Are we ready for genetic testing in metabolic dysfunction-associated steatotic liver disease?

United European Gastroenterol J. 2024 Jun;12(5):638-648. doi: 10.1002/ueg2.12556. Epub 2024 Apr 24.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), with its steadily increasing prevalence, represents now a major problem in public health. A proper referral could benefit from tools allowing more precise risk stratification. To this end, in recent decades, several genetic variants that may help predict and refine the risk of development and progression of MASLD have been investigated. In this review, we aim to discuss the role genetics in MASLD plays in everyday clinical practice. We performed a comprehensive literature search of PubMed for relevant publications. Available evidence highlights the emergence of genetic-based noninvasive algorithms for diagnosing fatty liver, metabolic dysfunction-associated steatohepatitis, fibrosis progression and occurrence of liver-related outcomes including hepatocellular carcinoma. Nevertheless, their accuracy is not optimal and application in everyday clinical practice remains challenging. Furthermore, susceptible genetic markers have recently become subjects of great scientific interest as therapeutic targets in precision medicine. In conclusion, decisional algorithms based on genetic testing in MASLD to facilitate the clinician decisions on management and treatment are under growing investigation and could benefit from artificial intelligence methodology.

Keywords: MASH; MASLD; PNPLA3; genetic; metabolic dysfunction associated steatotic liver disease; steatohepatitis.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics
  • Disease Progression
  • Fatty Liver / diagnosis
  • Fatty Liver / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / genetics
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / genetics

Substances

  • Genetic Markers