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.

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.

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.

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.

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.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction.

Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twenty-seven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality.

Atualização das recomendações da Sociedade Brasileira de Hepatologia para o diagnóstico e tratamento do carcinoma hepatocellular / Brazilian society of hepatology updated recommendations for diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE).

Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.

Clinical Significance of Serum Adiponectin and Resistin Levels in Liver Cirrhosis.

INTRODUCTION: Adiponectin and resistin levels are increased in patients with cirrhosis, but it prognostic significance is unknown. We sought to investigate the factors associated with adiponectin and resistin levels and its clinical significance in patients with cirrhosis. MATERIALS AND METHODS: This was a prospective cohort study that included 122 subjects with cirrhosis who attended an outpatient clinic and were initially evaluated in 2012. Serum adiponectin and resistin levels were measured in samples collected in 2012 (adiponectin and resistin) and 2014 (adiponectin). Thirty healthy subjects served as a control group. RESULTS: Higher adiponectin (21.59 µ g/mL vs. 12.52 µg/mL, P < 0.001) and resistin levels (3.83 ng/mL vs. 2.66 ng/mL, P < 0.001) were observed among patients with cirrhosis compared to controls. Patients classified as Child-Pugh B/C had higher adiponectin levels in relation to Child-Pugh A patients. At second measurement, adiponectin levels increased significantly in non-transplant patients and decreased in liver transplant recipients. Univariate Cox analysis showed that among patients with alcoholic liver disease, adiponectin levels were associated with lower transplant-free survival (HR = 1.034, 95% CI 1.006 - 1.062, P = 0.016). The transplant-free survival was significantly lower among patients with alcoholic liver disease and adiponectin ≥ 17 µg/mL (26.55 months, 95% CI 21.40-31.70) as compared to those with levels < 17 µg/mL (33.76 months, 95% CI 30.70-36.82) (P = 0.045). No relationship was found between the levels of resistin and survival. CONCLUSION: Adiponectin but not resistin levels were associated with intensity of liver dysfunction and worse prognosis in patients with alcoholic liver disease, suggesting a potential as a prognostic biomarker.

Circulating insulin-like growth factor-binding protein 3 as prognostic biomarker in liver cirrhosis.

AIM: To investigate the prognostic significance of insulin-like growth factor-binding protein 3 (IGFBP-3) in patients with cirrhosis. METHODS: Prospective study that included two cohorts: outpatients with stable cirrhosis (n = 138) and patients hospitalized for acute decompensation (n = 189). Development of complications, mortality or liver transplantation was assessed by periodical phone calls and during outpatient visits. The cohort of stable cirrhosis also underwent clinical and laboratory evaluation yearly (2013 and 2014) in predefined study visits. In patients with stable cirrhosis, IGFBP-3 levels were measured at baseline (2012) and at second re-evaluation (2014). In hospitalized subjects, IGFBP-3 levels were measured in serum samples collected in the first and in the third day after admission and stored at -80 °C. IGFBP-3 levels were measured by immunochemiluminescence. RESULTS: IGFBP-3 levels were lower in hospitalized patients as compared to outpatients (0.94 mcg/mL vs 1.69 mcg/mL, P < 0.001) and increased after liver transplantation (3.81 mcg/mL vs 1.33 mcg/mL, P = 0.008). During the follow-up of the stable cohort, 17 patients died and 11 received liver transplantation. Bivariate analysis showed that death or transplant was associated with lower IGFBP-3 levels (1.44 mcg/mL vs 1.74 mcg/mL, P = 0.027). The Kaplan-Meier transplant-free survival probability was 88.6% in patients with IGFBP-3 ≥ 1.67 mcg/mL and 72.1% for those with IGFBP3 < 1.67 mcg/mL (P = 0.015). In the hospitalized cohort, 30-d mortality was 24.3% and was independently associated with creatinine, INR, SpO2/FiO2 ratio and IGFBP-3 levels in the logistic regression. The 90-d transplant-free survival probability was 80.4% in patients with IGFBP-3 ≥ 0.86 mcg/mL and 56.1% for those with IGFBP3 < 0.86 mcg/mL (P < 0.001). CONCLUSION: Lower IGFBP-3 levels were associated with worse outcomes in patients with cirrhosis, and might represent a promising prognostic tool that can be incorporated in clinical practice.

Clinical and laboratory characteristics of patients with thyroid diseases with and without alanine aminotransferase levels above the upper tertile – Cross-sectional analytical study

Objective Thyroid disease affects 6.6% of the general population. The liver is fundamental in metabolizing thyroid hormones, and hepatocytes are often affected in thyroid disease. We aimed to compare clinical and laboratory parameters among thyroid disease patients with alanine aminotransferase (ALT) levels above vs. below the upper tertile. Subjects and methods A retrospective cross-sectional analytical study was conducted in the endocrinology clinic at Polydoro Ernani de São Thiago University Hospital. Patients with thyroid disease between August 2012 and January 2014 were included in the study. Clinical and laboratory parameters were collected from medical records. Results One hundred patients were included, of which 14.0% were male, with a mean age of 49.1 ± 14.4 years. ALT levels ranged from 9 to 90 U/L, and the ALT upper tertile was defined as 0,64 times the upper normal limit (xUNL). Patients with ALT levels above the upper tertile exhibited a higher proportion of systemic arterial hypertension (SAH), a higher mean abdominal circumference and a higher frequency of elevated TSH levels than did patients with ALT levels below the upper tertile. In multivariate analysis, ALT ≥ 0.64 (xUNL) was independently associated with abdominal circumference (odds ratio [OR] = 0.087, 95% confidence interval [CI] 0012-0167, P = 0.022). ALT (xUNL) correlated positively with total cholesterol (r = 0.213, P = 0.042). Conclusions In patients with thyroid diseases, it was observed that those with ALT above the upper tertile are associated with abdominal circumference and ALT levels correlate with total cholesterol.

Clinical and laboratory characteristics of patients with thyroid diseases with and without alanine aminotransferase levels above the upper tertile - Cross-sectional analytical study.

Objective Thyroid disease affects 6.6% of the general population. The liver is fundamental in metabolizing thyroid hormones, and hepatocytes are often affected in thyroid disease. We aimed to compare clinical and laboratory parameters among thyroid disease patients with alanine aminotransferase (ALT) levels above vs. below the upper tertile. Subjects and methods A retrospective cross-sectional analytical study was conducted in the endocrinology clinic at Polydoro Ernani de São Thiago University Hospital. Patients with thyroid disease between August 2012 and January 2014 were included in the study. Clinical and laboratory parameters were collected from medical records. Results One hundred patients were included, of which 14.0% were male, with a mean age of 49.1 ± 14.4 years. ALT levels ranged from 9 to 90 U/L, and the ALT upper tertile was defined as 0,64 times the upper normal limit (xUNL). Patients with ALT levels above the upper tertile exhibited a higher proportion of systemic arterial hypertension (SAH), a higher mean abdominal circumference and a higher frequency of elevated TSH levels than did patients with ALT levels below the upper tertile. In multivariate analysis, ALT ≥ 0.64 (xUNL) was independently associated with abdominal circumference (odds ratio [OR] = 0.087, 95% confidence interval [CI] 0012-0167, P = 0.022). ALT (xUNL) correlated positively with total cholesterol (r = 0.213, P = 0.042). Conclusions In patients with thyroid diseases, it was observed that those with ALT above the upper tertile are associated with abdominal circumference and ALT levels correlate with total cholesterol.