Earlier this week over 8,000 delegates attended The Liver Meeting (#TLM2023), hosted by the American Association for the Study of Liver Diseases (AASLD) and held in Boston, MA from November 10-14. There was a lot of research featured across many sessions and presentations, and we learnt a lot about where the field is heading.
We have chosen some of our own highlights from the congress to reflect on in this blog post.
Highlight 1: 3D MR elastography identifies portal hypertension in cirrhosis: a prospective multicentre study
Xialong Qi orally presented the abstract titled “Three-dimensional MR elastography identifies portal hypertension in cirrhosis: a prospective multicentre study” as part of the Portal hypertension: varices and bleeding session. He presented some very interesting data from a prospective trial that used magnetic resonance elastography (MRE) to measure both liver and spleen stiffness, among other endpoints, to identify portal hypertension.
Portal hypertension, elevated pressure in the portal venous system, is considered a hallmark of liver cirrhosis. As increased portal pressure increases the risk for compensation and severe complications such as variceal bleeding and ascites, it is an important biomarker in patients with cirrhosis. Portal hypertension is currently measured via hepatic venous pressure gradient (HVPG), a complex and highly invasive procedure, meaning there is an unmet need for effective, non-invasive biomarkers for portal hypertension, you can read more about this here.
MRE is an imaging technique that uses mechanical waves that are then captured using specialised magnetic resonance imaging that allows for quantification of tissue stiffness and other mechanical properties. In the presented abstract, three-dimensional MRE (3D-MRE) was used in patients with cirrhosis to identify clinically significant portal hypertension (HVPG > 10mmHg), and severe portal hypertension (HVPG > 12mmHg). This study demonstrated that spleen stiffness had the strongest correlation with HVPG.
We found this very interesting for a few reasons. Unlike when portal hypertension was discussed at EASL earlier this year, here imaging, and in particular MRE, was presented as a very promising non-invasive way to detect and predict HVPG and portal hypertension. As a technique, it offers high accuracy and high spatial resolution, but some other advantages of MRE are that it is relatively quick assessment, doesn’t require contrast media, and enables large coverage of the liver and spleen. At Antaros Medical, we are applying 2D and 3D MRE-derived stiffness of the liver and spleen to study the effects of drugs in development for patients with fibrotic liver disease.
Highlight 2: A CCR2-targeted PET probe for liver fibrosis detection and staging in pre-clinical models
Abstract #3453-A presented work in which the investigators pre-clinically evaluated a novel Positron Emission Tomography (PET) tracer for assessing fibrogenesis through activated hepatic stellate cells and Kupffer cells. This was another highlight for us, because it reiterates the importance of new methods for assessing and measuring fibrosis.
CC-chemokine receptor 2 (CCR2) is increasingly expressed on activated hepatic stellate cells (HSCs) and Kupffer cells (liver macrophages). [68GA]-DOTA-ECL1i is a PET tracer with high specificity to CCR2, which was assessed in this study in both normal and injured livers to evaluate its utility for assessment of early phases of fibrogenesis. While the degree of fibrosis at the time of the PET/CT imaging were not reported, the results showed that the tracer could allow for the detection of activated HSCs and macrophages in the liver.
Current methods to assess and measure fibrosis are either invasive or not sensitive enough to detect early fibrosis, and this is greatly affecting drug development. There is an unmet need for non-invasive methods to detect, stage, and study the molecular processes that drive the pathology of fibrosis and will enable the assessment of treatment effects. PET tracers are emerging as important biomarkers due to their ability to detect even small changes at a molecular level.
This abstract, and the level of activity in the field in general, provide support for the use of PET tracers to non-invasively assess fibrosis. Alongside others, we are working to develop tracers and techniques to meet the need for non-invasive ways to look at fibrotic processes, including inflammation and fibrogenesis.
Highlight 3: Lean individuals with MASLD have more severe liver disease and poorer clinical outcomes
In a new type of session at the meeting, Jacqueline O’Leary chose a few of the papers published in Hepatology over the last year that she thinks will be the most impactful. During this ‘Editor’s Cut: MASLD & ESLD’ session several exciting publications were featured, but we found the presentation about ‘Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study)’ particularly interesting.
Despite obesity being a major risk for metabolic dysfunction-associated steatotic liver disease (MASLD; previously NAFLD), it can also occur in individuals with a body mass index (BMI) < 25, considered lean MASLD. The prevalence of lean MASLD is relatively low. In this study of a large longitudinal prospective French cohort, 14% of those with MASLD were identified as having lean MASLD. There have also been fewer studies looking at this cohort, and the data that has been made available, has been mixed and inconclusive.
This paper by Nabi et al. showed that while lean MASLD is associated with a better metabolic profile, it is also associated with poorer clinical outcomes, particularly with regards to hepatic events and chronic kidney disease. The risk of death from all causes was also three times higher for lean MASLD than for non-lean MASLD. It was also interesting that lean MASLD patients were significantly younger and had a higher rate of advanced fibrosis at baseline.
What we found most interesting about this study and the discussion around it was that while the prevalence of lean MASLD is considered relatively low, these individuals are shown to have more severe liver disease and poorer clinical outcomes. Closer study of this group could help to further our understanding of MASLD and the underlying pathology, particularly how it differs from the processes and mechanisms that are linked to obesity. It will also be interesting to see what implications these insights might have for drug development in MASLD.
In summary, there was a lot of science presented at this years’ TLM, though we chose some of our personal highlights to reflect on in this post:
- 3D MR Elastography identifies portal hypertension in cirrhosis: a prospective multicentre study, Xialong Qi
- A CCR2-targeted PET probe for liver fibrosis detection and staging in pre-clinical models, Tuo Shao
- Editor’s Cut: MASLD & ESLD, Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes, Jacqueline O’Leary
We are already looking forward to attending The Liver Meeting 2024 next year in San Diego, CA.
The views and opinions expressed in this article are solely those of the contributing author/s. These views and opinions do not necessarily represent those of Antaros Medical.
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