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

January 27, 2015 updated by: University of Arkansas
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • University of Toronto
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • University of Arkansas for Medical Sciences
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatocellular carcinoma
Time Frame: 3 years
According to standard imaging surveillance protocol, and confirmatory CT/MRI/biopsy
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk factors for hepatocellular carcinoma
Time Frame: Change from baseline to 3 years
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
Change from baseline to 3 years
Profile with lowest risk for hepatocellular carcinoma
Time Frame: Change from baseline to 3 years
Composite of regression of fibrosis plus other specific conditions decreasing incidence of hepatocellular carcinoma to <1.5% / year
Change from baseline to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Regression of liver fibrosis
Time Frame: Change from baseline to 3 years
According to Fibrotest/Fibrosure and transient elastography
Change from baseline to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arkansas

Collaborators

University of Toronto
University of North Carolina, Chapel Hill
University of Calgary

Investigators

  • Principal Investigator: Andres Duarte-Rojo, MD, MSc, University of Arkansas
  • Principal Investigator: Jonathan A Dranoff, MD, University of Arkansas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

April 2, 2013

First Submitted That Met QC Criteria

April 9, 2013

First Posted (Estimate)

April 15, 2013

Study Record Updates

Last Update Posted (Estimate)

January 28, 2015

Last Update Submitted That Met QC Criteria

January 27, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 137855

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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