Repurposing of Antiplatelet Agent: Cilostazol for the Treatment of Alcohol-Related Liver Disease

Abstract

Alcohol-related liver disease (ALD) is a serious global health concern, characterized by liver inflammation and progressive fibrosis. There are no Food and Drug Administration-approved drugs, thus effective treatments are needed. Severe alcoholic hepatitis (AH) is the most severe manifestation of ALD, with a 28-day mortality rate ranging from 20% to 50%. For decades, pentoxifylline, an antiplatelet agent, has been used off-label for the treatment of severe AH owing to its tumor necrosis factor-α inhibition properties. However, the STOPAH trial did not reveal the survival benefit of pentoxifylline. Consequently, pentoxifylline is no longer recommended as the first-line therapy for severe AH. In contrast, cilostazol is widely used as an antiplatelet agent in cardiovascular medicine and demonstrates promising results. Cilostazol is a selective phosphodiesterase type 3 inhibitor, whereas pentoxifylline is non-selective. Recent studies using experimental models of alcohol-induced liver injury and other liver diseases have yielded promising results. Although cilostazol shows promise for hepatoprotective effects, it has not yet been evaluated in human clinical trials. In this review, we will explore the mechanism underlying the hepatoprotective effects of cilostazol, along with the pathophysiology of alcohol-induced liver injury, addressing the pressing need for effective therapeutic options for patients with ALD.