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Category: Inflammation

International NASH Day: New Antibodies Discovered Play Significant Role in NAFLD

June 10th, 2021 celebrates International NASH Day which is part of an ongoing effort supported by CMHC partner, the Global Liver Institute to spread awareness of nonalcoholic steatohepatitis (NASH), the advanced form of nonalcoholic fatty liver disease (NAFLD), as well as actions to address the condition. Currently, the global burden of NAFLD is estimated at a worldwide prevalence of 11%, representing nearly 900 million cases, and has demonstrated a 33% increase over the course of the past 30 years.

Although many patients may experience buildup of fat in the liver without symptoms or health repercussions, in some cases excess fat contributes to inflammation and damage to liver cells even causing cirrhosis. Without appropriate treatment or management, such cases can lead to the development of NAFLD and consequently, to nonalcoholic steatohepatitis. As this condition is an advanced form of disease, it is increasingly important to pinpoint intervention targets and develop effective treatment methods to halt its progression.

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Inflammation and risk of T2DM: Insights from the CANTOS trial

Data from several studies have suggested that persistent low-grade inflammation has an important role in the pathophysiology of many cardiometabolic conditions. Inflammatory markers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) have been associated with increased risk of cardiovascular adverse events, as well as insulin resistance and hyperglycemia. Canakinumab is a human monoclonal antibody that targets interleukin-1 (IL-1), which is upstream of IL-6 and hs-CRP, thereby decreasing IL-1 signaling and consequent inflammation. Last year, the authors of the CANTOS trial demonstrated that treatment with canakinumab led to the reduction of cardiovascular events independent of lipid levels in patients with prior myocardial infarction and high levels of hs-CRP (≥2 mg/L). The results of this landmark trial served as important proof-of-concept to support the inflammation hypothesis in the pathophysiology of atherothrombosis.

Because inflammation has been shown to play a role in insulin resistance, defective insulin secretion, and the development of type 2 diabetes in pre-clinical experiments and observational studies, authors of the CANTOS trial also tested the hypothesis that canakinumab treatment reduces the risk of incident type 2 diabetes (T2D). A key secondary endpoint of the CANTOS trial was to assess the effect of canakinumab in reducing the progression of prediabetes to diabetes by measuring the rates of new-onset T2D in prediabetic patients. To do so, the trial enrolled a total of 10,061 patients, out of which 4,057 (40.3%) had baseline diabetes, 4,960 (49.3%) had pre-diabetes, and 1,044 (10.4%) were normoglycemic. Results from this highly anticipated study were recently published in the Journal of the American College of Cardiology by Everett and colleagues.

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