Effect of Long-term Carvedilol to Prevent Decompensation or Death in Patients With Asymptomatic Child-Pugh A5 to B8 Cirrhosis and Clinically Significant Portal Hypertension: a Multicenter Double-blind Randomized Control Trial

Inclusion Criteria: * Male or female≥ 18 years of age * Cirrhosis related to hepatitis C or hepatitis B virus without viral replication for at least 2 years. Or Cirrhosis related to alcohol consumption (active or abstinent) Or Cirrhosis related to metabolic syndrome or cryptogenic with BMI \< 30 kg/m2 * 2 TE-LSM (Fibroscan®) performed in fasting conditions, using either the M or the XL probe \>=25 kPa, within 12 months before inclusion * Absence of medium or large varices or small varices with red signs at endoscopy within 3 months before inclusion * Child-Pugh A5 to B8 * Affiliation to a French social security system. * Written informed consent obtained from the participant or participant's legal representative * For child-bearing aged women, contraception using oral contraceptive, or intrauterine device or mechanical contraception Exclusion Criteria: * History of overt ascites or encephalopathy \<12 months before inclusion * Treatment with either diuretics or lactulose or rifaximin \<3 months before inclusion * Any history of portal hypertension related bleeding * Baseline heart rate \<65/min or systolic blood pressure \<100 mm Hg * Previous transjugular intrahepatic portosystemic shunt (TIPSS) or liver transplantation * Previous history or active hepatocellular carcinoma * Glomerular filtration rate (CKD-Epi) \< 30 mL/min * Strict indication to selective or nonselective beta-blockers: history of acute myocardial infarction, congestive heart failure * Strict contraindication to selective or nonselective beta-blockers: * decompensated congestive heart failure * grade 2 or 3 atrioventricular block * sinus node dysfunction without pacemaker * severe asthma according to WHO classification \[63\] * severe Chronic Obstructive Pulmonary Disease, defined stage 3 or 4 of the GOLD classification, i.e.FEV1\<50% of the predicted value (https://goldcopd.org/) * severe Raynaud disease, defined as repetitive episodes of biphasic colour (at least two) of pallor, cyanosis, erythema, in addition to paresthesia or numbness, occurring in both cold and normal environments \[64\]. * Known hypersensitivity to carvedilol * Concomitant use of Cimétidin * Concomitant use of class I antiarythmic agents (except lidocaïn) (i.e.cibenzoline, disopyramide, flécaïnide, hydroquinidine méxilétine, propafenone, quinidine) * Concomitant use of calcium antagonists: diltiazem, vérapamil and bépridil * Concomitant use of clonidine, méthyldopa, guanfacine, moxonidine, rilménidine * Concomitant use of fingolimod * Concomitant use of potent inhibitors (e.g. ketoconazole, HIV protease inhibitors) or inductors (e.g. rifampin, carbamazepine, phenytoin) of CYP3A4 (see appendix 7) * Pregnancy or breastfeeding * Non ability for participant to comply with the requirements of the study * Life expectancy \<12 months