NCT01831037

Brief Summary

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.

Trial Health

33
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2015

Longer than P75 for all trials

Geographic Reach
2 countries

4 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 2, 2013

Completed
13 days until next milestone

First Posted

Study publicly available on registry

April 15, 2013

Completed
2.2 years until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2019

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

January 28, 2015

Status Verified

January 1, 2015

Enrollment Period

3.9 years

First QC Date

April 2, 2013

Last Update Submit

January 27, 2015

Conditions

Chronic Hepatitis CChronic Hepatitis B

Keywords

Hepatocellular carcinomaRegressed cirrhosisHepatitis CHepatitis BNoninvasive markers of fibrosisFibroTestFibroSureFibroScanTransient elastography

Outcome Measures

Primary Outcomes (1)

  • Hepatocellular carcinoma

    According to standard imaging surveillance protocol, and confirmatory CT/MRI/biopsy

    3 years

Secondary Outcomes (2)

  • Risk factors for hepatocellular carcinoma

    Change from baseline to 3 years

  • Profile with lowest risk for hepatocellular carcinoma

    Change from baseline to 3 years

Other Outcomes (1)

  • Regression of liver fibrosis

    Change from baseline to 3 years

Study Arms (2)

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 fibrosisOther: Specific risk factors related to hepatocellular carcinoma

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.

Interventions

Regression of fibrosisOTHER

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).

Also known as: FibroTest, FibroSure, FibroScan (transient elastography)
Regression of fibrosis
Specific risk factors related to hepatocellular carcinomaOTHER

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.

Regression of fibrosis

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability 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

You may qualify if:

  • 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).

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72211, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Toronto

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (8)

  • El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012 May;142(6):1264-1273.e1. doi: 10.1053/j.gastro.2011.12.061.

    PMID: 22537432BACKGROUND

  • Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2. doi: 10.1002/hep.24199. No abstract available.

    PMID: 21374666BACKGROUND

  • European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.

    PMID: 22424438BACKGROUND

  • Barritt AS 4th, Fried MW. Maximizing opportunities and avoiding mistakes in triple therapy for hepatitis C virus. Gastroenterology. 2012 May;142(6):1314-1323.e1. doi: 10.1053/j.gastro.2012.02.013.

    PMID: 22537438BACKGROUND

  • van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Heathcote EJ, Manns MP, Kuske L, Zeuzem S, Hofmann WP, de Knegt RJ, Hansen BE, Janssen HL. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012 Dec 26;308(24):2584-93. doi: 10.1001/jama.2012.144878.

    PMID: 23268517BACKGROUND

  • Duarte-Rojo A, Altamirano JT, Feld JJ. Noninvasive markers of fibrosis: key concepts for improving accuracy in daily clinical practice. Ann Hepatol. 2012 Jul-Aug;11(4):426-39.

    PMID: 22700624BACKGROUND

  • Myers RP, Pomier-Layrargues G, Kirsch R, Pollett A, Duarte-Rojo A, Wong D, Beaton M, Levstik M, Crotty P, Elkashab M. Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients. Hepatology. 2012 Jan;55(1):199-208. doi: 10.1002/hep.24624. Epub 2011 Nov 18.

    PMID: 21898479BACKGROUND

  • Myers RP, Pomier-Layrargues G, Kirsch R, Pollett A, Beaton M, Levstik M, Duarte-Rojo A, Wong D, Crotty P, Elkashab M. Discordance in fibrosis staging between liver biopsy and transient elastography using the FibroScan XL probe. J Hepatol. 2012 Mar;56(3):564-70. doi: 10.1016/j.jhep.2011.10.007. Epub 2011 Oct 23.

    PMID: 22027584BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, PBMC for DNA isolation

MeSH Terms

Conditions

Hepatitis C, ChronicHepatitis B, ChronicCarcinoma, HepatocellularHepatitis CHepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsHepadnaviridae InfectionsDNA Virus InfectionsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by Site

Study Officials

  • Andres Duarte-Rojo, MD, MSc

    University of Arkansas

    PRINCIPAL INVESTIGATOR

  • Jonathan A Dranoff, MD

    University of Arkansas

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 2, 2013

First Posted

April 15, 2013

Study Start

July 1, 2015

Primary Completion

June 1, 2019

Study Completion

December 1, 2019

Last Updated

January 28, 2015

Record last verified: 2015-01

Locations

US(2)CA(2)