Prevalência de pancreatite aguda em pacientes com hipertrigliceridemia grave avaliados geneticamente

Abstract

Different entities use divergent cutoff points and nomenclatures for the quantitative classification of hypertriglyceridemia. Cases of severe hypertriglyceridemia are related to monogenic genetic causes associated with secondary factors more frequently than mild or moderate cases. Acute pancreatitis (AP) is the main complication related to severe hypertriglyceridemia. The primary etiology of hypertriglyceridemia most associated with the development of AP is Familial Chylomicronemia Syndrome (FCS), associated with pathogenic variants in the LPL gene or its regulators (APOA5, APOC2, GPIHBP1 and LMF1). The objective of the study was to describe the prevalence of AP in patients with severe hypertriglyceridemia genetically evaluated. This is a cross-sectional, descriptive study with an analytical component carried out between November 2020 and January 2023 in the adult and pediatric endocrinology outpatient clinics of the Walter Cantídio University Hospital/Federal University of Ceará/EBSERH, which are a reference for the care of severe dyslipidemias in Ceará. Severe hypertriglyceridemia was considered when serum triglycerides were measured above 885mg/dL. Data were collected through interviews, physical examinations, and medical record reviews, and included clinical and laboratory information, as well as results of a genetic panel for hypertriglyceridemia and BP performed by molecular analysis using next-generation sequencing of 45 genes. Blood levels of glycated hemoglobin, total cholesterol, HDL, triglycerides, TSH, and creatinine were obtained in all patients evaluated. Pearson's chi-square test and Fisher's exact test were used to investigate the association between categorical variables. A significance level of 5% was adopted. Sixty-eight patients with severe hypertriglyceridemia, with a median age of 43 years, were evaluated, 22 of whom had at least one previous episode of BP due to hypertriglyceridemia. The occurrence of BP episodes was related to the maintenance of persistently elevated triglyceride levels, with a higher prevalence in individuals who reached maximum serum triglyceride values above 2000 mg/dL. The identification of a pathogenic variant in the LPL gene was related to a higher prevalence of PA, even when compared to other genes that lead to the same genetic diagnosis. Thirty-nine patients with genetic variants related to hypertriglyceridemia were identified, of which 24% were related to FCS, 18% to inherited lipodystrophies, and 16% to polygenic etiologies. Twenty-nine patients did not present pathogenic genetic variants related to hypertriglyceridemia or pancreatitis. Patients with FCS, when compared to the others, had earlier detection of hypertriglyceridemia, higher prevalence and recurrence of AP, and higher serum triglyceride levels during follow-up. The prevalence of excessive alcohol consumption and uncontrolled diabetes, as well as higher body mass index values, was higher in the group without identified pathogenic variants. Four patients, despite severe phenotypic manifestations, did not have pathogenic genetic variants identified. In conclusion, the prevalence of AP in the patients with severe hypertriglyceridemia studied was 32.4%. The presence of higher serum triglyceride levels and the detection of a pathogenic variant in LPL in cases of FCS were associated with a higher risk of progression to AP. Patients with FCS had a more severe clinical presentation. A high prevalence of secondary factors for elevated serum triglycerides was identified, especially in patients without identified pathogenic genetic variants.