HEPATHER cohort: therapeutic options in the treatment of hepatitis B and C

HEPATHER: 12 years of research into hepatitis B and C

The ANRS CO22 HEPATHER cohort, entitled ‘Therapeutic options in the course of hepatitis B and C: a French national cohort’, is a large-scale cohort which began in August 2012, with the aim of improving knowledge of hepatitis B and C and their management.

It included 20,857 patients in 38 centres in France and Belgium, 40.7% of whom were women and 59.3% men:

• 6,192 patients mono-infected with hepatitis B virus (HBV),
• 14,575 patients mono-infected with hepatitis C virus (HCV),
• 90 patients co-infected with HBV/HCV.

Inclusions closed on 30 April 2019, and follow-up varied between 4 and 12 years depending on the participants. All visits were completed by 31 December 2024, the end date for clinical and biological data collection.

Analyses are still ongoing (completion of analyses expected by 31/12/2028) and new scientific publications are forthcoming. Since the start of the study, HEPATHER has made a major contribution to research, with 70 conference presentations and 59 scientific publications.

In particular, it has produced major results on the clinical efficacy and safety of direct-acting antivirals (DAAs) in the treatment of hepatitis C. These results have led to changes in national recommendations for patient management. As a result, monitoring of hepatitis C patients is now complete, given the efficacy of current treatments.

What makes the HEPATHER cohort unique

The HEPATHER cohort, launched in 2012, is one of the largest of its kind in France.. But apart from its size, what made it original was the inclusion of infected patients regardless of the treatment they were receiving or were about to receive. “Other cohorts at the time were essentially therapeutic, focusing on patients at the time they started a new treatment. In HEPATHER, we wanted to follow patients throughout their course of treatment, including those who were not yet being treated. This non-interventional approach was more representative of real life,” adds Pr Fabrice Carrat.

SNDS linkage and data enrichment

The HEPATHER cohort was also one of the first studies to link specific cohort data with data from the French national health data system, enabling the identification of side-effects by cross-referencing data.

HEPATHER cohort: what’s next?

The study is continuing for patients with hepatitis B, thanks to a new cohort project funded by the ANRS Emerging infectious diseases, the ANRS 0551s HEPAT-B project. This is a new national cohort dedicated to HBV, with a specific 4-year follow-up and an expected start of enrolment in September 2025.

HEPAT-B follows on from the HEPATER cohort, focusing on patients with hepatitis B. The follow-up of the 5,000 to 6,000 patients already included in HEPATHER will be extended, by collecting new clinical and biological data. The aim is to document the effectiveness of current and future treatments for hepatitis B, and also to identify early biomarkers of complications such as liver cancer.

Publications

• 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. PMID: 30765123.

In 2024:

• Abbas M, Cormier P, Marcellin F, Bourlière M, Penaranda L, Carrat F, et al. Minimal clinically important differences in health-related quality of life after treatment with direct-acting antivirals for chronic hepatitis C: ANRS CO22 HEPATHER cohort (PROQOL-HCV). Qual Life Res. 2024.
• Barré T, Bourlière M, Parlati L, Ramier C, Marcellin F, Protopopescu C, et al. Hepatitis C virus cure from direct-acting antivirals and mortality: Are people with and without a history of injection drug use in the same boat? (ANRS CO22 Hepather cohort). Drug Alcohol Rev. 2024.
• Barré T, Parlati L, Bourlière M, Ramier C, Marcellin F, Protopopescu C, et al. Socioeconomic deprivation weighs heavily on liver fibrosis and mortality after hepatitis C cure (ANRS CO22 Hepather). J Viral Hepat. 2024.
• Nahon P, Lusivika-Nzinga C, Merle P, Zoulim F, Decaens T, Ganne-Carrié N, et al. Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis. J Hepatol. 2025 Feb 26;S0168-8278(25)00084-4. doi:10.1016/j.jhep.2025.

You can find news about the HEPATHER cohort on its dedicated website or search for it in the directory on the France Cohortes website.

Funding and promotion of the HEPATHER cohort

The ANRS CO22 HEPATHER cohort is financed and promoted by Inserm-ANRS MIE, in collaboration with AFEF; with an institutional partnership (ANR via France 2030 ‘Programmes d’investissements d’avenir’) and industrial partnership (MSD, Janssen, Gilead, BMS, Roche, Abbvie). It has received financial support as part of the Equipements d’Excellence programme, wave 2 – 2011, and a public-private partnership in collaboration with Inserm Transfert.