Nonalcoholic Fatty Liver Disease Risk and Proprotein Convertase Subtilisin Kexin 9 in Familial Hypercholesterolemia Under Statin Treatment

Nutrients. 2024 Oct 29;16(21):3686. doi: 10.3390/nu16213686.

Abstract

Background/objectives: Fatty acids are involved in some hepatic disorders. The proprotein convertase subtilisin kexin 9 (PCSK9) inhibits the uptake of low-density lipoproteins (LDLs), which contain lipids, into the liver and may thus be associated with nonalcoholic fatty liver disease (NAFLD), a cardiovascular disorder (CVD) risk. Statins reduce blood LDL-cholesterol (LDL-C) levels and CVD risk and can attenuate the development of NAFLD while increasing blood PCSK9 levels.

Methods: We investigated the correlation between PCSK9 and liver conditions in patients with familial hypercholesterolemia (FH), a CVD risk population with elevated blood LDL-C levels, under statin treatment. Blood tests for lipids, PCSK9, and liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were performed in patients with FH taking statins (n = 25, mean age = 57 years, 12% of males). The ALT:AST ratio was used as a marker of NAFLD risk.

Results: The mean LDL-C level was 3.38 mmol/L, and the median PCSK9 level was 312 ng/mL. The median ALT:AST ratio was 0.88. A significant negative correlation was observed between the PCSK9 and ALT:AST ratio (β = -0.67, p < 0.05).

Conclusions: Their negative correlation might give a hypothetical insight into the effect of statin treatment on the development of NAFLD, in relation to PCSK9 behavior, in patients with FH.

Keywords: HMG-CoA reductase inhibitor; fatty acids; fatty liver disease; lipid-lowering therapy.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Cholesterol, LDL* / blood
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hyperlipoproteinemia Type II* / blood
  • Hyperlipoproteinemia Type II* / drug therapy
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease* / blood
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Proprotein Convertase 9* / blood
  • Risk Factors

Substances

  • Proprotein Convertase 9
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 protein, human
  • Cholesterol, LDL
  • Alanine Transaminase
  • Aspartate Aminotransferases
  • Biomarkers

Grants and funding

This research received no external funding.