Background: Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide and is associated with the risk of many extrahepatic diseases. However, whether NAFLD is a risk marker or a common cause of extrahepatic diseases is unclear.
Methods: We searched PubMed to identify NAFLD-related extrahepatic diseases. Genetic instrumental variables (IVs) for NAFLD surrogated by chronically elevated alanine transaminase levels and eligible extrahepatic diseases were retrieved from the corresponding genome-wide association analysis. We proposed a procedure for Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and extrahepatic diseases. The Bonferroni method was used to correct the bias of multiple testing.
Results: In total, 34 extrahepatic diseases were included and 54 SNPs were used as IVs for NAFLD. The MR analysis gave a robust and significant (or suggestive) estimate for the association between NAFLD and 9 extrahepatic diseases: type 2 diabetes (odds ratio [OR] = 1.182, 95 % confidence interval [CI] 1.125-1.243, P = 5.40 × 10), cholelithiasis (OR = 1.171, 95%CI 1.083-1.266, P = 7.47 × 10), diabetic hypoglycemia (OR = 1.170, 95%CI 1.071-1.279, P = 5.14 × 10), myocardial infarction (OR = 1.122, 95%CI 1.057-1.190, P = 1.46 × 10), hypertension (OR = 1.060, 95%CI 1.029-1.093, P = 1.18 × 10), coronary artery disease (OR = 1.052, 95%CI 1.010-1.097, P = 1.58 × 10), heart failure (OR = 1.047, 95%CI 1.006-1.090, P = 2.44 × 10), dementia (OR = 0.881, 95%CI 0.806-0.962, P = 5.01 × 10), and pancreatic cancer (OR = 0.802, 95%CI 0.654-0.983, P = 3.32 × 10). Validation analyses using IVs from biopsy-confirmed and imaging-determined NAFLD reported similar results to the main analysis. For the remaining 25 outcomes, no significant or definitive association was yielded in MR analysis.
Conclusions: Genetic evidence suggests putative causal relationships between NAFLD and a set of extrahepatic diseases, indicating that NAFLD deserves high priority in clinical practice.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.metabol.2022.155270 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Risk of Serious Bacterial and Non-Bacterial Infections in People With MASLD.
Liver Int
April 2025
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease globally. MASLD is a multisystem disease where metabolic dysfunction plays a key role in the development of MASLD and its most relevant liver-related morbidities and extrahepatic complications, such as cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers. Among the least examined MASLD-related extrahepatic complications, an ever-increasing number of observational studies have reported a positive association between MASLD and the risk of serious bacterial infections (SBI) requiring hospital admission.
View Article and Find Full Text PDF[Hepatocellular carcinoma (HCC)].
Med Trop Sante Int
December 2024
AP-HP. Centre Université Paris Centre, Groupe hospitalier Cochin Port Royal, Département médical universitaire de Cancérologie et spécialités médico-chirurgicales, Service des maladies du foie, Paris, France; Université Paris Cité, F-75006, Paris, France.
Primary liver cancers are tumors that develop from different liver cells. Hepatocellular carcinoma (HCC), which develops from hepatocytes, accounts for approximately 75-85% of primary liver cancers.HCC is the 6 leading cause of cancer worldwide and the 3 leading cause of cancer-related death.
View Article and Find Full Text PDFGut microbiota analysis in cirrhosis and non-cirrhotic portal hypertension suggests that portal hypertension can be main factor of cirrhosis-specific dysbiosis.
Sci Rep
March 2025
Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation.
Gut dysbiosis plays an important role in cirrhosis, but the mechanism of its development was not established. The aim of the study was to test the hypothesis that portal hypertension can be the main factor in the development of gut dysbiosis in cirrhosis. This cross-sectional study included 25 patients with chronic non-cirrhotic portal hypertension due to extrahepatic portal vein obstruction after portal vein thrombosis (PVT) (NCPVT group), 29 cirrhotic patients without PVT (CirNoPVT), 15 cirrhotic patients with chronic PVT (CPVT), and 22 healthy controls.
View Article and Find Full Text PDFA Markov Model Unveiling the Impact of Resmetirom on the Natural History of MASLD Patients: A Sistematic Review and Meta-Analysis.
Liver Int
April 2025
Section of Gastroenterology and Hepatology, Department of Health Promotion, Maternal and Child Health, Internal and Specialty Medicine of Excellence (PROMISE), University of Palermo, Palermo, Italy.
Background And Aim: The MAESTRO-NASH phase 3 trial reported that a 52-week treatment of Resmetirom is effective in improving fibrosis and metabolic dysfunction-associated steatohepatitis (MASH) in patients with MASH and F2 or F3 fibrosis, while data on the impact on 5-year and long-term clinical outcomes are still lacking. We simulated the transition probabilities of disease progression in MASLD patients with F2 or F3 fibrosis and the effect of Resmetirom treatment on clinical outcomes.
Methods: A meta-analysis of literature data formed transition matrices for fibrosis stages and complications, defined as compensated (CC) and decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and mortality-liver-related mortality (LR-M), cardiovascular mortality (CV-M) and extra-hepatic cancer mortality (EHC-M).
The Effect of Nonalcoholic Fatty Liver Disease on Extrahepatic Cancers: Evidence From Population-Based Cohort and Mendelian Randomization.
Health Sci Rep
March 2025
Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital Capital Medical University Beijing China.
Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is an escalating global health concern with significant implications for cancers. A better understanding of the causal relationship between NAFLD and extrahepatic cancers might help in clinical management of NAFLD and prevent its adverse outcomes.
Methods: This study encompassed two complementary approaches.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!