There is an urgent as yet unmet need to develop highly effective and safe
therapeutics for
nonalcoholic fatty liver disease (
NAFLD). The remarkable progress in understanding
NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as
therapy targets. Areas covered: This article reviews the safety and tolerability data of the
NAFLD therapies and explains the mechanistic basis for each of the established and
investigational drugs. Treatment targets include:
weight loss, anti-metabolic agents such as
lipid lowering and anti-diabetic drugs,
inflammation,
fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis. Expert opinion: Current
therapies continue to remain suboptimal.
Weight loss is effective but hard to achieve. Traditional and endoscopic bariatric procedures are promising although more randomized trials are needed and the long-term safety remains to be established. Clinical trials have demonstrated the efficacy of several drugs for the treatment of NASH. Of these, there remains some uncertainty about the long-term safety of
vitamin E.
Pioglitazone is associated with
osteopenia, fluid retention and
weight gain.
Obeticholic acid causes
pruritus in a substantial proportion of subjects and
elafibranor has been associated with transient rises in
creatinine. Several exciting
therapies are under development and results of clinical and post-marketing trials will help elucidate their safety.