The Relationship between Pathogenesis and Possible Treatments for the MASLD-Cirrhosis Spectrum

Int J Mol Sci. 2024 Apr 16;25(8):4397. doi: 10.3390/ijms25084397.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a term that entails a broad spectrum of conditions that vary in severity. Its development is influenced by multiple factors such as environment, microbiome, comorbidities, and genetic factors. MASLD is closely related to metabolic syndrome as it is caused by an alteration in the metabolism of fatty acids due to the accumulation of lipids because of an imbalance between its absorption and elimination in the liver. Its progression to fibrosis is due to a constant flow of fatty acids through the mitochondria and the inability of the liver to slow down this metabolic load, which generates oxidative stress and lipid peroxidation, triggering cell death. The development and progression of MASLD are closely related to unhealthy lifestyle habits, and nutritional epigenetic and genetic mechanisms have also been implicated. Currently, lifestyle modification is the first-line treatment for MASLD and nonalcoholic steatohepatitis; weight loss of ≥10% produces resolution of steatohepatitis and fibrosis regression. In many patients, body weight reduction cannot be achieved; therefore, pharmacological treatment should be offered in particular populations.

Keywords: diet; fibrosis; hepatic steatosis; metabolic syndrome; sedentarism; steatohepatitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver / therapy
  • Humans
  • Life Style
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis* / etiology
  • Liver Cirrhosis* / metabolism
  • Liver Cirrhosis* / pathology
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / therapy
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / therapy
  • Oxidative Stress

Grants and funding

We received educational and research support from Medica Sur Clinic and Foundation.