> Moderate to advanced liver fibrosis, (F2 or high

> Moderate to advanced liver fibrosis, (F2 or higher), an established risk factor for liver cirrhosis and overall mortality, affects at least one out of six (15%) patients with Type 2 Diabetes.

> USA population 332,000,000
> 25% of that is 83,000,000 with NAFLD
> 25% of that is 20,000,000 with NASH
> 25% of that is 5,000,000 with Stage 4 hepatic fibrosis
> 10% of that is 500,000 with Hepatocellular Carcinoma

> World population 7.8 billion people
> 25% of that is 2 billion people with NAFLD
> 25% of that is 500,000,000 people with NASH
> 25% of that is 125,000,000 people with Stage 4 hepatic fibrosis
> 10% of that is 10,000,000 people with Hepatocellular Carcinoma

> I believe the colored patients above will be well served with leronlimab.

> Fibrosis is the most important predictor of mortality in NAFLD. The greater the Fibrosis stage, the greater the mortality rate.

> Resmetirom - selective thyromimetic. Only reduces liver fat or steatosis. Does not remove fibrosis. A combo drug using Resmetirom for steatosis and Leronlimab for fibrosis could make an excellent partnership.

Fibrosis-4 (FIB-4) Calculator: https://www.hepatitisc.uw.edu/page/clinical-c...tors/fib-4
The Fibrosis-4 score helps to estimate the amount of scarring in the liver.
FIB-4 =
(Age (years)
x
AST Level (U/L)) /
(Platelet Count (109/L)
x √ALT (U/L))

Interpretation:
Using a lower cutoff value of 1.45, a FIB-4 score <1.45 had a negative predictive value of 90% for advanced fibrosis (Ishak fibrosis score 4-6 which includes early bridging fibrosis to cirrhosis). In contrast, a FIB-4 >2.67 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis.

Everyone with a FIB-4 score of >2.67 would do very well with Leronlimab.

The following is an ELF - enhanced Liver Fibrosis lab
https://files.labcorp.com/testmenu-d8/sample_...550659.pdf

If a patient is measured with a FIB-4 between 1.3 and 2.67 , then it becomes necessary to measure ELF. If ELF is less than 9.5, then there is little fibrosis; but if ELF is greater than 9.5, the level of fibrosis would be high and that patient with equivocal FIB-4, would do very well with Leronlimab treatment.

> Fibrosis Stage and NOT NAS level predicts mortality and time to development of severe liver disease. The Risk of Mortality increases with increasing stage of Fibrosis and the higher the Fibrosis Stage, F3 to F4, the more dramatic the risk of death.

> LSM: liver stiffness measure: > 12.0 kPa by transient elastography is High Risk of clinically significant liver fibrosis
> " The presence of steatosis largely serves as a "biomarker" or risk factor for steatohepatitis with fibrosis, but its mere presence (or even severity) does not necessarily imply a greater risk of severe disease, nor should it be considered a treatment target per se. "
> LSM 8 -12 is intermediate risk. In this case, ELF and apply same rationale, where less than 9.5 would mean less fibrosis and more than 9.5 would mean definitive evidence of fibrosis.

> All the calculator's mentioned here Rule out Fibrosis well.

> "Because of the slow progression of NASH, the FDA recommends liver histological improvements as endpoints reasonably likely to predict clinical benefit to support accelerated approval."

> FDA would consider improvement of just 1 stage in liver Fibrosis without worsening of Liver Steatosis as grounds for accelerated approval.