Evaluation of portal pressure by doppler ultrasound in patients with cirrhosis before and after simvastatin administration – a randomized controlled trial

Abstract

Background: Portal hypertension is one of the most frequent complications of cirrhosis. β-adrenergic blockers, with or without organic nitrates, are currently used as hypotensive agents. Statins such as simvastatin seem to be safe for patients with chronic liver diseases and exert multiple pleiotropic actions. This study aimed to assess PTH using Doppler ultrasound in patients with cirrhosis before and after simvastatin administration. Methods: This randomized controlled clinical trial was conducted on 40 patients with cirrhosis who were randomized into 2 groups: group I included 20 patients with cirrhosis who were administered 20 mg of simvastatin daily for 2 weeks and then 40 mg daily for another 2 weeks, and group II included 20 patients with cirrhosis who did not receive simvastatin as a control group. All patients underwent full clinical examination, laboratory investigations, and abdominal Doppler ultrasound at baseline and after 30 days to evaluate portal vein diameter, blood flow volume, direction and velocity of portal vein blood flow, hepatic artery resistance and pulsatility indices, splenic artery resistance index, portal hypertension index (PHI), liver vascular index, and modified liver vascular index (MLVI). Results: There was a highly significant decrease in the hepatic artery resistance index in group I, from 0.785 ± 0.088 to 0.717 ± 0.086 (P < 0.001). There was a significant decrease in the PHI in group I , from 3.915 ± 0.973 m/sec to 3.605 ± 1.168 m/sec (P = 0.024). Additionally, there was a significant increase in the MLVI in group I from 11.540 ± 3.266 cm/sec to 13.305 ± 3.222 cm/sec, an increase of 15.3% from baseline (P = 0.009). No significant adverse effects were detected. Conclusions: Simvastatin is safe and effective in lowering portal hypertension. [ClinicalTrials.gov Identifier: NCT02994485]

Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: a systematic review and meta-analysis

“…Five studies [21, 24, 26, 32, 35] reported parameters of hepatic portal vessel pressure with follow-up duration less than 3 months. In these studies, three important hepatic portal hemodynamic indexes, hepatic venous pressure gradient (HVPG), free hepatic vein pressure (FHVP), and wedged hepatic venous pressures (WHVP) which could reflect the degree of portal hypertension, were included.…”

“…a hepatic venous pressure gradient (HVPG); b wedged hepatic venous pressures (WHVP); c free hepatic vein pressure (FHVP). 5 studies ( a ) and 3 studies ( b & c ) - Abraldes et al, [21]; Bishnu et al, [24]; Elwan et al, [26]; Pollo-Flores et al, [32]; and Wani et al, [35]…”

“…Previous investigation indicated that statin could improve the resilience and compliance of portal vessels by promoting the production of vascular endothelium-derived relaxing factor, namely, nitric oxide [48–52]. Furthermore, clinical studies hinted that statin could mitigate hepatic portal hypertension as well with a short therapeutic duration (mean value of follow-up period: 3 months) [21, 24, 26, 32, 35]. Moreover, statin was proved to function as a kind of free radical eliminated agent which could relieve oxidative stress reaction in liver cirrhosis progression [53, 54].…”

“…Inflammatory reaction could be suppressed by statin through inhibiting and eliminating the over-produced free radical or other pernicious by-product in liver cirrhosis [55, 56], and hence hepatic cell injury and fibrosis could be partly prevented from underlying this mechanism. Given myalgia (muscular damage and creatine kinase elevation) as one of the most common drug-related adverse reactions clinical studies were designed to assess its incidence in statin treated liver cirrhosis, and most of which confirmed the safety of statin use [26, 32]. Portal hypertension as a marker of decompensated liver cirrhosis could further exacerbate liver cirrhosis to form a vicious cycle [57–59], and statin could break this circle by lowering hepatic portal vascular pressure to improve the prognosis of liver cirrhosis.…”

Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

“…The anti-inflammatory effects of statins seem to be steps ahead of other agents concerning testing in human trials, mainly due to the similar effect of statins on portal hypertension ( 93 , 97 , 102 , 117 ). Novel research implies the anti-inflammatory effects of statins as key drives in lowering the portal pressure, but the immunological impact needs further exploration in humans ( 89 , 91 ).…”