Personalized therapy when tackling nonalcoholic fatty liver disease: a focus on sex, genes, and drugs

Expert Opin Drug Metab Toxicol. 2018 Aug;14(8):831-841. doi: 10.1080/17425255.2018.1492552. Epub 2018 Jul 3.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease in the world. It describes a term for a group of hepatic diseases including steatosis, fibrosis, and cirrhosis that can finally lead to hepatocellular carcinoma. There are many factors influencing NAFLD initiation and progression, such as obesity, dyslipidemia, insulin resistance, genetic factors, and hormonal changes. However, there is also lean-NAFLD which is not associated with obesity. NAFLD is considered to be a sexually dimorphic disease. In most cases, men have a higher prevalence for the disease compared to premenopausal women. Areas covered: In this review, we first summarize the NAFLD disease epidemiology, pathology, and diagnosis. We describe NAFLD progression with the focus on sexual and genetic differences for disease development and pharmacological treatment. Personalized treatment for multifactorial NAFLD is discussed in consideration of different factors, including genetics, gender and sex. Expert opinion: The livers of female and male NAFLD patients have different metabolic capacities which influence the metabolism of all drugs applied to such patients. This aspect is not yet sufficiently taken into account. The liver computational models might quicken the pace toward assessing personalized disease progression and treatment options.

Keywords: NAFLD genetics; NAFLD treatment; Nonalcoholic fatty liver disease (NAFD); cytochrome P450; drug metabolism; hormonal differences; lean NAFLD; personalized therapy; sexual dimorphism.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Precision Medicine / methods*
  • Prevalence
  • Risk Factors
  • Sex Factors