lsm

 Alina Allen and Ian Rowe lead the Surfers in considering biopathological shortcomings in fibrosis as a solitary endpoint. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.

This conversation focuses on flaws in biopsy as a measurement device and also in fibrosis as a solitary endpoint.

In the rest of the discussion, the group discusses challenges in proving that NITs can accurate measure and differentiate between different drugs in terms of therapeutic efficacy. One challenge is with the current metrics. We speak frequently about the challenges with biopsy and with fibrosis being an ordinal variable, but as Alina notes, being too tied for fibrosis means we focus solely on one measure of improvement and downplay others, such as steatosis.

The conversation is too rich and nuanced to be captured in a paragraph or two. This episode is worth two or three listens to capture all its points.

Alina Allen and Stephen Harrison spearhead a discussion on how MRE results can provide a foundation for developing Subpart H Clinical Trial Endpoints from non-invasive testing data. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.

 For NASH to move "beyond the biopsy," researchers must develop reliable clinical trial endpoints using non-invasive tests. This conversation winds up centering around MRE's ability to provide those metrics.

It starts with two different points. Ian Rowe comments on the power of message in dealing with patients. Specifically, he notes that the word "cirrhosis" does not engender strongly emotional or motivated responses whereas the word "cancer" certainly does so. Next, Stephen Harrison asks how cleanly we can translate MRE results into transient elastography readings. Ian suggests the answer is "not very clearnly."

Then the meat of the conversation starts, as Stephen asks whether MRE and LSM can lead us to a viable Subpart H surrogate endpoint. For this to work, he notes, we would have to translate LSM and/or liver function readings into a metric that then translates into an outcome. Alina Allen notes that MRE has the benefit of producing consistently read results without the reader variability issues we find with biopsy. Stephen pushes further, noting that it would be a major step to link magnitude of effect to a one-level fibrosis change, Alina reveals that the number falls consistently around 19%. Alina notes that we have no similar relationship for MELD scores, but the group agrees in the end it should be possible to design trials around MRE-based outputs.

Alina Allen and Ian Rowe discuss how Liver Stiffness Measurements (LSM) can improve individual patient treatment in pre-cirrhotic and compensated cirrhotic patients. Their comments stem from Alina's presentation of the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.

Ian starts this section by noting the challenges in relying on fibrosis when managing individual patients practically and wonders whether LSM might do a better job here. Alina endorses this thought emphatically. She notes that while there may be a benefit in clinical trials to separate an F2 from an F3, F levels have minimal impact on clinical recommendations for pre-cirrhotic patients. Conversely, LSM provides guidance on how quickly a patient is progressing toward cirrhosis regardless of fibrosis level, which can affect aggressiveness of recommendations and frequency of monitoring, among other issues.

During this conversation, Ian shares that he is conducting community-based research with over 3,000 patients so far in Leeds. This study is revealing similar results, with liver stiffness predicting progression up to a "tipping point" at which liver function begins to matter more. This can become germane to any specialist or primary care physician when treating patients.

Toward the end of the conversation, Louise Campbell notes that these same metrics can help identify patients who are failing sooner, which will leave more time for compassionate palliative care and end of life planning.

Alina Allen and Ian Rowe join the Surfers to discuss the recent Mayo Clinic paper, "MRE for Prediction of Long-Term Progression and Outcome in Chronic Liver Disease: A Retrospective Study." In this conversation, Alina summarizes the paper, after which Stephen Harrison asks questions about availability of subgroup analysis.

 This paper was recently published in the journal Hepatology. While previous Mayo Clinic work focused solely on NASH patients, this retrospective look focused on 1,200 patients with assorted liver diseases who underwent MRE for the first time between 2007 and 2009 and tracked patients through 2020. In this analysis, MRE had strong ability to predict future outcomes, with the strongest results predicting which patients with some level of fibrosis would progress to compensated cirrhosis. In this group, every one-level increase in LSM translate into slightly more than a two-fold increase in risk of cirrhosis. MRE also provides robust prediction of progressing from compensated cirrhosis to decompensation, with every one-level increase in LSM translating to a 22% increase in the likelihood of progressing to decompensation. Prediction is lower in predicting outcomes for decompensated patients, largely because at this point liver function assumes greater relevance than stiffness. As Alina states, "this is why we use a MELD score for transplantation priorities" and similar issues.

The other important point Alina makes (and Ian Rowe has made in past episodes) is that biomarkers provide continuous numbers to plot progression over time, as compared to fibrosis level which is ordinal with four levels, or other metrics that have a high zone, a low zone and a gray zone between them. Continuous variables are easier to track for individual patients and provide richer statistical analyses.

When Alina finishes, Stephen Harrison asks questions about population subtypes in this study. Alina points out that the northern midwest is fairly homogenous demographically and the clinical charts from which researchers derived data did not have genetic information.

Scott Ratliff - LSM for the PLL Archers - joins the podcast to discuss tips for improving mental toughness plus his favorite types of goalies to play for.