Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension

Inclusion Criteria: * \- Age ≥ 18 years * Written informed consent to participate in the study * Medical insurance coverage * For child-bearing aged women, contraception using oestroprogestative, progestative, intrauterine device, or mechanical contraception * Diagnosis of cirrhosis based on a liver biopsy, or on clinical, biological, endoscopic, and radiological evidence * Active cause of cirrhosis, or resolution (alcohol cessation, sustained virological response to direct-acting antiviral treatment for HCV, initiation of nucleoside/nucleotide analog treatment for HBV) for at least 6 months * Child-Pugh A or B * High likelihood of HVPG ≥ 12 mm Hg based on investigator's judgement, or on the following criteria: 1. Investigator's judgement 2. active cause of cirrhosis and: * History of clinical ascites * Or history of variceal bleeding * Or liver stiffness by VCTE ≥ 35 kPa on carvedilol in the last two years * or spleen stiffness by VCTE ≥ 55 kPa on carvedilol in the last two years * or liver surface nodularity ≥ 2,9 in the last two years * or HVPG \&gt; 16 mm Hg prior to starting NSBB * or Laennec 4c cirrhosis on histology 3. or resolution of the cause of cirrhosis for at least 6 months and: * history of clinical ascites in the last 6 months * or history of variceal bleeding in the last 6 months * or liver stiffness by VCTE ≥ 35 kPa on carvedilol in the last 6 months * or spleen stiffness by VCTE ≥ 55 kPa on carvedilol in the last 6 months * or liver surface nodularity ≥ 2,9 in the last 12 months * or Laennec 4c cirrhosis on histology in the last 12 months * Treatment with carvedilol (≥ 6,25 mg/day) at a stable dose for at least one month * Absence of hepatocellular carcinoma outside at least one nodule \&gt; 3 cm in diameter, or more than 3 nodules, on ultrasound, CT-scan or MRI performed during the previous 6 months Exclusion Criteria: * Serum total bilirubin \> 50 µmol/L * Prothrombin ratio \< 50 % * Transaminases \> 5 ULN * Need for at least one paracentesis for ascites fluid evacuation in the last 6 months * Expected follow-up \< 3 months * Known hypersensitivity to the active substance or any of the excipients * History of lactic acidosis, diabetic acidocetosis, or diabetic precoma * Ongoing condition that may lead to acute kidney injury or hypoxia: dehydration, severe infection, shock, cardiac decompensation, respiratory failure, or myocardial infarction within the past month * Known hypersensitivity to all the iodin-containing contrast agents * Known hypersensitivity to lidocaine for local anesthesia * Known hypersensitivity to beta-lactam antibiotics if the patient has a history of valve replacement * Alcohol consumption \> 14 units/week for women or \> 21 units/week for men, current or abstinent for less than 6 months * Biliary cirrhosis * Hepatocellular carcinoma with at least one nodule \> 3 cm in diameter, or more than 3 nodules * Cholangiocarcinoma * Extra-hepatic cancer without remission * Severe chronic kidney disease defined as estimated glomerular filtration rate \< 30 mL/min/1,73m2 using the MDRD-6 formula * Ongoing treatment with metformin, or discontinued for less than 3 months * Treatment with statins started or discontinued for less than 3 months * Treatment with nucleoside/nucleotide analogue for HBV, or direct-acting antiviral treatment for HCV, started for less than 6 months * Complete portal vein thrombosis (main portal trunk, or right branch), or portal cavernoma * History of TIPS (transjugular intrahepatic portosystemic shunt) / surgical portosystemic derivation / liver transplantation / major hepatectomy * Ongoing participation in another interventional therapeutic trial * Pregnant or breastfeeding women * Patients unable to give consent (under guardianship or curatorship) * Non-randomisation criteria: HVPG \< 12 mm Hg at the catheterism performed during the first follow-up visit