Significant but partial lipoprotein lipase functional loss caused by a novel occurrence of rare LPL biallelic variants.

BACKGROUND: Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive familial chylomicronemia syndrome. However, rare biallelic LPL variants resulting in significant but partial loss of function are rarely documented. This study reports a novel occurrence of such rare biallelic LPL variants in a Chinese patient with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) during pregnancy and provides an in-depth functional characterization. METHODS: The complete coding sequences and adjacent intronic regions of the LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes were analyzed by Sanger sequencing. The aim was to identify rare variants, including nonsense, frameshift, missense, small in-frame deletions or insertions, and canonical splice site mutations. The functional impact of identified LPL missense variants on protein expression, secretion, and activity was assessed in HEK293T cells through single and co-transfection experiments, with and without heparin treatment. RESULTS: Two rare LPL missense variants were identified in the patient: the previously reported c.809G > A (p.Arg270His) and a novel c.331G > C (p.Val111Leu). Genetic testing confirmed these variants were inherited biallelically. Functional analysis showed that the p.Arg270His variant resulted in a near-complete loss of LPL function due to effects on protein synthesis/stability, secretion, and enzymatic activity. In contrast, the p.Val111Leu variant retained approximately 32.3% of wild-type activity, without impacting protein synthesis, stability, or secretion. Co-transfection experiments indicated a combined activity level of 20.7%, suggesting no dominant negative interaction between the variants. The patient's post-heparin plasma LPL activity was about 35% of control levels. CONCLUSIONS: This study presents a novel case of partial but significant loss-of-function biallelic LPL variants in a patient with HTG-AP during pregnancy. Our findings enhance the understanding of the nuanced relationship between LPL genotypes and clinical phenotypes, highlighting the importance of residual LPL function in disease manifestation and severity. Additionally, our study underscores the challenges in classifying partial loss-of-function variants in classical Mendelian disease genes according to the American College of Medical Genetics and Genomics (ACMG)'s variant classification guidelines.

Updates in Drug Treatment of Severe Hypertriglyceridemia.

PURPOSE OF REVIEW: To provide an insight into the new pharmacological options for the treatment of severe hypertriglyceridemia (sHTG). RECENT FINDINGS: sHTG is difficult to treat. The majority of the traditional pharmacological agents available have limited success in both robustly decreasing triglyceride levels and/or in reducing the incidence of acute pancreatitis (AP), the most severe complication of sHTG. Therapeutic options with novel mechanisms of action have been developed, such as antisense oligonucleotides (ASO) and small interfering RNA (siRNA) targeting APOC3 and ANGPTL3. The review discusses also 2 abandoned drugs for sHTG treatment, evinacumab and vupanorsen. The ASO targeting APOC3, volanesorsen, is approved for use in patients with familial chylomicronemia syndrome (FCS) in Europe. Olezarsen, an N-acetylgalactosamine (GalNAc)-conjugated ASO with the same target, seems to have a better safety and efficacy profile. siRNA targeting APOC3 and ANGPTL3, namely ARO-APOC3 and ARO-ANG3, are also promising for the treatment of sHTG. However, the ultimate clinical goal of any sHTG treatment, the decrease in the risk of AP, has not been definitively achieved till now by any pharmacotherapy, either approved or in development.

Effect of TPE vs medical management on patient outcomes in the setting of hypertriglyceridemia-induced acute pancreatitis with severely elevated triglycerides.

OBJECTIVES: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) accounts for 1 to 10% of pancreatitis cases, and is associated with a more severe clinical course. Therapeutic plasma exchange (TPE) is a potential treatment option for quickly lowering plasma triglycerides (TG). Current ASFA guidelines define HTG-AP as a Category III disorder, indicating the role of apheresis is not firmly established. Here, we examine clinical data regarding its effectiveness on morbidity and mortality in patients with HTG-AP presenting with severely elevated plasma triglycerides (>4000 mg/dl). METHODS: We retrospectively examined clinical data and outcomes from 67 consecutive episodes of HTG-AP over a 5-year period in which either medical management alone or medical management plus adjunct TPE was employed to reduce plasma triglycerides. RESULTS: 16/67 admissions involved TPE, initiated at a mean of 0.7 days from the time of presentation, while 51 received medical management alone. After only one TPE procedure, the mean TG values decreased from 4103 to 1045 mg/dl (a reduction of 74.7%), and those receiving TPE reached plasma TG < 1000 mg/dl 0.99 days faster than the medical group. One patient in the TPE group died. However, when excluding patients with hospital courses complicated by multiple organ dysfunction, there was no significant difference in mortality or hospital length of stay (LOS) between the groups. CONCLUSIONS: In uncomplicated cases of HTG-AP with an absence of multiorgan dysfunction, there is no significant benefit to either mortality or LOS when adding adjunct TPE to medical management, even when patients present with severely elevated levels of TG.

Predictability and efficacy of therapeutic plasma exchange for hypertriglyceridemia induced acute pancreatitis.

BACKGROUND: Hypertriglyceridemia induced acute pancreatitis is associated with more severe clinical course than acute pancreatitis caused by other etiologies. Therapeutic plasma exchange (TPE) is a potential treatment for patients with severe hypertriglyceridemia induced acute pancreatitis due to its rapid effect in lowering triglycerides (TG) levels and reducing inflammatory cytokines. However, clinical data regarding the effectiveness and safety of TPE is limited. METHODS: We retrospectively reviewed eight cases of hypertriglyceridemia induced acute pancreatitis and treated with TPE. Patients' demographic data, personal history, clinical course, laboratory results, apheresis data and clinical outcome were collected and analyzed. RESULTS: At initial presentation, the average TG levels for the eight patients was 3381.6 mg/dl (SD: 1491.6 mg/dl). Twelve procedures were performed on the eight patients in the study, and TG levels decreased by an average of 2673.2 mg/dl (SD: 2306.3 mg/dl) with a corresponding average reduction rate of 60.3 % (SD:21.1 %), ranging from 14.6%-84.9%. A 60 % or greater reduction was achieved in 66.7 % of all the procedures; however, the degree of reduction for each procedure was not predictable, even among repeat procedures on the same patient. CONCLUSIONS: Our study indicates that TPE is an effective and safe treatment option for patients with hypertriglyceridemia induced acute pancreatitis. However, due to the unpredictability of TG removal, repeat procedures may be necessary for some patients.

Role of mean platelet volume in hypertriglyceridemia-induced acute pancreatitis during pregnancy.

BACKGROUND: Hypertriglyceridemia-induced acute pancreatitis during pregnancy (HTG-APP) is a rare but severe disease with high maternal-fetal mortality risk, which constitutes a systemic inflammatory process accompanied by thrombosis and bleeding disorders. However, the role of mean platelet volume (MPV) in HTG-APP remains unclear. METHODS: In the retrospective study, we collected 45 patients with HTG-APP as the HTG-APP group and 49 pregnant females with hypertriglyceridemia as the control group. MPV and other relevant variables at onset and remission were collected and compared. RESULTS: MPV were significantly higher in the HTG-APP group than in the control group (P < 0.001), and lower in remission than on onset (P = 0.002). According to the severity of acute pancreatitis, all subjects were classified into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups. There was a significant difference in MPV on onset among the three groups (P = 0.048), and the SAP patients had the highest levels of MPV. In addition, only in the SAP group, MPV was lower in remission than on onset (P = 0.010). Logistic regression analyses revealed that MPV was significantly associated with SAP (odds ratio = 2.077, 95% confdence interval, 1.038-4.154; P = 0.039). CONCLUSIONS: These results may indicate an important role of mean platelet volume in evaluating the severity of HTG-APP.

Dynamic changes of lipid profile in severe hypertriglyceridemia-induced acute pancreatitis patients under double filtration plasmapheresis: a retrospective observational study.

BACKGROUND: To investigate the dynamic change of lipid profile under double filtration plasmapheresis (DFPP) in severe hypertriglyceridemia-induced acute pancreatitis (sHTGP) patients and ascertain the association between these changes and the clinical prognosis. METHODS: sHTGP patients admitted within 72 h after disease onset were included, and all the patients received DFPP within 24 h after admission. Lipid profile were detected on admission, consecutive 4 days after DFPP and at discharge. RESULTS: There were 47 sHTGP patients enrolled in this study. At admission, all the parameters of lipid profile changed significantly except for low density lipoprotein. In the first day after DFPP, the serum level of TG, cholesterol and very low density lipoprotein declined significantly, while the high-density lipoprotein (HDL) as well as apoprotein A1 elevated obviously (P < 0.05). TG maintained the downward trend in the following three days and the other parameters kept steady. Linear regression analysis showed that HDL was negatively correlated with the duration of hospitalization among three adjusted models (P = 0.043, P = 0.029, P = 0.025 respectively). CONCLUSION: There was distinct fluctuation of the lipid profile upon the burst of sHTGP and the parameters changed significantly in the first day after DFPP. Among these parameters, HDL may serve as a biomarker for disease prognosis in patients with sHTGP.

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.

Clinical features and treatment of hypertriglyceridemia-induced acute pancreatitis during pregnancy: A retrospective study.

AIM: To analyze the features and treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) during pregnancy. METHODS: A retrospective study of 21 pregnant women diagnosed with acute pancreatitis (AP) was performed. Patients were divided into acute biliary pancreatitis (ABP), HTGP, and idiopathic groups according to etiology. RESULTS: 95% of the patients were in the third trimester of gestation. The percentage of patients with HTGP was higher than that of ABP (48% vs.14%). The percentage of severe acute pancreatitis (SAP) in the HTGP group was higher than that in the ABP group (40.0% vs.0%). The Ranson scores for moderately severe acute pancreatitis (MSAP) and SAP in the HTGP group were significantly different (2.50 ± 0.58 vs.3.60 ± 0.89, P < 0.05, respectively). The mean serum triglyceride (TG) levels in the MSAP and SAP HTGP groups were not significantly different (18.81 ± 11.13 vs. 30.53 ± 24.20 mmol/L, P > 0.05, respectively). In the HTGP group, there were five patients given plasma exchange therapy and five not. Plasmapheresis decreased the incidence of systemic inflammatory response syndrome (SIRS) from 100% to 28.6% and the TG level from 20.36 ± 7.41 mmol/L to 5.23 ± 3.62 mmol/L (P < 0.05). The length of hospitalization of the plasmapheresis group was shorter than that of the nonplasmapheresis group (17.3 ± 6.7 days vs. 37.0 ± 20.8 days). CONCLUSIONS: Plasma exchange may be safe and effectively administered for HTGP patients during pregnancy with SIRS or multiple organ dysfunction syndrome (MODS). J. Clin. Apheresis 31:571-578, 2016. © 2015 Wiley Periodicals, Inc.

Trends and Outcomes of US Hypertriglyceridemia-Induced Acute Pancreatitis Hospitalizations in Hispanic Americans: Epidemiology from 2016 to 2020.

OBJECTIVE: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) hospitalizations are increasing in the USA; however, the impact of race and ethnicity on key outcomes in Hispanic and non-Hispanic white HTG-AP hospitalizations has not been studied. METHODS: We queried the National Inpatient Sample (NIS) between 2016 and 2020 identifying all patients with discharge diagnosis AP. HTG-AP hospitalizations were identified for Hispanic and non-Hispanic white patients. Primary outcomes included yearly rate of HTG-AP and in-hospital mortality from HTG-AP. Secondary outcomes were length of stay (LOS) and inflation-adjusted hospital costs. RESULTS: HTG-AP hospitalizations accounted for 5.9% of all AP hospitalizations; 17,440 and 48,235 hospitalizations included a Hispanic and non-Hispanic white patient, respectively. The yearly rate of HTG-AP hospitalizations per 100,000 adult population was statistically higher for Hispanics compared to non-Hispanic whites. The HTG-AP hospitalization rate increased for both Hispanics and non-Hispanic whites (both ptrend < 0.001); however, the trends were not statistically different. The number of observed in-hospital deaths for Hispanics was too low to report, precluding subsequent analysis. Hispanics were younger, more likely to be female, more commonly Medicaid recipients, and from zip codes with lower income quartiles. Despite clinically similar rates of plasmapheresis use and LOS, adjusted hospital costs were 18.9% higher for Hispanics compared to non-Hispanic whites (95% CI, 15.4 to 22.6% higher, p < 0.001). CONCLUSIONS: HTG-AP incidence is increasing in the USA in Hispanic and non-Hispanic whites. Despite clinically similar outcomes, HTG-AP hospitalizations in Hispanic patients were associated with $26,805,280 in excess costs compared to non-Hispanic white hospitalizations.

Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) is steadily increasing in China, becoming the second leading cause of AP. Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies. HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components. However, the impact of metabolic syndrome components on HTG-AP clinical outcomes remains unclear. AIM: To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP. METHODS: In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University, we collected data on patient demographics, clinical scores, complications, and clinical outcomes. Subsequently, we analyzed the influence of the presence and number of individual metabolic syndrome components, including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), on the aforementioned parameters in HTG-AP patients. RESULTS: This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP, with low HDL-C being the most significant risk factor for clinical outcomes. The risk of complications increased with the number of metabolic syndrome components. Adjusted for age and sex, patients with high-component metabolic syndrome had significantly higher risks of renal failure [odds ratio (OR) = 3.02, 95%CI: 1.12-8.11)], SAP (OR = 5.05, 95%CI: 2.04-12.49), and intensive care unit admission (OR = 6.41, 95%CI: 2.42-16.97) compared to those without metabolic syndrome. CONCLUSION: The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTG-AP, making it crucial to monitor these components for effective disease management.

Hypertriglyceridemia-Induced Acute Pancreatitis in Pregnancy: A Case Report in Anesthetic Management.

Severe hypertriglyceridemia in pregnancy, defined as triglycerides >1000 mg/dL, is a rare but high-acuity condition that can precipitate several complications for the mother and fetus, in particular hypertriglyceridemia-induced acute pancreatitis (HTGAP). The treatments employed in the management of hypertriglyceridemia-induced acute pancreatitis (HTGAP) have the potential to significantly alter the anesthetic course of an impending or emergent delivery. In this report, we present two cases of HTGAP, one complicated by a concomitant COVID-19 infection and each with a unique approach to anesthetic management in the setting of two very different and cofounded clinical presentations.

Approach to the Management of Hypertriglyceridemia Complicated With Acute Pancreatitis in Pregnancy: A Case Report.

This is a case of a 32-year-old woman, Gravida 3 para 2, previous two cesarean sections, who presented to our emergency department at 24+3 weeks of gestation complaining of severe epigastric pain radiating to the back. She was diagnosed with severe hypertriglyceridemia complicated with acute pancreatitis and was managed by a multi-disciplinary team, which included obstetrics, gastroenterology, endocrinology, hematology, nutrition, and ICU team. Initially, conservative treatment was employed for her management. She was placed on nil per oral status and initiated on a normal saline infusion at a rate of 150 ml/hour, along with insulin infusion at 0.1 unit/kg/hour and dextrose (D5) at 80 ml/hour. Additionally, she received omeprazole, meropenem, clexane (40 mg once daily subcutaneous injection), iron, vitamin supplements, and analgesics as required. Subsequently, due to the failure of the initial conservative medical management, the patient was admitted to the ICU. Plasmapheresis was performed after the insertion of a vascath, using 3000 ml of albumin 5% as replacement fluid and oral calcium. Following this, she was prescribed Omacor (Omega 3) at a dosage of 2 grams orally twice daily, along with a low carbohydrate and fat diet, to manage her triglyceride levels. After the removal of the central line, her triglycerides increased to 14.3 mmol/L, leading to the initiation of fenofibrate at a daily dose of one tablet. With persistent elevation to 16.4 mmol/L, Lipitor at 40 mg once daily was introduced. Following this intervention, her triglyceride levels stabilized, and her overall condition improved. She was discharged at 25+1 weeks with a prescribed regimen, and scheduled follow-ups were arranged in the endocrine and obstetrics clinics. At 36 weeks of gestation, she presented to the emergency room with abdominal, back, and leg pain. Fetal distress, indicated by fetal tachycardia (170-180 bpm) on cardiotocography, prompted an urgent category 1 cesarean section, which proceeded without complications.

Enhancing predictive accuracy in hypertriglyceridemia-induced acute pancreatitis: Role of red cell distribution width and prospective studies.

This letter addresses the study titled "Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis" by Lv et al published in the World Journal of Experimental Medicine. The study offers a valuable analysis of red cell distribution width (RDW) as a predictive marker for persistent organ failure in patients with hypertriglyceridemia-induced acute pancreatitis. The study results suggest that RDW, combined with the Bedside Index for Severity in Acute Pancreatitis score, could enhance the predictive accuracy for severe outcomes. Further investigation into the role of RDW in different severities of acute pancreatitis is recommended. Additionally, the need for large-scale and multicenter prospective studies to validate these findings is emphasized.

Case Report: Acute Pancreatitis in an Uncontrolled Diabetic Patient Presenting With a Skin Rash Later Found to Be Eruptive Xanthoma, a Dermatological Manifestation and Diagnostic Clue to Recognizing Hypertriglyceridemia as the Cause of Disease.

Acute pancreatitis results from any insult that leads to inflammation of the organ. Hypertriglyceridemia is one of the risk factors associated with acute pancreatitis. The typical presentation is abdominal pain, nausea, and vomiting. We present a unique case in which the patient's condition was further complicated by diabetic ketoacidosis. Consequently, he presented somnolent to the emergency room, providing a limited history only pertaining to generalized weakness and a skin rash. The patient was found to have hypertriglyceridemia-induced pancreatitis, which was appropriately managed in the intensive care unit. The skin lesions were diagnosed as xanthomas, which are associated with hypertriglyceridemia and acute pancreatitis secondary to hypertriglyceridemia. The patient was discharged on fibrate therapy, dietary counseling, and strict monitoring by his primary care physician. This unique case highlights the importance of recognizing dermatological conditions and their associated diseases to allow for prompt diagnosis and treatment in the face of limited history.

Acute Pancreatitis With Normal Amylase and Lipase: A Diagnostic Dilemma.

Acute pancreatitis is a common and potentially life-threatening condition. It is characterized by inflammation of the pancreas, most often leading to elevated levels of pancreatic enzymes in the blood. In a subset of patients, however, conventional biomarker levels may remain within the reference range. Such instances have the potential to create a diagnostic challenge for healthcare professionals and can lead to misdiagnosis or delayed treatment. This article presents the intriguing clinical scenario of acute pancreatitis with normal amylase and lipase, discusses factors that may lead to normoenzymatic presentation, and reminds clinicians of the diagnostic criteria for acute pancreatitis, which does not necessarily require elevated pancreatic enzymes.

Severe Hypertriglyceridemia: A 10-Year Review in a Portuguese Hospital.

INTRODUCTION: Severe hypertriglyceridemia (SHTG) is a rare condition associated with serious complications, such as acute pancreatitis (AP), and the best treatment is still a matter of discussion. The aim of this study is to outline the demographics, management, and outcomes (recurrence and mortality) of complications in patients with SHTG. MATERIAL AND METHODS: A retrospective, observational, and analytical study was carried out by obtaining clinical data from the electronic health records of patients with SHTG admitted to the Internal and Intensive Medicine units from the 1st of January 2009 to the 31st of December 2020 in a university hospital. RESULTS: The cohort included 17 patients. The most common complication was AP (13/17 = 76.5%). Admission to the intensive care unit (ICU) was observed in 84.2%. Among patients with AP, the most commonly administered therapies were insulin (82.4%) and fibrates (76.5%). Plasmapheresis was used in 58.8%, and the criteria for using this technique were mainly based on clinical and laboratory abnormalities. There were no deaths. The readmission rate at 30 days was 36.3%. CONCLUSION: This study shows the morbidity profile associated with SHTG, with a high level of ICU admissions and also a high level of the use of plasmapheresis. In our population, this approach had good results, and this should be highlighted as there are no clear international guidelines for this intervention. Distinguishing between patients with familial chylomicronemia syndrome or with multifactorial chylomicronemia is important as recent specific therapy for lipoprotein lipase (LPL) genetic deficit is available. In the near future, the performance of a genetic study should be considered in patients with SHTG as an attempt to avoid the high recurrence rate of complications of this disease.

Recurrence for patients with first episode of hypertriglyceridemia-induced acute pancreatitis: A prospective cohort study.

BACKGROUND: Data on recurrent hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are scarce. OBJECTIVE: To investigate the incidence and risk factors for recurrence of HTG-AP, and the effect of triglyceride (TG) lowering drugs post index attack on recurrence. METHODS: This study was a prospective cohort study of adult patients with first episode of HTG-AP from December 2019 to February 2021 who were followed until recurrence or death, or February 2022. The cumulative incidence function and Fine and Gray's competing-risk model were applied to the analyses. RESULTS: A total of 317 patients were enrolled, and the 12-month and 18-month cumulative recurrence incidences were 8% and 22%, respectively. The cumulative recurrence incidence was 2 times higher in patients whose serum TG levels post index attack were ≥5.65 mmol/L (subdistribution hazard ratio [SHR], 2.00; 95% confidence interval [CI], 1.05-3.80; P = 0.034) compared to patients with TG <5.65 mmol/L. The recurrence rate was 3.3 times higher in patients whose glucose levels post index attack were ≥7.0 mmol/L (SHR, 3.31; 95% CI, 1.56-7.03; P = 0.002) than in patients with glucose <7.0 mmol/L). Compared to TG lowering drugs for less than 1 month post index attack, treatment for longer than 12 months decreased the incidence of recurrence by 75% (SHR, 0.25; 95% CI, 0.08-0.80; P = 0.019). CONCLUSIONS: The HTG-AP recurrence incidence is high and closely associated with high levels of TGs and glucose post index attack. Long-term TG lowering drugs treatment significantly decreases this recurrence.

Acute Pancreatitis Secondary to Pembrolizumab-Induced Hypertriglyceridemia.

Pembrolizumab is a humanized monoclonal antibody targeted against programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is used alone or in combination with many chemotherapy regimens for a wide variety of cancers. It has been reported to cause various side effects including endocrinopathies, colitis, rash, and pneumonitis. Hypertriglyceridemia (HTG) has been recently added to its side effect profile with a possible pathogenic mechanism involving autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GP1HBP1). We are presenting a case of acute pancreatitis secondary to HTG in a cervical cancer patient. HTG was successfully treated with insulin infusion. As the patient's symptoms improved, she was started on the diet. She was discharged on statin and fibrate therapy. We are reporting this case to increase awareness of this rare side effect, inpatient management, and outpatient screening while on immunotherapy.

Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Compared with patients with other causes of acute pancreatitis, those with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are more likely to develop persistent organ failure (POF). Therefore, recognizing the individuals at risk of developing POF early in the HTG-AP process is a vital for improving outcomes. Bedside index for severity in acute pancreatitis (BISAP), a simple parameter that is obtained 24 h after admission, is an ideal index to predict HTG-AP severity; however, the suboptimal sensitivity limits its clinical application. Hence, current clinical scoring systems and biochemical parameters are not sufficient for predicting HTG-AP severity. AIM: To elucidate the early predictive value of red cell distribution width (RDW) for POF in HTG-AP. METHODS: In total, 102 patients with HTG-AP were retrospectively enrolled. Demographic and clinical data, including RDW, were collected from all patients on admission. RESULTS: Based on the Revised Atlanta Classification, 37 (33%) of 102 patients with HTG-AP were diagnosed with POF. On admission, RDW was significantly higher in patients with HTG-AP and POF than in those without POF (14.4% vs 12.5%, P < 0.001). The receiver operating characteristic curve demonstrated a good discriminative power of RDW for POF with a cutoff of 13.1%, where the area under the curve (AUC), sensitivity, and specificity were 0.85, 82.4%, and 77.9%, respectively. When the RDW was ≥ 13.1% and one point was added to the original BISAP to obtain a new BISAP score, we achieved a higher AUC, sensitivity, and specificity of 0.89, 91.2%, and 67.6%, respectively. CONCLUSION: RDW is a promising predictor of POF in patients with HTG-AP, and the addition of RDW can promote the sensitivity of BISAP.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.