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Background: Most of hepatocellular carcinoma (HCC) arises on the background of chronic inflammation. The presence of infiltrating inflammatory cells is associated with tumour initiation, progression and clinical response to treatment. The influence of white blood cell (WBC) subtype counts on HCC progression remains unclear. Methods: In this study, we performed a Mendelian randomization (MR) study with the validation of two datasets. The summary data for WBC counts were extracted from a recent large GWAS of individuals of European ancestry. The GWAS data related to HCC were obtained from the UK Biobank (UKB). Univariable and multivariable MR analyses were used to identify risk factors genetically associated with HCC risks. Results: In the discovery dataset, multivariable MR analysis revealed that sum basophil neutrophil counts had an independent causal effect on the occurrence of HCC, with the sum basophil neutrophil counts as follows: (OR = 0.437, P = 0.003, CI 0.252–0.757). Similarly, in the validation dataset, total basophil neutrophil counts were also been identified as an independent risk factor for HCC. The sum basophil neutrophil counts were as follows: (OR = 0.574, P = 0.021, CI 0.358–0.920). Conclusion: In the European population, genetically predicted lower total basophil neutrophil counts might be an independent risk factor for HCC. [ABSTRACT FROM AUTHOR]

Introduction: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas., Methods: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content., Results: Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179-1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058-1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132-1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192-7.234), pancreatic cancer (HR 1.976, 95% CI 1.054-3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122-1.593, P = 0.001)., Discussion: FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)