Happy New Year to everyone. With the path outlined
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I put this together thinking there was a correlation between HIV and MASH which occurs only in the liver and I think that happens because the liver is the only organ that can regenerate.
MGK, a very good outline of the disease process in NASH. The correlation in MASH is the same correlation you would see in other organs where fibrosis is occurring due to high levels of immune activation because of HIV under ART. The difference between MASH and other disease states involving HIV is mainly due to the regeneration of liver tissue as you mention. But the regeneration just means you'd live longer than otherwise. No regeneration and you'd die of liver disease much sooner.
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Now, this is my opinion. I'm thinking that if the endpoint becomes only one or two or a just a few specific Biomarkers which do not reflect the entire situation as a whole, then it might become a futile pursuit. I'm thinking that the whole state of inflammation is better represented and captured by the cumulative effect of many Biomarkers that are strategically combined into one formula or into an equation. That equation might output a number or a value which the level of, depicts or communicates the cumulative inflammatory or proliferative effect of what is happening in that patient. That number should actually measure and capture the state of inflammation or proliferation in that patient. I believe that this is what shall be necessary,
I think you've done a very good job of outlining exactly how they're going to do it. Capturing the thousand alterations made by leronlimab would be cost prohibitive but the broader that panel the better.
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For example, in the following: OBESITY AND WEIGHT GAIN IN PERSONS WITH HIV the accumulation of steatosis or fat on the liver in patients with MASH. This can be correlated to the development of cardiovascular disease (CVD) in people living with HIV.
Chronic inflammation can cause a preferential difference favoring white fat cells (pro-inflammatory) vs. brown fat cells (high energy burning). This furthers the course of a pro-inflammatory state and can lead to additional weight gain, a vicious little cycle.
That's not the only vicious little cycle. Chronic inflammation leads to mitochondrial damage and the mitochondria are what process the chemicals broken down from food into energy. With a crippling of energy processing you see a higher weight gain and increased inflammation.
Leronlimab can fix both problems.