For reducing inflammation, targets include nuclear receptor agonists (such as obeticholic acid), modulators of lipo-toxicity (such as acetyl-CoA carboxylase inhibitors) or modification of genetic variants (such as PNPLA3 gene silencing). Furthermore, liver macrophages are of vital importance to the development of NASH due to their role in regulating inflammatory, fibrogenic and tissue repair responses. From this, there have been some positive phase 3 clinical trials recently. This has stemmed from the farnesoid X receptor agonist obeticholic acid and the thyroid hormone receptor-b agonist resmetirom. However, overlapping causes and related factors make developing a single drug difficult. For example, metabolic injury leads to inflammation, which then leads to fibrosis. However, this process is incredibly oversimplified – the steps are intertwined, making developing a single drug difficult due to the ‘order’ of events. Some emerging developments for treating NASH include using cell therapy-based anti-inflammatory and antifibrotic approaches. This includes individualised treatments such as reprogrammed macrophages to accelerate repair processes. Furthermore, advances in technology, including that of artificial intelligence and single-cell sequencing, could guide future personalised treatments for patients with NASH.
This review by Tacke F et al. aimed to discuss current targets for treating NASH, as well as what the future holds in this field of research.
The heterogeneity of NASH, whether due to the genetics of the patient or due to divergent disease drivers and causes, presents difficulties for developing effective treatments for this disease. Understanding relevant targets, as well as making use of technological and pharmacological advances, could hold the power to develop treatments for NASH.