Trial Information

CIRRAL: Hepatocellular Carcinoma in Patients With Uncomplicated Alcoholic Cirrhosis: Incidence and Predictive Factors. A Multicentric Prospective Cohort

Patients will be selected for the study if they met all the inclusion criteria, without any
of the non-inclusion criteria, ie compensated Child Pugh A alcoholic cirrhosis without viral
chronic hepatitis B or C, and without any detectable HCC. They will be offered, during a
consultation as part of their usual care, to participate in the study. An information note
will be issued. Patients agreeing to participate should date and sign informed consent.
Usual biological tests and liver ultrasonography will be performed if not done within 90
days prior to inclusion. During this visit, 20 ml of blood will be collected for freezing
and storage of serum and plasma, and constitution of a DNA library.

From the reviews conducted at baseline, patients with at least one exclusion criteria (ie
decompensation of cirrhosis, Child Pugh score ≥ 7, co-infection with HBV or HCV, or liver
focal lesion suggestive of HCC will be excluded (and their serum samples achieved for the
BioBank will be destroyed):

Monitoring: According to current guidelines, patients will have periodical surveillance with
liver ultrasonography and medical consultation at least every 6 months, blood tests at least
every year, periodic assessment of esophageal and gastric varices (every 1 to 3 years) and
prevention of their rupture if any. An additional blood sampling of 20 ml will be taken at
baseline and every year in order to perform serum, plasma, and DNA libraries; Data will be
standardized and centralized in a single database.

Statistical Analysis: Methods for censored data with competitive risks. Number of subjects
to include: The planned number is 1200 subjects included in 3 years. Assuming a minimal
annual incidence of HCC about 2% in patients with alcoholic cirrhosis, and a proportion of
lost to follow-up of around 20% in this poorly compliant population, a sample of 3000
patients could demonstrate the existence of predictive factors for the occurrence of HCC
associated with a relative risk at least equal to 2, with a power of 90%. However, the
enrollment of 3000 patients recruited in three years is not a realistic goal. For practical
reasons and since the data currently available are very limited regarding the precise
incidence of HCC and the strength of association between risk factors and HCC in patients
with alcoholic cirrhosis, the minimum number of patients included in the cohort CIRRAL was
set at 1200. Regarding an expected percentage of patients lost to follow close to 20%, the
final number of patients with sufficient follow-up will be 1000.

Expected results

1. description of the incidence of HCC occurrence in patients with alcoholic cirrhosis;

2. identification of predictive factors for the occurrence of HCC c) identification of
prognostic factors for survival. In addition, nested scientific projects will use the
database and collected samples of this prospective cohort, thus constituting
significant savings of resources. However, these nested scientific projects should
include a specific need of organization and financing clean, and may involve only a
fraction of the population included. The areas involved are very varied (immunology,
genetics, imaging, evaluation of fibrosis, biostatistics, , quality of life, economy,
etc.).