Higher Risk Of Acute Pancreatitis Research Articles

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.

Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials

ABSTRACT Background The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. Research design and methods A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes. Results The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC025 = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC025 = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC025 = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; P = 0.03). Conclusion Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.

Statins exposure and acute pancreatitis: a retrospective cohort study using a large national insurance database

ObjectivesThe association between the use of statins and the incidence of acute pancreatitis (AP) has yielded inconsistent findings. While statins have been implicated as an aetiology for drug-induced pancreatitis, more...

S51 Trends in Acute Pancreatitis With Cannabis Use Disorder and Subsequent Acute Kidney Injury in Young Adults: Evidence From Nationwide Cohort

Introduction: Cannabis has been a well-recognized etiology of acute pancreatitis (AP) over last decade with some controversies. With increased availability of cannabis for recreational and medicinal purposes in managing chronic pain, it is essential to evaluate potential risk to multi-organ system. However, there is scarcity of large-scale data on the burden and risk of AP and subsequent acute kidney injury (AKI) among cannabis users. Methods: Using weighted discharges from the National Inpatient Sample (2016-2019), young (18-44 years) patients primarily admitted for AP with concomitant cannabis use disorder (CUD) were identified. Primary endpoints included odds and trends in AP with vs. without CUD, subsequent trends in AKI with associated sex/racial disparities and all-cause mortality. Secondary endpoints included patient disposition, hospital stay, and cost. Results: Of total 395,215 AP admissions, 29,815 (7.5%) were among patients with CUD. Crude rate of AP in CUD cohort was slightly higher vs. non-CUD admissions (n=29,815, 1.4 % vs. n=365,400, 1.1%), however, with slightly lower odds when adjusted for confounders (aOR 0.94, 95%CI:0.90-0.97, p< 0.001). The AP-CUD cohort often consisted of younger (median 33 vs 35 years), male (67.5% vs. 53.9%), blacks (28.9% vs 17.6%), patients from lowest income quartile, Medicaid enrollees vs. non-CUD cohort. Alcohol abuse, smoking, and drug abuse were significant higher in the AP-CUD cohort. Rate of AKI in AP-CUD cohort was 7% vs 6.5 % in non-CUD. Interestingly, among AP-CUD cohort, the rate of AKI was higher in males (8.3%, ptrend =0.092) vs females (4.3%, ptrend =0.104) with steady trends. The burden and trend of AKI in AP-CUD cohort was higher in Hispanics (Hispanic 9.3%, black 8.6%, white 5.6%; H: 9.1% in 2016 to 11.9% in 2017 ptrend< 0.004) (Figure). There was no significant difference in all-cause mortality between CUD and non-CUD cohorts (aOR 0.40; 95%CI:0.16-1.03, p=0.058). Routine discharges and median length of stay were comparable between cohorts (3 days) with an average cost was $25,724 in the AP-CUD cohort. Conclusion: There was a higher crude rate of AP admissions in the young CUD cohort, however, when adjusted for confounders, CUD was not independently associated with higher risk of AP, subsequent inpatient mortality, or rising trends in AKI. Hispanics demonstrated concerning trends in AKI. Future studies are warranted assessing long-term impact of polysubstance use on AP admissions and outcomes.Figure 1.: Trends in Acute Kidney Injury among Acute Pancreatitis admissions with Cannabis users by sex and race.

Underweight Is Associated with a Higher Risk of Acute Pancreatitis in Type 2 Diabetes: A Nationwide Cohort Study.

Type 2 diabetes is known as a risk factor for acute pancreatitis, but the risk of acute pancreatitis according to glycemic status and body mass index (BMI) has remained unknown. Therefore, we aim to investigate the risk of acute pancreatitis according to BMI and glycemic status. We included 3,912,496 subjects from the Korean National Health Insurance System cohort who underwent the National Health Screening program in 2009. Each subject’s clinical course was examined through follow-ups until December 2018. BMI and glycemic status were each categorized into five groups. Hazard ratios (HRs) of acute pancreatitis according to BMI and glycemic status were calculated. The adjusted HRs of acute pancreatitis were the highest in the underweight group (BMI < 18.5) in all five glycemic status categories. The HR of acute pancreatitis in the underweight group increased as the glycemic status worsened, excluding the category of diabetes for more than five years (HR 1.381 for normal fasting glucose; 1.805 for impaired fasting glucose; 2.332 for new-onset diabetes; 4.51 for diabetes duration <5 years; 4.135 for diabetes duration ≥5 years). We found that the risk of acute pancreatitis was further increased in the underweight group, depending on the status and duration of type 2 diabetes.

Hypertriglyceridemia: rationale, design and implementation of the Australian Hypertriglyceridemia Registry.

Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (ASCVD), aortic stenosis, hepatic steatosis and pancreatitis. We briefly review the aetiology and treatment of HTG and familial chylomicronemia syndrome (FCS), as well as the implementation of a clinical quality registry for improving care, the Australian Hypertriglyceridemia (AUSTRIG) Registry. There is a need to improve the detection of individuals with severe HTG and FCS, who could benefit from more intense and novel treatments to prevent end-organ damage. Patient registries provide valuable data for advancing care of individuals with severe HTG at high risk of acute pancreatitis, steatohepatitis and ASCVD. However, there is a paucity of registries of such patients. We outline the design and implementation of the AUSTRIG Registry. Clinical registries can be employed in many ways for improving outcomes for patients with HTG, through the collation and analysis of data for enabling health service planning, clinical trials and audits, and for better informing and empowering registrants.

Abstract 10357: ARO-APOC3, an Investigational RNAi Therapeutic, Shows Similar Efficacy and Safety in Genetically Confirmed FCS and Non-FCS Participants with Severe Hypertriglyceridemia

Background: Familial chylomicronemia syndrome (FCS) is an ultrarare condition caused by biallelic pathogenic DNA variants in lipolysis-associated genes, resulting in severe hypertriglyceridemia (HTG) and associated with high risk of acute pancreatitis with few therapeutic options. In a 16-week Phase 1 study (NCT03783377), subcutaneously administered ARO-APOC3 reduced serum apolipoprotein C3 (APOC3) and TG in healthy volunteers and participants (pts) with HTG and was well tolerated. Purpose: To report on the safety/pharmacodynamic (PD) effects of ARO-APOC3 in both FCS pts with biallelic pathogenic variants and pts with severely elevated TG at screening (&gt;880 mg/dL) but without biallelic pathogenic variants (chylomicronemia (MCM)). Methods: Four genetically confirmed FCS pts received 50 mg ARO-APOC3 and 26 MCM pts received 10, 25, 50, or 100 mg ARO-APOC3 on Days 1 and 29. Since similar PD responses were observed among MCM pts, results were pooled across dose levels. Safety and PD responses were examined. Maximal mean/median changes from baseline for APOC3, TG, non-HDL-C, and HDL-C were reported. Results: Baseline/demographics were comparable between groups, except for mean BMI (22.1 [FCS] and 30.5 [MCM] kg/m 2 ), and mean baseline HDL-C , which were lower in FCS pts (Table 1) (p&lt;0.0001 for both). Mean APOC3 was reduced by 98% and 96% in FCS and MCM pts, respectively. Both groups also showed similar maximum median reductions in TG of 91% and 90%, respectively. Similar to the full study, non-HDL-C was reduced and HDL-C increased with treatment in both groups (Table 1). AEs were similar between groups, suggesting a comparable safety profile. Conclusions: In patients with severe HTG, ARO-APOC3 was safe, and consistently decreased APOC3, TG, and non-HDL-C, and increased HDL-C, regardless of underlying genetic cause of HTG, and may represent a promising RNAi therapeutic for the treatment of severe HTG.

S0077 Probable Association of Idiopathic Pancreatitis With Smoking of Tobacco

INTRODUCTION: Acute pancreatitis is a serious disease with high morbidity and mortality rates. Research shows that among the primary admissions for acute pancreatitis, 26.9% had gallstone pancreatitis, 25.1% had alcoholic pancreatitis and 36.5% had idiopathic pancreatitis. Idiopathic pancreatitis accounted for a higher mortality rate than both gallstone pancreatitis and alcoholic pancreatitis patients (Chen et al., 2013).1 Recent studies have shown that cigarette smoking can also be a risk factor of acute pancreatitis. The two main metabolites from cigarette smoke are nicotine and NNK, which cause histologic changes to the pancreas. There is also indirect evidence that nicotine and acrolein cause ductal secretion due to CFTR dysfunction. As mentioned above, this can be a direct cause of inducing an attack of acute pancreatitis (Barreto, 2016).2 METHODS: This study is a retrospective chart review of adult patients that would include all adults (age >18 years), both genders, of all ethnic backgrounds, adults presenting with symptoms consistent with acute pancreatitis. The rate of pancreatitis will be compared among tobacco smokers and non-tobacco smokers. The association between pancreatitis and tobacco use will be tested for significance at P < 0.05 with Chi-square analysis. The magnitude of the risk of use will be calculated using Odds Ratio. RESULTS: There was 301 total number of patients in the study. Mean age was 58.76 (SD: 14.13) years and predominantly male (n = 164, 54.5%). There is a 2.32 (odds ratio) higher risk of acute pancreatitis and a smoker. This study showed a significance of P-value <0.0001 between idiopathic pancreatitis and tobacco use. CONCLUSION: Tobacco use is a risk factor for chronic pancreatitis but has not been associated directly with acute pancreatitis previously. There were multiple case reports in the literature that reported tobacco use associated with acute pancreatitis. This study has shown a significant association between tobacco use and acute idiopathic pancreatitis.Table 1.: smoking_use * idiopathic_acute_pancreatitis CrosstabulationTable 2.: Chi-Square Tests

Intermittent chylomicronemia caused by intermittent GPIHBP1 autoantibodies

Chylomicronemia caused by a deficiency in lipoprotein lipase (LPL) or GPIHBP1 (the endothelial cell protein that transports LPL to the capillary lumen) is typically diagnosed during childhood and represents a serious, lifelong medical problem. Affected patients have high plasma triglyceride levels (>1500 mg/dL) and a high risk of acute pancreatitis. However, chylomicronemia frequently presents later in life in the absence of an obvious monogenic cause. In these cases, the etiology for the chylomicronemia is presumed to be “multifactorial” (involving diabetes, drugs, alcohol, or polygenic factors), but on a practical level, the underlying cause generally remains a mystery. Here, we describe a 15-year-old female with chylomicronemia caused by GPIHBP1 autoantibodies (which abolish LPL transport to the capillary lumen). Remarkably, chylomicronemia in this patient was intermittent, interspersed between periods when the plasma triglyceride levels were normal. GPIHBP1 autoantibodies were easily detectable during episodes of chylomicronemia but were undetectable during periods of normotriglyceridemia. During the episodes of chylomicronemia (when GPIHBP1 autoantibodies were present), plasma LPL levels were low, consistent with impaired LPL transport into capillaries. During periods of normotriglyceridemia, when GPIHBP1 autoantibodies were absent, plasma LPL levels normalized. Because the chylomicronemia in this patient was accompanied by debilitating episodes of acute pancreatitis, the patient was ultimately treated with immunosuppressive drugs, which resulted in disappearance of GPIHBP1 autoantibodies and normalization of plasma triglyceride levels. GPIHBP1 autoantibodies need to be considered in patients who present with unexplained acquired cases of chylomicronemia.

Body Mass Index, Triglycerides, and Risk of Acute Pancreatitis: A Population-Based Study of 118 000 Individuals

The incidence of acute pancreatitis is rising worldwide and currently no curative treatment exists. Clarification of preventable risk factors is important for the reduction of morbidity and mortality from acute pancreatitis. In this study, we tested the hypothesis that the risk of acute pancreatitis associated with body mass index (BMI) is partly mediated through elevated triglycerides. We included 118 085 individuals from 2 prospective cohort studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, with BMI measured at baseline. Diagnosis of acute pancreatitis was assessed from the national Danish registries, as hospitalization or death due to acute pancreatitis. Higher BMI was associated with higher risk of acute pancreatitis with a multivariable-adjusted hazard ratio of 1.4 (95% CI, 1.1-1.8) for BMI of 25-29.9, 2.1 (1.6-2.9) for BMI of 30-34.9, and 2.8 (1.8-4.3) for BMI > 35, compared with individuals with BMI of 18.5-24.9. Triglycerides mediated 29% (95% CI, 12%-46%; P = 0.001) of the association between BMI and risk of acute pancreatitis in the age- and sex-adjusted model and 22% (6%-39%; P = 0.008) in the multivariable-adjusted model. Higher BMI is associated with higher risk of acute pancreatitis in individuals from the general population, partly mediated through higher triglycerides. This indicates a potential for preventing acute pancreatitis by reducing BMI and triglycerides in individuals with high values.

External Validation of a Predictive Model for Acute Pancreatitis Risk in Patients with Severe Hypertriglyceridemia

Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model. Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride [TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC). Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age. Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options. Abbreviations: AP = acute pancreatitis; ASCVD = atherosclerotic cardiovascular disease; AUROC = area under the receiver operating characteristic curve; FRAX = fracture risk assessment tool; HTG = hypertriglyceridemia; OR = odds ratio; TG = triglyceride level.

Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population.

How mild-to-moderate hypertriglyceridemia (2-10 mmol/L; 177-886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20-100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%-18%, P = 3 × 10-17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%-4.4%, P = 6 × 10-17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10-6), with hazard ratios of 1.5 (95% CI, 0.9-2.5), 2.0 (95% CI, 1.1-3.6), 2.2 (95% CI, 1.0-4.7), 4.2 (95% CI, 1.6-11.5), and 7.7 (95% CI, 3.0-19.8) in individuals with nonfasting triglycerides of 1.00-1.99 mmol/L (89-176 mg/dL; 46% of the population), 2.00-2.99 mmol/L (177-265 mg/dL; 17%), 3.00-3.99 mmol/L (266-353 mg/dL; 6%), 4.00-4.99 mmol/L (354-442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10-4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.

The effect of selective serotonin re-uptake inhibitors on risk of type II diabetes mellitus and acute pancreatitis: a meta-analysis

To explore the effect of selective serotonin re-uptake inhibitors (SSRIs) on risk of type II diabetes mellitus (T2DM) and acute pancreatitis (AP), expecting to provide guidance for clinic. Literature was retrieved by searching Pubmed, Embase, Cochrane and Scopus and hand searching of reference lists of related articles. Stata 14.0 was utilized for processing and analysis, and adjusted odds ratios (aORs) were applied. Our study included 113898 T2DM patients and 284131 controls from nine studies and 17548 AP patients and 108108 controls from four studies. The pooled aORs of SSRIs on the risk of T2DM and AP were 1.38 (95% confidence interval (CI) = 1.24–1.54) and 1.26 (95% CI = 1.13–1.40), respectively. Study design, quality, ethnicity, follow-up, and sample size of patients were the resources of heterogeneity. Subgroup analysis showed that 2 weeks is a high-risk time for AP after SSRIs use, with 1.48-fold-times as much after it. This meta-analysis provides evidence of a significant positive association between SSRIs use and risks of T2DM or AP, and duration of 2 weeks of SSRIs use has higher risk of AP, which should be paid much attention to.

Acetaminophen-Induced Pancreatitis: A Rare Complication of Acetaminophen Hepatotoxicity

Acetaminophen induced pancreatitis is uncommon and the mechanism of injury is not well understood. To date, only six cases have been reported. A 46 year old Hispanic woman presented with 4 weeks of worsening abdominal pain. The pain was located in the bilateral flanks, described as constant, and associated with chills. For this pain she took 1300 mg of acetaminophen every 4 hours in addition to acetaminophen PM with minimal relief. Eventually the pain migraited to the right upper quadrant. She had a medical history of obesity s/p gastric bypass, biliary colic s/p cholecystectomy, seizures, and hypertension. Initial evaluation revealed normal vital signs; however, several laboratory abnormalities were found: AST/ALT = 3472/1223, lipase of 4664, and serum Acetaminophen level of 69.8. CT of abdomen and pelvis demonstrated pyelonephritis, hepatomegaly, and acute pancreatitis. She was admitted to ICU and treated with NAC therapy for acetaminophen hepatotoxicity, intravenous hydration, and antibiotics for pyelonephritis. Evaluation of common causes of pancreatitis (e.g. ethanol, choledocolithiasis, hypertriglyceridemia) was negative. Medication list was reviewed and no common offending agents were appreciated. Tesitng for infectious etiologies such mumps and salmonella were negative. Her serum calcium was within normal limits. Given her negative workup, it was determined that although rare, the most likely cause seemed to be acetaminophen toxicity. The patient's pancreatitis improved with cessation of acetaminophen and concurrent treatment of drug toxicity, as evidenced by resolution of abdominal pain and down trending lipase levels (4664 on admission, down to 440 two days later). A repeat CT 2 weeks later confirmed nearly resolved pancreatitis. Our proposed mechanism of action is hepatic inflammation/damage leads to inflammation (e.g. seeding) of surrounding organs. Data from a 2015 large cohort study demonstrated patients with acute acetaminophen hepatic toxicity exhibit a 2.4 fold higher risk of acute pancreatitis within the first year of follow up (1). Our case shows treatment of acetaminophen toxicity may mollify associated pancreatitis. Further research is needed concerning the mechanisms of acetaminophen toxicity given the drug's widespread availability and complications.1411_A.tif Figure 1: CT Scan of the Abdomen and Pelvis at time of Admission. In this figure above we can see acute peripancreatic inflammation. The arrow points towards an area of possible necrosis, underscoring the severity of this pancreatitis1411_B.tif Figure 2: AST/ALT/Lipase (IU/L) over a period of time. The figure above shows that treatment of the patient's liver failure coincided concurrent down trending of her lipase levels, and clinical resolution of her pancreatitis

The Risk of Acute Pancreatitis After Initiation of Dipeptidyl Peptidase 4 Inhibitors: Testing a Hypothesis of Subgroup Differences in Older U.S. Adults.

To examine whether dipeptidyl peptidase 4 inhibitors (DPP-4I) increase acute pancreatitis risk in older patients and whether the association varies by age, sex, and history of cardiovascular disease (CVD). We conducted a cohort study of DPP-4I initiators versus thiazolidinedione (TZD) or sulfonylurea initiators using U.S. Medicare beneficiaries, 2007-2014. Eligible initiators were aged 66 years or older without history of pancreatic disease or alcohol-related diseases. Patients were followed up for hospitalization due to acute pancreatitis and censored at 90 days after treatment changes. Weighted Cox models were used to estimate the hazard ratio (HR) for acute pancreatitis. Analyses were performed overall as well as within subgroups defined by age, sex, and CVD history. We found no increased risk of acute pancreatitis comparing 49,374 DPP-4I initiators to 132,223 sulfonylurea initiators (weighted HR 1.01; 95% CI 0.83-1.24) and comparing 57,301 DPP-4I initiators to 32,612 TZD initiators (weighted HR 1.11; 95% CI 0.76-1.62). Age and sex did not modify the association. Among patients with CVD, acute pancreatitis incidence was elevated in initiators of DPP-4I and sulfonylurea (2.3 and 2.4 per 1,000 person-years, respectively) but not in TZD initiators (1.5). Among patients with CVD, higher risk of acute pancreatitis was observed with DPP-4I compared with TZD (weighted HR 1.84; 95% CI 1.02-3.35) but not compared with sulfonylurea. Our study provides evidence that DPP-4I is not associated with an increased risk of acute pancreatitis in older adults overall. The positive association observed in patients with CVD could be due to chance or bias but merits further investigation.

Association between dipeptidyl peptidase-4 inhibitor drugs and risk of acute pancreatitis: A meta-analysis.

Background:Previous studies have reported conflicting results for the relationship between dipeptidyl peptidase-4 (DPP-4) inhibitor drugs and acute pancreatitis. The aim of this study was to investigate the association between DPP-4 inhibitors and an increased risk of acute pancreatitis using meta-analysis.Methods:We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane library from inception to March 4, 2017. Original articles with data on DPP-4 inhibitors and acute pancreatitis were included. We used random-effects models or fixed-effects models to combine the relative risks (RRs), odds ratio (OR), and hazard ratio (HRs) with 95% confidence intervals (CIs) in randomized controlled studies, case–control study and cohort study, respectively.Results:Five case–control studies, 5 randomized controlled studies, and 3 cohort studies were selected of the 451 retrieved abstracts. A higher risk of acute pancreatitis was observed with the following RR/OR and 95%CI: RR 1.67 (1.08–2.59) in randomized controlled studies and OR 1.45 (1.30–1.61) in case–control studies. However, the pooled HR of the 3 cohort studies failed to confirm this association.Conclusion:There is a marginally higher risk of acute pancreatitis with DPP-4 inhibitors. However, this risk was not observed in cohort studies. Thus, further clinical trials are required to confirm this finding.

Nonfasting Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis

ImportanceSevere hypertriglyceridemia is associated with increased risk of acute pancreatitis. However, the threshold above which triglycerides are associated with acute pancreatitis is unclear.ObjectiveTo test the hypothesis that nonfasting mild-to-moderate hypertriglyceridemia (177-885 mg/dL; 2-10 mmol/L) is also associated with acute pancreatitis.Design, Setting, and ParticipantsThis prospective cohort study examines individuals from the Copenhagen General Population Study in 2003 to 2015 and the Copenhagen City Heart Study initiated in 1976 to 1978 with follow-up examinations in 1981 to1983, 1991 to 1994, and in 2001 to 2003. Median follow-up was 6.7 years (interquartile range, 4.0-9.4 years); and includes 116 550 individuals with a triglyceride measurement from the Copenhagen General Population Study (n = 98 649) and the Copenhagen City Heart Study (n = 17 901). All individuals were followed until the occurrence of an event, death, emigration, or end of follow-up (November 2014), whichever came first.ExposuresPlasma levels of nonfasting triglycerides.Main Outcomes and MeasuresHazard ratios (HRs) for acute pancreatitis (n = 434) and myocardial infarction (n = 3942).ResultsOverall, 116 550 individuals were included in this study (median [interquartile range] age, 57 [47-66] years). Compared with individuals with plasma triglyceride levels less than 89 mg/dL (<1 mmol/L), the multivariable adjusted HRs for acute pancreatitis were 1.6 (95% CI, 1.0-2.6; 4.3 events/10 000 person-years) for individuals with triglyceride levels of 89 mg/dL to 176 mg/dL (1.00 mmol/L-1.99 mmol/L), 2.3 (95% CI, 1.3-4.0; 5.5 events/10 000 person-years) for 177 mg/dL to 265 mg/dL (2.00 mmol/L-2.99 mmol/L), 2.9 (95% CI, 1.4-5.9; 6.3 events/10 000 person-years) for 366 mg/dL to 353 mg/dL (3.00 mmol/L-3.99 mmol/L), 3.9 (95% CI, 1.5-10.0; 7.5 events/10 000 person-years) for 354 mg/dL-442 mg/dL (4.00 mmol/L-4.99 mmol/L), and 8.7 (95% CI, 3.7-20.0; 12 events/10 000 person-years) for individuals with triglyceride levels greater than or equal to 443 mg/dL (≥5.00 mmol/L) (trend, P = 6 × 10−8). Corresponding HRs for myocardial infarction were 1.6 (95% CI, 1.4-1.9; 41 events/10 000 person-years), 2.2 (95% CI, 1.9-2.7; 57 events/10 000 person-years), 3.2 (95% CI, 2.6-4.1; 72 events/10 000 person-years), 2.8 (95% CI, 2.0-3.9; 68 events/10 000 person-years), and 3.4 (95% CI, 2.4-4.7; 78 events/10 000 person-years) (trend, P = 6 × 10−31), respectively. The multivariable adjusted HR for acute pancreatitis was 1.17 (95% CI, 1.10-1.24) per 89 mg/dL (1 mmol/L) higher triglycerides. When stratified by sex, age, education, smoking, hypertension, statin use, study cohort, diabetes, body mass index (calculated as weight in kilograms divided by height in meters squared), alcohol intake, and gallstone disease, these results were similar with no statistical evidence of interaction.Conclusions and RelevanceNonfasting mild-to-moderate hypertriglyceridemia from 177 mg/dL (2 mmol/L) and above is associated with high risk of acute pancreatitis, with HR estimates higher than for myocardial infarction.

Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases

Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma. A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications. Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication. Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy.

Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

Hyper-Homocysteinemia: A Potential Indicator of Acute Pancreatitis

Objectives: Hyper-homocysteinemia, reportedly, is closely associated with some known vascular dysfunctions, thrombosis and even inflammations. However, till now rare studies were directed to the association between hyperhomocysteinemia and acute pancreatitis (AP). The illumination of this potential association is expected to benefit therapies of AP. In this regard, this study aims at digging the underlying association between hyper-homocysteinemia and AP. Methods: In this study, 160 patients with AP were involved. The plasma levels of homocysteine of these patients were measured. The patients were divided into two groups, based on the serum homocysteine concentration. Patients with high plasma homocysteine concentrations (C>15 µmol/L) were classified as Group 1, while the rest with normal plasma homocysteine concentrations (5 µmol/L ≤ C ≤ 15 µmol/L) were identified as Group 2. Then, the lipid levels for the two groups were studied to detect whether there existed a synergistic effect of hyper-homocysteinemia and hypertriglyceride on AP. Results: Almost half (46.9%) of the patients with AP were found to bear hyper-homocysteinemia in this study. However, patients in Group 1 were found to have lower triglyceride and total cholesterol levels than those in Group 2, with P=0.038 and P=0.046 respectively. In addition, more patients in Group 2 had hyper-triglyceride and hyper-total cholesterol than those in Group 1, though the differences were not significantly observed. Conclusions: In conclusion, these studies showed that hyper-homocysteinemia may be a very important indicator of a high risk of AP. So, more attention should be paid to hyper-homocysteinemia in the progress of AP.