Risk Of Pancreatitis Research Articles

Pancreatic involvement in celiac disease.

Celiac disease (CD) is well recognized as a systemic, chronic autoimmune disease mainly characterized by gluten-sensitive enteropathy in genetically predisposed individuals but with various extraintestinal features. One of the affected organs in CD is the pancreas, consisting of both endocrine and exocrine alterations. Over the last decades there has been increasing interest in the pancreatic changes in CD, and this has been reflected by a great number of publications looking at this extraintestinal involvement during the course of CD. While pancreatic endocrine changes in CD, focusing on type 1 diabetes mellitus, are well documented in the literature, the relationship with the exocrine pancreas has been less studied. This review summarizes currently available evidence with regard to pancreatic exocrine alterations in CD, focusing on risk of pancreatitis in CD patients, association with autoimmune pancreatitis, prevalence and outcomes of pancreatic exocrine insufficiency in newly diagnosed and gluten-free diet treated CD patients, and the link with cystic fibrosis. In addition, we discuss mechanisms behind the associated pancreatic exocrine impairment in CD and highlight the recommendations for clinical practice.

Risk Factors and Clinical Presentation in Dogs with Increased Serum Pancreatic Lipase Concentrations-A Descriptive Analysis.

Simple SummaryOver the past several years, there has been an increasing importance placed on clinical presentation as part of a diagnosis of pancreatitis, and yet there is comparatively little data investigating the full array of clinical signs that may be seen in dogs with pancreatitis. Our study showed that dogs with increased pancreatic lipase immunoreactivity concentrations could display a wide range of clinical signs, which may be related to pancreatitis or a concurrent disease. Non-specific clinical signs, such as anorexia, were prevalent. Additionally, overt abdominal pain was infrequently reported, and veterinarians should be cautious in ruling out pancreatitis due to a lack of abdominal pain alone. Additionally, limited data is available on potential risk factors for pancreatitis in dogs; this information could be important in the development of disease prevention strategies. In our study, the most common concurrent disease was hepatobiliary abnormalities. Additional studies are needed to determine whether this is a causative or associative relationship. Drug use reflected common prescribing practices, and anti-epileptic drug use was low despite prior studies documenting clear associations between phenobarbital and potassium bromide and drug-associated pancreatitis. Adult maintenance diets, in addition to human foods and dog treats, were commonly fed prior to the development of an increased pancreatic lipase concentration.Limited data exist regarding the full array of clinical signs seen in dogs with pancreatitis and potential risk factors for the disease. Laboratory submissions from the Gastrointestinal Laboratory at Texas A&M University were retrospectively reviewed for dogs with an increased serum pancreatic lipase immunoreactivity (cPLI) concentration (≥400 µg/L), and an internet-based survey was distributed to the attending veterinarian and/or technician on each case. The survey contained questions related to (i) clinical signs, (ii) prior gastrointestinal upset, (iii) comorbidities, (iv) pre-existing medical therapies, and (v) dietary history. One hundred and seventy (170) survey responses were recorded. The top three clinical signs reported were inappetence (62%), diarrhea (53%), and vomiting (49%). Abdominal pain was noted in only 32% of dogs, likely associated with poor pain detection. Additionally, the majority of dogs (71%) had prior episodes of gastrointestinal upset within the past 12 months, lending support for the commonality of recurrent acute pancreatitis, or acute on chronic disease. Hepatobiliary abnormalities (24%) were the most common concurrent disease, and endocrine disorders were seen in a low proportion of respondents (5–8%). Adult maintenance diets (65%), dog treats (40%), and human foods (29%) were commonly consumed by dogs prior to the discovery of increased cPLI concentration.

Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study

BackgroundAssessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.MethodsWe used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6–7 years follow up.ResultsTriglyceride concentration was available for 1,530,411 individuals (mean age 56·6 ± 15·6 years, 51·4% female), with a median of 1·3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0·21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13·55 (95% CI 9·15–20·06)); chronic pancreatitis (HR 25·19 (14·91–42·55)); and high risk for diabetes (HR 5·28 (4·51–6·18)) and all-cause mortality (HR 3·62 (2·82–4·65)) when compared to the reference category of ≤ 1·7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those ≤ 40 years compared to > 40 years.ConclusionsWe highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.

Effects of age, obesity, and body surface area on asparaginase-associated toxicities during acute lymphoblastic leukemia induction therapy: A report from the Children’s Oncology Group.

7000 Background: Asparaginase is integral to pediatric-inspired regimens (PIR) to treat acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). However, asparaginase-associated toxicities (AAT) often preclude delivery of planned therapy. Older age, obesity and/or large body surface area (BSA) have been associated with higher risk of AAT in PIR, but data are conflicting, and the impact of dose modification based on these factors is unknown. Methods: We examined induction toxicity data from patients ages 1-30 years enrolled in the frontline Children’s Oncology Group (COG) trials for high-risk B-ALL (AALL0232, 2004-2011) and T-ALL (AALL0434, 2007-2014). During Induction, patients received pegaspargase (2,500 IU/m2 without prescribed dose-capping) plus daunorubicin, vincristine, and prednisone or dexamethasone. AAT were defined as CTCAE v4 hyperbilirubinemia (Grade ≥3), elevated alanine aminotransferase (ALT) (Grade ≥4), thrombosis (any), or pancreatitis (any, included consolidation phase). Obesity was classified using population norms as body mass index (BMI) ≥30 (or ≥95th percentile for age/sex). BSA was analyzed continuously and dichotomized at 1.5 m2 (equivalent to pegaspargase 3,750 IU, the threshold for permissible dose-capping in PIR). The association of AAT with end-Induction minimal residual disease (MRD) ≥0.01% was assessed. Results: Among 4,925 patients, 25% were ≥15 years, 39% had BSA >1.5m2, and 18% had obesity. Multivariable logistic analyses inclusive of BMI and BSA together found increased risk for any AAT in age groups ≥10 years (10-15y, odds ratio (OR) 2.0, 15-20y OR 2.2, ≥21 OR 3.3, p=0.002). Only patients with both obesity and high BSA (>1.5m2) were at additional risk (OR 3.3, p<0.0001). Similarly, risks for hyperbilirubinemia, ALT elevations, and thrombosis were increased in patients with both high BSA and obesity (OR 3.5, 95% confidence interval [CI] 2.2-5.7), OR 3.3, 95%CI 1.7-6.6, and OR 3.1 95%CI 1.5-6.5, respectively), but not in those with high BSA without obesity. The risk of hyperbilirubinemia was greater with increasing obesity (p<0.0001) and was also higher in all age groups ≥10 years (OR 6.3-7.9, p<0.0001). Age was not associated with thrombosis or ALT elevation; risk for pancreatitis was associated with Hispanic ethnicity, but not with age, BMI, or BSA. AAT were not associated with pooled trial MRD ≥0.01%. Conclusions: We report here the largest dataset of AAT in children and AYAs receiving ALL Induction therapy without routinely prescribed dose-capping of pegaspargase. Risk for AAT was increased in patients >10 years and in those with obesity, but not high BSA alone. Dose capping may not be necessary for children and AYAs with high BSA without obesity. Prospective studies of AAT pharmacogenomics and modifiable risk factors will support safer dosing in PIR. Clinical trial information: NCT00075725, NCT00408005.

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally. We found strong enrichment of CTRC variants p.A73T, p.V235I, p.K247_R254del, and p.R245W in CP cases versus controls, yielding OR values of 6.5 (95% confidence interval (CI) 2.4–17.8), 4.5 (CI 2.2–9.1), 5.4 (CI 2.6–11.0), and 2.6 (CI 1.6–4.2), respectively. Subgroup analysis demonstrated disease association of variants p.K247_R254del and p.R245W in alcoholic CP with similar effect sizes as seen in the overall CP group. Homozygosity or compound heterozygosity were rare and seemed to be associated with higher risk. We also identified a so far unreported linkage disequilibrium between variant p.K247_R254del and the common c.180C>T (p.G60 =) haplotype. Taken together, the results indicate that heterozygous loss-of-function CTRC variants increase the risk for CP approximately 3-7-fold. This meta-analysis confirms the clinical significance of CTRC variants and provides further justification for the genetic screening of CP patients.

The Integral Method for Predicting the Risk of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

The objective: development of a method for determining the individual risk of post-ERCP pancreatitis (PEP) before endoscopic intervention.Subjects and Methods. A prospective observational study of the results of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) was performed in 1,210 patients. The primary end point was the development of PEP. Multiple regression logistic analysis was used to determine the risk of developing PEP.Results. A model of independent variables was determined, which significantly (p = 0.0001) affected the risk of developing PEP. Based on the results of the logistic analysis, regression coefficients were calculated for all significant patient-dependent factors (gender, age, preoperative level of amylasemia and bilirubinemia, and nature of the underlying disease). The risk of PEP decreased in men (by 47.5%), with an increase in the age of patients (for 1 year by 2.3%) and bilirubin (with an increase of 1 μmol/l by 0.3%) but increased with an increase in amylase activity blood serum (by 0.7% for each 1 U/l). A formula has been developed to assess the individual risk of PEP at the stage of preparing a patient for therapeutic ERCP.Conclusion. Analysis of patient-dependent factors makes it possible to reliably determine the risk of developing PEP. It was determined that a female gender, young age (under 40 years old), sphincter of Oddi dysfunction increased the risk of PEP, while a male sex, stenting of the main pancreatic duct, and jaundice reduced this risk. The use of the proposed formula will help predict a significant (p = 0.0001) degree of risk of PEP before performing primary therapeutic ERCP in a particular patient.

Abstract #1185032: A case of early-onset severe hypertriglyceridemia found with monogenic chylomicronemia during adulthood

Severe hypertriglyceridemia is defined as a serum triglyceride (TG) level above 1000mg/dL. Compared with moderate hypertriglyceridemia, which is more common, severe hypertriglyceridemia is present in 0.4% of general population. The latter owns a risk of recurrent pancreatitis, and the need of intensive care unit and mortality is higher compared to cases of pancreatitis with normal TG levels. Evaluation of severe hypertriglyceridemia should consist of assessment of underlying conditions and consideration of genetic testing for lipoprotein lipase (LPL) and its regulating genes.

Abstract #1185191: Acquired Generalized Lipodystrophy Presenting As Severe Insulin Resistance

Roughly 100-150 cases are reported in the literature of acquired generalized lipodystrophy (AGL). This rare disorder is characterized by leptin deficiency resulting from low adipose mass and metabolic derangements such as hypertriglyceridemia and severe insulin resistance. These metabolic derangements lead to increased risk for pancreatitis, nonalcoholic fatty liver disease, and adverse cardiovascular events. The most common progression of AGL is onset of symptoms in childhood or adolescence with progression of complications into adulthood.

Investigation of the potential association between the use of fluoxetine and occurrence of acute pancreatitis: a Danish register-based cohort study.

BackgroundThere is currently conflicting evidence of the association between the use of selective serotonin reuptake inhibitors (SSRIs) and acute pancreatitis. The SSRI fluoxetine has been suspected to be the driver of this serious outcome. Therefore, this study aims to investigate the potential association between fluoxetine use and the occurrence of acute pancreatitis.MethodsWe conducted a nationwide cohort study using Danish register-based data from 1996 to 2016. The exposed group were new users of fluoxetine (1-year washout). The control subjects were new users of citalopram or SSRIs, excluding fluoxetine. The outcome was an incident diagnosis of acute pancreatitis with a 5-year washout. We used an intention-to-treat approach following patients for a maximum of 6 months. Cox regression analyses were performed, estimating hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age/sex, comorbidities and co-medications, using propensity score adjustment and matching.ResultsIn the propensity score-matched analyses, 61 783 fluoxetine users were included. The incidence rates among users of fluoxetine and other SSRIs were 5.33 (3.05–8.66) and 5.36 (3.06–8.70) per 10 000 person-years, respectively. No increased risk of acute pancreatitis was identified following fluoxetine exposure compared with either citalopram [HR 1.00, 95% CI 0.50–2.00) or other SSRIs (0.76, 0.40–1.46).ConclusionsFluoxetine use was not associated with an increased risk of acute pancreatitis compared with citalopram or other SSRIs. The absolute risk of acute pancreatitis was low and did not vary between different SSRIs. Further research is needed to determine whether there is a class effect on the risk of acute pancreatitis.

The Evolving Story of Multifactorial Chylomicronemia Syndrome.

Multifactorial chylomicronemia syndrome (MCS or type V hyperlipoproteinemia) is the most frequent cause of severe hypertriglyceridemia and is associated with an increased risk of acute pancreatitis, cardiovascular disease, and non-alcoholic steatohepatitis. The estimated prevalence of MCS in the North American population is 1:600–1:250 and is increasing due to the increasing prevalence of obesity, metabolic syndrome, and type 2 diabetes. Differentiating between familial chylomicronemia syndrome and MCS is crucial due to their very different treatments. In recent years, several cohort studies have helped to differentiate these two conditions, and recent evidence suggests that MCS itself is a heterogeneous condition. This mini-review will summarize recent literature on MCS, with a specific focus on the genetic determinants of the metabolic risk and the latest developments concerning the pharmacological and non-pharmacological treatment options for these patients. Possible research directions in this field will also be discussed.

NSAIDs are not enough - a double blinded randomized controlled trial on the impact of intensive hydration for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

Pancreatitis is the most common complication following endoscopic retrograde cholangiopancreatography (ERCP). In patients receiving NSAID prophylaxis, we aimed to assess whether periprocedural intensive hydration (IH) resulted in a lower incidence of PEP when compared to standard hydration (SH). Prospective, single-center, double-blinded randomized controlled trial, with inclusion of consecutive patients submitted to inaugural ERCP between January 2015 and December 2018. Patients were randomized on admission, in a 1:1 ratio, to either SH-Ringer's Lactate (RL) at a rate of 1.5 mL/kg/h during and for 8 h following the procedure, or IH-RL at a rate of 3 mL/kg/h during and for 8 h following the procedure, with an additional bolus of 20 mL/kg at the end of the procedure. PEP incidence and severity were assessed according to the Atlanta Guidelines. A total of 155 patients were randomized (83 to IH, 72 to SH). PEP was observed in 8,4% (n = 13) of the patients, and was significantly less frequent in IH patients when compared to SH (3,6% vs 13,9%, P = 0,021; relative risk 0.233 [95% IC, 0.061-0.881]); five patients in the SH group developed moderate to severe PEP, in contrast to 0 patients in the IH group (6.9% vs 0.0%, P = 0,020). Intensive hydration significantly decreased the risk of post-ERCP pancreatitis by four-fold. Moreover, no cases of moderate or severe pancreatitis were observed in patients submitted to this intervention. Associated with nonsteroidal anti-inflammatory drugs, intensive hydration could constitute a new standard of care for patients undergoing ERCP.

Valproate: Not All Boxed Warnings Are Created Equal.

Valproate has undergone significant changes in labeling to the boxed warnings associated with it. This review will analyze evidence regarding the valproate-boxed warnings for teratogenicity, hepatotoxicity, and pancreatitis, with a particular emphasis on the fetal risk. A review of Pubmed, Cochrane Central Register, Google Scholar, manufacturer websites, and product labeling was performed from 1963 to February 2022, using the following search terms: valproate, valproic acid, depakote, teratogenicity, birth defects, fetal risk, hepatotoxicity, and pancreatitis. Relevant English-language studies and those conduced in humans were considered. Product labeling was also reviewed. There is a significant fetal risk following in utero valproate exposure (risk of malformation development: 8.6% in 360 women in North America). Current labeling in the United States recommends co-prescribing effective contraception for women of childbearing age. The risk of hepatotoxicity and pancreatitis is much lower in the general population (1/20 000 and 1/40 000 patients, respectively) compared with those patients with certain risk factors who are taking valproate (1/500). Overstated monitoring recommendations for the potential risk of hepatotoxicity and pancreatitis distracts from a much more common and severe risk of fetal harm. Clinicians must be diligent about discussing this risk with patients and documenting when this discussion occurs. Changes to the current recommendations for monitoring of the boxed warnings associated with valproate therapy should be considered, such as more stringent monitoring requirements for the inherent fetal risk. This could be accomplished through a Risk Evaluation and Mitigation Strategy program or through institution-based policies and procedures. In addition, monitoring recommendations for the risk of hepatotoxicity and pancreatitis should account for contributing risk factors.

Chronic pancreatitis and cancer risk in a matched cohort study using national claims data in South Korea

This study aimed to examine the association between chronic pancreatitis (CP) and cancer incidence and mortality among the Korean population. Based on a cancer-free cohort of 8,317,616 individuals between 2002 and 2010, a matched cohort study was conducted, including 10,899 patients with CP, matched for sex and age with 32,697 individuals without CP. The case and control groups were followed up until the date of onset of cancer or death or the end of follow-up date (December 31, 2018). Cox proportional hazards regression was performed to assess the risk of cancer incidence and mortality. Compared to the control group, patients with CP had a higher risk of all cancers with a hazard ratio (HR) of 1.2 [95% confidence interval (CI) 1.1–1.3]. CP was associated with an increased risk of esophageal cancer (HR 3.9, 95% CI 1.8–8.5) and pancreatic cancer (HR 3.9, 95% CI 2.7–5.5) and a decreased risk of colorectal cancer (HR 0.7, 95% CI 0.5–0.9). Regarding cancer mortality, patients with CP had a 1.2-fold risk of all cancer mortality (95% CI 1.1–1.4), compared with the control group. Patients with CP had a higher risk of death from esophageal cancer (HR 3.5, 95% CI 1.5–8.0) and pancreatic cancer (HR 3.3, 95% CI 2.3–4.7) but had a lower risk of death due to stomach cancer (HR 0.4, 95% CI 0.2–0.8). Patients with CP had a higher risk for both incidence and mortality of all cancer types, especially pancreatic and esophageal cancers, compared with the sex- and age-matched control group.

Association of Smoking and Alcohol with Acute Pancreatitis in Patients presenting in Tertiary Care Hospital Lahore

Introduction: Acute pancreatitis refers to the reversible inflammatory process of pancreas. Various researches report that smoking and heavy alcohol consumption increase the risk of acute pancreatitis. Material and methods: This research, carried out at Department of Surgery in Mayo Hospital, Lahore, has a sample size of 294, sampling technique being non probability sampling. Inclusion and exclusion criteria were applied. Results: Alcoholism and smoking were found to be the risk factors for acute pancreatitis among people participating in this study. Discussion: Both smoking and alcoholism are risk factors for acute pancreatitis, this is supported by various researches done in the past. Strength of this study includes a large sample size as well as inclusion of both cases and controls. However, effect of smoking and alcoholism on outcome of these patients has not been studied in this research. Conclusion: Public health measures for awareness and timely management of the diagnosed cases can reduce the disease burden and disease severity. Key words: Alcoholism, cigarette smoking, acute pancreatitis.

Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia.

Accumulating evidence points to the causal role of triglyceride-rich lipoproteins and their cholesterol-enriched remnants in atherogenesis. Genetic studies in particular have not only revealed a relationship between plasma triglyceride levels and the risk of atherosclerotic cardiovascular disease, but have also identified key proteins responsible for the regulation of triglyceride transport. Kinetic studies in humans using stable isotope tracers have been especially useful in delineating the function of these proteins and revealing the hitherto unappreciated complexity of triglyceride-rich lipoprotein metabolism. Given that triglyceride is an essential energy source for mammals, triglyceride transport is regulated by numerous mechanisms that balance availability with the energy demands of the body. Ongoing investigations are focused on determining the consequences of dysregulation as a result of either dietary imprudence or genetic variation that increases the risk of atherosclerosis and pancreatitis. The identification of molecular control mechanisms involved in triglyceride metabolism has laid the groundwork for a 'precision-medicine' approach to therapy. Novel pharmacological agents under development have specific molecular targets within a regulatory framework, and their deployment heralds a new era in lipid-lowering-mediated prevention of disease. In this Review, we outline what is known about the dysregulation of triglyceride transport in human hypertriglyceridaemia.

Single-operator peroral pancreatoscopy in the preoperative diagnostics of suspected main duct intraductal papillary mucinous neoplasms: efficacy and novel insights on complications

BackgroundDistinguishing intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic lesions is essential since IPMNs carry the risk of becoming malignant. Differentiating the main pancreatic duct involving IPMNs (MD-IPMNs) through conventional imaging is deficient. Single-operator peroral pancreatoscopy (SOPP) represents a promising method offering additional information on suspected lesions in the pancreatic main duct (MD). We aimed to determine the role of SOPP in the preoperative diagnostics of suspected MD-IPMNs and identify factors contributing to SOPP-related complications.Materials and MethodsIn this primarily retrospective study, SOPPs were performed at three high-volume centers on suspected MD-IPMNs. Primary outcome was the clinical impact of SOPP to subsequent patient care. Additionally, we documented post-SOPP complications and analyzed several assumed patient- and procedure-related risk factors.ResultsOne hundred and one (101) SOPPs were performed. Subsequent clinical management was affected due to the findings in 86 (85%) cases. Surgery was planned for 29 (29%) patients. A condition other than IPMN explaining MD dilatation was found in 28 (28%) cases. In 35 (35%) cases, follow-up with MRI was continued. Post-SOPP pancreatitis occurred in 20 (20%) patients and one of them was fatal. A decrease in odds of post-SOPP pancreatitis was seen as the MD diameter increases (OR 0.714 for 1.0 mm increase in MD diameter, CI 95% 0.514–0.993, p = 0.045). Furthermore, a correlation between lower MD diameter values and higher severity post-SOPP pancreatitis was seen (TJT = 599, SE = 116.6, z = − 2.31; p = 0.020). History of pancreatitis after endoscopic retrograde cholangiopancreatography was a confirmed risk factor for post-SOPP pancreatitis. Conclusions between complications and other risk factors could not be drawn.ConclusionSOPP aids clinical decision-making in suspected MD-IPMNs. Risk for post-SOPP pancreatitis is not negligible compared to non-invasive imaging methods. The risk for pancreatitis decreases as the diameter of the MD increases.

Review article: role of glucagon-like peptide-1 receptor agonists in non-alcoholic steatohepatitis, obesity and diabetes-what hepatologists need to know.

SummaryBackgroundNon‐alcoholic steatohepatitis (NASH) is characterised by hepatic lipid accumulation, cell injury, inflammation and fibrosis. Insulin resistance, a hallmark of type 2 diabetes (T2D) and obesity, is a key pathogenic driver of NASH. Other than difficult‐to‐maintain lifestyle changes, there are no approved treatments for NASH. Due to their effects on multiple pathophysiological processes, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have been tested in disorders related to insulin resistance and metabolic defects.AimsTo summarise studies of GLP‐1RAs relevant to the treatment of NASH.MethodsPubMed searches were performed and results were compiled.ResultsLarge trials with GLP‐1RAs in T2D demonstrate highly effective glucose lowering, with body weight loss, and in some cases, reduced cardiovascular events and improved liver transaminases. The GLP‐1RAs, liraglutide and semaglutide, were associated with clinically relevant, sustained body weight reduction in individuals with overweight or obesity and without T2D. In a phase II trial in NASH, liraglutide reduced metabolic dysfunction, insulin resistance and lipotoxicity in key organs associated with NASH pathogenesis. Furthermore, liraglutide and semaglutide led to histological resolution of NASH in ~40% to 60% of patients, although a statistically significant effect on fibrosis has not been confirmed. Regarding safety, GLP‐1RAs are associated with gastrointestinal and gallbladder‐related adverse events, with the latter perhaps related to weight loss. Meta‐analyses do not indicate increased risk of acute pancreatitis, pancreatic cancer or other malignancies with GLP‐1RAs.ConclusionsThese studies support the use of GLP‐1RAs for the improvement of underlying metabolic dysfunction observed in NASH and suggest further long‐term phase III trials are warranted.

The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence.

Approximately 25–50% of the population worldwide exhibits serum triglycerides (TG) (≥150 mg/dL) which are associated with an increased level of highly atherogenic remnant-like particles, non-alcoholic fatty liver disease, and pancreatitis risk. High serum TG levels could be related to cardiovascular disease, which is the most prevalent cause of mortality in Western countries. The etiology of hypertriglyceridemia (HTG) is multifactorial and can be classified as primary and secondary causes. Among the primary causes are genetic disorders. On the other hand, secondary causes of HTG comprise lifestyle factors, medical conditions, and drugs. Among lifestyle changes, adequate diets and nutrition are the initial steps to treat and prevent serum lipid alterations. Dietary intervention for HTG is recommended in order to modify the amount of macronutrients. Macronutrient distribution changes such as fat or protein, low-carbohydrate diets, and caloric restriction seem to be effective strategies in reducing TG levels. Particularly, the Mediterranean diet is the dietary pattern with the most consistent evidence for efficacy in HTG while the use of omega-3 supplements consumption is the dietary component with the highest number of randomized clinical trials (RCT) carried out with effective results on reducing TG. The aim of this review was to provide a better comprehension between human nutrition and lipid metabolism.

Sphincter of Oddi dysfunction.

Sphincter of Oddi dysfunction (SOD) is a benign non-tumoral disorder of the major papilla. It occurs mainly after cholecystectomy but can also occur before surgery. Biliary pain and biliary colic are the most frequent symptoms although recurrent pancreatic pain or pancreatitis can also be presenting symptoms. In about half of the cases, there is a fibrotic stricture of the sphincter of Oddi, probably secondary to the passage of biliary stones, while in the remaining half, the syndrome is due to ampullary motility disorders. The diagnosis of SOD first requires exclusion of choledocholithiasis or ampullary tumor, by means of ERCP, endoscopic ultrasound or magnetic resonance imaging. Findings on biliary manometry will establish the diagnosis, but this technique is performed less and less often because its high risk of inducing pancreatitis discourages its use as a diagnostic procedure. Biliary scintigraphy offers a risk-free alternative albeit with lower sensitivity. Medical treatment relies on the administration of trimebutine and nitroglycerine when pain occurs. Their efficacy is moderate. Sometimes patients are referred for endoscopic sphincterotomy. Endoscopic treatment should be performed only for patients with biliary pain associated with hepatic function disorders and/or bile duct dilatation. Practicians and patients should be aware that endoscopic sphincterotomy in this clinical setting is associated with a high risk of pancreatitis and its efficacy is limited in patients with pain but without laboratory anomalies or dilatation of the biliary duct (type III Milwaukee classification). Patients with Milwaukee classification type III disorders have mostly functional complaints or psychosocial disabilities and require only medical management.

HLA variants associated with azathioprine-induced pancreatitis in patients with Crohn's disease.

The immunosuppressant drug azathioprine is associated with a 4% risk of acute pancreatitis in patients with inflammatory bowel disease (IBD). Studies have demonstrated an increased risk in carriers of HLA‐DQA1*02:01 and HLA‐DRB1*07:01. We investigated whether these human leukocyte antigen (HLA) types were associated with azathioprine‐induced pancreatitis also in Swedish patients with IBD, and whether the type of disease affected the association. Nineteen individuals with IBD who developed acute pancreatitis after initiation of azathioprine were genotyped and compared with a population control cohort (n = 4891) and a control group matched for disease (n = 81). HLA‐DQA1*02:01 and HLA‐DRB1*07:01 were in full linkage disequilibrium, and were significantly associated with acute pancreatitis both when cases were compared with population controls (OR 3.97 [95% CI 1.57–9.97], p = 0.0035) and matched controls (OR 3.55 [95% CI 1.23–10.98], p = 0.0275). In a disease‐specific analysis, the correlation was positive in patients with Crohn's disease versus matched controls (OR 9.27 [95% CI 1.86–46.19], p = 0.0066), but not in those with ulcerative colitis versus matched controls (OR 0.69 [95% CI 0.07–6.74], p = 0.749). In patients with Crohn's disease, we estimated the conditional risk of carriers of HLA‐DQA1*02:01‐HLA‐DRB1*07:01 to 7.3%, and the conditional risk of a non‐carrier to 2.2%. We conclude that HLA‐DQA1*02:01‐HLA‐DRB1*07:01 is a marker for increased risk of acute pancreatitis in individuals of Swedish genetic origin, treated with azathioprine for Crohn's disease.