Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking.
Drs Yaron Rotman and Arun Sanyal from Maryland, USA reviewed the therapy for NAFLD.
Although the mainstay of treatment of NAFLD is weight loss, the team point out that it is hard to maintain, prompting the need for pharmacotherapy as well.
A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents.
The researchers identified that NAFLD therapies target 4 main pathways.
|A second approach is targeting oxidative stress and inflammation|
The team report that the dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress.
Medications in this group include peroxisome proliferator-activator receptor agonists, medications targeting the bile acid-farnesoid X receptor axis, inhibitors of de novo lipogenesis, incretins, and fibroblast growth factor (FGF)-21 or FGF-19 analogues.
The team found that a second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress.
Medications from this group include antioxidants, medications with a target in the tumour necrosis factor α pathway, and immune modulators.
The researchers note that a third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators.
Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics will be an important element of therapy.
Dr Rotman's team concludes, "It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease."