Risk Of Pancreatitis Research Articles

The causal relationship between the gut microbiota and acute pancreatitis: A 2-sample Mendelian randomization study.

Several observational studies have reported a correlation between the gut microbiota (GM) and the risk of acute pancreatitis (AP). However, the causal relationship between them remains uncertain. We conducted a 2-sample Mendelian randomization (MR) study using pooled data from genome-wide association studies of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) and AP patients. We evaluated the causal relationship between the GM and AP using methods such as inverse-variance weighting, MR-Egger, weighted medians, simple mode, and weighted mode. Cochran Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to examine the heterogeneity, multipotency, and outlier values of the variables, respectively. The reverse causal relationship between AP and the GM was assessed with reverse MR. In total, 5 gut microbial taxa were significantly associated with AP. The inverse-variance weighting results indicated that Acidaminococcaceae (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.66-1.00, P = .045) and Ruminococcaceae UCG004 (OR: 0.85, 95% CI: 0.72-0.99, P = .040) were protective factors against the occurrence of AP. Coprococcus 3 (OR: 1.32, 95% CI: 1.03-1.70, P = .030), Eisenbergiella (OR: 1.13, 95% CI: 1.00-1.28, P = .043), and the Eubacterium fissicatena group (OR: 1.18, 95% CI: 1.05-1.33, P = .006) were risk factors for the development of AP. A comprehensive sensitivity analysis proved our results to be reliable. Reverse MR analysis did not indicate any causal relationship between AP and the GM. This study revealed a complex causal relationship between 5 GM taxa and AP, providing new insights into the diagnostic and therapeutic potential of the GM in AP patients.

Efficacy and safety of uncovered self-expandable metal stents for distal malignant biliary obstruction in unresectable non-pancreatic cancer.

The efficacy of uncovered self-expandable metal stents (UCSEMS) versus fully covered self-expandable metal stents for distal malignant biliary obstruction remains controversial. Additionally, the heterogeneity of the disease conditions has been indicated in previous studies because pancreatic and non-pancreatic cancers have different characteristics in clinical course. Therefore, the etiology of biliary obstruction necessitates investigations stratified by primary disease. This study aimed to evaluate the outcomes of UCSEMS, specifically for non-pancreatic cancer-induced distal malignant biliary obstruction. We conducted a single-center retrospective review to evaluate the time to recurrent biliary obstruction and frequency of adverse events (AEs) in patients receiving UCSEMS for unresectable non-pancreatic cancer-induced malignant biliary obstruction. Overall, 32 patients were enrolled in the study between January 2016 and December 2023. The median time to recurrent biliary obstructionwas 140 days. AE rates were low at 3.1% for both pancreatitis and cholecystitis, suggesting a potential benefit of UCSEMS in reducing post-procedural AEs. UCSEMS may reduce the risk of post-procedural AEs and should be considered in patients at high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. However, the patency period may be shorter, necessitating future comparative research with fully covered self-expandable metal stentsto determine the optimal stent choice.

Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Prediction for post-ERCP pancreatitis in non-elderly patients with common bile duct stones: a cross-sectional study at a major Chinese tertiary hospital (2015–2023)

BackgroundPost-ERCP pancreatitis is one of the most common adverse events in ERCP-related procedures. The purpose of this study is to construct an online model to predict the risk of post-ERCP pancreatitis in non-elderly patients with common bile duct stones through screening of relevant clinical parameters.MethodsA total of 919 cases were selected from 7154 cases from a major Chinese tertiary hospital. Multivariable logistic regression model was fitted using the variables selected by the LASSO regression from 28 potential predictor variables. The internal and external validation was assessed by evaluating the receiver operating characteristic curve and the area under curve. Restricted cubic spline modelling was used to explore non-linear associations. The interactive Web application developed for risk prediction was built using the R “shiny” package.ResultsThe incidence of post-ERCP pancreatitis was 5.22% (48/919) and significantly higher in non-elderly patients with female, high blood pressure, the history of pancreatitis, difficult intubation, endoscopic sphincterotomy, lower alkaline phosphatase and smaller diameter of common bile duct. The predictive performance in the test and external validation set was 0.915 (95% CI, 0.858–0.972) and 0.838 (95% CI, 0.689–0.986), respectively. The multivariate restricted cubic spline results showed that the incidence of pancreatitis was increased at 33–50 years old, neutrophil percentage > 58.90%, hemoglobin > 131 g/L, platelet < 203.04 or > 241.40 × 109/L, total bilirubin > 18.39 umol / L, aspartate amino transferase < 36.56 IU / L, alkaline phosphatase < 124.92 IU / L, Albumin < 42.21 g / L and common bile duct diameter between 7.25 and 10.02 mm. In addition, a web server was developed that supports query for immediate PEP risk.ConclusionThe visualized networked version of the above model is able to most accurately predict the risk of PEP in non-elderly patients with choledocholithiasis and allows clinicians to assess the risk of PEP in real time and provide preventive treatment measures as early as possible.

Pancreatitis with use of new diabetic medications: a real-world data study using the post-marketing FDA adverse event reporting system (FAERS) database.

Background: Pancreatitis is characterized by inflammation of the pancreas and significantly affects quality of life. Less than 5% of pancreatitis cases are drug-induced, but recent evidence suggests a substantial risk associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The aim of this study was to compare the risk of developing pancreatitis between those using GLP-1 RAs and those using sodium-glucose transport protein 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. Methods: This study was done using the FDA Adverse Event Reporting System (FAERS) database from 2019 to 2021. This database contains information from diverse submissions from healthcare providers, patients, and manufacturers. To ensure fairness and accuracy, the risk of pancreatitis associated with other hypoglycemic agents (SGLT2 inhibitors and DPP-4 inhibitors) was also investigated. Traditional and Bayesian statistical analysis methods were used to identify disproportionate statistics and included the reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM), and information component (IC). A drug-adverse-event combination that met the criteria of all four indices was deemed a signal. Results: The analysis of 2,313 pancreatitis reports linked to hypoglycemic agents revealed a predominant association with GLP-1 RA (70.2%) compared to DPP-4 inhibitors (15%) and SGLT2 (14.7%). Most of these reports involved female patients (50.4%), and the highest incidence occurred in those over 50 years old (38.4%). Additionally, 17.7% of the reports were associated with serious events. The ROR was significant for the risk of pancreatitis when using DPP-4 (13.2, 95% confidence interval (CI) 11.84-14.70), while the ROR for GLP-1 was 9.65 (95% CI 9.17-10.16). The EBGM was highest with DPP-4 (12.25), followed by GLP-1 (8.64), while IC was highest with DPP-4 inhibitors (3.61). Liraglutide had the greatest association with pancreatitis among the GLP-1 RAs (ROR: 6.83, 95% CI 6.60-7.07). Conclusion: The findings show that pancreatitis has a strong link with DPP-4 inhibitors and GPL1 agonists, which pose a greater risk. Among the GLP-1 agonist medications, liraglutide has been found to have an association with pancreatitis.

Hypertriglyceridemia-Induced Acute Pancreatitis-The Milky Way Constellation-The Seven-Year Experience of a Large Tertiary Centre.

(1) Background: Hypertriglyceridemia (HTG) is a well-known metabolic condition associated with an increased risk of acute pancreatitis. In this study, we tried to establish whether there are any significant disparities concerning recurrence rate, intensive care unit (ICU) admission, hospital (ICU and total) length of stay (LoS), morphology, severity and age between HTG-induced acute pancreatitis and any other known cause of pancreatitis (OAP). (2) Methods: The research was a retrospective unicentric cohort study, using information from the Bucharest Acute Pancreatitis Index (BUC-API) registry, a database of 1855 consecutive cases of acute pancreatitis. (3) Results: We found a weak association between HTG-AP and recurrence. The HTG-AP patients were younger, with a median of 44.5 years, and had a longer ICU stay than the OAP patients. In addition, we identified that the HTG-AP patients were more likely to develop acute peripancreatic fluid collection (APFC), to be admitted in ICU, to have a more severe course of disease and to be cared for in a gastroenterology ward. (4) Conclusions: Hypertriglyceridemia-induced APs have a more severe course. The typical patient with HTG-AP is a middle-aged male, with previous episodes of AP, admitted in the gastroenterology ward, with a longer ICU stay and longer length of hospitalization, more likely to evolve in a severe acute pancreatitis (SAP) and with a higher probability of developing APFC.

Alcohol Exposure and Disease Associations: A Mendelian Randomization and Meta-Analysis on Weekly Consumption and Problematic Drinking.

Alcohol consumption significantly impacts disease burden and has been linked to various diseases in observational studies. However, comprehensive meta-analyses using Mendelian randomization (MR) to examine drinking patterns are limited. We aimed to evaluate the health risks of alcohol use by integrating findings from MR studies. A thorough search was conducted for MR studies focused on alcohol exposure. We utilized two sets of instrumental variables-alcohol consumption and problematic alcohol use-and summary statistics from the FinnGen consortium R9 release to perform de novo MR analyses. Our meta-analysis encompassed 64 published and 151 de novo MR analyses across 76 distinct primary outcomes. Results show that a genetic predisposition to alcohol consumption, independent of smoking, significantly correlates with a decreased risk of Parkinson's disease, prostate hyperplasia, and rheumatoid arthritis. It was also associated with an increased risk of chronic pancreatitis, colorectal cancer, and head and neck cancers. Additionally, a genetic predisposition to problematic alcohol use is strongly associated with increased risks of alcoholic liver disease, cirrhosis, both acute and chronic pancreatitis, and pneumonia. Evidence from our MR study supports the notion that alcohol consumption and problematic alcohol use are causally associated with a range of diseases, predominantly by increasing the risk.

Extracellular volume fraction derived from dual-energy CT: a potential predictor for acute pancreatitis after pancreatoduodenectomy.

To investigate the value of extracellular volume (ECV) fraction and fat fraction (FF) derived from dual- energy CT (DECT) for predicting postpancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD). This retrospective study included patients who underwent DECT and PD between April 2022 and September 2022. PPAP was determined according to the International Study Group for Pancreatic Surgery (ISGPS) definition. Iodine concentration (IC) and FF of the pancreatic parenchyma were measured on preoperative DECT. The ECV fraction was calculated from iodine map images of the equilibrium phase. The independent predictors for PPAP were assessed by univariate and multivariable logistic regression analysisand receiver operating characteristic (ROC) curve analysis. Sixty-nine patients were retrospectively enrolled (median age, 60 years; interquartile range, 55-70 years; 47 men). Of these, nine patients (13.0%) developed PPAP. These patients had lower portal venous phase IC, equilibrium phase IC, FF, and ECV fraction, and higher pancreatic parenchymal-to-portal venous phase IC ratio and pancreatic parenchymal-to-equilibrium phase IC ratio, compared with patients without PPAP. After multivariable analysis, ECV fraction was independently associated with PPAP (odd ratio [OR], 0.87; 95% confidence interval [CI]: 0.79, 0.96; p < 0.001), with an area under the curve (AUC) of 0.839 (sensitivity 100.0%, specificity 58.3%). A lower ECV fraction is independently associated with the occurrence of PPAP after PD. ECV fraction may serve as a potential predictor for PPAP after PD. DECT-derived ECV fraction of pancreatic parenchyma is a promising biomarker for surgeons to preoperatively identify patients with higher risk for postpancreatectomy acute pancreatitis after PD and offer selective perioperative management. PPAP is a complication of pancreatic surgery, early identification of higher-risk patients allows for risk mitigation. Lower DECT-derived ECV fraction was independently associated with the occurrence of PPAP after PD. DECT aids in preoperative PAPP risk stratification, allowing for appropriate treatment to minimize complications.

ADVERSE EVENTS ASSOCIATED WITH GLP1–RECEPTOR AGONISTS TREATMENT IN DIABETIC PATIENTS WITH HIGH CARDIOVASCULAR RISK: A META–ANALYSIS

Abstract Background GLP1–receptor agonists (GLP1–RA) have been associated with a reduction of cardiovascular (CV) outcomes in diabetic patients with high cardiovascular risk. However, these drugs have some adverse effects. The aim of this study was to assess the relative risk (RR) of adverse effects in patients with a high risk of developing CV disease treated with GLP1–agonists. Methods we considered randomized controlled trials (RCTs) aimed to assess the cardiovascular effects of GLP1–RA in diabetic patients with high CV risk. The following outcomes were explored: pancreatitis, severe hypoglycemia, renal and urinary serious adverse events (SAE), gastrointestinal SAE and AE, pancreatic cancer, and neoplasms. Results 8 RCTs, enrolling 60008 patients, were included in the analysis. There was no difference between GLP1–RA and placebo in the risk of pancreatitis (RR 0.99; 95% CI 0.73–1.35; p=0.972), severe hypoglycemia (0.93; 95% CI 0.76–1.15; p=0.501), renal and urinary SAE (0.94; 95% CI 0.82–1.07; p=0.339), pancreatic cancer (RR 0.98; 95% CI 0.56–1.70; p=0.936) and neoplasms (RR 1.02; 95% CI 0.95–1.09; p=0.547) (Fig 1 A e B). Conversely, GLP1–agonist treatment was associated with an increased risk of gastrointestinal AE (RR 1.95; 95% CI 1.23–3.06; p=0.004) (Fig 2). However, when gastrointestinal SAE were considered, GLP1–agonists demonstrated similar risk compared to placebo (RR 1.09; 95% CI 0.92–1.28; p= 0.318) (Fig 2). Conclusion in diabetic patients with high cardiovascular risk, the treatment with GLP1–RA has been associated with an increased risk of gastrointestinal AE. No difference in severe gastrointestinal AE has been associated with GLP1–RA.

The effect of incretin-based drugs on the riks of acute pancreatitis: a review.

In recent years, new hypoglycaemic drugs that affect the incretin system have become increasingly popular in the treatment of type 2 diabetes mellitus (T2DM): glucagon-like receptor 1 agonists (GLP1RAs), dipeptidyl peptidase 4 inhibitors (DPP4is) and the recently developed dual glucagon-like receptor 1 agonist and glucose-dependent insulinotropic polypeptide (tirzepatide). Their main role of these drugs is to normalise blood glucose levels. In addition, GLP1RAs are approved for the treatment of excessive body weight. The efficacy of drugs affecting the incretin system is well described in the literature, however, there are still only few reports about their safety. This review aims to summarize the results of current research and meta-analyses on risk of acute pancreatitis (AP) during incretin-affecting drugs treatment. A narrative review was performed using present literature in an attempt to identify the relationship between AP and incretin-affecting drugs. The following keywords were used: acute pancreatitis, glucagon-like receptor 1 agonists, dipeptidyl peptidase 4 inhibitors and tirzepatide. It was demonstrated that the use of DPP4is is safe for the majority of patients with T2DM, whereas a risk of AP should be noted in case of GLP1RAs therapy. To date, most studies found no significant association between tirzepatide therapy and the increased risk of AP. The majority of studies have shown that DPP4is, GLP1RAs and tirzepatide are effective and safe in most T2DM patients. However, the follow-up time for patients treated with tirzepatide is short, therefore more studies are required to confirm the safety of this drug.

Gallstones as a cause in presumed acute alcoholic pancreatitis: observational multicentre study.

Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis. Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up. A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038). Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.

Early detection of severe hypertriglyceridemia using teleconsultation in a clinical laboratory setting

BackgroundTeleconsultation in the context of clinical laboratories is a valuable tool for the early detection of dyslipidemia and prevention of cardiovascular risk. Here, we describe a patient who was referred to the Lipid Unit of the Virgen Macarena Hospital due to an alert for severe hypertriglyceridemia through its teleconsultation program. Case presentationA comprehensive clinical and biochemical study of the patient was carried out, and genetic testing was performed on the patient and his family. The proband and his family showed mild to severe hypertriglyceridemia and various secondary factors, together with a genetic background associated with a triglyceride-raising effect. ConclusionThis extensive study has identified a family at high risk of cardiovascular disease and acute pancreatitis. These findings can help maximize lifestyle changes and improve the clinical management of their dyslipidemia.

Risk of acute pancreatitis among new users of empagliflozin compared to sulfonylureas in patients with type 2 diabetes: A post-authorization safety study.

This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.

Multicenter comparative study on the usefulness of the optimal electrosurgical unit setting in endoscopic papillectomy for ampullary neoplasms (with video).

Endoscopic papillectomy (EP) is less invasive than surgery but procedure-related adverse events (AEs) still frequently occur. This study compared the benefits of EP using a new optimal endoCUT setting on the VIO (Erbe) electrosurgical unit (VIO-EP) with those using the conventional electrosurgical unit setting (ICC-EP, Erbe). This multicenter, retrospective, comparative cohort study included 57 patients who underwent VIO-EP and 91 who underwent ICC-EP. The primary outcome was occurrence of EP-related AEs. Secondary outcomes were pathological findings (the resection margins, the R0 resection, and residual lesions). Pancreatitis tended to be less common in the VIO-EP group (5.3% vs. 9.9%, p = .248). Evaluation of computed tomography images showed that pancreatitis was confined to the pancreatic head in 77.8% of cases in the ICC-EP group and in 33.3% of those in the VIO-EP group. After exclusion of cases of delayed bleeding, pancreatitis tended to be less common in the VIO-EP group; this finding was not statistically significant (2.3% vs. 8.2%, p = .184). In pathological findings, residual lesions were significantly less common in the VIO-EP group. The risks of pancreatitis and residual lesions after EP may be lower when the VIO electrosurgical unit is used with the optimal setting.

A quality improvement project to improve treatment of severe hypertriglyceridemia in veterans.

Severe hypertriglyceridemia (sHTG) is associated with an increased risk of acute pancreatitis. Prompt recognition and treatment of sHTG is key for prevention of acute pancreatitis and its associated life-threatening complications. Patients with sHTG at a primary care clinic within the Veterans Affairs Eastern Colorado Health Care System were receiving suboptimal treatment that did not align with evidence-based guidelines. We initiated a quality improvement (QI) project to improve the management of sHTG in an outpatient primary care clinic. Veterans with a triglyceride level between 500 and 1,500 mg/dl were included in the project. Project interventions included provider education, patient education, and targeted electronic consultations (e-consults) with treatment recommendations. The primary outcome was to decrease the percentage of patients with triglycerides ≥500 mg/dl by 25%. The secondary outcome was to decrease the mean triglyceride level of the patient population by 15%. Education on evaluation and treatment of sHTG was given to 100% (n = 21) of primary care clinicians. Overall, 72.8% (95% CI [62.6-81.6%]) of patients (n = 67) received appropriate written education materials, and 72.8% (95% CI [62.6-81.6%]) of patients (n = 67) received a targeted e-consult. The percentage of patients with sHTG decreased by 47%. Average triglyceride level decreased from 651 to 483 mg/dl (25.8% decrease). A multipronged QI project consisting of provider education, patient education, and targeted e-consults resulted in decreased triglyceride levels and improved access to specialist expertise. Clinical implications include decreased prevalence of sHTG and risk of acute pancreatitis among patients in the project.

Familial chylomicronemia syndrome: case reports of siblings with deletions of the GPIHBP1 gene

BackgroundFamilial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1).Case presentationA 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior. His elder brother also demonstrated an elevated triglyceride level of 2133 mg/dL at the age of 9. Lipoprotein electrophoresis revealed the presence of chylomicrons, an increase in the proportion of pre-beta lipoproteins, and low serum lipoprotein lipase levels. The patient’s parents and first elder brother had stable lipid profiles. For suspected FCS, genetic testing was performed using the next-generation sequencing-based analysis of 31 lipid metabolism-associated genes, which revealed no pathogenic variants. However, copy number variant screening using sequencing depth information suggested large heterozygous deletion encompassing all the coding exons of GPIHBP1. A real-time quantitative polymerase chain reaction was performed to validate the deletion site. The results showed that the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. During the follow-up period of 17 months, the patient did not develop pancreatitis, following dietary intervention.ConclusionThese siblings’ case of familial chylomicronemia syndrome caused by rare GPIHBP1 deletions highlight the implementation of copy number variants—beyond next-generation sequencing—as an important consideration in diagnosis. Accurate genetic diagnosis is necessary to establish the etiology of severe hypertriglyceridemia, which increases the risk of pancreatitis.

Association of polymorphic loci of the GSS gene with the risk of acute biliary pancreatitis

Aim. To investigate the role of single nucleotide polymorphisms (SNPs) rs13041792, rs1801310, and rs6088660 in the GSS gene and environmental factors in the development of acute biliary pancreatitis (ABP) and its complications.Materials and methods. The material for the study was blood samples obtained from 84 patients with ABP and 573 healthy individuals. Both groups were comparable in terms of gender and age. To diagnose ABP, we used the clinical guidelines recommended by the working group of the Russian Society of Surgeons. DNA was isolated by phenol / chloroform extraction. Multiplex genotyping of SNPs was performed by the iPLEX assay on the MALDITOF MassARRAY-4 genetic analyzer. Statistical data processing was performed using Statistica 10 and SNPStats software.Results. We found that insufficient consumption of fresh vegetables and fruits increased the probability of ABP in carriers of genotypes G/A-A/A at rs1801310 in GSS (р = 0.02). The analysis revealed the association of the T allele at rs6088660 with the odds for developing acute pancreatitis (р = 0.007) and digestive fistulas (р = 0.02). A high probability of death was associated with rs1801310 (G/A genotype, р = 0.002) and rs6088660 (C/T genotype, р = 0.01) in the GSS gene.Conclusion. SNPs rs6088660 and rs1801310 in the GSS gene can be used to predict the course of ABP.

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. 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. 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). 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.

Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia

Severe hypertriglyceridemia (sHTG) confers increased risk of atherosclerotic cardiovascular disease (ASCVD), nonalcoholic steatohepatitis, and acute pancreatitis. Despite available treatments, persistent ASCVD and acute pancreatitis-associated morbidity from sHTG remains. To determine the tolerability, efficacy, and dose of plozasiran, an APOC3-targeted small interfering-RNA (siRNA) drug, for lowering triglyceride and apolipoprotein C3 (APOC3, regulator of triglyceride metabolism) levels and evaluate its effects on other lipid parameters in patients with sHTG. The Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2) was a placebo-controlled, double-blind, dose-ranging, phase 2b randomized clinical trial enrolling adults with sHTG at 74 centers across the US, Europe, New Zealand, Australia, and Canada from May 31, 2021, to August 31, 2023. Eligible patients had fasting triglyceride levels in the range of 500 to 4000 mg/dL (to convert to millimoles per liter, multiply by 0.0113) while receiving stable lipid-lowering treatment. Participants received 2 subcutaneous doses of plozasiran (10, 25, or 50 mg) or matched placebo on day 1 and at week 12 and were followed up through week 48. The primary end point evaluated the placebo-subtracted difference in means of percentage triglyceride change at week 24. Mixed-model repeated measures were used for statistical modeling. Of 229 patients, 226 (mean [SD] age, 55 [11] years; 176 male [78%]) were included in the primary analysis. Baseline mean (SD) triglyceride level was 897 (625) mg/dL and plasma APOC3 level was 32 (16) mg/dL. Plozasiran induced significant dose-dependent placebo-adjusted least squares (LS)-mean reductions in triglyceride levels (primary end point) of -57% (95% CI, -71.9% to -42.1%; P < .001), driven by placebo-adjusted reductions in APOC3 of -77% (95% CI, -89.1% to -65.8%; P < .001) at week 24 with the highest dose. Among plozasiran-treated patients, 144 of 159 (90.6%) achieved a triglyceride level of less than 500 mg/dL. Plozasiran was associated with dose-dependent increases in low-density lipoprotein cholesterol (LDL-C) level, which was significant in patients receiving the highest dose (placebo-adjusted LS-mean increase 60% (95% CI, 31%-89%; P < .001). However, apolipoprotein B (ApoB) levels did not increase, and non-high-density lipoprotein cholesterol (HDL-C) levels decreased significantly at all doses, with a placebo-adjusted change of -20% at the highest dose. There were also significant durable reductions in remnant cholesterol and ApoB48 as well as increases in HDL-C level through week 48. Adverse event rates were similar in plozasiran-treated patients vs placebo. Serious adverse events were mild to moderate, not considered treatment related, and none led to discontinuation or death. In this randomized clinical trial of patients with sHTG, plozasiran decreased triglyceride levels, which fell below the 500 mg/dL threshold of acute pancreatitis risk in most participants. Other triglyceride-related lipoprotein parameters improved. An increase in LDL-C level was observed but with no change in ApoB level and a decrease in non-HDL-C level. The safety profile was generally favorable at all doses. Additional studies will be required to determine whether plozasiran favorably modulates the risk of sHTG-associated complications. ClinicalTrials.gov Identifier: NCT04720534.

Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.