PNPLA3 as a driver of steatotic liver disease: navigating from pathobiology to the clinics via epidemiology DOI Open Access
Ralf Weiskirchen, Amedeo Lonardo

Journal of Translational Genetics and Genomics, Journal Year: 2024, Volume and Issue: 8(4), P. 355 - 77

Published: Dec. 7, 2024

Steatotic liver disease (SLD), particularly metabolic dysfunction-associated SLD, represents a significant public health concern worldwide. Among the various factors implicated in development and progression of this condition, patatin-like phospholipase domain-containing protein 3 (PNPLA3 ) gene has emerged as critical player. Variants PNPLA3 are associated with altered lipid metabolism, leading to increased hepatic fat accumulation subsequent inflammation fibrosis. Understanding role not only enhances our comprehension pathomechanisms driving SLD but also informs potential therapeutic strategies. The molecular mechanisms through which variants contribute dysregulation hepatocyte injury critically discussed present review article. We extensively analyze clinical cohorts population-based studies underpinning association between polymorphisms risk developing its liver-related protean extrahepatic outcomes, concert other modifiers, notably including age, sex, ethnicity adults children. discuss increasingly recognized played by transplantation, autoimmune hepatitis, acquired immunodeficiency syndrome. Finally, we examine implications diagnostics regarding stratification targeted therapies for patients affected context precision medicine approaches.

Language: Английский

Distinct metabolic perturbations link liver steatosis and incident CVD in lean but not obese PWH DOI Creative Commons
Louise E. van Eekeren, Nadira Vadaq, Marc J. T. Blaauw

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 11, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a key risk factor for cardiovascular (CVD), potentially driven by shared metabolic mechanisms. perturbations associated with MASLD and CVD remain underexplored in people HIV (PWH). We used data from the longitudinal multicenter 2000HIV study comprising 1895 virally suppressed PWH, out of which 970 had available carotid artery measurements. Transient elastography controlled attenuation parameter (CAP) was performed assessment steatosis (CAP > 263 dB/m) fibrosis (LSM ≥ 7.0). Historic future incident within 2-year follow-up, defined as myocardial infarction, stroke, peripheral arterial disease, angina pectoris, were extracted medical files, while atherosclerotic plaque(s) arteries assessed using ultrasonography. analyzed mass spectrometry-based untargeted metabolomics (n = 500 metabolites) nuclear magnetic resonance spectroscopy targeted lipids other metabolites 246 metabolites). PWH more likely to have plaques (47% vs. 36%; P value 0.003) history (11% 6.8%; 0.021) than without steatosis. These associations only significant lean contrast those BMI 25 kg/m2. pathways primarily involved lipid amino acid metabolism, they validated lipoproteomic Interestingly, metabolomic signatures mostly distinct parameters. However, several shared, especially PWH. include arachidonic metabolism formation prostaglandin, purine cholecalciferol glycine, serine, alanine, threonine metabolism. disturbances linked diverge across categories Lean unlike their overweight/obese counterparts, show common between CVD, particularly involving This suggests that may face heightened due pathways, opening avenues interventions, such aspirin therapy, mitigate this risk.

Language: Английский

Citations

0
Challenges of HIV Management in an Aging Population DOI
Alvin G. Thomas, Jennifer Hoy

Current HIV/AIDS Reports, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 12, 2024

Language: Английский

Citations

2
Editorial: Enhancing targeted screening of people living with HIV for liver fibrosis DOI Open Access
Shui Shan Lee, Grace Lui

Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 60(10), P. 1453 - 1454

Published: Oct. 17, 2024

LINKED CONTENT This article is linked to Allende et al paper. To view this article, visit https://doi.org/10.1111/apt.18236 .

Language: Английский

Citations

0
Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study DOI Creative Commons
Louise E. van Eekeren, Quirijn de Mast, Elise M. G. Meeder

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 109, P. 105407 - 105407

Published: Oct. 18, 2024

Language: Английский

Citations

0
PNPLA3 as a driver of steatotic liver disease: navigating from pathobiology to the clinics via epidemiology DOI Open Access
Ralf Weiskirchen, Amedeo Lonardo

Journal of Translational Genetics and Genomics, Journal Year: 2024, Volume and Issue: 8(4), P. 355 - 77

Published: Dec. 7, 2024

Steatotic liver disease (SLD), particularly metabolic dysfunction-associated SLD, represents a significant public health concern worldwide. Among the various factors implicated in development and progression of this condition, patatin-like phospholipase domain-containing protein 3 (PNPLA3 ) gene has emerged as critical player. Variants PNPLA3 are associated with altered lipid metabolism, leading to increased hepatic fat accumulation subsequent inflammation fibrosis. Understanding role not only enhances our comprehension pathomechanisms driving SLD but also informs potential therapeutic strategies. The molecular mechanisms through which variants contribute dysregulation hepatocyte injury critically discussed present review article. We extensively analyze clinical cohorts population-based studies underpinning association between polymorphisms risk developing its liver-related protean extrahepatic outcomes, concert other modifiers, notably including age, sex, ethnicity adults children. discuss increasingly recognized played by transplantation, autoimmune hepatitis, acquired immunodeficiency syndrome. Finally, we examine implications diagnostics regarding stratification targeted therapies for patients affected context precision medicine approaches.

Language: Английский

Citations

0