NASH Treatment in 2022: review of current and future therapies for non-alcoholic steatohepatitis

Prof. Stephen Harrison (USA) reviews current and future therapies for Non-Alcoholic Steatohepatitis (NASH). After a focus on the pathogenesis of NASH and the different pathways on how underlying steatohepatitis is developed, he presents his expert perspective on how patient outcomes can be improved.
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Hello, I’m Steven Harrison a visiting professor of hepatology at the Radcliffe Department of Medicine University of Oxford, the medical director of Pinnacle Clinical Research and the president of Pinnacle Clinical Research and the president of Summit Clinical Research.

It is my distinct privilege and honor today to talk to you about NASH treatment in 2022 to understand where we are with Nash therapy. We must take a brief tour through the pathogenesis of this disease and understand that there are multiple different Pathways by which patients develop underlying Steatohepatitis.

There are three main ways that disease presents in these patients:

  • Number one – insulin resistance: All of these patients are insulin resistant and / or have diabetes. What happens with insulin resistance is dipocytes become dysfunctional and they release free fatty acids that are very toxic to the liver. They taken up in the cortal vein and get delivered to the liver where the liver has a couple of options.

Those toxic free fatty acids can be esterified to triglyceride and stored as fat. They can be burned through beta oxidation within the mitochondria.
They can also be repackaged and shipped out of the liver in the form of very low density lipoprotein in patients with underlying Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

There’s a disproportional amount of upregulated De Novo Lipogenesis and this provides another opportunity for Target Therapeutics.

So in addition as livers become full of toxic free fatty acids, Mitochondrial dysfunction begins to take place endoplasmic reticulum stress an increased in the unfolded protein response ensues and drives pro-inflammatory mediators accentuated by the development of reactive oxygen species as well. This leads to apoptosis and subsequent activation of a padic stellate cells. There’s also an overlay of dysfunctional regulation with the immune cell pathways and that can also contribute.

In addition, the microbiome may be playing a role here as well and genetic influences such as hsd17 beta 13 and P and pla3 may also be contributing to underlying pathogenesis of disease. Now all of these provide opportunities for drug targets. Many you see listed here and I’ve broken them down into metabolic anti-inflammatory and anti-fibrotic.

The majority of therapies being developed today for NASH…

Prof. Stephen Harrison

Prof. Stephen Harrison

With over 20 years in the industry, Dr. Harrison has formed a multitude of global and local relationships with like-minded physicians and experts to raise awareness of liver disease and find a treatment for the patients that need it most.


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