study about simvastatin in portal hypertension in compensated cirrhosis

Conditions: Portal Hypertension.; Liver Cirrhosis

Summary: the purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.

decompensation of cirrhosis is associated with a dramatic reduction of survival. progression of portal hypertension (pht) is the main determinant of decompensation that appears when portal pressure gradient (ppg) is ≥10mmhg (clinically significant htp). 40% of compensated cirrhotic patients have mild pht. however, with progression of disease 41% develop clinically significant pht. in cirrhosis, pht results from increased resistance to blood flow, with a dynamic component due to decreased nitric oxide (no) bioavailability. in advanced disease increased portal venous inflow also contributes to pht. beta-blockers have not been useful in compensated cirrhosis with mild pht. in early cirrhosis, vasodilators may be more adequate. statins, drugs that inhibit the activity of hmg-coa reductase, induce selective hepatic vasodilation due to an enhanced bioavailability of no. acutely, they decreases hepatic resistance, while with long-term use statins decreases ppg without deleterious effects on systemic circulation. this multicenter, randomized, double-blind placebo-controlled study is aimed at assessing whether treatment with simvastatin may prevent progression of mild pht (with ppg between 6 and 10 mmhg) to clinically significant pht. patients with compensated cirrhosis, without previous decompensation, without esophageal varices at risk and with ppg between 6 and 10 mmhg will be included. the calculated sample size is 80 patients and the duration of the study 4 years (2 years including and a follow-up of at least 2 year).

Eligibility criteria:
inclusion criteria: * liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound * portal hypertension gradient between6 mmhg and10 mmhg * absence of esophageal and gastric varices or small esophageal varices without red signs * absence previous episodes of gastrointestinal hemorrhage, ascites, encephalopathy or jaundice * written informed consent exclusion criteria: * age \ 80 years, * presence or history of ascites, clinical or ultrasound, * previous decompensation of liver cirrhosis, ascites or sbp, bleeding varices, large varices, hepatic encephalopathy, jaundice, * thrombosis splenoportal, * hepatocellular carcinoma; * child-pugh \>7 point * any comorbidity that leads to a restriction therapy and / or a life expectancy \<12 months * absolute contraindication to treatment with statins or allergy simvastatin; * concomitant potent cyp3a4 inhibitors (eg., itraconazole, ketoconazole, protease inhibitors, hiv, erythromycin, clarithromycin, telithromycin and nefazodone), * pretreatment (\<1 month) with simvastatin or other lipid-lowering, * previous episodes of rhabdomyolysis, * active alcoholic hepatitis, * refusal to participate in the study or the informed consent claim; * pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic derivations; * pregnancy and lactation.