Hypertriglyceridemia-associated Acute Pancreatitis Research Articles

Prediction of severe hypertriglyceridemia-associated acute pancreatitis using a nomogram based on CT findings and blood biomarkers.

Hypertriglyceridemia is a common cause of acute pancreatitis (AP). Fatty liver, a manifestation of metabolic syndrome, is related to the severity of AP. The present study aimed to construct an accurate predictive model for severe AP (SAP) by combining the fatty liver infiltration on a computerized tomography (CT) scan with a series of blood biomarkers in patients with hypertriglyceridemia-associated AP (HTG-AP). A total of 213 patients diagnosed with HTG-AP were included in the present retrospective study. Clinical information and imageological findings were retrospectively analyzed. The model was constructed from independent risk factors using univariate analysis, the least absolute shrinkage and selection operator method. Subsequently, the data from the training group of 111 patients with HTG-AP was analyzed using logistic regression analysis. The efficacy of the model was verified using an external validation group of 102 patients through the receiver operating characteristic curve (ROC). Independent predictors, including serum calcium, C-reactive protein, lactate dehydrogenase and liver-to-spleen CT attenuation ratio (L/S ratio), were incorporated into the nomogram model for SAP in HTG-AP. The model achieved a sensitivity of 91.3% and a specificity of 88.6% in the training group. Compared with the Ranson model, the established nomogram model exhibited a better discriminative ability in the training group [area under the curve (AUC): 0.957] and external validation group (AUC: 0.930), as well as better calibration and clinical benefits. The present study demonstrates that the constructed nomogram based on CT findings and blood biomarkers is useful for the accurate prediction of SAP in HTG-AP.

Impact of therapeutic plasmapheresis on the duration of organ failure in patients with hypertriglyceridemia-associated acute pancreatitis

BackgroundPlasmapheresis is widely used for severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) to remove excessive triglycerides from plasma. This study aimed to evaluate whether plasmapheresis could improve the duration of organ failure in HTG-AP patients.MethodsWe analyzed a cohort of patients from a multicenter, prospective, long-running registry (the PERFORM) collecting HTG-AP patients admitted to the study sites within 72 h from the onset of symptoms. This study was based on data collected from November 2020 to March 2023. Patients who had organ failure at enrollment were involved in the analyses. The primary outcome was time to organ failure resolution within 14 days. Multivariable Cox regression model was used to evaluate the association between plasmapheresis and time to organ failure resolution. Directed acyclic graph (DAG) was used to identify potential confounders.ResultsA total of 122 HTG-AP patients were included (median [IQR] sequential organ failure assessment (SOFA) score at enrollment, 3.00 [2.00–4.00]). Among the study patients, 46 underwent plasmapheresis, and 76 received medical treatment. The DAG revealed that baseline serum triglyceride, APACHE II score, respiratory failure, cardiovascular failure, and renal failure were potential confounders. After adjusting for the selected confounders, there was no significant difference in time to organ failure resolution between patients undergoing plasmapheresis and those receiving exclusive medical treatment (HR = 1.07; 95%CI 0.68–1.68; P = 0.777). Moreover, the use of plasmapheresis was associated with higher ICU requirements (97.8% [45/46] vs. 65.8% [50/76]; OR, 19.33; 95%CI 2.20 to 169.81; P = 0.008).ConclusionsIn HTG-AP patients with early organ failure, plasmapheresis was not associated with accelerated organ failure resolution compared to medical treatment but may be associated with more ICU admissions.Trial registration: The PERFORM study was registered in the Chinese Clinical Trial Registry (ChiCTR2000039541). Registered 30 October 2020.

Recurrence of hypertriglyceridemia-associated acute pancreatitis: A multicenter, prospective cohort study

ObjectivesThere are scarce prospective data on recurrent hypertriglyceridemia-associated acute pancreatitis (HTG-AP). This study aimed to investigate the incidence, potential prognostic factors, and clinical relevance of recurrent HTG-AP. MethodsThis study is a multicenter, prospective cohort study. Adult patients with the first HTG-AP attack enrolled in the PERFORM registry between November 2020 and December 2021 were involved. All the study patients were followed up for more than two years with a two-round schedule. The Cox proportional-hazards model was applied to analyze the potential factors. Quality of life was evaluated using the EuroQol five-dimensional five-level health scale (EQ-5D-5L). ResultsA total of 184 patients from 25 sites were included in the study, and 161 patients completed the two-round follow-up. Among them, the mean follow-up time for the study patients was 31±4 months, and the incidence rate of recurrent HTG-AP attack was 23 % (37/161). All patients with recurrent episodes required readmission to the hospital. The EQ visual analog scale (VAS) score was significantly lower in patients with recurrent episodes compared to those without (76±10 vs. 82±12; P = 0.02) at the latest follow-up. Age <40 years old (hazard ratio [HR], 3.6; 95 % confidence interval [CI], 1.5–8.7; P = 0.004) and a history of diabetes (HR, 2.6; 95 %CI, 1.3–5.1; P = 0.005) were identified as potential predictor factors for recurrence. ConclusionsRecurrence of HTG-AP is common, especially for younger patients with diabetes. Recurrence necessitated additional hospital readmissions and was associated with compromised quality of life.

Early Plasmapheresis Among Patients With Hypertriglyceridemia–Associated Acute Pancreatitis

The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing. Plasmapheresis is theoretically effective in removing triglyceride from plasma, but whether it confers clinical benefits is unclear. To assess the association between plasmapheresis and the incidence and duration of organ failure among patients with HTG-AP. This is an a priori analysis of data from a multicenter, prospective cohort study with patients enrolled from 28 sites across China. Patients with HTG-AP were admitted within 72 hours from the disease onset. The first patient was enrolled on November 7th, 2020, and the last on November 30th, 2021. The follow-up of the 300th patient was completed on January 30th, 2022. Data were analyzed from April to May 2022. Receiving plasmapheresis. The choice of triglyceride-lowering therapies was at the discretion of the treating physicians. The primary outcome was organ failure-free days to 14 days of enrollment. Secondary outcomes included other measures for organ failure, intensive care unit (ICU) admission, duration of ICU and hospital stays, incidence of infected pancreatic necrosis, and 60-day mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were used to control potential confounders. Overall, 267 patients with HTG-AP were enrolled (185 [69.3%] were male; median [IQR] age, 37 [31-43] years), among whom 211 underwent conventional medical treatment and 56 underwent plasmapheresis. PSM created 47 pairs of patients with balanced baseline characteristics. In the matched cohort, no difference was detected concerning organ failure-free days between patients undergoing plasmapheresis or not (median [IQR], 12.0 [8.0-14.0] vs 13.0 [8.0-14.0]; P = .94). Moreover, more patients in the plasmapheresis group required ICU admission (44 [93.6%] vs 24 [51.1%]; P < .001). The IPTW results conformed to the results from the PSM analysis. In this large multicenter cohort study of patients with HTG-AP, plasmapheresis was commonly used to lower plasma triglyceride. However, after adjusting for confounders, plasmapheresis was not associated with the incidence and duration of organ failure, but with increased ICU requirements.

Acute Management of Hypertriglyceridemia With a Disease-Specific Intravenous Insulin Infusion Order Set.

Hypertriglyceridemia-associated acute pancreatitis is a disease lacking a standardized management approach. The main objective of this study was to evaluate the safety and efficacy of a continuous intravenous insulin infusion order set specifically designed for managing hypertriglyceridemia. This study compared the safety and efficacy of a standardized (postintervention) approach to managing hypertriglyceridemia to a nonstandardized (preintervention) approach. The primary efficacy outcome was the percentage of patients who achieved a triglyceride level less than 500 mg/dL. Additional outcomes included the time to achieving a triglyceride level less than 500 mg/dL and the percent reduction in triglyceride levels. The primary safety outcome was the number of patients who experienced hypoglycemia (glucose less than 70 mg/dL). Twenty patients were included in both the preintervention and postintervention groups. There was a significantly greater reduction in triglyceride levels observed in the postintervention group. The number of patients who achieved a triglyceride level less than 500 mg/dL in the preintervention and postintervention groups were 10 (50%) and 17 (85%), respectively, P = 0.018. Within the postintervention group, the time to achieving a triglyceride level less than 500 mg/dL in those with and without diabetes was 56.8 hours (38.2-64.0) versus 27.6 hours (19.7-45.0), respectively, P = 0.028. Our findings demonstrate that insulin infusions are safe and effective when therapy is standardized and accounts for nursing to patient ratios. Our results provide the medical community with a standardized approach to acutely managing hypertriglyceridemia.

Effectiveness of an Intravenous Insulin-Based Treatment Protocol for the Management of Hypertriglyceridemia-Associated Acute Pancreatitis.

There is burgeoning interest in intravenous insulin for hypertriglyceridemia-induced acute pancreatitis (HTG-AP) as a less invasive alternative to plasmapheresis; however, there are few published descriptions of disease-specific insulin protocols. To compare the efficacy and safety of an insulin infusion-based protocol with nonstandardized medical therapy for HTG-AP. This is a retrospective analysis before and after creation of an HTG-AP-specific insulin infusion treatment protocol. Inclusion criteria were age ≥18 years, an initial triglyceride level >1000 mg/dL, and a diagnosis of AP. The primary outcome of the study was time to a triglyceride level ≤1000 mg/dL. Sixty-seven patients were included in this study (26 pre-protocol and 41 in the HTG-AP insulin protocol group). Baseline characteristics between the groups were similar, with median initial triglyceride levels >3500 mg/dL. There was a trend toward patients treated with the HTG-AP-specific infusion reaching a triglyceride level ≤1000 mg/dL faster (43.3 [24.9-72.1] vs 26.9 [17.7-51.1] hours; P = 0.07). Those treated to ≤500 mg/dL achieved this faster with the disease-specific infusion (49.2 [29.4-67.8] vs 70.9 [36.3-107.2] hours, P = 0.04). Hypoglycemia was numerically lower in the HTG-AP-specific insulin infusion group despite higher insulin infusion rates (7.3% vs 19.2%). No patient in the HTG-AP-specific protocol group required plasmapheresis. The use of an HTG-AP-specific insulin infusion protocol, compared with antecedent nonstandardized care, resulted in prompter achievement of a triglyceride level ≤500 mg/dL and a strong trend toward faster achievement of ≤1000 mg/dL without an increased risk of hypoglycemia. While intravenous insulin may be considered the initial medical therapy for HTG-AP, further studies are needed to determine the optimal dosing.

Hypertriglyceridemia-associated acute pancreatitis: Response to continuous insulin infusion.

To assess the response of serum triglycerides (TG) to continuous insulin infusion (CII) in adults with hypertriglyceridemia-associated acute pancreatitis (HTGP). Retrospective analysis of TG response to standardized CII therapy in 77 adults admitted to intensive care with TG >1000 mg/dL and HTGP. Participants had initial TG 3869.0 [2713.5, 5443.5] mg/dL and were 39.3 ± 9.7 years old, 66.2% males, 58.4% Hispanic, BMI 30.2 [27.0, 34.8] kg/m2, 74.0% with diabetes mellitus (DM) and 50.6% with excess alcohol use. TG-goal, defined as ≤1,000 ± 100 mg/dL, was achieved in 95%. Among the 73 TG-goal achievers (responders), 53.4% reached TG-goal in <36 hours after CII initiation (rapid responders). When compared to slow responders taking≥36 hours, rapid responders had lower initial TG (2862.0 [1965.0, 4519.0] vs 4814.5 [3368.8, 6900.0] mg/dL), BMI (29.4 [25.9, 32.8] vs 31.9 [28.2, 38.3] kg/m2), DM prevalence (56.4 vs 94.1%), and reached TG-50% (half of respective initial TG) faster (12.0 [6.0, 17.0] vs 18.5 [13.0, 32.8] hours). Those with DM (n = 57) vs non-DM (n = 20) were obese (31.4 [28.0, 35.6] vs 27.8 [23.6, 30.3] kg/m2), took longer to reach TG-final (41.0 [25.0, 60.5] vs 14.5 [12.5, 25.5] hours) and used more daily insulin (1.7 [1.3, 2.1] vs 1.1 [0.5, 1.9] U/kg/day). Among those with DM, the rapid responders had higher daily use of insulin vs slow responders 1.9 [1.4, 2.3] vs 1.6 [1.1, 1.8] U/kg/day. All results significant. In multivariable analysis, predictors of faster TG response were absence of DM, lower BMI and initial TG. CII was effective in reaching TG-goal in 95% of patients with HTGP. Half achieved TG-goal within 36 hours. Presence of DM, higher BMI and initial TG slowed the time to reach TG-goal. These baseline parameters and rate of decline to TG-50% may be real-time indicators to initiate and adjust the CII for quicker response.

Variations in Gut Microbiome are Associated with Prognosis of Hypertriglyceridemia-Associated Acute Pancreatitis.

Hypertriglyceridemia-associated acute pancreatitis (HTGAP) is linked with increased severity and morbidity. Intestinal flora plays an important role in the progression of acute pancreatitis (AP). However, pathogenetic association between gut microbiota and HTGAP remains unknown. In this study, we enrolled 30 HTGAP patients and 30 patients with AP that is evoked by other causes. The V3–V4 regions of 16S rRNA sequences of the gut microbiota were analyzed. Clinical characteristics, microbial diversity, taxonomic profile, microbiome composition, microbiological phenotype, and functional pathways were compared between the two groups. Our results showed that the HTGAP group had a higher proportion of severe AP (46.7% vs. 20.0%), organ failure (56.7% vs. 30.0%), and a longer hospital stay (18.0 days vs. 6.5 days). HTGAP group also had poorer microbial diversity, higher abundances of Escherichia/Shigella and Enterococcus, but lower abundances of Dorea longicatena, Blautia wexlerae, and Bacteroides ovatus as compared with non-HTGAP group. Correlation analysis revealed that gut bacterial taxonomic and functional changes were linked with local and systemic complications, ICU admission, and mortality. This study revealed that alterations of gut microbiota were associated with disease severity and poor prognosis in HTGAP patients, indicating a potential pathophysiological link between gut microbiota and hypertriglyceridemia related acute pancreatitis.

Incidence and Management of Hypertriglyceridemia-Associated Acute Pancreatitis: A Prospective Case Series in a Single Australian Tertiary Centre.

Background: Hypertriglyceridemia-associated acute pancreatitis (HTGAP) has been linked with increased severity and morbidity. In this study, triglyceride levels were measured in all patients admitted with acute pancreatitis (AP) to establish the incidence of HTGAP in an Australian center. Methods: A prospective cohort with AP was collated over an 18-month period in a single tertiary referral hospital. HTGAP was defined as AP with triglycerides ≥ 11.2 mmol/L (1000 mg/dL). Incidence, clinical co-morbidities, severity and management strategies were recorded. Results: Of the 292 episodes of AP, 248 (85%) had triglycerides measured and were included. HTGAP was diagnosed in 10 of 248 (4%) AP cases. Type 2 diabetes, obesity, alcohol misuse and gallstones were common cofactors. The HTGAP group demonstrated severe hypertriglyceridemia compared to the non-HTGAP group (median 51 mmol/L vs. 1.3 mmol/L). Intensive care unit (ICU) admissions were significantly increased (odds ratio (OR) 16; 95% CI 4–62) in the HTGAP group (5/10 vs. 14/238 admissions, p < 0.001) and constituted 26% (5/19) of total ICU admissions for AP. Four patients received intravenous insulin with fasting and had a rapid reduction in triglyceride levels by 65–77% within 24 h; one patient had mild hypoglycemia secondary to therapy. Conclusion: HTGAP occurred in 4% of AP cases and was associated with higher risk of ICU admission. Intravenous insulin and fasting appear safe and efficacious for acutely lowering triglyceride levels in HTGAP.

Intravenous Insulin Versus Conservative Management in Hypertriglyceridemia-Associated Acute Pancreatitis.

Context and ObjectiveHypertriglyceridemia is implicated in ~5% of cases of acute pancreatitis. It is assumed that intravenous insulin is effective in lowering triglyceride (TG) concentrations in hypertriglyceridemia-associated acute pancreatitis (HAAP). However, the efficacy of intravenous insulin versus conservative management alone is not known.Design and SettingCharts of 106 patients who were admitted with HAAP and had TG concentrations >1000 mg/dL at admission were reviewed. Patients who received intravenous insulin for at least 8 hours were included in the intravenous insulin group, while the rest were considered to have received conservative management. We compared the change in TG concentrations from baseline in the 2 groups.ResultsFifty-one patients received intravenous insulin while 55 patients were managed conservatively. Baseline TG concentrations were higher in the intravenous insulin group (median [25th, 75th percentile] 3307 [2106, 4425] mg/dL vs 2304 [1416, 2720] mg/dL; P < 0.001). The TG concentrations declined rapidly in both groups, reaching below 1000 mg/dL by day 3 and < 500 mg/dL by day 4. TG concentrations in the intravenous insulin group had decreased by 69% and 85% on days 2 and 4, respectively. The fall in the conservative management group was 63% and 79%, which was not statistically different than the change in the intravenous insulin group.ConclusionOur results show that intravenous insulin did not result in a more rapid fall in TG compared with conservative treatment in patients with HAAP. Fasting and intravenous fluids were effective in lowering TG concentrations rapidly, with no further contribution from insulin.

A 16-year trend of etiology in acute pancreatitis: The increasing proportion of hypertriglyceridemia-associated acute pancreatitis and its adverse effect on prognosis

Acute pancreatitis (AP) is an acute inflammation of the pancreas, which caused increasing global health and economic burden. Longitudinal trends of disease etiology and its influence on prognosis remains unclear. The aim of this study was to analyze the trend of etiology in moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) and to evaluate the influence of the changing pattern of etiology. A 16-year cohort study was undertaken in a tertiary hospital. Patients who presented with MSAP or SAP from January 2001 to December 2016 were continuously enrolled. Demographic data, clinical manifestations, treatment strategy, and prognosis were recorded and verified. A total of 475 patients were included, among whom 173 (36.4%) had gallstone-associated pancreatitis and 108 (22.7%) had hypertriglyceridemia (HTG)-associated pancreatitis. The annual admission for MSAP and SAP rose steadily over the 16-year period (r=0.907, P<.001), with an annually increasing proportion of HTG-associated pancreatitis (from 14.3% to 35.5%, r=0.710, P=.015). Compared with gallstone-associated pancreatitis, hypertriglyceridemia-associated pancreatitis had significantly higher percentages of multiple organ dysfunction syndrome (MODS) (24.1% vs 12.1%, P=.009, FDR=0.029) and cardiovascular failure (17.6% vs 4.6%, P<.001, FDR<0.001). Positive correlations were found between the annual proportion of HTG-associated pancreatitis and MODS (r=0.574, P=.005) and between HTG-associated pancreatitis and cardiovascular failure (r=0.512, P=.029). Regression analysis showed that HTG was an independent risk factor for both MODS (P=.004) and cardiovascular failure (P=.009). The number of annually admitted MSAP and SAP cases increased during the last 16years along with an increasing proportion of HTG-associated AP. The increasing trend of HTG-associated AP might contribute to more frequently occurring MODS and cardiovascular failure.

Therapeutic plasmapheresis for hypertriglyceridemia-associated acute pancreatitis: case series and review of the literature.

Severe hypertriglyceridemia (HTG) is the third leading cause of acute pancreatitis (AP) in the United States. The current standard of care includes management of HTG using pharmacological therapy. More recently, plasmapheresis has been proposed as a therapeutic tool for decreasing triglyceride (TG) levels, especially in critically ill patients. Few studies are available to ascertain overall benefits of plasmapheresis over traditional management. To analyze the outcomes of patients treated with plasmapheresis for severe HTG-associated pancreatitis. We conducted a retrospective chart review of three patients with severe HTG- associated (TGs greater than 1000 mg/dl; 11.29 mmol/l) AP at the Methodist University Hospital. All the patients underwent plasmapheresis as part of their treatment. The average TG level before plasmapheresis was 3532 mg/dl (range: 2524-4562 mg/dl; 39.9 mmol/l; range: 28.5-51.6 mmol/l). All patients made a full recovery, with a significant improvement in TG levels after plasmapheresis. The mean number of sessions was 1.3 (range 1-2), and mean TG level after plasmapheresis was 1051 mg/dl (range: 509-1771 mg/dl; 11.9 mmol/l; range: 5.8-20 mmol/l). After the first session, the average reduction of TG level was 2481 mg/dl (range 753-3750 mg/dl; 28 mmol/l; range: 8.5-42.4 mmol/l) or approximately 70%. None of the patients developed complications related to plasmapheresis. Plasmapheresis can be an effective and rapid treatment option in patients with severe HTG and complications. However, further research, including randomized controlled studies, is necessary.

Role of myosin light chain kinase in hypertriglyceridemia-associated acute pancreatitis in rats

Role of myosin light chain kinase in hypertriglyceridemia-associated acute pancreatitis in rats

Double Filtration Plasma Apheresis Shortens Hospital Admission Duration of Patients With Severe Hypertriglyceridemia-Associated Acute Pancreatitis.

The treatment effectiveness of double filtration plasma apheresis (DFPP) on severe hypertriglyceridemia-associated acute pancreatitis (STAP) has been questioned because the currently defined serum triglyceride level--1000 mg/dL--is too low for STAP. Given this, we aimed to investigate DFPP effectiveness when we elevated STAP definition to 5000 mg/dL serum triglyceride. We performed nested case-control studies for STAP patients and divided them into groups "with" or "without" DFPP. We further recruited outpatient asymptomatic hypertriglyceridemia patients with STAP history, then divided them into groups "with" or "without" prophylactic DFPP once every 3 to 6 months for 2 years. We observed hospitalization duration and STAP recurrence between patients with and patients without DFPP. Twelve STAP patients receiving DFPP had a median hospitalization of 5 days, whereas 24 patients without DFPP had 10 days (P = 0.009). Six outpatient referrals with STAP history receiving prophylactic DFPP showed no STAP recurrences whereas 6 without DFPP showed 3 recurrences (P = 0.046). For the 25 patients whose serum triglyceride exceeded 5000 mg/dL, 11 receiving DFPP had median hospitalization of 5 days while 14 without DFPP had 11 days (P = 0.012). When applied to serum triglyceride in excess of 5000 mg/dL, DFPP removes oxidized and inflammatory lipoproteins, shortens hospitalization duration, and minimizes STAP recurrence.

Heparin Treatment for Severe Hypertriglyceridemia in Diabetic Ketoacidosis

In a patient with diabetic ketoacidosis complicated by severe elevation of plasma triglyceride concentrations, treatment with low-level intravenous unfractionated heparin led to prompt reduction in plasma triglyceride concentration and may have prevented the development of hypertriglyceridemia-associated acute pancreatitis. This article reviews the rationale for this treatment and surveys prior publications using heparin in this and similar settings.

Hypertriglyceridemia-associated Acute Pancreatitis with Chylous Ascites in Pregnancy

Both cholesterol and triglyceride levels in serum increase progressively during pregnancy. Hypertriglyceridemia is a well-recognized cause of acute pancreatitis, while pancreatitis-associated chylous ascites has rarely been reported. We report a 28-year-old female with coexistence of hypertriglyceridemia, acute pancreatitis, and chylous ascites during pregnancy. After emergency cesarean section, she was treated with nil per os, intravenous hydration, antibiotics, and analgesics as required. Due to the development of positive peritonitis 5 days later, an exploratory laparotomy was performed. Surgical interventions included pancreatic necrosectomy, right hemicolectomy and ileostomy, cholecystostomy, gastrostomy, and feeding jejunostomy. Postoperative treatment included antibiotics, total parenteral nutrition, and then low-fat diet with medium-chain triglyceride supplementation. She was discharged on the 43rd day after surgery and was free of symptoms during 6 months of follow-up. Ileocolostomy was performed 6 months after discharge. Fasting lipid profile should be regularly monitored during pregnancy due to the association of hypertriglyceridemia with development of acute pancreatitis in the mother.