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Objective:To analyze the correlation between the severity of acute pancreatitis (AP) and the levels of zonulin, zonula occludens protein-1 (ZO-1), tumor necrosis factor -α (TNF -α) in the peripheral blood of patients with acute pancreatitis (AP), and the value of predicting moderate and severe AP.Methods:The clinical data of 115 AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from June 2020 to January 2022 were retrospectively analyzed. They were divided into mild group (69 cases) and moderate severe group (46 cases). The blood levels of zonulin, ZO-1, and TNF-α were measured for all patients on the 1st, 3rd, and 7th day after admission, and the results of the two group tests were compared. The correlation between zonulin, ZO-1, TNF -α and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores on the 1st day was and the value of various indicators for predicting moderate to severe AP were analyzed.Results:The C-reactive protein (CRP) levels of AP patients in the moderate to severe group were higher than those in the mild group, and the difference was statistically significant (all P<0.05). The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group showed an upward trend on the 1st, 3rd, and 7th days after admission. The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group were higher than those in the mild group at the same time point, and the differences were statistically significant (all P<0.05). The APACHE Ⅱ score of AP patients on the first day of admission was positively correlated with the levels of zonulin, ZO-1, and TNF -α ( r=0.736, 0.552, 0.621, all P<0.05). Zonulin had the highest area under the curve (AUC) for predicting moderate to severe AP, at 0.892, with an optimal threshold of 2.075 pg/ml. Zonulin had the highest sensitivity, at 0.804, and ZO-1 had the highest specificity, at 0.926. Using zonulin ≥2.075 pg/ml, ZO-1≥399.4 ng/ml, and TNF -α≥40.88 pg/ml as thresholds; the sensitivity and specificity obtained from parallel experiments were 0.976 and 0.710, respectively; The sensitivity and specificity obtained from the series of experiments were 0.326 and 0.999, respectively. Conclusions:There is a correlation between the serum levels of zonulin, ZO-1, and TNF -α in AP patients and the severity of AP. Zonulin, ZO-1, and TNF -α have certain clinical value in predicting moderate to severe AP.
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ABSTRACT Background: Inflammatory bowel disease (IBD) comprises the spectrum between Crohn's disease (CD) and ulcerative colitis (UC), a condition whose prevalence in countries such as Brazil has increased significantly in recent years. Changes in the intestinal epithelial barrier function and, consequently, an increase in intestinal permeability, have been suggested as important factors in the pathogenesis of different autoimmune conditions, including IBD. Therefore, there is a need for a practical tool to assess gut barrier integrity in these patients. Objective: To study factors associated with serum zonulin levels, a marker of intestinal permeability, in patients with IBD. Methods: This was a cross-sectional observational study that included 117 patients with IBD and 32 healthy controls. Disease activity was assessed by the Simple Clinical Colitis Activity Index (SCCAI) in UC and by the Harvey-Bradshaw Index (HBI) in CD subjects. Zonulin levels were measured by ELISA and inflammatory cytokines by Cytometric Bead Array, using commercially available kits. Results: The mean age of IBD patients was 44.0±15.9 years, 66.7% were female, 57 subjects were diagnosed with CD and 60 with UC. At evaluation, clinical remission was observed in 56.7% of CD patients and in 59.2% of UC subjects. No differences were observed in zonulin levels when comparing IBD patients with the control group (95.28 ng/mL vs 96.61 ng/mL, P=0.573) and when comparing patients with CD to those with UC (79.68 ng/mL vs 106.10 ng/mL, P=0.887). Among IBD group, zonulin concentrations were higher among females, correlated positively with body mass index (BMI) and age; and negatively with hemoglobin and hematocrit. In patients with UC, zonulin correlated negatively with hemoglobin, hematocrit, and albumin; and positively with BMI and SCCAI. Among CD patients, zonulin was positively correlated with age and BMI, but not with HBI. No correlations were observed between zonulin and circulating cytokines in IBD patients. Conclusion: In this cohort mostly comprised of patients in clinical remission, serum zonulin levels were not higher in patients with IBD than healthy controls, and correlated with variables not linked to baseline disease, such as sex, age and BMI. However, zonulin correlated with clinical and laboratory parameters of disease severity and activity among subjects with UC, but not among patients with CD. These findings indicate a potential role for zonulin as a biomarker in IBD, particularly in UC.
RESUMO Contexto: A doença inflamatória intestinal (DII) compreende o espectro entre a doença de Crohn (DC) e a colite ulcerativa, condição esta cuja prevalência em países como o Brasil vem aumentando significativamente nos últimos anos. Alterações na função da barreira epitelial intestinal e, consequentemente, um aumento da permeabilidade intestinal, têm sido sugeridos como fatores importantes envolvidos na patogênese de diferentes condições autoimunes, dentre elas, a DII. Desta forma, existe a necessidade de uma ferramenta prática para avaliar a integridade da barreira epitelial intestinal nestes pacientes. Objetivo: Estudar os fatores associados com os níveis séricos de zonulina, um marcador da permeabilidade intestinal, em pacientes com DII. Métodos: Estudo observacional transversal que incluiu 117 pacientes com DII e 32 indivíduos que compuseram o grupo controle. A atividade da doença foi avaliada pelo Simple Cliniical Colitis Activity Index (SCCAI) na colite ulcerativa e pelo índice de Harvey-Bradshaw (IHB) em pacientes com DC. Os níveis de zonulina foram quantificados por ELISA e os níveis das citocinas inflamatórias pelo Cytometric Bead Array, utilizando kits comercialmente disponíveis. Resultados: A média de idade dos pacientes com DII foi de 44,0±15,9 anos, 66,7% eram do sexo feminino, 57 pacientes eram portadores de DC e 60 pacientes eram portadores de colite ulcerativa. No momento da avaliação clínico-laboratorial, 56,7% dos pacientes com DC encontravam-se em remissão clínica e, dentre os pacientes com colite ulcerativa, 59,2% deles assim se encontravam. Não foram observadas diferenças nos níveis séricos de zonulina entre pacientes com DII e grupo controle (95,28 ng/mL vs 96,61 ng/mL; P=0,573), assim como entre pacientes com DC e pacientes com colite ulcerativa (79,68 ng/mL vs 106,10 ng/mL, P=0,887). Dentre os pacientes com DII, as concentrações de zonulina foram mais elevadas no sexo feminino e correlacionaram-se positivamente com o índice de massa corporal (IMC) e com a idade, correlacionando-se negativamente com os níveis de hemoglobina e hematócrito. Nos pacientes com colite ulcerativa, as concentrações de zonulina correlacionaram-se negativamente com os parâmetros hemoglobina, hematócrito e albumina e, positivamente, com o IMC e com o SCCAI. Dentre os pacientes com DC, a zonulina sérica correlacionou-se positivamente com a idade e com o IMC, mas não com o IHB. Não foram observadas correlações entre os níveis de zonulina e as citocinas circulantes nos pacientes com DII. Conclusão: Nesta coorte constituída majoritariamente por pacientes em remissão clínica, os níveis séricos de zonulina não se mostraram aumentados em pacientes com DII em relação a indivíduos controles e correlacionaram-se com variáveis não relacionadas à doença de base, como com o sexo, com a idade e com o IMC. No entanto, os níveis séricos de zonulina correlacionaram-se com parâmetros clínicos e laboratoriais de gravidade e atividade da doença dentre os pacientes com colite ulcerativa, mas não dentre os pacientes com DC. Estes achados indicam um potencial papel da zonulina sérica como um biomarcador na DII, principalmente na colite ulcerativa.
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Resumen En los últimos meses, se ha comunicado globalmente, un aumento de casos de hepatitis de etiología no precisada. La población más afectada son los niños bajo los 5 años, pero con un rango etario hasta los 16 años. Clínicamente, se presentan con una hepatitis colestásica con pródromos de síntomas digestivos (deposiciones alteradas, náuseas y vómitos) y en que en el estudio etiológico pareciera haber una asociación directa o indirecta con infección por adenovirus. En general, la evolución es benigna, pero cerca de 13% ha requerido ingreso a unidad de cuidados intensivos y 10%, trasplante hepático. Las hipótesis sobre su etiología son varias, la mayoría relacionadas con algún agente infeccioso, ya sea como gatillante o actor principal. No se ha evidenciado hasta ahora la presencia de algún tóxico común ni la inmunización contra SARS-CoV-2 como causa de enfermedad. Se presenta una revisión sobre los datos disponibles a la fecha y posibles hipótesis de la etiopatogenia.
Abstract In recent months there has been an increase in cases reports of hepatitis of unknown origin. The most affected population are children under 5 years of age, but it has been described in adolescents up to 16 years of age. The clinical presentation consists of cholestatic hepatitis with a prodrome of diarrhea, nausea, and vomiting. Prognosis is generally benign but, on average, 13% of patients have required admission to an intensive care unit and 10% a liver transplant. Etiological studies have associated this entity to adenoviral infections, but hypotheses include other infectious agents, either as a triggering factor or as its main etiology, toxins, and even immunizations against SARS-CoV-2. In the following review we present the data available to date regarding the different pathogenesis theories.