EASL Congress 2024 - Wrap up on Metabolism, Alcohol & Toxicity

Summary

In this presentation, Dr. Yan Shaten discusses key findings from EASL abstracts on alcohol and non-alcoholic (metabolic) liver diseases. He highlights studies investigating alcohol-related liver disease, including mechanistic insights from RNA sequencing and new therapeutic targets like GP1 agonists for alcohol abstinence. He also reviews advances in metabolic liver disease, covering non-invasive biomarkers, clinical guidelines, and novel therapies aimed at fibrosis regression. The talk emphasizes the growing importance of biomarkers over liver biopsies in guiding treatment and highlights promising new drugs in both alcohol-related and metabolic liver disease research.

Takeaways

• 📊 The majority of patients with advanced liver disease are linked to harmful alcohol consumption or metabolic causes.
• 🧬 A study from Barcelona using RNA sequencing revealed key cellular differences between healthy controls, alcoholic liver disease patients, and severe alcoholic hepatitis cases.
• 🐹 A hamster model study showed a reduction in alcohol consumption with the use of incretin-based drugs, suggesting a potential anti-craving mechanism.
• 💊 Metadoxine was associated with higher abstinence rates and fewer complications in alcoholic cirrhosis patients in a retrospective cohort study from Mexico.
• 📖 New 2024 guidelines for managing metabolic-associated liver diseases (MALD) were released, outlining treatment options and liver transplantation recommendations.
• 📉 Non-invasive tests like liver stiffness measurement were highlighted for their diagnostic and prognostic significance in liver disease progression.
• 🔬 Resmetirom, a thyroid hormone receptor beta agonist, showed promising histological and non-invasive marker improvements in reducing liver fibrosis.
• 💉 FGF21 agonists were presented as a potential treatment for reducing liver fat and improving fibrosis, with longer-duration treatments showing durable responses.
• 💡 The field of NASH (Non-alcoholic Steatohepatitis) treatment is expanding with several promising drug classes, including GP1 and dual agonists targeting fibrosis and inflammation.
• 📈 Novel mechanisms like transglutaminase inhibitors and DGAT2 antisense therapies are being explored for their potential in reducing liver fibrosis and improving patient outcomes.

Q & A

What are the main causes of advanced liver disease according to the speaker?

The main causes of advanced liver disease mentioned are harmful alcohol consumption and metabolically driven liver diseases.

What unique approach did the Barcelona group use in their study on alcoholic liver disease?

The Barcelona group used RNA sequencing to analyze various liver cell populations, such as myoid cells, endothelial cells, and hepatocytes, to compare the expression patterns and pathways in healthy controls, early alcoholic liver disease, and severe alcoholic hepatitis patients.

What is the significance of the hamster model in alcohol-related liver disease research?

The hamster model, especially the obese hamster model, was used to study alcohol consumption. It highlighted a natural preference for alcohol in hamsters, and the study showed that treatment with the drug Incron reduced alcohol consumption, suggesting its anti-craving effect through the central nervous system.

What were the results of the metadoxine study from Mexico?

The retrospective cohort study showed that patients exposed to metadoxine had a lower relapse rate and fewer complications from end-stage liver disease, including a lower incidence of hepatic encephalopathy, suggesting a benefit in promoting alcohol abstinence.

What is the significance of the new 2024 practice guideline for metabolic-associated liver disease (MLD)?

The new 2024 guideline, a joint effort by EASL, EASD, and EAO, highlights the therapeutic options available for metabolic-associated liver disease and emphasizes the lack of approved medications specifically for liver disease, focusing on treating comorbidities like diabetes, dyslipidemia, and obesity.

How do non-invasive tests contribute to liver disease management according to the VCT prognosis study?

Non-invasive tests, particularly liver stiffness measurements, were shown to have prognostic value. The study demonstrated that changes in liver stiffness categories were significantly associated with liver-related events, highlighting the utility of these biomarkers in managing patients and predicting outcomes.

What is the significance of the FDA approval for patients with metabolic liver disease (MLD)?

The FDA's approval of treatment for patients with MLD marks a significant advancement in the field, with data showing improvement in both histological features of fibrosis regression and non-invasive markers in ongoing clinical trials.

What role do FGF21 agonists play in treating metabolic liver disease?

FGF21 agonists, such as efruxifermin, are promising in reducing liver fat and fibrosis in metabolic liver disease. Long-term studies have shown durability in fibrosis improvement, with ongoing research exploring safety aspects like bone mineral density reduction.

How do dual agonists like cotadutide perform in treating liver fibrosis?

Dual agonists like cotadutide show promising results in resolving non-alcoholic steatohepatitis (NASH) and improving liver fibrosis, with substantial improvement in patients' fibrosis stages and non-invasive markers.

What are the potential future directions for drug development in liver disease treatment?

Future directions for liver disease treatment include continued exploration of various mechanisms such as GP1 receptor agonists, dual agonists, FGF21 agonists, and newer approaches like transglutaminase inhibitors and anti-sense molecules targeting DGAT.