Liver fibrosis is the main predictor of events in patients with nonalcoholic fatty liver disease (NAFLD), and its evolution is characterized by a nonlinear trend mostly affected by metabolic risk factors, severity of liver inflammation and steatosis, and weight loss. The rs738409 C>G common variant in PNPLA3 gene has been associated with severity of fibrosis and risk of liver-related events in NAFLD. Noninvasive tests as Fibrosis-4 (FIB-4) and liver stiffness measurement (LSM) are useful to rule-out advanced fibrosis and they could be reliable to predict fibrosis progression. We aimed to evaluate in patients with NAFLD whether PNPLA3 rs738409 C>G variant impacts on fibrosis progression, noninvasively assessed by FIB-4 and LSM.
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Type 2 diabetes and the minor allele of PNPLA3 consistently identify high-risk metabolic dysfunction associated steatotic liver disease.
Diabetes Res Clin Pract
December 2024
The Global NASH Council, Washington, DC, United States; Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, United States; Center for Outcomes Research in Liver Diseases, Washington DC, United States.
Background: Association of genetic factors with non-invasive tests (NITs) for MASLD has not been well established.
Methods: Clinical and laboratory data, liver biopsy and/or liver stiffness measurement (LSM) by transient elastography were collected from MASLD patients seen in tertiary care hepatology practices. Minor allele frequency for genomic loci rs641738 (MBOAT7), rs58542926 (TM6SF2), rs738409 (PNPLA3), rs62305723 (HSD1713B) were evaluated for association with high ELF (≥11.
Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.
Liver Int
October 2024
Regenerative Medicine and Fibrosis Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK.
Article Synopsis
- The PNPLA3 I148M variant is linked to the development of Metabolic Associated Steatosis Liver Disease (MASLD) and contributes to liver fibrosis, but the exact mechanisms are not fully understood.
- Recent studies indicate that this variant impacts the activation of hepatic stellate cells (HSCs) and macrophages, leading to inflammation and fibrosis.
- While findings regarding PNPLA3's function are inconsistent, it has been shown to cause lipid accumulation in liver cells, triggering processes that promote fibrosis through various signaling pathways.
PNPLA3 rs738409, environmental factors and liver-related mortality in the US population.
J Hepatol
October 2024
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address:
Article Synopsis
- The study investigates the link between the PNPLA3 gene variant (rs738409 C>G), environmental factors, and liver-related death (LRD) in a sample of 4,361 adults from NHANES III over a mean follow-up of 23 years.
- It finds that the G-allele of PNPLA3 is associated with a significantly increased risk of LRD, particularly when coupled with non-heavy alcohol intake, high cholesterol consumption, and smoking.
- Additionally, a healthy diet (high in monounsaturated fats and coffee) and lower BMI may reduce the risk linked to the G-allele, indicating that lifestyle choices can influence the genetic risk of LRD.
Global Epidemiological Impact of PNPLA3 I148M on Liver Disease.
Liver Int
October 2024
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased exponentially over the past three decades, in parallel with the global rise in obesity and type 2 diabetes. It is currently the most common cause of liver-related morbidity and mortality. Although obesity has been identified as a key factor in the increased prevalence of MASLD, individual differences in susceptibility are significantly influenced by genetic factors.
View Article and Find Full Text PDFPNPLA3 I148 M genetic variant in autoimmune hepatitis characterises advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related mortality.
J Transl Autoimmun
December 2024
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
Background: Autoimmune hepatitis (AIH) is a relatively rare autoimmune disease with a strong genetic background. The patatin-like phospholipase domain-containing protein 3 () (38409 C/G) variant has been associated with hepatic inflammation and fibrosis in chronic hepatic diseases beyond metabolic dysfunction-associated steatotic liver disease (MASLD).
Aim: Our aim was to investigate the significance of variant in AIH.
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