Users

stories:

interview

with

Stephen

Harrison

At that point, we do two things:
1) We look individually at the AST and see if it is above 20, and we look at the kPa and determine if it is greater than 8.5. and that the CAP™ is greater than 280.
2) If that indeed happens, then we move the patient forward into the queue to be considered for a clinical trial at Pinnacle.

We also generate the FibroScan^®  FAST^TM Score by adding the CAP™, kPa plus AST.  If it is greater than 0.67, we put them into our F2 for higher studies. If it is greater than 0.35 but less than 0.67, we put them either in a noninvasive trial or a study that will take F1 patients in addition to F2s and F3s –but they span the spectrum usually from F1 to F3. That is how we use FibroScan^® up until the point that they screen for a trial.
Many of our trials then also include FibroScan^® along the way, either as a baseline into treatment or a baseline midpoint into treatment, noninvasive test parameter as a secondary or exploratory endpoint.

For instance, we just lost a patient today when they came back with an HbA1c at 14.5 and almost every study excludes patients with HbA1c more than 9.5. We would not have known that prior to seeing the results because we did not have any historical A1c to draw from and the patient thought she was much better controlled than she actually was, which is a common occurrence.
Then we move forward to an imaging gate, usually an MRI.  We’ll lose a certain number of people based upon the magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) or the magnetic resonance elastography (MRE), which are requirements for some studies and the early phase clinical trial work that we are doing.
The last gate is the liver biopsy gate. Historically, pre-FibroScan^®  and liver biochemistry analysis, liver biopsy screen fail rates were between 60-65%, just for that gate alone –not to mention the lab and the initial screen fails that you get prior to even going to liver biopsy.
So that contributes to the high screen fail rate. Where we have been able to improve that screen fail rate is twofold, using FibroScan^®:
The first is the CAP™ function. If a study has an MRI in three criteria for a certain amount of liver fat based on MRI-PDFF, we can adjust the CAP™ to help us achieve that certain MRI-PDFF threshold with about an 80-85% accuracy. That minimizes the screen fail rate on MRI to somewhere between 15-20%.  Subsequently, by combining in a sequential fashion a liver biochemistry test with FibroScan^®, we have been able to drive the liver biopsy screen fail rate down from 60-65% to 30-35%.

These are incremental advances, no doubt. But overall, this has improved our screen fail numbers. However, we still have work to do and we continue to refine the system.

We are hopeful that FibroScan^®-AST (Fast™) may be the next incremental advance in allowing us to do that.

The Fast™ Score is a combination of three components: two physical biomarkers: liver stiffness by VCTE™ and CAP™, estimating fibrosis and steatosis from an examination with FibroScan^®, plus AST, a readily available blood marker of inflammation.

FibroScan^® and tools like Fast™ support diagnosis efficiency at the point of care, improving diagnostic accuracy and reducing costs. Fast™ is inexpensive, reducing unnecessary, invasive assessments and the need for expensive, complex blood tests. It’s simple to determine and interpret – requiring just three numbers entered into a calculator on the myFibroScan app. Furthermore, the clinician can set the threshold for referral based on their goals, balancing sensitivity vs. specificity.

But you can equip yourself with tools like FibroScan^® that can help you be successful in this arena –much like you use vital signs because they’re vital, I look at FibroScan^® as a sixth vital sign to help us achieve success by pre-identifying patients at a greater likelihood of passing through the gates that I’ve alluded to earlier.

The first one is, diagnosis of at-risk NASH patients—those who will likely progress if therapy is not provided. That is the group of patients we want to key in on. I think utilizing app with FibroScan^® helps us to exclude most patients that do not fit that category. Then combined with routine liver biochemistries, we can better identify that group that is likely to progress.

The second context of use is monitoring for therapeutic efficacy of the drug in question. Here we have early preliminary data from the Regenerate trial through a post-talk analysis recently presented by Jérôme Boursier group, showing that we can utilize FibroScan^®, the liver stiffness measurement, to correlate with improvement in histopathology. Previous work has shown that a 25% reduction in FibroScan^® kPa correlates to improvement in histopathology.

I am hopeful that as we move forward and we utilize different mechanisms of action to treat this disease, studies will be utilizing FibroScan^® as a noninvasive tool along the way, such that similar work can be generated like the Regenerate trial, showing that improvement in histopathology is correlated to improvement in FibroScan^® kPa. When the time comes to prescribe the drug, providers will feel comfortable in utilizing vibration-controlled transient elastography (VCTE™) to assess both compliance with the drug and overall efficacy.

A more aggressive management approach should be brought forward to include consideration of evaluation for a clinical trial, further evaluation with MR elastography and/or liver biopsy.  
If you are in the range where the CAP™ is elevated above 280, which the kPa is between 6 and 8.5 This is where I ask the patient to look at the liver biochemistry panel, as well as family history of liver disease. And if you are in the at-risk group there, then I would proceed as if your kPa were greater than 8.5.

If we’re able to continue to generate positive research as it relates to VCTE™, I would love to be able to point to a point of care test that’s readily available in my clinical practice that can actually be linked to a long-term outcome.  This gets me back to the third context of use of a noninvasive test, which is the ability of that noninvasive test to predict how a patient feels, functions or survives over the long-term.

We’re in the middle of data generation now, but we’re hopeful that not only can we use VCTE™ for the first and second context of use that I’ve highlighted, but also for that third one, so that we can provide a full service point of care test to our patients at the time they come into clinic and reassure them along the way that they’re either getting better or that at worst case, they’ve stabilized their disease.

Another way to say that is this: there are a roughly 100 million Americans with fatty liver, but only about 20 million have NASH and are at risk of disease progression over the long-term.

We have identified a test that can really reassure us that you are in that 80% category. You are in the group that has fatty liver but doesn’t have NASH with fibrosis. That is a patient where we can institute lifestyle modification and one that does not to move forward with expensive testing and medication.

Simply through foundational lifestyle modification, these patients can begin to affect a positive outcome. In addition, if we’re able to identify those patients with fatty liver, we can correlate that fatty liver to a risk of developing diabetes or other potential comorbidities.  With aggressive management, we may now prevent the development of those long-term comorbidities down the road.