Incidence of de Novo Hepatocellular Carcinoma After Antiviral Agents for HCV.

December 14, 2018 updated by: Maria Julia Cremona, Austral University, Argentina

Incidence of de Novo Hepatocellular Carcinoma After Direct-acting Antiviral Agents for HCV: a Multicenter Prospective Cohort Study From Latin America.

The main risk factor for development of hepatocellular carcinoma (HCC) is cirrhosis of any etiology, with an annual incidence risk between 1-6%; currently the leading cause of death in patients with cirrhosis and the 2nd cause of death by cancer worldwide. Chronic hepatitis C (HCV) is the first single cause associated to cirrhosis and HCC in the Western world.

With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of HCC is lower in patients with virologic cure after treatment with pegINF schemes. However, recently published data, open up more controversy regarding the incidence of HCC after virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients treated with DAA has been observed, opening a paradox yet unexplained.

This project proposes to answer the following clinical research question: in patients with HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular carcinoma? To answer this question a prospective longitudinal cohort study of patients with Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.

A minimum of 210 patients will be included with clinical or histological or non-invasive diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without hepatocellular carcinoma at the time of enrollment. From this cohort, patients who develop HCC during follow-up will be identified. Routine screening will be done through ultrasound every 6 months in all subjects enrolled and the diagnosis of HCC will be according to recommendations of European and American guidelines.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Name of the study:

INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS WITH HEPATITIS C INFECTION, TRETAED WITH DIRECT ANTIVIRAL AGENTS IN LATIN AMERICA: A MULTICENTER PROSPECTIVE COHORT STUDY

With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of HCC is lower in patients with virologic cure after treatment with pegINF schemes. However, recently published data, open up more controversy regarding the incidence of HCC after virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients treated with DAA has been observed, opening a paradox yet unexplained.

This project proposes to answer the following clinical research question: in patients with HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular carcinoma? To answer this question a prospective longitudinal cohort study of patients with Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.

A minimum of 210 patients will be included with clinical or histological or non-invasive diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without hepatocellular carcinoma at the time of enrollement. From this cohort, patients who develop HCC during follow-up will be identified. Routine screening will be done through ultrasound every 6 months in all subjects enrolled and the diagnosis of HCC will be according to recommendations of European and American guidelines.

However, preliminary results presented at the last European Congress of Hepatology in Barcelona, Spain, and early published in Journal of Heaptology, open up more controversy regarding the incidence of HCC after virologic cure post DAA. An unexpected higher incidence and recurrence of HCC after treatment with these new drugs has been observed, opening a paradox yet unexplained. Of particular interest then, is to clarify and find if there is a change in the incidence of HCC in HCV cirrhosis after treatment with DAA in our region. It is relevant on the other hand; that this study would be the first longitudinal cohort study evaluating the development of HCC in patients with cirrhosis in Latin America. It is then expected that the results would be extremely important to the medical science from this region.

Clinical Research Question In patients with HCV cirrhosis treated DAA, is there a change in the incidence of hepatocellular carcinoma? Primary Objective To evaluate the incidence of HCC after treatment with DAA in patients with Child Pugh A or B cirrhosis and chronic HCV infection.

Secondary Objectives

Secondary objectives will be related to:

  • Incidence of HCC between cured and uncured of HCV with DAA.
  • Impact of routine screening on survival in patients with HCC.
  • Risk factors for development of hepatocellular carcinoma in patients with HCV treated with DAA.
  • Adverse events and incidence of cirrhosis decompensation after DAA.

Study Type

Observational

Enrollment (Anticipated)

2200

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

A consecutive non-probability sampling of subjects with clinical, histological or non-invasive diagnosis of cirrhosis, functional status Child Pugh class A or B with chronic HCV infection treated with DAA will be made. On a cohort of patients with these characteristics that meet the following eligibility criteria, a minimum 3-year follow-up will be done.

Description

Inclusion Criteria:

  • Signed Informed Consent (CI) obtained prior to any study specific procedure. Patients should be able to understand written informed and be ready to sign it (ANNEX I).
  • Men and women 18 years or older.
  • Clinical, histological or non-invasive diagnosis of cirrhosis, according to the American Association for the Study of Liver Diseases, AASLD criteria) [15].
  • Child Pugh A or B (ANNEX II). Child Pugh classification should be calculated based on clinical findings and laboratory results during the selection period.
  • Chronic Hepatitis C, defined as positive viremia with real time PCR method.
  • Current or prior treatment with DAA, including any interferon-free scheme, either in a clinical protocol or treated in the daily practice.
  • Co-infection with HIV infection is allowed or Hepatitis B.

Exclusion Criteria:

  • • Prior diagnosis of Hepatocellular to treatment with DAA.

    • Previous liver transplantation.
    • Drug addiction, medical, psychological or social problems that may interfere with the patient's participation in the study or evaluation of the results.
    • Pregnancy and/or breastfeeding.
    • Close relationship with the research center; eg close family member of the researcher, dependent (eg employee or student research center that could access study records and data CRF).

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV
Time Frame: Three year period
Cumulative incidence, Hazard ratios (95% CI)
Three year period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness of direct-acting antivirals for HCV
Time Frame: Three year period
Achievement of RVS
Three year period
Adverse events after direct-acting antivirals for HCV
Time Frame: Three year period
Safety
Three year period

Collaborators and Investigators

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

Sponsor

Austral University, Argentina

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 (Actual)

May 1, 2016

Primary Completion (Anticipated)

December 1, 2020

Study Completion (Anticipated)

January 1, 2021

Study Registration Dates

First Submitted

December 12, 2018

First Submitted That Met QC Criteria

December 12, 2018

First Posted (Actual)

December 14, 2018

Study Record Updates

Last Update Posted (Actual)

December 19, 2018

Last Update Submitted That Met QC Criteria

December 14, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-062

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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