EASL Congress 2026: Key Trials to Watch in Liver Disease Management

The landscape of hepatology is continually evolving, driven by ongoing research into the pathophysiology and treatment of chronic liver diseases. NAFLD and NASH represent a growing global health burden, with an estimated prevalence of NAFLD affecting 25% of the global population and NASH affecting 3-5% of adults.¹ Current management primarily relies on lifestyle modifications, but pharmacological interventions are urgently needed for patients with advanced fibrosis. Similarly, despite effective antiviral therapies, a complete cure for chronic HBV infection remains elusive for most patients, necessitating lifelong treatment and surveillance.² In HCC, while systemic therapies have improved outcomes, there is still a need for more effective first-line and subsequent-line treatments, particularly for patients with advanced disease.³

Key Trials to Watch at EASL 2026

Several late-stage clinical trials are expected to report significant findings at EASL 2026, potentially influencing clinical practice. In NASH, attention will be focused on agents targeting distinct pathogenic pathways. For instance, trials evaluating GLP-1 receptor agonists, such as semaglutide, are exploring their efficacy in achieving histological improvement in NASH. The phase 3 STELLAR trials for resmetirom, a thyroid hormone receptor-beta agonist, have already demonstrated significant histological improvement in NASH, with a resolution of NASH and no worsening of fibrosis in 25.9% of patients receiving 80 mg and 36.6% of patients receiving 100 mg, compared to 9.7% on placebo (p < 0.0001 for both doses).⁴ Further data on long-term outcomes and safety profiles from similar agents will be critical. Additionally, studies on farnesoid X receptor (FXR) agonists, like obeticholic acid, which showed a 24% histological improvement in NASH with fibrosis compared to 13% with placebo (p=0.0002) in the REGENERATE trial, will be closely scrutinised for their benefit-risk profiles, particularly concerning pruritus and lipid alterations.⁵

For chronic HBV infection, research is moving beyond viral suppression towards functional cure, defined as HBsAg loss with or without anti-HBs seroconversion. Trials investigating novel therapeutic classes, including siRNA agents, capsid assembly modulators, and immunomodulators, are anticipated. For example, the REEF-1 study, a phase 2b trial evaluating the siRNA agent JNJ-3989 in combination with nucleos(t)ide analogues, has shown promising HBsAg reductions.⁶ Further data on sustained HBsAg loss rates post-treatment cessation will be crucial. The efficacy and safety of these agents, alone or in combination, in achieving durable HBsAg seroclearance will be a primary focus.⁷

In HCC, advancements in systemic therapy continue to be a priority. Trials evaluating novel immune checkpoint inhibitors (ICIs) in combination with anti-angiogenic agents or other targeted therapies are expected to report. The IMbrave150 trial established atezolizumab plus bevacizumab as a first-line standard of care for unresectable HCC, demonstrating a median overall survival of 19.2 months compared to 13.4 months with sorafenib (HR 0.66, 95% CI 0.52-0.85; p < 0.001).⁸ Subsequent trials are exploring similar combinations or novel agents in different lines of therapy. Data on biomarkers predicting response to ICIs and strategies to overcome resistance will also be of significant interest.⁹

Limitations and Future Directions

While these trials offer considerable promise, limitations often include patient selection biases, relatively short follow-up periods for chronic conditions, and the challenge of translating histological endpoints into clinically meaningful outcomes, particularly in NASH. The long-term impact of these novel therapies on liver-related morbidity and mortality, as well as their cost-effectiveness, will require further investigation. Future research will need to focus on real-world effectiveness, identifying optimal patient populations for specific therapies, and developing combination strategies to achieve more comprehensive and durable responses across these complex liver diseases. The integration of artificial intelligence and advanced imaging techniques in patient stratification and response monitoring also represents a significant area for future development.¹⁰