Intermittently Scanned Continuous Glucose Monitoring Performance in Patients With Liver Cirrhosis.

AIM: To evaluate the use of intermittently scanned continuous glucose monitoring (isCGM) in patients with liver cirrhosis (LC). METHODS: Observational study including 30 outpatients with LC (Child-Pugh B/C): 10 without diabetes (DM) (G1), 10 with newly diagnosed DM by oral glucose tolerance test (G2), and 10 with a previous DM diagnosis (G3). isCGM (FreeStyle Libre Pro) was used for 56 days (four sensors/patient). Blood tests were performed at baseline and after 28 and 56 days. RESULTS: No differences were found in the baseline characteristics, except for higher age in G3. There were significant differences between G1, G2 and G3 in glucose management indicator (GMI) (5.28 ± 0.17, 6.03 ± 0.59, 6.86 ± 1.08%, P < .001), HbA1c (4.82 ± 0.39, 5.34 ± 1.26, 6.97 ± 1.47%, P < .001), average glucose (82.79 ± 7.06, 113.39 ± 24.32, 149.14 ± 45.31mg/dL, P < .001), time in range (TIR) (70.89 ± 9.76, 80.2 ± 13.55, 57.96 ± 17.96%, P = .006), and glucose variability (26.1 ± 5.0, 28.21 ± 5.39, 35.31 ± 6.85%, P = .004). There was discordance between GMI and HbA1c when all groups were considered together, with a mean difference of 0.35% (95% SD 0.17, 0.63). In G1, the mean difference was 0.46% (95% SD 0.19, 0.73) and in G2 0.69% (95% SD 0.45, 1.33). GMI and HbA1c were concordant in G3, with a mean difference of -0.10 % (95% SD [-0.59, 0.38]). CONCLUSION: Disagreements were found between the GMI and HbA1c levels in patients with LC. isCGM was able to detect abnormalities in glycemic control that would not be detected by monitoring with HbA1c, suggesting that isCGM can be useful in assessing glycemic control in patients with LC.

Acute abdominal perforation as a clinical presentation of coeliac disease.

Intestinal perforation is described in coeliac disease in the setting of refractoriness or Enteropathy-Associated T-cell Lymphoma (EATL). We report the case of a man with untreated coeliac disease who presented intestinal perforation and was diagnosed with EATL over one year later.

Hepatitis B and Celiac Disease: A Cause for Concern?

Some theories suggest that the development of the immune response to clear hepatitis B triggers the intestinal tissue damage seen in celiac disease in genetically predisposed individuals. Although the role of hepatitis B virus infection in the development of autoimmune diseases has been widely discussed in the literature, it remains a controversial topic. Our objective is to review whether there is an association between hepatitis B and celiac disease and the particularities of vaccination against hepatitis B in celiac patients.

Algunas teorías sugieren que el desarrollo de la respuesta inmunitaria para la eliminación de la hepatitis B desencadena el daño del tejido intestinal observado en la enfermedad celíaca en individuos genéticamente predispuestos. Aunque el papel de la infección por el virus de la hepatitis B en el desarrollo de enfermedades autoinmunes se ha discutido ampliamente en la literatura, sigue siendo un tema controvertido. Nuestro objetivo es revisar si existe una asociación entre la hepatitis B y la enfermedad celíaca y las particularidades de la vacunación contra la hepatitis B en pacientes celíacos.

Fatty liver and celiac disease: Why worry?

Celiac disease (CD) is a chronic inflammatory intestinal disorder mediated by the ingestion of gluten in genetically susceptible individuals. Liver involvement in CD has been widely described, and active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, fatty liver in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. Non-alcoholic fatty liver disease is estimated to affect approximately 25% of the world's adult population and is the world's leading cause of chronic liver disease. In view of both diseases' global significance, and to their correlation, this study reviews the available literature on fatty liver and CD and verifies particularities of the clinical setting.

Characteristics and Factors Associated with Inflammatory Activity on Liver Biopsy in Autoimmune Hepatitis Patients Aged 50 Years or Older

Introduction: Autoimmune hepatitis is a liver inflammatory disorder characterized by portal lymphoplasmacytic hepatitis with interface activity and lobular inflammation. Objective: The objective of this study is to identify clinical features associated with advanced age and significant inflammation in liver histology. Methods: This cross-sectional analytical study evaluated the medical records of adult patients with hepatitis who received treatment in the gastroenterology and hepatology ward of a tertiary university hospital. Bivariate analysis was conducted to identify characteristics associated with an age of 50 years or older and significant histological inflammatory activity. Results: A total of 47 patients were included, with a mean age of 42.8 ± 16.0 (43.0) years. Among them, 80.9% were women, and 31.9% were 50 years or older. Liver biopsy was performed on 31 patients, and 29.0% exhibited significant inflammation. When comparing age groups, individuals aged 50 years and older had a higher median γ-glutamyl transferase (GGT; 129 vs. 282 U/L; p = 0.034) and a higher proportion of significant inflammation (50% vs. 6.7%; p = 0.024). Patients with significant inflammation on liver biopsy had a higher mean age (63.7 ± 14.0 vs. 41.0 ± 14.4; p = 0.001) and a higher proportion of patients aged 50 years or older (85.7% vs. 66.7%; p = 0.024) compared to those with mild inflammation. Conclusions: Individuals aged 50 years and older exhibited a higher median GGT and a greater proportion of significant inflammation in liver histology.

Introducción: la hepatitis autoinmune es un trastorno inflamatorio hepático caracterizado histológicamente por hepatitis linfoplasmocítica portal con actividad de interfase e inflamación lobulillar. Objetivos: identificar las características clínicas asociadas con la edad avanzada y con una inflamación significativa en la histología hepática. Métodos: estudio analítico transversal que evaluó historias clínicas de pacientes adultos con hepatitis atendidos en la sala de gastroenterología y hepatología de un hospital universitario terciario. Se realizó un análisis bivariado para identificar las características asociadas a la edad igual o mayor a 50 años y la actividad inflamatoria histológica significativa. Resultados: se incluyó a 47 pacientes con una edad media de 42,8 ± 16,0 (43,0) años. Además, el 80,9% de ellos eran mujeres y el 31,9% tenían 50 años o más. 31 pacientes fueron sometidos a biopsia hepática y el 29,0% presentó inflamación significativa. Cuando se comparó en términos de edad, los individuos de 50 años o más presentaron medianas más altas de γ-glutamiltransferasa (GGT; 129 frente a 282 U/L; p = 0,034) y una mayor proporción de inflamación significativa (50% frente a 6,7%; p = 0,024). Los pacientes con inflamación significativa en la biopsia hepática presentaron mayor edad media (63,7 ± 14,0 frente a 41,0 ± 14,4; p = 0,001) y mayor proporción de pacientes con edad igual o superior a 50 años (85,7% frente a 66,7%; p = 0,024) que las personas con inflamación leve. Conclusiones: los individuos de 50 años o más presentaron medianas más altas de GGT y mayor proporción de inflamación significativa en la histología hepática.

Celiac disease screening in patients with cryptogenic cirrhosis.

We write a letter to the editor commenting the article "Who to screen and how to screen for celiac disease". We discuss the present literature on cirrhosis and celiac disease (CD) and recommend screening and treating CD in individuals with cryptogenic cirrhosis.

Elevated calprotectin levels are associated with mortality in patients with acute decompensation of liver cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is related to systemic inflammation and elevated circulating cytokines. In this context, biomarkers of inflammation, such as calprotectin, may be of prognostic value. AIM: To evaluate serum calprotectin levels in patients hospitalized for complications of cirrhosis. METHODS: This is a prospective cohort study that included 200 subjects hospitalized for complications of cirrhosis, 20 outpatients with stable cirrhosis, and 20 healthy controls. Serum calprotectin was measured by enzyme-linked immunosorbant assay. RESULTS: Calprotectin levels were higher among groups with cirrhosis when compared to healthy controls. Higher median calprotectin was related to Child-Pugh C, ascites, and hepatic encephalopathy. Higher calprotectin was related to acute-on-chronic liver failure (ACLF) and infection in the bivariate, but not in multivariate analysis. Calprotectin was not associated with survival among patients with ACLF; however, in patients with AD without ACLF, higher calprotectin was associated with a lower 30-d survival, even after adjustment for chronic liver failure-consortium (CLIF-C) AD score. A high-risk group (CLIF-C AD score ≥ 60 and calprotectin ≥ 580 ng/mL) was identified, which had a 30-d survival (27.3%) similar to that of patients with grade 3 ACLF (23.3%). CONCLUSION: Serum calprotectin is associated with prognosis in patients with AD without ACLF and may be useful in clinical practice to early identify patients with a very low short-term survival.

Flash glucose monitoring system in special situations

ABSTRACT The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

FACTORS ASSOCIATED WITH CIRCULATING ZONULIN IN INFLAMMATORY BOWEL DISEASE.

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.

Flash glucose monitoring system in special situations.

The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

Fatores associados com os níveis séricos de zonulina na doença inflamatória intestinal / Factors associated with circulating zonulin in inflammatory bowel disease

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.

NEUTROPHIL-LYMPHOCYTE RATIO PREDICTS SHORT-TERM MORTALITY IN PATIENTS HOSPITALIZED FOR ACUTE DECOMPENSATION OF CIRRHOSIS.

BACKGROUND: Individuals with cirrhosis have a chronic systemic inflammation associated with an immune dysfunction, affecting the progression of the liver disease. The neutrophil-lymphocyte ratio (NLR) was proposed as a marker of systemic inflammatory response and survival in patients with cirrhosis. OBJECTIVE: Evaluate the prognostic role of NLR in cirrhotic patients and its relation with inflammatory cytokines(IL-6, IL-10 and IL-17). METHODS: In this prospective study two groups were evaluated: 1) Stable cirrhotic in outpatient follow-up (n=193); 2) Hospitalized cirrhotic for acute decompensation for at least 48 hours (n=334) with admission and 48 hours tests evaluation. Circulating inflammatory cytokines were available for 130 hospitalized patients. RESULTS: In outpatients with stable cirrhosis, NLR correlated with MELD score and other variables associated with severity of disease. However, after a median of 32 months of follow up NLR was not associated with mortality (HR 1.058, 95%CI 0.900-1.243; P=0.495). In hospitalized patients, NLR at 48-hour after admission was independently associated with 90-day survival (HR 1.061, 95%CI 1.020-1.103; P=0.003) in multivariate Cox-regression analysis. The 90-day Kaplan-Meier survival probability was 87% for patients with a 48-hour NLR <3.6 and 62% for NLR ≥3.6 (P<0.001). Elevation of NLR in the first 48 hours was also independently associated with mortality (HR 2.038, 95%CI 1295-3207; P=0.002). The 90-day Kaplan-Meier survival probability was 83% when NLR did not increase and 62% when NLR increased (P<0.001). IL-6, IL-10 and IL-17 at admission were positively correlated with both admission and 48-hour NLR. Lower levels of baseline IL-10 were associated with NLR increase during first 48-hour. CONCLUSION: NLR evaluated at 48 hours of hospitalization and its early increase after admission were independently associated with short-term mortality in patients hospitalized for acute decompensation of cirrhosis.

Razão neutrófilo-linfócito prediz mortalidade em curto prazo em pacientes hospitalizados com cirrose hepática descompensada / Neutrophil-lymphocyte ratio predicts short-term mortality in patients hospitalized for acute decompensation of cirrhosis

ABSTRACT BACKGROUND: Individuals with cirrhosis have a chronic systemic inflammation associated with an immune dysfunction, affecting the progression of the liver disease. The neutrophil-lymphocyte ratio (NLR) was proposed as a marker of systemic inflammatory response and survival in patients with cirrhosis. OBJECTIVE: Evaluate the prognostic role of NLR in cirrhotic patients and its relation with inflammatory cytokines(IL-6, IL-10 and IL-17). METHODS: In this prospective study two groups were evaluated: 1) Stable cirrhotic in outpatient follow-up (n=193); 2) Hospitalized cirrhotic for acute decompensation for at least 48 hours (n=334) with admission and 48 hours tests evaluation. Circulating inflammatory cytokines were available for 130 hospitalized patients. RESULTS: In outpatients with stable cirrhosis, NLR correlated with MELD score and other variables associated with severity of disease. However, after a median of 32 months of follow up NLR was not associated with mortality (HR 1.058, 95%CI 0.900-1.243; P=0.495). In hospitalized patients, NLR at 48-hour after admission was independently associated with 90-day survival (HR 1.061, 95%CI 1.020-1.103; P=0.003) in multivariate Cox-regression analysis. The 90-day Kaplan-Meier survival probability was 87% for patients with a 48-hour NLR <3.6 and 62% for NLR ≥3.6 (P<0.001). Elevation of NLR in the first 48 hours was also independently associated with mortality (HR 2.038, 95%CI 1295-3207; P=0.002). The 90-day Kaplan-Meier survival probability was 83% when NLR did not increase and 62% when NLR increased (P<0.001). IL-6, IL-10 and IL-17 at admission were positively correlated with both admission and 48-hour NLR. Lower levels of baseline IL-10 were associated with NLR increase during first 48-hour. CONCLUSION: NLR evaluated at 48 hours of hospitalization and its early increase after admission were independently associated with short-term mortality in patients hospitalized for acute decompensation of cirrhosis.

RESUMO CONTEXTO: Na cirrose há um quadro crônico de inflamação sistêmica associada a disfunção imune, que impactam na progressão da doença hepática. A razão neutrófilo-linfócito (RNL) foi proposta como um marcador de resposta inflamatória sistêmica e sobrevida em pacientes com cirrose hepática. OBJETIVO: Avaliar o papel de RNL como marcador prognóstico em portadores de cirrose hepática e sua relação com citocinas inflamatórias (IL-6, IL-10 e IL-17). MÉTODOS: É um estudo prospectivo com duas coortes: 1) pacientes cirróticos estáveis em acompanhamento ambulatorial (n=193); 2) pacientes cirróticos hospitalizados por descompensação aguda por no mínimo 48 horas (n=334) com avaliação de exames de admissão de 48 horas. Citocinas inflamatórias séricas estavam disponíveis em 130 pacientes hospitalizados. RESULTADOS: Nos pacientes ambulatoriais com cirrose estável, RNL se correlacionou com MELD e outras variáveis associadas com gravidade da doença. Entretanto, após uma mediana de 32 meses de seguimento, RNL não apresentou associação com mortalidade (HR 1.058, 95%CI 0.900-1.243; P=0.495). Nos pacientes hospitalizados, RNL de 48 horas após a admissão apresentou associação independente com sobrevida em 90 dias (HR 1.061, 95%CI 1.020-1.103; P=0.003) na regressão multivariada de Cox. A probabilidade de sobrevivência pela curva de Kaplan-Meier em 90 dias foi de 87% em pacientes com RNL de 48 horas <3.6 e 62% nos pacientes com RNL ≥3.6 (P<0.001). A elevação de RNL nas primeiras 48 horas também foi um fator independente associado a mortalidade (HR 2.038, 95%CI 1295-3207; P=0.002). A avaliação de sobrevida em 90 dias pela curva de Kaplan-Meier foi de 83% nos pacientes em que RNL não apresentou elevação e 62% nos que apresentaram elevação de RNL (P<0.001). IL-6, IL-10 e IL-17 na admissão se correlacionaram positivamente com RNL de admissão e de 48 horas. Níveis mais baixos de IL-10 basal foram associados com elevação de RNL nas primeiras 48 horas. CONCLUSÃO: RNL avaliada em 48 horas de hospitalização e sua elevação precoce após a admissão foram fatores independentemente associados a mortalidade em curto prazo nos pacientes hospitalizados com descompensação aguda da cirrose.

Systemic Inflammatory Response Syndrome in Patients Hospitalized for Acute Decompensation of Cirrhosis.

Background: Although recently challenged, systemic inflammatory response syndrome (SIRS) criteria are still commonly used in daily practice to define sepsis. However, several factors in liver cirrhosis may negatively impact its prognostic ability. Goals. To investigate the factors associated with the presence of SIRS, the characteristics of SIRS related to infection, and its prognostic value among patients hospitalized for acute decompensation of cirrhosis. Study. In this cohort study from two tertiary hospitals, 543 patients were followed up, up to 90 days. Data collection, including the prognostic models, was within 48 hours of admission. Results: SIRS was present in 42.7% of the sample and was independently associated with upper gastrointestinal bleeding (UGB), ACLF, infection, and negatively related to beta-blockers. SIRS was associated with mortality in univariate analysis, but not in multiple Cox regression analysis. The Kaplan-Meier survival probability of patients without SIRS was 73.0% and for those with SIRS was 64.7%. The presence of SIRS was not significantly associated with mortality when considering patients with or without infection, separately. Infection in SIRS patients was independently associated with Child-Pugh C and inversely related to UGB. Among subjects with SIRS, mortality was independently related to the presence of infection, ACLF, and Child-Pugh C. Conclusions: SIRS was common in hospitalized patients with cirrhosis and was of no prognostic value, even in the presence of infection.

B-cell compartment abnormalities are associated with ACLF and mortality in patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis profoundly affects the immune system, leading to an immunological imbalance known as cirrhosis-associated immune dysfunction. AIMS: This study aimed to investigate B-cell disturbances in patients with acute decompensation (AD) of cirrhosis and assess relationships with prognosis and mortality. METHODS: The study included 39 patients with AD of cirrhosis, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Circulating B-cell subsets and cytokine plasma levels were determined by flow cytometry. RESULTS: Cirrhotic groups showed higher percentages of naïve B cells, and lower percentages of CD27+ memory B cells (MBCs) than CTR. Further analysis comparing SC and AD revealed that the latter had higher frequencies of double-negative (DN) B cells and plasmablasts. Patients with more advanced liver disease exhibited a B-cell maturation shift toward MBCs and plasmablasts. Acute-on-chronic liver failure (ACLF) was associated with higher DN frequency. The Kaplan-Meier one-year survival probability was 92.9% in patients with >1.3% of transitional B cells and 27.3% in patients with <1.3%. CONCLUSIONS: B-cell subsets are markedly altered in cirrhotic patients, and cell profiles differ between stable and decompensated liver disease. Increased frequencies of DN B cells and reduced proportions of transitional B cells may be of great relevance in predicting ACLF and mortality, respectively.

Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients.

Liver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.

Low sodium to potassium ratio in spot urine sample is associated with progression to acute kidney injury and mortality in hospitalized patients with cirrhosis.

BACKGROUND: sodium to potassium ratio in spot urine sample (Na/Kur) is a surrogate marker of sodium excretion that is recommended for the management of patients with ascites due to cirrhosis. AIMS: to investigate Na/Kur ratio and fractional excretion of sodium (FENa) in patients admitted with decompensated cirrhosis, evaluating its relationship with acute kidney injury (AKI) and prognosis. METHODS: prospective cohort study included 225 adult subjects. Urine samples were obtained within 48 h of hospitalization. RESULTS: AKI at admission was observed in 32.9% of patients and was associated with lower Na/Kur ratio, but not FENa. Among 151 subjects initially without kidney dysfunction, AKI at some point during hospitalization occurred in 26.2% and was independently associated with low Na/Kur ratio at admission. AKI was observed in 44% of the patients with Na/Kur ratio < 1 and only in 8% when values ≥ 2. Na/Kur ratio at admission was independently associated with 30-day mortality, with Kaplan-Meier survival probability of 78.8% for Na/Kur ratio < 1 and 93.6% for values ≥ 1. CONCLUSIONS: low Na/Kur ratio in spot urine sample is associated with progression to AKI and lower short-term survival in patients hospitalized for decompensated cirrhosis.

GUT MICROBIOTA, PREBIOTICS, PROBIOTICS, AND SYNBIOTICS IN GASTROINTESTINAL AND LIVER DISEASES: PROCEEDINGS OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN NUCLEUS FOR THE STUDY OF HELICOBACTER PYLORI AND MICROBIOTA (NBEHPM), AND BRAZILIAN FEDERATION OF GASTROENTEROLOGY (FBG).

Over the last years, there is growing evidence that microorganisms are involved in the maintenance of our health and are related to various diseases, both intestinal and extraintestinal. Changes in the gut microbiota appears to be a key element in the pathogenesis of hepatic and gastrointestinal disorders, including non-alcoholic fatty liver disease, alcoholic liver disease, liver cirrhosis, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile - associated diarrhea. In 2019, the Brazilian Society of Hepatology (SBH) in cooperation with the Brazilian Nucleus for the Study of Helicobacter Pylori and Microbiota (NBEHPM), and Brazilian Federation of Gastroenterology (FBG) sponsored a joint meeting on gut microbiota and the use of prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to provide practical information about this topic, addressing the latest discoveries and indicating areas for future studies.

Microbiota intestinal, prebióticos, probióticos e simbióticos em doenças gastrointestinais e hepáticas: procedimentos de reunião conjunta da Sociedade Brasileira de Hepatologia (SBH), Núcleo Brasileiro de Estudos do Helicobacter pylori e Microbiota (NBEHPM) e Federação Brasileira de Gastroenterologia (FBG) / Gut microbiota, prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases: proceedings of a joint meeting of the brazilian society of hepatology (sbh), brazilian nucleus for the study of helicobacter pylori and microbiota (nbehpm), and brazilian federation of gastroenterology (fbg)

ABSTRACT Over the last years, there is growing evidence that microorganisms are involved in the maintenance of our health and are related to various diseases, both intestinal and extraintestinal. Changes in the gut microbiota appears to be a key element in the pathogenesis of hepatic and gastrointestinal disorders, including non-alcoholic fatty liver disease, alcoholic liver disease, liver cirrhosis, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile - associated diarrhea. In 2019, the Brazilian Society of Hepatology (SBH) in cooperation with the Brazilian Nucleus for the Study of Helicobacter Pylori and Microbiota (NBEHPM), and Brazilian Federation of Gastroenterology (FBG) sponsored a joint meeting on gut microbiota and the use of prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to provide practical information about this topic, addressing the latest discoveries and indicating areas for future studies.

RESUMO Nos últimos anos, um volume crescente de evidências indica que os microrganismos estão envolvidos na manutenção da saúde humana e também estão relacionados a várias doenças, tanto intestinais quanto extraintestinais. Alterações na microbiota intestinal parecem ser um elemento chave na patogênese de doenças hepáticas e gastrointestinais, incluindo doença hepática gordurosa não-alcoólica, doença hepática alcoólica, cirrose hepática, doenças inflamatórias intestinais, síndrome do intestino irritável e diarreia associada ao Clostridium difficile. Em 2019, a Sociedade Brasileira de Hepatologia (SBH) em colaboração com o Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM) e a Federação Brasileira de Gastroenterologia (FBG) realizaram um encontro exclusivamente voltado para a discussão sobre microbiota e uso de prebióticos, probióticos e simbióticos em doenças hepáticas e gastrointestinais. Este texto resume os principais pontos discutidos durante o evento, e tem a intenção de fornecer informações práticas sobre o assunto, abordando as descobertas mais recentes e indicando áreas para estudos futuros.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.