HEPATHER: trial | Bending the Curve: Trial by Trial

HEPATHER

Therapeutic Option for Hepatitis B and C: a French Cohort (ANRS CO22 Hepather)

Phase observationalN = 9,895NCT01953458

Population

Adults with chronic HCV infection enrolled from 32 French centres; patients with chronic hepatitis B, previous decompensated cirrhosis, hepatocellular carcinoma or liver transplantation, or treatment with interferon-ribavirin regimens were excluded.

Design

Prospective cohort from 32 expert hepatology centres in France (ClinicalTrials.gov NCT01953458, observational; registry enrolment 20,902, whereas the paper analysed 9895 of 10,166 eligible patients enrolled 6 August 2012 to 31 December 2015). DAA exposure was analysed as a time-dependent variable in Cox models. Observational: arm roles label treated versus untreated, not randomised assignment.

Primary endpoint

All-cause mortality, Incidence of hepatocellular carcinoma, Incidence of decompensated cirrhosis

Arms

DAA initiated (experimental, n = 7,344): Direct-acting antiviral treatment initiated during follow-up
Untreated (control, n = 2,551): No direct-acting antiviral treatment at the final follow-up visit

People

Carrat F, ANRS CO22 Hepather

Incidence of hepatocellular carcinomaHR 0.66 (95% CI 0.46–0.93)All-cause mortalityHR 0.48 (95% CI 0.33–0.70)Incidence of decompensated cirrhosisHR 1.14 (95% CI 0.57–2.27)

Show the numbers

Results reported for HEPATHER
Endpoint	Analysis	DAA initiated	Untreated	Effect
Incidence of hepatocellular carcinoma9895 patients with follow-up information (97% of 10,166 eligible)Hepatocellular carcinoma reported during follow-up, DAA exposure as time-dependent covariate; hazard ratio adjusted for the variables listed in the paper.	primarymedian follow-up 33.4 monthsCarrat 2019	—	—	HR 0.66 (95% CI 0.46–0.93)Unadjusted hazard ratio 2.77 (95% CI 2.07-3.71). 258 patients reported hepatocellular carcinoma (187 treated, 71 untreated). Adjusted for age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive status, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables and MELD score in patients with cirrhosis.
All-cause mortality9895 patients with follow-up information (97% of 10,166 eligible)	primarymedian follow-up 33.4 monthsCarrat 2019	—	—	HR 0.48 (95% CI 0.33–0.70)Adjusted hazard ratio. 218 patients died (129 treated, 89 untreated).
Incidence of decompensated cirrhosis9895 patients with follow-up information (97% of 10,166 eligible)	primarymedian follow-up 33.4 monthsCarrat 2019	—	—	HR 1.14 (95% CI 0.57–2.27)Adjusted hazard ratio, not associated with DAA exposure. Unadjusted hazard ratio 3.83 (95% CI 2.29-6.42). 106 patients had decompensated cirrhosis (74 treated, 32 untreated).

Results reported for HEPATHER
Endpoint	Analysis	DAA initiated	Untreated	Effect
Incidence of hepatocellular carcinoma9895 patients with follow-up information (97% of 10,166 eligible)Hepatocellular carcinoma reported during follow-up, DAA exposure as time-dependent covariate; hazard ratio adjusted for the variables listed in the paper.	primarymedian follow-up 33.4 monthsCarrat 2019	—	—	HR 0.66 (95% CI 0.46–0.93)Unadjusted hazard ratio 2.77 (95% CI 2.07-3.71). 258 patients reported hepatocellular carcinoma (187 treated, 71 untreated). Adjusted for age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive status, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables and MELD score in patients with cirrhosis.
All-cause mortality9895 patients with follow-up information (97% of 10,166 eligible)	primarymedian follow-up 33.4 monthsCarrat 2019	—	—	HR 0.48 (95% CI 0.33–0.70)Adjusted hazard ratio. 218 patients died (129 treated, 89 untreated).
Incidence of decompensated cirrhosis9895 patients with follow-up information (97% of 10,166 eligible)	primarymedian follow-up 33.4 monthsCarrat 2019	—	—	HR 1.14 (95% CI 0.57–2.27)Adjusted hazard ratio, not associated with DAA exposure. Unadjusted hazard ratio 3.83 (95% CI 2.29-6.42). 106 patients had decompensated cirrhosis (74 treated, 32 untreated).

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
Incidence of hepatocellular carcinoma	0.66	0.46–0.93
All-cause mortality	0.48	0.33–0.7
Incidence of decompensated cirrhosis	1.14	0.57–2.27

Appears in

2012 Hepatitis C clearance and HCC: interferon-era SVR, then DAA debate

Sources

Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet. 2019;393(10179):1453-1464.
PubMed DOI