HTG-induced Acute Pancreatitis Research Articles

Hypertriglyceridemia and acute pancreatitis: clinical and basic research—a narrative review

Hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP), and the incidence of HTG-induced AP (HTG-AP) is rising worldwide as a result of changes in lifestyle and dietary habits. In China, HTG accounts for 10% to 20% of the causes of AP, even becoming the second leading cause of AP. The presentation and diagnosis of HTG-AP is similar to that of AP from other causes, however, the complication rates and severe AP are significantly higher in patients with HTG-AP than in patients with other etiologies. Regarding the management of HTG-AP, the initial management is similar to that of AP from other causes and mainly includes fluid resuscitation, pain control, and nutritional support. In addition to supportive care, it is necessary to take appropriate measures to decrease serum TG levels, in order to alleviate the progression of AP and prevent recurrence. This review aims to summarize existing clinical and basic research evidence of HTG-AP and seeks to highlight the epidemiology, definition, pathogenesis, clinical course, diagnosis, management, prevention of recurrence, and specific clinical scenarios, such as HTG-AP during pregnancy, HTG-AP with diabetic ketoacidosis.

Mechanisms linking hypertriglyceridemia to acute pancreatitis.

Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG-induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG-induced AP or AP in the presence of HTG and determining possible treatments are needed.

Hypertriglyceridemia Induced Acute Pancreatitis: A Learn from New Cases

An increased risk of morbidity and mortality is associated with acute pancreatitis (AP) brought on by hypertriglyceridemia (HTG). It is essential to locate the root cause as soon as possible and give those affected the attention they need. The treatment plan includes efforts to lower blood triglyceride levels and supportive care. HTG-induced AP has a similar clinical course to people with other types of acute pancreatitis. However, HTG-induced AP patients have significantly higher clinical severity and associated consequences. As a result, therapy and preventing sickness recurrence depend on a correct diagnosis. At the moment, there are no acknowledged standards for the treatment of HTG-induced AP. Some therapy approaches that effectively decrease serum triglycerides include fibric acids, apheresis/plasmapheresis, insulin, heparin, and omega-3 fatty acids. Following acute phase care, lifestyle modifications, including dietary and drug therapy, are essential for long-term HTG-induced AP control and relapse prevention. To create complete and efficient HTG-induced AP treatment guidelines, more study is required.

Plasmapheresis compared with conventional treatment for hypertriglyceridemia-induced acute pancreatitis: A systematic review and meta-analysis.

The treatment of acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) remains controversial with regard to plasmapheresis vs conventional treatment. We reviewed relevant articles to explore the efficacy of plasmapheresis in the management of HTG-induced AP. We systematically reviewed studies that compared plasmapheresis with conventional treatment for HTG-induced AP using three databases: PubMed, Embase, and Cochrane Library, as well as relevant references. The primary outcomes were 24 h triglyceride reduction rate and in-hospital mortality. A total of 791 articles were retrieved. Finally, 15 observational studies (1080 participants) were included, most of which were historical cohort studies. Compared with conventional treatment, plasmapheresis assisted in the reduction of serum triglyceride (TG) levels in the first 24 h after hospital admission (standardized mean difference [SMD]: 0.58; 95% confidence interval [CI]: 0.17 to 0.99; P=0.005). However, it resulted in increased hospitalization costs (thousand yuan) (weighted mean difference [WMD]: 24.32; 95% CI: 12.96 to 35.68; P < 0.001). With regard to in-hospital mortality, although the mortality rate in the plasmapheresis group was higher than that in the conventional treatment group (relative risk [RR]: 1.74; 95% CI: 1.03 to 2.94; P=0.038), the result was disturbed by confounding factors as per the subgroup and sensitivity analysis, as well as trial sequential analysis (TSA). No significant differences were found in other outcomes, including systematic complications, local complications, the requirement for surgery, and hospitalization duration. The effect of plasmapheresis in HTG-induced AP is not superior to that of conventional treatment, even resulting in a greater economic burden to patients and health care system. High quality randomized control trials are required to obtain a more a definitive understanding of this issue.

Complications of Hypertriglyceridemia in Pregnancy and Its Impact on Neonates: a Hospital-Based Study From Odisha.

ObjectiveHypertriglyceridemia (HTG) in pregnancy causes an increased risk for maternal and fetal complications. But, reports on the impact of HTG in pregnancy on maternal and fetal outcomes are scarce in developing countries. We aim to determine the maternal and neonatal complications of HTG in pregnancy.Materials and methodsThis prospective observational study was conducted on 150 pregnant women with HTG in the department of obstetrics and gynecology, KIMS, Bhubaneswar, from December 2019 to November 2020. Measurement of triglycerides during the first trimester, second trimester, and delivery was done. Maternal complications and neonatal outcomes in HTG mothers and mothers with normal triglyceride levels were compared.ResultsOut of 150 HTG cases, hypothyroidism, preeclampsia, acute pancreatitis, and sickle cell crisis occurred in 41 (27.3%), 22 (14.7%), six (4%), and three (2%) cases, respectively. The triglyceridemia (TG) levels raised from 133.7±48.2 mg/dl in the first trimester to 232.8±151.0 mg/dl in the third trimester. There is a significant increase in TG levels at the time of delivery compared to the first and second trimesters (p< .001). Out of 140 neonates, 30 (21.4%) were preterm, eight (5.7%) had intrauterine growth restriction (IUGR), and four (6.06%) were macrosomic. Intrauterine death, preterm, and macrosomia are significantly associated with maternal HTG compared to normal mothers (p < .032). All mortalities were due to acute pancreatitis (6; 4%) among mothers and four intrauterine fetal death.ConclusionThere is a steady increase in TG levels in the successive trimesters of pregnancy. Gestational severe hypertriglyceridemia causes life-threatening complications. HTG-induced acute pancreatitis needs to be managed aggressively to prevent maternal death. Neonates of HTG mothers suffer from complications like prematurity, IUGR, and macrosomia.

GPIHBP1 autoantibody is an independent risk factor for the recurrence of hypertriglyceridemia-induced acute pancreatitis

GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.

Clinical Outcomes and Predictors of Thirty-Day Readmissions of Hypertriglyceridemia-Induced Acute Pancreatitis.

BackgroundHypertriglyceridemia (HTG) is a well-established cause of acute pancreatitis often leading to significant morbidity, mortality, and healthcare burden. This study aimed to describe the rate, reasons, and predictors of HTG-induced acute pancreatitis (HTG-AP) in the USA.MethodsThis retrospective study analyzed the Nationwide Readmissions Database (NRD) for 2018 to determine all adults (≥ 18 years) readmitted within 30 days of an index hospitalization of HTG-AP. Hospitalization characteristics and adverse outcomes for 30-day readmissions were highlighted and compared with index admissions of HTG-AP. Furthermore, independent predictors for 30-day readmissions of HTG-AP were also identified. P values ≤ 0.05 were considered statistically significant.ResultsIn 2018, the rate of 30-day readmission of HTG-AP was noted to be 13.5%. At the time of readmission, AP (45.2%) was identified as the most common principal diagnosis, followed by chronic pancreatitis (6.3%) and unspecified sepsis (4.8%). Compared to index admissions, 30-day readmissions of HTG-AP had a higher proportion of patients with Charlson Comorbidity Index (CCI) scores ≥ 3 (48.5% vs. 33.8%, P < 0.001). Furthermore, we noted higher rates of inpatient mortality (1.7% vs. 0.7%, odds ratio (OR): 2.55, 95% confidence interval (CI): 1.83 - 3.57, P < 0.001), mean length of stay (LOS) (5.6 vs. 4.1 days, OR: 1.5, 95% CI: 1.2 - 1.7, P < 0.001), and mean total healthcare charge (THC) ($56,799 vs. $36,078, OR: 18,702, 95% CI: 15,136 - 22,267, P < 0.001) for 30-day readmissions of HTG-AP compared to index admissions. Independent predictors for 30-day all-cause readmissions of HTG-AP included hypertension, protein energy malnutrition (PEM), CCI scores ≥ 3, chronic kidney disease and discharge against medical advice.ConclusionsAP was the principal diagnosis on presentation in only 45.2% patients for 30-day readmissions of HTG-AP. Compared to index admissions, 30-day readmissions of HTG-AP had a higher comorbidity burden, inpatient mortality, mean LOS and mean THC.

Therapeutic plasma exchange for the management of hypertriglyceridemia-induced acute pancreatitis

<b>BACKGROUND:</b> Hypertriglyceridemia (HTG) is the third-most important cause of acute pancreatitis (AP) and its early diagnosis is essential to prevent AP-associated morbidity and mortality. Therapeutic plasma exchange (TPE) is a promising treatment option for improving patient outcomes and prognosis in HTG-induced AP (HTG-AP). <b>OBJECTIVE:</b> This study assessed the severity of disease in patients with HTG-AP and evaluated the therapeutic effects, safety, and procedural challenges of TPE in its management. <b>METHODS:</b> Patients with HTG-AP, diagnosed according to the Atlanta classification, and exhibiting serum triglyceride (TG) concentrations ≥11.3 mmol/L were included in the study. Consenting patients received TPE using the PRISMAFLEX^® system (TPE group), and the remaining were treated in accordance with the guidelines of Vietnam's Ministry of Health, 2015 (non-TPE group). The duration of hospital or intensive care unit (ICU) stay in patients and mortality rates were compared between the TPE and non-TPE groups. The reduction in serum TG levels was also evaluated in the TPE group. <b>RESULTS:</b> This prospective study included 165 patients with HTG-AP (<i>n</i> = 83, TPE group; <i>n</i> = 82, non-TPE group). The mean age of the patients was 41.0 ± 9.3 years. The duration of hospital and ICU stay was significantly lower in the TPE group compared to that of the non-TPE group (<i>P</i> < 0.05). A significant reduction in TG levels over baseline was noted in patients who received TPE (77%; <i>P</i> < 0.05), which was observed after the first TPE session (70.81%; <i>P</i> < 0.05). <b>CONCLUSION:</b> TPE using the PRISMAFLEX^® system is safe and well-tolerated in patients with HTG-AP and is associated with minimal technical constraints.

Hypertriglyceridemia induced acute pancreatitis: 4 years' experience from a tertiary care institute and quick literature review.

ABSTRACTHypertriglyceridemia (HTG) is infrequent but an established etiology that can trigger recurrent episodes of acute pancreatitis. The risk of acute pancreatitis is significant when serum triglycerides levels surpass >1000 mg/dL. Although the severity of HTG-induced acute pancreatitis (HTG-AP) may be correlated to higher HTG levels in the early stages, the overall clinical outcomes are similar to other aetiologies. The initial management also differs from the routine recommendations with additional diagnostic and therapeutic challenges. This retrospective case series includes a 4-year experience with HTG-AP at our facility and a brief literature review.

Hypertriglyceridemia-induced pancreatitis treated with continuous insulin infusion-Case series.

There are no definitive treatment guidelines for hypertriglyceridemia (HTG)-induced acute pancreatitis (AP). The aim of this retrospective study was to evaluate the efficacy of insulin in decreasing triglyceride(TG) levels in patients with HTG-induced AP. We included 17 cases of HTG-induced AP treated with continuous insulin aspart for 4 days. Fifteen patients were male, two were female. The mean TG level at admission was 56.53 ± 25.29 mmol/L. The mean APACHE II score was 10.2 ± 5.7, Ranson 4.2 ± 1.7and Balthazar 6.5 ± 2.6, implying a severe form of the disease. In an 8-year period, 17 patients with a diagnosis of HTG-induced APwere treated with a continuous infusion of 5% dextrose and insulin aspart in an attempt to lower TG levels. TG levels were assessed on admission,the secondand fourth day of therapy. The patient outcome, complicationsand recurrence of AP were monitored. A significant reduction of TG levels was observed in all patients on Day 4. All patients survived, with one forming a giant pseudocyst as a disease complication, one needing haemodialyses treatment due to an acute kidney injury, and one developing acute respiratory distress syndrome that required mechanical ventilation for 4 days. All patients recovered completely. Our study showed that continuous insulin aspart infusion decreases TG levels in HTG-induced AP from a mean TG level of 56.53 mmol/L on Day 1 to 21.75 mmol/L on Day 2and finally to 6.86 mmol/L on Day 4. We consider this therapy very efficient, safe, simple to administer and monitor.

Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis.

The etiology of hypertriglyceridemia (HTG) and acute pancreatitis (AP) is complex. Herein, we dissected the underlying etiology in a patient with HTG and AP. The patient had a 20-year history of heavy alcohol consumption and an 8-year history of mild HTG. He was hospitalized for alcohol-triggered AP, with a plasma triglyceride (TG) level up to 21.4 mmol/L. A temporary rise in post-heparin LPL concentration (1.5–2.5 times of controls) was noted during the early days of AP whilst LPL activity was consistently low (50∼70% of controls). His TG level rapidly decreased to normal in response to treatment, and remained normal to borderline high during a ∼3-year follow-up period during which he had abstained completely from alcohol. Sequencing of the five primary HTG genes (i.e., LPL, APOC2, APOA5, GPIHBP1 and LMF1) identified two heterozygous variants. One was the common APOA5 c.553G > T (p.Gly185Cys) variant, which has been previously associated with altered TG levels as well as HTG-induced acute pancreatitis (HTG-AP). The other was a rare variant in the LPL gene, c.756T > G (p.Ile252Met), which was predicted to be likely pathogenic and found experimentally to cause a 40% loss of LPL activity without affecting either protein synthesis or secretion. We provide evidence that both a gene-gene interaction (between the common APOA5 variant and the rare LPL variant) and a gene-environment interaction (between alcohol and digenic inheritance) might have contributed to the development of mild HTG and alcohol-triggered AP in the patient, thereby improving our understanding of the complex etiology of HTG and HTG-AP.

Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta-analysis

The main causes of acute pancreatitis (AP) are biliary disease, alcohol consumption, hypertriglyceridaemia (HTG) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this meta-analysis was to evaluate the effects of these aetiological factors on the severity and outcome of AP. Pubmed and Embase were searched between 01/01/2012 and 31/05/2020. Included articles involved adult alcoholic, biliary, HTG- or post-ERCP AP (PAP) patients. Primary outcome was severity, secondary outcomes were organ failures, intensive care unit admission, recurrence rate, pancreatic necrosis, mortality, length of hospital stay, pseudocyst, fluid collection and systematic inflammatory response syndrome. Data were analysed from 127 eligible studies. The risk for non-mild (moderately severe and severe) condition was the highest in HTG-induced AP (HTG-AP) followed by alcoholic AP (AAP), biliary AP (BAP) and PAP. Recurrence rate was significantly lower among BAP vs. HTG-AP or AAP patients (OR = 2.69 and 2.98, 95% CI 1.55–4.65 and 2.22–4.01, respectively). Mortality rate was significantly greater in HTG-AP vs. AAP or BAP (OR = 1.72 and 1.50, 95% CI 1.04–2.84 and 0.96–2.35, respectively), pancreatic necrosis occurred more frequently in AAP than BAP patients (OR = 1.58, 95% CI 1.08–2.30). Overall, there is a potential association between aetiology and the development and course of AP. HTG-AP is associated with the highest number of complications. Furthermore, AAP is likely to be more severe than BAP or PAP. Greater emphasis should be placed on determining aetiology on admission.

Gene–environment interaction between APOA5 c.553G>T and pregnancy in hypertriglyceridemia-induced acute pancreatitis

The etiology of hypertriglyceridemia (HTG) and, consequently, HTG-induced acute pancreatitis (HTG-AP), is complex. Herein, we explore a possible gene-environment interaction between APOA5 c.553G>T (p.185Gly>Cys, rs2075291), a common variant associated with altered triglyceride levels, and pregnancy in HTG-AP. We enrolled 318 Chinese HTG-AP patients and divided them into 3 distinct groups: Group 1, male patients (n=183); Group 2, female patients whose disease was unrelated to pregnancy (n=105); and Group 3, female patients whose disease was related to pregnancy (n=30). APOA5 rs2075291 genotype status was determined by Sanger sequencing. A total of 362 healthy Han Chinese subjects were used as controls. Data on body mass index, peak triglyceride level, age of disease onset, episode number, and clinical severity of HTG-AP were collected from each patient. Multiple comparisons, between patient groups, between patient groups and controls, or within each patient group, were performed. A robust association of APOA5 rs2075291 with HTG-AP in general, and HTG-AP during pregnancy in particular, was demonstrated. The minor T allele showed a stronger association with Group 3 patients than with either Group 1 or Group 2 patients. This stronger association was due mainly to the much higher frequency of TT genotype in Group 3 patients (20%) than that (<6%) in Group 1 and Group 2 patients. Moreover, the TT genotype was associated with a significantly higher peak triglyceride level in Group 3 patients compared with the GG genotype. Our findings provide evidence for an interaction between APOA5 rs2075291 and pregnancy in HTG-AP.

Clinical features and outcomes of hypertriglyceridemia-induced acute pancreatitis: Propensity score matching analysis from a prospective acute pancreatitis registry

BackgroundHypertriglyceridemia (HTG) is a well-known cause of acute pancreatitis (AP) and elevation of serum triglycerides (TG) to ≥1000 mg/dl is strongly indicative of HTG-induced AP (HTG-AP). HTG-AP is potentially associated with persistent organ failure and poor prognosis. Here, we compared differences in clinical features and outcomes between patients with HTG-AP and patients with AP due to other causes. MethodsA prospective AP registry was constructed in Gil Medical Center between June 2014 and May 2018. In total, 499 patients with AP were included for whom serum TG data at admission were available. ResultsHTG-AP was present in 52 patients (10.4%); these patients were younger than patients with AP due to other causes (39.62 ± 10.12 vs. 51.62 ± 17.41, p < 0.001). After propensity score matching adjusted by age, the factors associated with severity were more common in the HTG-AP group; these factors included the presence of systemic inflammatory response syndrome, Ranson’s score ≥3, acute physiology, age, chronic health evaluation (APACHE) II score ≥8 at admission, and C-reactive protein level >10 mg/dl after 24 h of hospitalization. There were no significant differences in complications or severity based on the revised Atlanta classification 2012. In addition, recurrence was more frequent in the HTG-AP group (25.0% vs. 6.4%, p < 0.001). ConclusionHTG-AP occurred in younger patients and showed more frequent recurrences than AP with other causes. Although factors related to severe feature were more common in HTG-AP during early phase, overall severity and prognosis were not different between the two groups.

27 Assessment of the Impact of Hypertriglyceridemia on Organ Failure During Acute Pancreatitis: A Different Perspective

INTRODUCTION: Hypertriglyceridemia (HTG) may impact acute pancreatitis (AP) outcomes. This study investigates the effect of different serum triglycerides (TG) thresholds on the development of persistent or multiple organ failures in patients with AP. METHODS: Cohort study of a prospectively maintained database of patients admitted with AP at a tertiary center in the last 15 years. We strictly included patients who met AP diagnosis by Revised Atlanta Classification. Severity of HTG was determined by the American Endocrine Society guidelines. Control group: AP (including all common etiologies, except HTG-induced AP). Study groups included other common HTG scenarios: 1) HTG-AP (i.e. HTG-induced AP), 2) HTG-AP + DKA (i.e. Triad), and 3) AP + diabetes ketoacidosis (AP-DKA). We assessed the levels of TG and its impact on organ failure. Multivariable logistic regression models were constructed using STATA software version 9.4. RESULTS: 2,654 patients were reviewed, of whom 124 patients had the triad (HTG-AP, DKA), 100 had HTG-AP only (triglyceride levels &gt;1,000 mg/dL), 67 had AP + DKA and we included 101 with AP-only as control for the analysis. Overall, any level of hypertriglyceridemia in all of the three study groups (HTG related syndromes) had higher odds for developing organ failure when compared to the control group (Table 1). All study groups had higher odds to develop ARDS, AKI, ileus, and shock. The highest odds ratios for organ failures were: HTG-AP patients with moderate levels of HTG were almost 25 times more likely to develop ARDS. AP-DKA patients with moderate levels of HTG were 32 times more likely to develop AKI. HTG-AP patients with severe HTG levels were 16 times more likely to develop ileus. HTG-AP patients with moderate HTG levels were 7 times more likely to develop shock. Interestingly, all study groups had lower odds to develop SIRS, persistent SIRS at 24 or48 hrs, and myocardial infarction (MI) (Table 1). CONCLUSION: Increased TG levels were associated with the development of multiple organ failure among AP patients, particularly in the settings of HTG-induced AP, the Triad of HTG-AP-DKA, and AP-DKA. Interestingly, HTG did not correlate with SIRS (transient or persistent), which one could have expected. It seems that the severe organ failure is driven by direct lipotoxicity from HTG rather than pancreatitis-inflammation (i.e. SIRS).

Subsets associated with developing acute pancreatitis in patients with severe hypertriglyceridemia and the severity of pancreatitis

Background and objectivesHypertriglyceridemia (HTG) is a rare but well-recognized cause for acute pancreatitis (AP). This study aimed to determine subsets related to development of AP in patients with severe HTG and the severity of HTG-induced AP (HTG-AP). MethodsPatients who had severe HTG (serum triglyceride level >1,000 mg/dL) more than once between Jan. 2010 and Dec. 2017 in a single institute were evaluated retrospectively. Patients were divided into two groups, with AP or without AP, and were compared. HTG-APs in patients with severe HTG were compared to APs due to other causes during the same period. ResultsSixty-three patients (19.3%) presented with AP of a total 326 patients with severe HTG. The AP group displayed younger age, more alcohol consumption and diabetes mellitus, and higher initial/maximum serum levels of triglyceride, glucose, HbA1c, total cholesterol, and calculated non-high-density lipoprotein cholesterol (p < 0.05). HTG-APs were clinically more severe compared with 277 APs due to other causes in terms of CRP (p < 0.001), CT severity index (p = 0.002), revised Atlanta classification (p < 0.001), and hospital stay (p = 0.011). In logistic regression analysis, maximum serum triglyceride level (OR 2.706, p = 0.015), alcohol consumption amount (OR 5.292, p < 0.001), and age (OR 0.358, p = 0.017) were independently associated with development of AP in patients with severe HTG. ConclusionsDevelopment of AP in patient with severe HTG was independently associated with younger age, higher serum TG level, and more alcohol consumption. HTG-APs are clinically more severe than APs due to other causes.

The role of plasma exchange in hypertriglyceridemia-induced acute pancreatitis.

Hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) leads to higher morbidity and mortality compared with other etiologies. The role of plasma exchange (PE) in this context is still not well established. We aimed to assess the clinical outcomes of patients with HTG-induced AP who underwent PE and compare it with those who did not. We retrospectively evaluated the data of patients who were admitted with HTG-induced AP between January 2013 and May 2018. The endpoint of the study was to assess the clinical outcomes, which included complication rates, mortality, and pancreatitis recurrence rate. Overall, 41 patients were included in the final analysis. Of these, 12 (29.2%) underwent PE. Patients undergoing PE had more severe pancreatitis on the basis of the Japanese Severity Score [10 (83.3%) vs. 14 (48.3%), P=0.03, respectively). Although mortality was higher in patients who underwent PE [three (25.0%) vs. zero, P<0.01, respectively], there was no difference in terms of complications and recurrence rates. Over a median 21 months of follow-up, 11 (26.8%) patients had recurrent AP. Although PE effectively reduced plasma triglyceride levels, there was no decrease in mortality or recurrences.

Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking

BackgroundHypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG.MethodsA Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes.ResultsThe patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene.ConclusionsThis is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.

Everolimus-Induced Hypertriglyceridemia Manifesting as Acute Pancreatitis

Everolimus is used in the treatment of many advanced cancers like renal and breast cancer. Hypertriglyceridemia (HTG) is a known adverse effect of the drug. However, acute pancreatitis (AP) is not commonly reported. A 46-year-old Hispanic female with recurrent breast cancer had been treated with Everolimus (10 mg/day) for 6 weeks, who then developed elevated triglycerides (TG) and the Everolimus was stopped. Three days later, she presented to the emergency center with nausea and severe, mid-epigastric pain radiating to her back. Lab values included: sodium 127 mEq/L, lipase 795 U/L, blood glucose > 700 mg/dl, with normal calcium. The serum was milky in appearance, with TG > 1590 mg/dL. There was no history of diabetes or alcohol use. She was diagnosed with diabetic ketoacidosis (DKA) and admitted to the medical ICU for intravenous fluids, insulin drip and pain control. Despite resolution of ketoacidosis, her pain worsened and she remained anorexic. Gastroenterology was consulted and diagnosed her with AP due to HTG. After several days, her TG decreased to 336 mg/dL with above treatment, coinciding with improvement of her symptoms (Figure 1). Her diet was advanced and she was discharged with fenofibrates. TG level four months later normalized. Everolimus treatment was not re-attempted. Hypertriglyceridemia and drugs are common causes of AP. There are two main causes of HTG-induced AP (HTG-AP): primary (usually genetic or idiopathic) and secondary. The pathogenesis of HTG associated with mTOR inhibitors is unclear, but may be related to slow degradation of apolipoprotein B100 leading to dyslipidemia. Hyperlipidemia is thought to cause AP when the pancreatic lipase hydrolyzes the excess TGs circulating in the serum damaging the free fatty acids which in turn accumulate in the pancreas leading to severe inflammation of the pancreas. HTG also leads to impaired clearance of chylomicrons leading to pancreatic capillary hyperviscosity causing ischemia. HTG-induced AP may be clinically evident when TG levels exceed 1000 mg/dL. Treatment involves IV insulin, IV heparin, or plasmapheresis (in absence of hyperglycemia) with fenofibrates for long term management. Our patient likely had secondary HTG due to Everolimus. Awareness of Everolimus causing HTG-AP is important for gastroenterologists, especially those who may treat cancer patients.Figure: Timeline showing introduction of Everolimus and development of Hypertriglyceridemia.

Management of Very Severe Hypertriglyceridemia With and Without Plasma Exchange

Acute pancreatitis (AP) is a potentially life-threatening complication of severe hypertriglyceridemia (HTG). The risk of AP markedly increases with triglyceride (TG) levels > 22.6 mmol/L (normal < 1.7 mmol/L), but can be prevented by maintaining TG < 11.3 mmol/L. Usual management of HTG-induced AP includes cessation of oral intake, fluid replacement, and correction of secondary factors that predispose to HTG. Plasma TG levels typically fall with these conservative measures. Recently, several anecdotal reports of plasma exchange (PLEx) in the early stages of HTG-induced AP have demonstrated dramatic TG reductions in acute setting.