5-metil-tetraidrofolato nel trattamento dell'ipertensione portale in pazienti con cirrosi e in profilassi farmacologica con beta-bloccanti per il rischio di sanguinamento da varici esofagee: trial randomizzato in doppio cieco controllato con placebo

Introduction: Cirrhosis is frequently complicated by the increase of portal pressure and development of esophageal varices, ascites and upper gastrointestinal bleeding. The mechanism of action of β-blockers in reducing the value of HVPG depends on a decreased portal inflow, secondary to the reduction of the index and to splanchnic vasoconstriction. Unfortunately, intrahepatic vascular resistance is poorly influenced by the action of beta-blockers. 5-methyltetrahydrofolate (5-MTHF) can improve vascular function through its action on eNOS and vascular oxidative stress Currently it is not known whether 5-MTHF may have the same effect on liver microcirculation. Objectives: to evaluate the efficacy of 3 months treatment with 5-MTHF in combination with propranolol compared to propranolol + placebo in terms of reduction of HVPG in cirrhotic patients with portal hypertension (PI). Secondary objectives are: a) to evaluate the tolerability of 5-MTHF in cirrhotic patients with PI; b) to evaluate if there is an improvement in the intrahepatic vascular tone mediated by the decrease of oxidative stress because of greater bioavailability of NO in patients with cirrhosis and PI. Results: in both groups there was a reduction in the HVPG value compared to baseline, but the change was significantly higher in the 5-MTHF group compared to the placebo group (20.8%, SD 15.4 in the 5-MTHF vs 9.2%, SD 21.3 in the placebo group, p=0.033). A similar reduction was noted for the value of elastometry measured with FibroScan® (21.8%, SD 34.7 in the 5-MTHF group vs. 4.4%, SD 32.5 in the placebo group, p = 0.064). Discussion: the comparison analysis between the treatment group and the placebo group shows a statistically significant difference in terms of reduction of porto-systemic pressure gradient. Further multi-center studies on larger cohorts are desirable to validate the use of 5-MTHF + placebo in reducing the portal pressure value measured with HVPG