I don't think it is a good idea to cast doubt on t
Post# of 155592
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Posted On: 07/02/2022 11:31:05 AM
I don't think it is a good idea to cast doubt on the validity of the biomarker data. I'm sure CR looked into this over the past 6 months when the data was so unusual. But it is what it is and likely correct.
We saw reductions in cT1 with 700 mg HM only. Not in 700 normal. We appreciated significant reductions in PDFF with 700 mg HM. 700 mg normal was worse than placebo because it increases CD8 natural killer cells like CR says.
It is very clear what happens when you have huge numbers of CCR5 and 700mg HM because that was demonstrated to work well. Why was the data acceptable to you in the HM group and not in the normal 700 group?
The only "greater effect" you purport would occur in the 700 mg group turned out to be a reduced reduction in both cT1 and PDFF except for the HM group.
I appreciate your dive into this, but some things I don't fully agree with. When you say a reduction in cT1 is a reduction in inflammation. In fact, the body scars and produces scar tissue in an effort to contain the dying hepatocytes. The hepatocytes are inflamed and being attacked by the immune system because they are dying. So, the HSCs or Hepatic stellate cells begin to induce scarring which is an effort to reduce and contain the inflammation. This is reduced quite plainly in the 350mg group, especially when the level of scarring was worse to begin with, but only in the 700mg HM group when there are more CCR5 receptors. In the 700mg normal group, scarring is hardly touched and steatosis increased. This increase of dosing in the normal group exacerbated the formation of fat and hardly touched scarring because, I would say, the systems were overwhelmed with the effect of LRM that it "Short Circuited" the system too quickly and the system did not know whether to be inflamed due to the scar tissue or fat, or be calm and do nothing because "nothing was wrong" as communicated by the fully bound CCR5. I think in NASH, the slow effect of 350mg is sufficient to slowly bring the systems into fibrosis resorption without overburdening the system with the strong blow of 700mg unless HM.
We saw reductions in cT1 with 700 mg HM only. Not in 700 normal. We appreciated significant reductions in PDFF with 700 mg HM. 700 mg normal was worse than placebo because it increases CD8 natural killer cells like CR says.
It is very clear what happens when you have huge numbers of CCR5 and 700mg HM because that was demonstrated to work well. Why was the data acceptable to you in the HM group and not in the normal 700 group?
The only "greater effect" you purport would occur in the 700 mg group turned out to be a reduced reduction in both cT1 and PDFF except for the HM group.
I appreciate your dive into this, but some things I don't fully agree with. When you say a reduction in cT1 is a reduction in inflammation. In fact, the body scars and produces scar tissue in an effort to contain the dying hepatocytes. The hepatocytes are inflamed and being attacked by the immune system because they are dying. So, the HSCs or Hepatic stellate cells begin to induce scarring which is an effort to reduce and contain the inflammation. This is reduced quite plainly in the 350mg group, especially when the level of scarring was worse to begin with, but only in the 700mg HM group when there are more CCR5 receptors. In the 700mg normal group, scarring is hardly touched and steatosis increased. This increase of dosing in the normal group exacerbated the formation of fat and hardly touched scarring because, I would say, the systems were overwhelmed with the effect of LRM that it "Short Circuited" the system too quickly and the system did not know whether to be inflamed due to the scar tissue or fat, or be calm and do nothing because "nothing was wrong" as communicated by the fully bound CCR5. I think in NASH, the slow effect of 350mg is sufficient to slowly bring the systems into fibrosis resorption without overburdening the system with the strong blow of 700mg unless HM.
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