Non-Alcoholic Fatty Liver Disease and Vitamin D in the UK Biobank: A Two-Sample Bidirectional Mendelian Randomisation Study

Evidence for a role for vitamin D in non-alcoholic fatty liver disease (NAFLD) pathogenesis is conflicting. As Mendelian randomisation (MR) avoids many limitations of conventional observational studies, this two-sample bidirectional MR analysis was conducted to determine the following: (i) whether genetically predicted 25-hydroxyvitamin D [25(OH)D] levels are a risk factor for NAFLD, and (ii) whether genetic risk for NAFLD influences 25(OH)D levels. Single-nucleotide polymorphisms (SNPs) associated with serum 25(OH)D levels were obtained from the European ancestry-derived SUNLIGHT consortium. SNPs associated with NAFLD or NASH (p-value < 1 × 10−5) were extracted from previous studies and supplemented by genome-wide association studies (GWASs) performed in the UK Biobank. These GWASs were done both without (primary analysis) and with (sensitivity analysis) the population-level exclusion of other liver diseases (e.g., alcoholic liver diseases, toxic liver diseases, viral hepatitis, etc.). Subsequently, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran’s Q statistic, MR-Egger regression intercept, MR pleiotropy residual sum and outlier (MR-PRESSO) analyses were used to assess pleiotropy. No causal association of genetically predicted serum 25(OH)D (per standard deviation increase) with risk of NAFLD was identified in either the primary analysis: n = 2757 cases, n = 460,161 controls, odds ratio (95% confidence interval): 0.95 (0.76, −1.18), p = 0.614; or the sensitivity analysis. Reciprocally, no causal association was identified between the genetic risk of NAFLD and serum 25(OH)D levels, OR = 1.00 (0.99, 1.02, p = 0.665). In conclusion, this MR analysis found no evidence of an association between serum 25(OH)D levels and NAFLD in a large European cohort

Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study

Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design: RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results: Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion: Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required

Progress is impossible without change: understanding the evolving nomenclature of steatotic liver disease and its effect on hepatology practice

\ua9 2024The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials

Clinical impact of sexual dimorphism in non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH)

: NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies