Cirrhosis as new indication for statins

Abstract

In the recent years, there have been an increasing number of reports on favourable effects of statins in patients with advanced chronic liver disease. These include reduction in portal pressure, improved liver sinusoidal endothelial and hepatic microvascular dysfunction, decreased fibrogenesis, protection against ischaemia/reperfusion injury, safe prolongation of ex vivo liver graft preservation, reduced sensitivity to endotoxin-mediated liver damage, protection from acute-on-chronic liver failure, prevention of liver injury following hypovolaemic shock and preventing/delaying progression of cirrhosis of any aetiology. Moreover, statins have been shown to have potential beneficial effects in the progression of other liver diseases, such as chronic sclerosing cholangitis and in preventing hepatocellular carcinoma. Because of these many theoretically favourable effects, statins have evolved from being considered a risk to kind of wonder drugs for patients with chronic liver diseases. The present article reviews the current knowledge on the potential applications of statins in chronic liver diseases, from its mechanistic background to objective evidence from clinical studies.

Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)

“…These data suggest that patients with aHCC do not have increased susceptibility to hepatotoxicity from statins and these results are consistent with a recent clinical trial in patients with aHCC treated with pravastatin 40 mg [23]. Further, recent observations have shown that patients with liver disease do not have a higher risk of statin-induced liver toxicity when compared to the general population [16,28]. The fact that the combination of sorafenib + pravastatin is safe and displays low toxicity is of pivotal importance in order to further deeply study its potential benefits in patients with HCC (i.e., earlier vs. advanced stages) in the future.…”

“…In line with this, a randomized double-blinded, placebo-controlled Phase II trial will examine the effects of pravastatin use versus placebo after 12 months of treatment on HCC recurrence in patients with liver cirrhosis (NCT03219372). Notably, previous studies and preclinical evidences have assessed the potential beneficial anti-inflammatory and antifibrotic effects of statins as well as the rationale for the use of statins in chronic liver disease including the setting of liver cirrhosis [16,28]. In this regard, the therapeutic efficacy of pravastatin may delay HCC development and should be addressed in these settings in a near future, particularly in patients with early stage disease and/or after tumor resection, during which the effects would probably be even more noticeable.…”

Aging and Chronic Liver Disease

“…However, the use of statins to treat different conditions have shown beneficial and pleiotropic properties in different chronic diseases, beside and independent of its cholesterol-lowering effects. [120][121][122] Their positive effects are not limited to healthspan amelioration, but to exert antiaging benefits increasing the lifespan in drosophila, mice, and even in humans. [123][124][125][126] Several mechanisms underlie the antiaging effects of statins.…”

“…76 Future works should further study its applicability at the bedside, always considering the optimal dose and the subpopulation of aged patients that would mostly benefit from this therapeutic opportunity. 122,133,135 Other drugs like metformin or rapamycin are well-known for their anti-aging effects. Remarkably, the Geroscience Interest Group inside the National Institute on Aging, pointed out that many of these drugs with antiaging effects were clinically approved for treating chronic diseases, and therefore, it would be interesting to screen for other drugs in this category, and test their potential to increase healthspan.…”

Improving Medication‐Related Outcomes in Chronic Liver Disease

“…(34)(35)(36)(37) Examples of clinically important PKPD changes in select medications (including PIMs) that occur in patients with cirrhosis are provided in Table 2. (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) To prevent ADRs due to these changes, health care professionals should carefully select an appropriate medication and dose adjust when prescribing.…”