Similarly, approximately 40% of patients with metabolic disorders concurrently possess non-alcoholic steatohepatitis (NASH), the most significant driver of hepatic fibrosis and progression to cirrhosis. Cultivating a substantial global public awareness of NASH and promoting stakeholder cooperation is crucial to successfully managing this progressive multisystem disease.
This review aims to explore the challenges and lessons derived from decades of research into NASH therapeutics, with a focus on multidisciplinary treatment strategies.
Stringent and potentially unsuitable efficacy endpoints may greatly contribute to the lack of licensed NASH therapeutics. Indeed, current efficacy endpoints may not accurately reflect NASH’s multisystem pathophysiology and comprehensively account for its deleterious effects on extrahepatic organs, including the heart. Accordingly, approved NASH pharmacotherapies must obligatorily consider its associated cardiometabolic risk factors. Similarly, current endpoints depend on liver biopsy-based histological assessments, which cannot feasibly be conducted to monitor treatment responses in clinical practice. Future research must thus validate existing non-invasive tools and imaging modalities as outcome parameters of treatment response to accelerate the development and approval of new therapeutics. Lastly, future research must evaluate the combination effects of glucose-lowering drugs, e.g. GLP-1, GIP, and glucagon receptor agonism, on NAFLD as a multisystem disease.