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

NCT03775798 | Unknown DMC FDA Drug

• 1 other identifier: 17-062
• Study Type: observational
• Target: 2,200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis C; Cirrhosis; Antiviral Drug Adverse Reaction

Keywords

direct acting antivirals; hepatitis c; hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV

  Cumulative incidence, Hazard ratios (95% CI)

  Three year period

Secondary Outcomes (2)

• Effectiveness of direct-acting antivirals for HCV

  Three year period

• Adverse events after direct-acting antivirals for HCV

  Three year period

Interventions

Direct antiviral agents for hepatitis C DRUG

Direct-acting antivirals for hepatitis C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Austral University, Argentina: lead

Study Sites (1)

Universidad Austral

Pilar, Buenos Aires, 1629, Argentina

RECRUITING

Related Publications (3)

• 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.

  PMID: 33248099 DERIVED

• 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.

  PMID: 32749710 DERIVED

• 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.

  PMID: 32113892 DERIVED

MeSH Terms

Conditions

Hepatitis C; Fibrosis; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Central Study Contacts

Maria Julia Cremona

CONTACT

MCREMONA@austral.edu.ar

Marcelo Silva, MD

CONTACT

msilva@cas.austral.edu.ar

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: UIC staff

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 14, 2018
• Study Start: May 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: January 1, 2021
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

AR (1)