Clinical trial NCT01953458: Therapeutic Option for Hepatitis B and C: a French Cohort
Official title: Therapeutic Option for Hepatitis B and C: a French Cohort
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Viral Hepatitis B
Viral Hepatitis C
Keywords: Hepatitis B and C
ANRS HEPATHER French Cohort
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Bristol-Myers Squibb
name: Gilead Sciences
name: Janssen-Cilag Ltd.
name: Merck Sharp & Dohme LLC
name: Roche Pharma AG
First posted: 2013-10-01
Enrollment: 20902
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HBV-positive patients and/or HCV-positive patients

Brief summary: * The cohort will integrate clinical, genetic, pharmacogenomics, environmental, biomarkers and behavioral data in a large number of patients and will be a leading equipment for crossdisciplinary and translational research on hepatitis.
* The cohort will be the main support for estimating the relative effects of treatments and for further cost-effectiveness studies on the management and treatment options in chronic HCV (Hepatitis C Virus)and HBV (Hepatitis B virus)infections.

Detailed description: General schedule of the study :

* Prospective multicenter national study
* Duration of inclusions:3 years
* Effective : 25000 patients
* Duration of the follow-up: 7-8 years
* Duration of the cohort: 10 years

Population :

Twenty-five thousands of people will be included and followed in investigator sites, 15000 with an hepatitis C and 10000 with an hepatitis B, according their usual follow-up of their liver disease.

We aim to include up to 50% patients naive of any HCV treatment at inclusion. Also HBV "cured" patients could be included (less than 10%).

Design study:

* During the recruitment visit, demographics, clinical, biological and virological data will be collected. The patient will move through several assessments involving questionnaires, measurements and blood sampling.
* Then the minimum follow-up is one medical visit per year. The follow-up (clinical data and biological collections) will be driven by events or based on protocols that will be developed on the cohort.
* There is no specific treatment in this cohort.

The scientific project is structured into 4 scientific thematic axes :

* Therapeutics:

  * To analyze the long term effects of therapy
  * To study predictors of virological response or fibrosis progression (or regression)and pharmacokinetic/pharmacodynamics either in HCV or HBV treatments
* Virology:

  * To understand the molecular mechanisms of antiviral treatment success and failure
  * To provide treatment recommendation to prevent resistance and achieve sustained or definitive control of infection
* Pathology and physiopathology :

  * To identify new pathophysiological targets responsible for chronic hepatitis severity,prognosis, and evolution.
  * To validate new therapeutic combinations based on pathophysiological researches
* Public Health:

  * To identify psychosocial and behavioral correlates of access to care, progression of liver disease and of the burden of chronic viral hepatitis B and C.
  * To evaluate the cost-effectiveness of HBV and HCV treatments and quality of life

Eligibility criteria: Inclusion Criteria:

* HBV-positive patients

  * Chronic hepatitis B defined by a positive HBsAg ( surface antigen of the hepatitis B virus) for at least 6 months
  * Acute hepatitis B defined as a recent appearance (\<6 months) of detectable HBs Ag,
  * Chronic hepatitis B with serological remission HbsAg-negative , HB DNA-negative,
  * With or without association with acute or chronic hepatitis D.
* HCV-positive patients

  * Chronic hepatitis C defined by the positivity for anti-HCV antibodies for at least 6 months and positive HCV-RNA
  * Acute hepatitis C defined by the recent appearance of HCV RNA (less than 6 months) in patients with risk factors (with or without positive antibodies)
  * Patients with cured hepatitis C defined by long-term eradication, either spontaneous, a positive anti-HCV antibodies associated to a negative RNA at two collection - 6 months interval time; either treatment defined by negative viremia 3 month after end of treatment.

Exclusion Criteria:

* HIV co-infected patients are not eligible to the cohort.
* So-called vulnerable populations (minors, people under guardianship or protection, or a private individual under protection from making legal or administrative decisions)
* Treatment ongoing hepatitis C during or stopped since less than 3 months
* Patients end of life
* Woman whose pregnancy is known

Primary outcomes:
measure: There is no specific primary outcome measure but we indicated below (see Description) a list of potential outcome measures according to the objectives.
timeFrame: From recruitment to the end of the cohort, with a minimum of one medical visit per year (the duration of follow-up is 7-8 years)
Secondary outcomes:
Other outcomes:
Locations:
city: Multiple Locations
country: France
Study officials:
affiliation: Hôpital Cochin, PARIS
name: Stanislas POL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sotty J, Bablon P, Lekbaby B, Augustin J, Girier-Dufournier M, Langlois L, Dorival C, Carrat F, Pol S, Fontaine H, Sarica N, Neuveut C, Housset C, Kremdsorf D, Schnuriger A, Soussan P. Diversity of the nucleic acid forms of circulating HBV in chronically infected patients and its impact on viral cycle. Hepatol Int. 2022 Dec;16(6):1259-1272. doi: 10.1007/s12072-022-10389-6. Epub 2022 Aug 4.
citation: Barre T, Carrat F, Ramier C, Fontaine H, Di Beo V, Bureau M, Dorival C, Larrey D, Delarocque-Astagneau E, Mathurin P, Marcellin F, Petrov-Sanchez V, Cagnot C, Carrieri P, Pol S, Protopopescu C; ANRS/AFEF Hepather study group. Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort. J Cannabis Res. 2022 Jun 11;4(1):31. doi: 10.1186/s42238-022-00138-9.
citation: Pageaux GP, Nzinga CL, Ganne N, Samuel D, Dorival C, Zoulim F, Cagnot C, Decaens T, Thabut D, Asselah T, Mathurin P, Habersetzer F, Bronowicki JP, Guyader D, Rosa I, Leroy V, Chazouilleres O, de Ledinghen V, Bourliere M, Causse X, Cales P, Metivier S, Loustaud-Ratti V, Riachi G, Alric L, Gelu-Simeon M, Minello A, Gournay J, Geist C, Tran A, Abergel A, Portal I, d'Alteroche L, Raffi F, Fontaine H, Carrat F, Pol S; French ANRS CO22 Hepather Cohort. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis. BMC Infect Dis. 2022 Jan 27;22(1):94. doi: 10.1186/s12879-022-07076-0.
citation: Poynard T, Lacombe JM, Deckmyn O, Peta V, Akhavan S, de Ledinghen V, Zoulim F, Samuel D, Mathurin P, Ratziu V, Thabut D, Housset C, Fontaine H, Pol S, Carrat F. External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV. JHEP Rep. 2021 Apr 24;3(4):100298. doi: 10.1016/j.jhepr.2021.100298. eCollection 2021 Aug.
citation: Barre T, Ramier C, Di Beo V, Carrat F, Fontaine H, Marcellin F, Carrieri P, Pol S, Protopopescu C; ANRS/AFEF Hepather study group. Liver fibrosis and all-cause mortality in chronic HCV-infected diabetic patients: A paradoxical association? (ANRS CO22 HEPATHER). Liver Int. 2021 Jul;41(7):1694-1698. doi: 10.1111/liv.14949. Epub 2021 May 28. No abstract available.
citation: Chalouni M, Pol S, Sogni P, Fontaine H, Lacombe K, Marc-Lacombe J, Esterle L, Dorival C, Bourliere M, Bani-Sadr F, de Ledinghen V, Zucman D, Larrey D, Salmon D, Carrat F, Wittkop L; ANRS CO13 HEPAVIH and ANRS CO22 HEPATHER cohort study groups. Increased mortality in HIV/HCV-coinfected compared to HCV-monoinfected patients in the DAA era due to non-liver-related death. J Hepatol. 2021 Jan;74(1):37-47. doi: 10.1016/j.jhep.2020.08.008. Epub 2020 Aug 14.
citation: Laurain A, Metivier S, Haour G, Larrey D, Dorival C, Hezode C, Zoulim F, Marcellin P, Bourliere M, Zarski JP, Thabut D, Alric L, Ganne-Carrie N, Cales P, Bronowicki JP, Riachi G, Geist C, Causse X, Abergel A, Chazouilleres O, Mathurin P, Guyader D, Samuel D, Tran A, Loustaud-Ratti V, Petrov-Sanchez V, Diallo A, Luzivika-Nzinga C, Fontaine H, Carrat F, Pol S; ANRS/AFEF HEPATHER study group. Safety and efficacy of the combination simeprevir-sofosbuvir in HCV genotype 1- and 4-mono-infected patients from the French ANRS CO22 hepather cohort. BMC Infect Dis. 2019 Apr 2;19(1):300. doi: 10.1186/s12879-019-3923-5.
citation: Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, De Ledinghen V, Larrey D, Haour G, Bronowicki JP, Zoulim F, Asselah T, Marcellin P, Thabut D, Leroy V, Tran A, Habersetzer F, Samuel D, Guyader D, Chazouilleres O, Mathurin P, Metivier S, Alric L, Riachi G, Gournay J, Abergel A, Cales P, Ganne N, Loustaud-Ratti V, D'Alteroche L, Causse X, Geist C, Minello A, Rosa I, Gelu-Simeon M, Portal I, Raffi F, Bourliere M, Pol S; French ANRS CO22 Hepather cohort. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet. 2019 Apr 6;393(10179):1453-1464. doi: 10.1016/S0140-6736(18)32111-1. Epub 2019 Feb 11.
citation: Pol S, Bourliere M, Lucier S, Hezode C, Dorival C, Larrey D, Bronowicki JP, Ledinghen VD, Zoulim F, Tran A, Metivier S, Zarski JP, Samuel D, Guyader D, Marcellin P, Minello A, Alric L, Thabut D, Chazouilleres O, Riachi G, Bourcier V, Mathurin P, Loustaud-Ratti V, D'Alteroche L, Fouchard-Hubert I, Habersetzer F, Causse X, Geist C, Rosa I, Gournay J, Saillard E, Billaud E, Petrov-Sanchez V, Diallo A, Fontaine H, Carrat F; ANRS/AFEF HEPATHER study group. Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients. J Hepatol. 2017 Jan;66(1):39-47. doi: 10.1016/j.jhep.2016.08.021. Epub 2016 Sep 10.