Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease

Simon, Tracey G.; Henson, Jacqueline B.; Osganian, Stephanie A.; Masia, Ricard; Chan, Andrew T.; Chung, Raymond T.; Corey, Kathleen E.

doi:10.1016/j.cgh.2019.04.061

Cited by 132 publications

(107 citation statements)

References 35 publications

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“…A further recent clinical study performed on a cohort of patients diagnosed with NAFLD indicates that aspirin administration is associated with an improvement of NAFLD features and a reduced risk of fibrosis progression. 86…”

Section: Platelets In Alcohol-related and Non-alcoholic Steatohepatitismentioning

confidence: 99%

Platelets in chronic liver disease, from bench to bedside

et al. 2019

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In the last decade, numerous studies revealed physiologic and pathophysiologic roles of platelets beyond haemostasis, a process to prevent and stop bleeding. These include the activation of the immune system and the promotion of inflammation, infection and cancer. Hence, the emerging view on the role of platelets has shiftedplatelets are now seen as alert "sentinels" of the immune compartment, rather than passive bystanders. Herein, we review well-established and newly discovered features of platelets that define their natural role in maintaining blood haemostasis, but also their functional relationship with other cells of the immune system. We focus on recent studies underlining functional involvement of platelets in chronic liver diseases and cancer, as well as the effects of anti-platelet therapy in these contexts. Finally, we illustrate the potential of platelets as possible diagnostic and therapeutic tools in liver disease based on recently developed methodologies.

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Section: Platelets In Alcohol-related and Non-alcoholic Steatohepatitismentioning

confidence: 99%

Platelets in chronic liver disease, from bench to bedside

et al. 2019

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“…The marked decrease in hepatic AA concentrations after icosabutate treatment suggests that substrate availability may explain the decreased HETE concentrations. In addition to the hepatic antifibrotic effects of PLA2 inhibitors in mice, the potential role of the arachidonic cascade in liver fibrosis is supported by recent findings that demonstrate the protective effect of aspirin on fibrosis progression in NASH patients . Finally, with respect to the reduction in hepatic oxidative stress after treatment with icosabutate, it has recently been proposed that oxidative stress drives NASH and fibrosis by activation of STAT1, which was the most inhibited upstream regulator in response to treatment with icosabutate.…”

Section: Discussionmentioning

confidence: 88%

Icosabutate Exerts Beneficial Effects Upon Insulin Sensitivity, Hepatic Inflammation, Lipotoxicity, and Fibrosis in Mice

et al. 2019

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Icosabutate is a structurally engineered eicosapentaenoic acid derivative under development for nonalcoholic steatohepatitis (NASH). In this study, we investigated the absorption and distribution properties of icosabutate in relation to liver targeting and used rodents to evaluate the effects of icosabutate on glucose metabolism, insulin resistance, as well as hepatic steatosis, inflammation, lipotoxicity, and fibrosis. The absorption, tissue distribution, and excretion of icosabutate was investigated in rats along with its effects in mouse models of insulin resistance (ob/ob) and metabolic inflammation/NASH (high‐fat/cholesterol‐fed APOE*3Leiden.CETP mice) and efficacy was compared with synthetic peroxisome proliferator‐activated receptor α (PPAR‐α) (fenofibrate) and/or PPAR‐γ/(α) (pioglitazone and rosiglitazone) agonists. Icosabutate was absorbed almost entirely through the portal vein, resulting in rapid hepatic accumulation. Icosabutate demonstrated potent insulin‐sensitizing effects in ob/ob mice, and unlike fenofibrate or pioglitazone, it significantly reduced plasma alanine aminotransferase. In high‐fat/cholesterol‐fed APOE*3Leiden.CETP mice, icosabutate, but not rosiglitazone, reduced microvesicular steatosis and hepatocellular hypertrophy. Although both rosiglitazone and icosabutate reduced hepatic inflammation, only icosabutate elicited antifibrotic effects in association with decreased hepatic concentrations of multiple lipotoxic lipid species and an oxidative stress marker. Hepatic gene‐expression analysis confirmed the changes in lipid metabolism, inflammatory and fibrogenic response, and energy metabolism, and revealed the involved upstream regulators. In conclusion, icosabutate selectively targets the liver through the portal vein and demonstrates broad beneficial effects following insulin sensitivity, hepatic microvesicular steatosis, inflammation, lipotoxicity, oxidative stress, and fibrosis. Icosabutate therefore offers a promising approach to the treatment of both dysregulated glucose/lipid metabolism and inflammatory disorders of the liver, including NASH.

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“…After the initial liver biopsy fibrosis was assessed very 3‐12 months by either the Fibrosis‐4 score, NAFLD fibrosis score or APRI score. Daily aspirin use resulted in a 37% reduction in the risk for developing advanced fibrosis . This finding may impact the recently revised guidelines regarding the non‐recommendation of aspirin for primary prevention of cardiovascular disease …”

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confidence: 88%