Study About Simvastatin in Portal Hypertension in Compensated Cirrhosis
Study About Simvastatin in Portal Hypertension in Compensated Cirrhosis
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).
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 <18 and> 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.