Matthew G Deneke, MD 501-686-5175 mdeneke@uams.edu

Locations
United States, Arkansas
University of Arkansas for Medical Sciences Not yet recruiting
Little Rock, Arkansas, United States, 72211
Contact: Andres Duarte-Rojo, MD, MSc    501-686-5175    aduarterojo@uams.edu   
Contact: Matthew G Deneke, MD    501-686-5175    mdeneke@uams.edu   
Sub-Investigator: Jonathan A Dranoff, MD         
Sub-Investigator: Paula K Roberson, PhD         
Sub-Investigator: Matthew G Deneke, MD         
Principal Investigator: Andres Duarte-Rojo, MD, MSc         
United States, North Carolina
University of North Carolina at Chapel Hill Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Jama M Darling, MD    919-966-2516    jdarling@med.unc.edu   
Contact: Sidney Barritt, MD    919-966-2516    sid_barritt@med.unc.edu   
Principal Investigator: Jama M Darling, MD         
Sub-Investigator: Sidney Barritt, MD         
Canada, Alberta
University of Calgary Not yet recruiting
Calgary, Alberta, Canada, T2N 4Z6
Contact: Robert P Myers, MD, MPH       rpmyers@ucalgary.ca   
Principal Investigator: Robert P Myers, MD, MPH         
Canada, Ontario
University of Toronto Not yet recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Jordan J Feld, MD, MPH    +(416) 603-6230    jordan.feld@uhn.ca   
Principal Investigator: Jordan J Feld, MD, MPH         
Sponsors and Collaborators
University of Arkansas
University of North Carolina, Chapel Hill
University of Toronto
University of Calgary
Investigators
Principal Investigator: Andres Duarte-Rojo, MD, MSc University of Arkansas
Principal Investigator: Jonathan A Dranoff, MD University of Arkansas
  More Information

Publications:

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01831037     History of Changes
Other Study ID Numbers: 137855
Study First Received: April 2, 2013
Last Updated: June 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arkansas:
Hepatocellular carcinoma
Regressed cirrhosis
Hepatitis C
Hepatitis B
Noninvasive markers of fibrosis
FibroTest
FibroSure
FibroScan
Transient elastography

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Fibrosis
Hepatitis, Chronic
Hepatitis B
Carcinoma, Hepatocellular
Hepatitis C, Chronic
Carcinoma
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Hepadnaviridae Infections
DNA Virus Infections
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on October 16, 2014