1. Introduction
Non-alcoholic steatohepatitis (NASH) represents an advanced form of
non-alcoholic fatty liver disease (NAFLD), characterized by inflammation
and fibrosis in the liver.1 Currently, it affects
approximately 20 to 30% of the global population, emerging as the
leading hepatic cause of morbidity and mortality.2 The
significant increase in the incidence of this condition and its
potentially lethal complications, such as cirrhosis or hepatocellular
carcinoma, highlight it as a significant challenge for public
health.3,4 It is important to emphasize that, to date,
there are no drugs approved by the Food and Drug Administration
specifically intended for the treatment of NASH, which emphasizes the
urgency of implementing effective strategies to address this
condition.5
Fibroblast growth factor 21 (FGF21), a hormone that regulates lipid and
glucose metabolism, has shown hepatoprotective effects in preclinical
studies. These findings suggest a potential therapeutic role for FGF21
in NAFLD, paving the way for the development of more effective
therapeutic strategies in addressing this
condition.6,7 Current literature and clinical practice
offer promising perspectives on the therapeutic potential of FGF21
analogs in NAFLD, highlighting their role as mediators of homeostasis
and inflammatory process in the disease metabolism. These analogs
demonstrate the ability to reduce liver fat, prevent hepatocyte damage
and suppress inflammation.8,9 However, the variability
in individual responses and the lack of consensus on assessment criteria
pose significant challenges to the clinical implementation of these
therapies.
Recently, two large, planned trials have investigated the role of FG21
analogs as a therapy of choice for clinical and laboratory benefits in
patients with NASH (Non-Alcoholic Steatohepatitis). These studies have
substantially increased the population of randomized patients receiving
efruxifermin, pegbelfermin, or pegozafermin as a strategy for resolving
NASH and improving metabolic profiles.10,11 Therefore,
we aimed to perform a meta-analysis of Randomized Controlled Trials
(RCTs) to assess the safety and efficacy of FGF21 analogs in the
treatment of NASH.