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

NCT ID: NCT03775798

Last Updated: 2018-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

2200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-05-01

Study Completion Date

2021-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hepatitis C Cirrhosis Antiviral Drug Adverse Reaction

Keywords

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direct acting antivirals hepatitis c hepatocellular carcinoma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Direct antiviral agents for hepatitis C

Direct-acting antivirals for hepatitis C

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Austral University, Argentina

OTHER

Sponsor Role lead

Responsible Party

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Maria Julia Cremona

UIC staff

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Universidad Austral

Pilar, Buenos Aires, Argentina

Site Status RECRUITING

Countries

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Argentina

Central Contacts

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Maria Julia Cremona

Role: CONTACT

Email: [email protected]

Marcelo Silva, MD

Role: CONTACT

Email: [email protected]

Facility Contacts

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Marcelo Silva, MD

Role: primary

Federico Piñero, MD, MSCE

Role: backup

References

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Braillon A. Achieving Virological Response in Patients With Hepatitis C Is Only Half Way for Effective Care. Clin Gastroenterol Hepatol. 2021 Mar;19(3):622-623. doi: 10.1016/j.cgh.2020.04.086. Epub 2020 Nov 26. No abstract available.

Reference Type DERIVED
PMID: 33248099 (View on PubMed)

Ridruejo E, Pinero F, Mendizabal M, Cheinquer H, Wolff FH, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Zuain MGV, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernandez N, Perez D, Hernandez N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varon A, Silva M; Latin American Liver Research Educational and Awareness Network (LALREAN). Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort. J Med Virol. 2020 Dec;92(12):3545-3555. doi: 10.1002/jmv.26383. Epub 2020 Aug 13.

Reference Type DERIVED
PMID: 32749710 (View on PubMed)

Mendizabal M, Pinero F, Ridruejo E, Herz Wolff F, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Videla Zuain MG, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernandez N, Perez D, Hernandez N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varon A, Rubinstein F, Cheinquer H, Silva M; Latin American Liver Research; Educational and Awareness Network (LALREAN). Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2554-2563.e3. doi: 10.1016/j.cgh.2020.02.044. Epub 2020 Feb 28.

Reference Type DERIVED
PMID: 32113892 (View on PubMed)

Other Identifiers

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17-062

Identifier Type: -

Identifier Source: org_study_id