Hepatic expression of tumor necrosis factor-α and evaluation of MAPK-p38 and NFκB signaling pathways in autoimmune hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients. METHODS AND RESULTS: Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls. CONCLUSIONS: The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.

BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

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 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

Lack of Association of Polymorphisms in IL22 and IL22RA1 Genes with Fibrosis Severity in Patients with Chronic Hepatitis C.

The IL-22 pathway has been shown to play an important role in the pathogenesis of liver fibrosis. However, little is known about the role of single-nucleotide polymorphisms (SNPs) in IL-22-related genes in relation to the severity of liver fibrosis. This study aimed to investigate the association of polymorphisms in IL22 and IL22RA1 genes with the severity of liver fibrosis in patients with chronic hepatitis C. A total of 326 patients (165 with mild fibrosis and 161 with severe fibrosis) were included. Four SNPs in IL22 (rs1179251, rs2227473, rs1012356, and rs2227485) and two in IL22RA1 (rs4648936 and rs3795299) were evaluated by real-time PCR. No significant association was observed between the polymorphisms studied and the severity of liver fibrosis. The SNPs rs1179251, rs2227473, rs1012356, and rs2227485 in IL22 and rs4648936 and rs3795299 in IL22RA1 may not be involved in the pathogenesis of liver fibrosis in patients with chronic hepatitis C.

Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages.

AIMS: Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Interleukin-22 (IL-22) plays a key role in liver disease, through either a protective or an adverse role, depending on the context. The relationship between IL-22 and its receptors IL-22R1 and IL-22BP (soluble inhibitor) in liver fibrosis is unknown. In this study, we assessed the presence and quantity of IL-22, IL-22R1, and IL-22BP-producing cells in liver tissues of patients with chronic hepatitis C. METHODS AND RESULTS: The number of IL-22-producing cells was significantly higher in stages F1, F2, and F3 when compared to F0 or F4 (p < 0.05). The immunostaining of IL-22R1 decreased as liver fibrosis increased from F1 to F4. On the other hand, the concentration of IL-22BP-producing cells was higher in patients with cirrhosis (F4). Furthermore, the IL-22BP:IL-22 ratio was highest in patients with cirrhosis. CONCLUSIONS: Our results suggest that IL-22, IL-22R1 and IL-22BP may be involved in the mechanisms of liver fibrosis in patients with chronic hepatitis C.

Clinical and laboratory parameters associated with li-rads as diagnostic of liver nodule in patients with cirrhosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Clinical and laboratory evaluation of a cirrhotic patient with a liver nodule may show alterations suggesting malignancy. There is a lack of questions related to diagnosis of HCC and evaluation of liver imaging reporting and data system (LI-RADS) could be a tool for early diagnosis of HCC. This aims to confirm an association between clinical and laboratory characteristics in cirrhotic patients with hepatic nodule after LI-RADS categorization. METHODS: A cross-sectional retrospective study was performed with 62 patients grouped according to LI-RADS algorithm. Differences between groups were confirmed using association tests and the Kappa test was employed to provide further confirmation. RESULTS: Associations were observed after univariate analysis with higher values of aspartate aminotransferase (AST) (P=0.008), alanine aminotransferase (ALT) (P=0.019), alkaline phosphatase (ALP) (P=0.0052), gamma glutamyl transferase (GGT) (P=0.0023), alpha-fetoprotein (AFP) (P=0.0001), nodule size (P=0.0001) and age (P=0.007) in LR 5 group compared to LR 3. Univariate analysis also revealed higher levels for the LR5 group of ALP (P=0.0228), AFP (P=0.022) and age (P=0.046) in relation to LR 1+2 group. AFP also had higher serum levels in the LR 4 group compared to LR 1+2 (P=0.004). After multivariate analysis, higher levels in LR5 group of nodule size (P=0.047) and ALP (P=0.027) were observed in relation to LR3, and were therefore considered predictors of HCC diagnosis. CONCLUSIONS: The study suggests that the combination of clinical-laboratory and radiological factors, such as heightened serum levels of ALP and hepatic nodule size, may support the screening of HCC in cirrhotic patients with hepatic nodules using the LI-RADS algorithm.

Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).

OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.

Factors Associated with 30-Day Mortality in Patients after Percutaneous Endoscopic Gastrostomy.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is the main accepted method for long-term tube feeding. The aim of this study is to investigate the risk factors associated with early mortality after PEG. METHODS: It is a retrospective survival analysis in a tertiary-level hospital. We reviewed the medical records of 277 patients with PEG placement. The data were analyzed by the Kaplan-Meier method. Multivariable Cox proportional regression models were also built to test the effects of PEG on mortality. RESULTS: A total of 277 patients who submitted to PEG were studied. One-hundred and sixty (58%) were female, mean age of 73.3 ± 15.7 years. Ninety-three patients (33.6%) had diabetes mellitus and 165 (59.6%) had blood hypertension. The indications for PEG placement were chronic neurologic dysphagia in 247 (89.5%) patients and tumors and other diseases in 29 (10.5%). The 30 days proportional mortality probability rate was 13%. In a multivariate Cox proportional regression model, preoperative ICU hospitalization (HR 1.79, 95% CI 1.36-2.36, P = 0.000) and hemoglobin (HR 0.91, 95% CI 0.85-0.98, P = 0.015) were predictors of early mortality. CONCLUSION: In patients who had underwent PEG tube insertion for long-term nutrition, anemia and previous ICU admission were predictors of mortality at four weeks. These factors may guide physicians to discourage the indication for PEG.

Prevalence of hepatitis A in the capitals of the States of North, Southeast and South regions of Brazil: decrease in prevalence and some consequences.

Hepatitis A virus (HAV) infection has been considered one of the leading causes of acute hepatitis. The aim of the present study was to estimate the prevalence of HAV among children and adolescents in a population-based study in the capitals of the States of the North, Southeast and South of Brazil and identify predictive factors for the infection. A multi-stage sampling was used to select subjects aged between 5-9 and 10-19 years. Individual and household levels aside from the level of variables in the areas were collected. The outcome was the total IgG antibodies to HAV levels detected using a commercial Enzyme Immuno Assay (EIA). The associations between HAV and the independent variables were assessed using the odds ratio. A multilevel analysis was performed by GLLAMM using the Stata software. The prevalence of HAV infection in the 5-9 and 10-19 age groups was 28.7% and 67.5%, respectively for the North, 20.6% and 37.7%, for the Southeast and 18.9% and 34.5% for the South Region. The prevalence of HAV increased according to age in all sites. Variables related to education at the individual level (North and South), family and area level (South and Southeast) and family income level (Southeast and South) were independently associated with HAV infection. This emphasizes the need for individualized strategies to prevent the infection.

Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.

Influence of LGALS3 and PNPLA3 genes in non-alcoholic steatohepatitis (NASH) in patients undergone bariatric surgery.

AIM: This study evaluated the genesPNPLA3 and LGALS3 in patients who have undergone bariatric surgery. METHODS: Individuals with NAFLD and NASH were evaluated, the DNA was extracted from total blood for genotyping of rs4644, rs4652 from LGALS3 and rs738409 from PNPLA3 genes, the total RNA was obtained from liver biopsy. For the detection of the molecular targets, real-time PCR through Taqman probes was used. RESULTS: From a total of 46 collected patients, of those 21 (456%) were included as NASH and 25 (544%) as steatosis group. This groups showed significant difference to aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Glutamyl transpeptidase (GGT) (p = 0.0108, p = 0.0090 and p = 0.0044). Regarding to gene expression in studied groups, hepatic steatosis vs NASH, we observed a higher expression of the LGALS3 gene in NASH (p = 0.0273). In addition, patients with C allele in homozygous for rs4644 and rs4652 of LGALS3 gene had higher expression, in NASH group (p = 0.0500 and p = 0.0242, respectively), furthermore for rs4644 both alleles in homozygous showed higher expression (AA/CC vs AC) (p = 0.0500), when analyzed PNPLA3 rs738409, NASH patients with G allele in homozygous had higher expression (p = 0.0494). CONCLUSIONS: Therefore, an increased expression of the LGALS3 gene in patients with NASH may be important in the etiopathogenesis of the disease, as well as the presence of rs4652 and rs4644 SNPs in the regulation of transcriptional levels of the gene in patients with NAFLD and NASH.

Hepatite C no sistema público de saúde brasileiro: impacto da doença / Hepatitis c in the brazilian public health care system: burden of disease

ABSTRACT BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é uma das principais causas de hepatite C crônica e provoca implicações graves para pacientes, familiares e sistema de saúde. OBJETIVO: Os objetivos deste estudo foram: analisar a gravidade da fibrose hepática, comorbidades e complicações da hepatite C; examinar a qualidade de vida relacionada à saúde (QVRS), a perda de produtividade e o uso de recursos e custos no sistema público por pacientes brasileiros com hepatite C crônica, genótipo tipo 1. MÉTODOS: Foi realizado um estudo transversal, multicêntrico em pacientes com hepatite C crônica genótipo-1 para avaliar a carga da doença no sistema público de saúde brasileiro entre novembro de 2014 e março de 2015. Os pacientes foram submetidos a uma elastografia hepática transitória (FibroScan) para avaliar a fibrose e a uma entrevista composta por um questionário desenvolvido para o estudo e cinco questionários padronizados: EQ-5D-3L, HCV-PRO, e WPAI:HepC. RESULTADOS: Foram recrutados 313 pacientes. A amostra foi composta predominantemente por mulheres (50,8%), caucasianos/brancos (55,9%) e indivíduos empregados (39,9%). A média de idade foi 56 (DP=10,4) anos. Em média, os pacientes com HCV esperaram 40,6 (DP=49,6) meses entre o diagnóstico e o primeiro tratamento. Ademais, 42,8% dos pacientes que realizaram o FibroScan tinham cirrose; a comorbidade mais frequente foi doença cardiovascular (62,6%) e a complicação mais comum as varizes esofágicas (54,5%). Os resultados também mostraram que "dor e desconforto" foi a dimensão de QVRS mais afetada (55,0% dos pacientes relataram alguns problemas) e que a média do escore do HCV-PRO foi 69,1 (DP=24,2). Em relação à perda de produtividade, o componente do WPAI:HepC mais afetado foi atividade diária (23,5%) e entre os pacientes empregados, presenteísmo foi mais frequente do que absenteísmo (18,5% vs 6,5%). Os custos diretos médicos totais com essa amostra foi de 12.305,72USD por paciente em um período de dois anos; o tratamento medicamentoso representou 95% desse total. CONCLUSÃO Esse estudo mostrou a maioria dos pacientes possui cirrose, apresenta alta prevalência de doenças cardiometabolicas e varizes esofágicas, QVRS reduzida principalmente em termos de dor/desconforto e dano na produtividade, especialmente presenteísmo. Adicionalmente, nós demonstramos que o HCV impõe uma carga econômica no sistema de saúde brasileiro e que os medicamentos correspondem à maioria dos custos.

Two sides of a coin: GG genotype of C7 provides protection against fibrosis severity while showing a higher risk for hepatocellular carcinoma in patients with hepatitis C.

The complement system (CS) is a key element of immunity against pathogens but also seems to influence other events, such as tumorigenesis and tissue repair. Complement component 7 (C7) is a key component of the lytic pathway of CS, leading to the formation of the membrane attack complex (MAC). This study aimed to investigate the existence of the association of a polymorphism in the C7 gene, rs1063499, with hepatic fibrosis and the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C. We analyzed 456 samples from patients with chronic hepatitis C. Real-time PCR was used for allelic discrimination. Patients were classified by their METAVIR score as F1 (n = 100), F2 (n = 83), F3 (n = 101) or F4 (n = 66); 106 patients were diagnosed with HCC. Patients carrying the G/G genotype of C7 had a lower chance of developing severe fibrosis in the recessive model (p = 0.042; OR: 0.65 95% CI 0.41-1.02). However, the G/G genotype frequency was higher in patients with HCC (P = 0.01; OR: 2.07 95% CI 1.20-3.53) and in those with larger tumors (p = 0.04). The G/G C7 genotype seems to be a protective factor against advanced fibrosis; however, it was associated with a higher risk of HCC and the occurrence of larger hepatic nodules, suggesting the involvement of C7 in the physiopathogenesis of HCC and fibrosis in patients with hepatitis C virus (HCV).

Molecular profile of mannan-binding lectin in hepatitis C patients with MBL gene polymorphisms by a modified mannan-coated nitrocellulose assay.

The aim of this study was to develop an assay to analyze the serum profile of Mannose-binding lectin (MBL) through a simple and "in-house" method (called "dot-N-man"). Furthermore, the study attempted to associate molecular masses of MBL to the profile of MBL gene polymorphisms in patients with hepatitis C. Heterogeneity in molecular masses of MBL is due to the impairment of oligomers formation, which is linked to genetic polymorphisms in the MBL gene. Individuals with AA genotype (wild-type) produce high-molecular-mass proteins, whereas AO and OO individuals produce intermediate and low-molecular-mass proteins, respectively. Sera of thirty patients carrying the hepatitis C virus (HCV) were investigated using MBL binding assay with mannan-coated nitrocellulose (dot-N-man). Purified MBL was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Dot-N-Man assay yielded MBL with molecular masses ranging between 55 and 320 kDa, comparable to low and high molecular mass forms of MBL. Nonreducing SDS-PAGE showed high molecular mass bands in all AA individuals while bands of 270 and 205 kDa were observed in sera for a number of patients with AO and OO genotypes, respectively. Immunoblotting confirmed the MBL samples obtained from the dot-N-man. These results provide new insights to understand the MBL molecular forms profile in patients infected with HCV- which could be useful in future investigations on the influence of the MBL structure/genotype on both the progression of infection and the response to hepatitis C therapy.

HEPATITIS C IN THE BRAZILIAN PUBLIC HEALTH CARE SYSTEM: BURDEN OF DISEASE.

BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

Doença de Crohn associada a tumor carcinoide gástrico: relato de caso e revisão de literatura / Crohns disease associated with gastric carcinoid tumor: a case report and literature review

Os tumores carcinoides gástricos são neoplasias raras, derivadas das células enterocromafins e podem associar-se a doenças inflamatórias intestinais, como a doença de Crohn. Atualmente, há aumento da incidência devido a maior realização de endoscopia digestiva alta. A abordagem depende do tipo, tamanho e número de lesões, além da presença de metástases. Este é o relato de caso de um paciente com doença de Crohn associada a tumor carcinoide gástrico.

The gastric carcinoid tumors are rare, derived from the enterochromaffin cells and may be associated with inflammatory bowel diseases such as Crohns disease. Currently, there is increased incidence due to higher performing endoscopy. The approach depends on the type, size, number of lesions and the presence of metastases. This is a case report of a patient with Crohns disease associated with gastric carcinoid tumor.

Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome.

The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0-F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.

TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factors in the North, South, and Southeast Regions of Brazil, 10-20 Years After the Beginning of Vaccination.

A population-based hepatitis survey was carried out to estimate the prevalence of hepatitis B virus (HBV) infection and its predictive factors for the state capitals from the north, south, and southeast regions of Brazil. A multistage cluster sampling was used to select, successively, census tracts, blocks, households, and residents in the age group 10-69 years in each state capital. The prevalence of hepatitis B surface antigen (HBsAg) was lower than 1% in the north, southeast, and south regions. Socioeconomic condition was associated with HBV infection in north and south regions. Variables related to the blood route transmission were associated with HBV infection only in the south whereas those related to sexual behavior were associated with HBV infection in the north and south regions. Drug use was associated in all regions, but the type of drug differed. The findings presented herein highlight the diversity of the potential transmission routes for hepatitis B transmission in Brazil. In one hand, it reinforces the importance of national control strategies of large impact already in course (immunization of infants, adolescents, and adults up to 49 years of age and blood supply screening). On the other hand, it shows that there is still room for further control measures targeted to different groups within each region.