National Cohort of Uncomplicated Alcoholic Cirrhosis
National Cohort of Uncomplicated Alcoholic Cirrhosis
Hepatocellular carcinoma (HCC) is a major public health problem, whose incidence is
 increasing in developed countries and is the leading cause of death in patients with
 cirrhosis. The diagnosis and the early management are key issues that could improve the
 prognosis. In France, alcoholic cirrhosis is the leading cause of HCC, while the aetiology of
 underlying chronic liver disease is mainly hepatitis C (HCV) in Southern Europe and Japan,
 and hepatitis B (HBV) in Asia and Africa. In the next years, due to the improved results of
 anti-viral therapies, this trend should be reinforced with a decreasing proportion of HCC
 related to viral cirrhosis and an increasing proportion of HCC related to alcoholic
 cirrhosis. However, natural history of alcoholic cirrhosis remains poorly understood, most
 studies being retrospective and including a small number of patients. This project is filed
 by the consortium CIRRAL including French Academic hospitals centers currently involved and
 referees in the field of alcoholic liver disease and HCC (8 at the moment, and more in the
 next months). It is a national multicenter prospective study that will include 1200 patients
 with alcoholic cirrhosis histologically proven over 3 years. The main goal of this cohort is
 to describe the natural history of a large number of patients with alcoholic cirrhosis
 prospectively followed, and to identify predictors of the occurrence of HCC.
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.).
Inclusion Criteria:

 -  age ≥ 18 years

 -  histologically proven cirrhosis

 -  no previous HCC (treated or not )

 -  excessive consumption of alcohol, considered as the main cause of cirrhosis

 -  signed informed consent.

 Exclusion Criteria:

 -  serious associated short-term life threatening disease (except associated HIV viral
 infection and the liver disease itself),

 -  decompensation of cirrhosis (bleeding or ascites),

 -  co-infection with HBV or HCV;

 -  liver focal lesion suggestive of HCC

 -  Child Pugh score ≥ 7 (Class B or C).

 -  patient under guardianship

 -  pregnant women

 -  inability to regular monitoring, for whatever reason