Clinical, biochemical and histological features related to treatment response and prognosis in autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.

A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. METHODS: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. RESULTS: ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). CONCLUSION: ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

ALKALINE PHOSPHATASE AND LIVER FIBROSIS AT DIAGNOSIS ARE ASSOCIATED WITH DEEP RESPONSE TO URSODEOXYCHOLIC ACID IN PRIMARY BILIARY CHOLANGITIS.

OBJECTIVE: Primary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40% of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation. PATIENT AND METHODS: Data from the Brazilian Cholestasis Study Group cohort were analyzed retrospectively. Patients were assessed for deep response, defined as normal alkaline phosphatase and bilirubin, after 1 year of UDCA treatment. Additionally, the performance of the UDCA response score in predicting deep response was evaluated. RESULTS: A total of 297 patients were analyzed, with 57.2% achieving an adequate response according to the Toronto criteria, while 22.9% reached deep response. Cirrhosis (OR 0.460; 95% CI 0.225-0.942; p=0.034) and elevated baseline alkaline phosphatase levels (OR 0.629; 95% CI 0.513-0.770; p<0.001) were associated with reduced odds of deep response. The UDCA response score exhibited moderate discrimination power (AUROC=0.769) but lacked calibration. CONCLUSIONS: Baseline ALP and liver fibrosis emerge as the most important prognostic factors to predict normalization of alkaline phosphatase and bilirubin after UDCA. The UDCA response score was inadequate for predicting deep response in the Brazilian PBC population.

Dietary pattern in women with polycystic ovary syndrome with and without associated non-alcoholic fatty liver disease: A cross-sectional study

Abstract Introduction Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women. Objective To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD. Method Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed. Results 87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups. Conclusions PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.

High prevalence of functional dyspepsia in nonalcoholic fatty liver disease: a cross-sectional study

Abstract BACKGROUND: Gastrointestinal (GI) symptoms are frequent complaints from individuals with nonalcoholic fatty liver disease (NAFLD). Dyspepsia is a universal clinical symptom and is among the most common GI complaints observed in the general population, but its prevalence in the population with NAFLD has not been previously investigated. OBJECTIVE: To compare the prevalence of functional dyspepsia (FD) between patients with NAFLD and controls without liver disease. DESIGN AND SETTING: Cross-sectional study at the Outpatient Liver Clinic, University Hospital, Belo Horizonte, Brazil. METHODS: We included 96 NAFLD patients and 105 controls without liver disease. All participants were assessed for GI symptoms in accordance with the Rome III criteria. Evaluation methods included a questionnaire for FD (validated in Brazil), laboratory tests and upper GI endoscopy. RESULTS: Mean age and sex were similar between the groups. The NAFLD group presented higher frequency of proton-pump inhibitor usage (31.3% vs 4.8%; P < 0.001) and prevalence of FD (25.0% versus 12.4%; P = 0.021). The symptom frequencies were as follows: postprandial distress, 22.9% versus 11.4% (P = 0.030); postprandial fullness, 18.8% versus 10.5% (P = 0.095); early satiation, 8.3% versus 5.7% (P = 0.466); and epigastric pain or burning, 18.8% versus 5.7% (P = 0.004), in NAFLD patients and controls, respectively. Multivariate analysis demonstrated that female sex (odds ratio, OR 6.97; 95% confidence interval, CI: 1.51-32.12; P = 0.013) and NAFLD diagnosis (OR 2.45; 95% CI: 1.14-5.27; P = 0.021) were independently associated with FD occurrence. CONCLUSION: FD occurs more frequently in individuals with NAFLD than in controls without hepatic disease.

Expressão da proteína B-Raf em carcinomas hepatocelulares relacionados à cirrose por hepatite C / B-raf protein immunoexpression in hepatocellular carcinoma due to hepatitis c virus related cirrhosis

ABSTRACT BACKGROUND: Hepatocarcinogenesis is a multistep process that lead to genetic changes in hepatocytes resulting in neoplasia. However, the mechanisms of malignant transformation seem to differ widely. To know carcinogenesis mechanisms is essential to develop new treatment and prevention methods. OBJECTIVE: The aim of this study is to analyze B-Raf protein immunoexpression in explants with hepatocellular carcinoma (HCC) related to hepatitis C (HCV), in adjacent cirrhotic tissue and in normal livers. We also associated the immunoexpression with known HCC related histopathogical prognostic features. METHODS: Livers from 35 patients with HCV related cirrhosis and HCC that underwent liver transplantation or hepatectomy at Clinical Hospital – UFMG and 25 normal livers from necropsy archives were studied. Tumors were classified according to: tumor size, vascular invasion and differentiation grade. B-Raf protein expression was determined by immunohistochemistry. RESULTS: B-Raf was strongly expressed in the HCV cirrhotic parenchyma cytoplasm of 17.1% cases and in 62.9% of HCC samples. Strong B-Raf protein staining was associated with tumor tissue (P<0.0001; OR=8.18 (2.62–26.63)). All normal livers showed weak or negative expression for B-Raf. There was no significant association among B-Raf scores and tumor differentiation grade (P=0.9485), tumor size (P=0.4427) or with vascular invasion (P=0.2666). CONCLUSION We found B-Raf protein immunostaining difference in normal livers, in the areas of HCV cirrhosis and in the hepatocarcinoma. We did not find association between B-Raf expression and histopathological markers of tumor progression. Our data suggests that B-Raf may play an important role in initial HCC carcinogenesis. Larger studies are needed to validate these observations.

RESUMO CONTEXTO: A hepatocarcinogênese é um processo de múltiplas etapas que leva a alterações genéticas nos hepatócitos, resultando em neoplasia. No entanto, os mecanismos da transformação maligna parecem diferir amplamente. Conhecer os mecanismos da carcinogênese é fundamental para o desenvolvimento de novos métodos de tratamento e prevenção. OBJETIVO: O objetivo deste estudo é analisar a imunoexpressão da proteína B-Raf em explantes de carcinoma hepatocelular (CHC), em tecido cirrótico relacionado à hepatite C adjacente e em fígados normais. Também analisamos a imunoexpressão com características histopatológicas prognósticas relacionadas ao CHC. MÉTODOS: Foram estudados fígados de 35 pacientes com CHC relacionado à cirrose por vírus C submetidos a transplante hepático ou hepatectomia no Hospital das Clínicas – UFMG e 25 fígados normais de arquivos de necropsia. Os tumores foram classificados de acordo com tamanho do tumor, invasão vascular e grau de diferenciação. A expressão de B-Raf foi determinada por imunohistoquímica. RESULTADOS: B-Raf foi fortemente expresso no citoplasma do parênquima cirrótico em 17,1% dos casos e em 62,9% das amostras de CHC. A forte expressão da proteína B-Raf foi associada ao tecido tumoral (P<0,0001; OR=8,18 (2,62–26,63)). Todos os fígados normais apresentaram expressão fraca ou negativa para B-Raf. Não houve associação significativa entre os escores B-Raf e o grau de diferenciação do tumor (P=0,9485), tamanho do tumor (P=0,4427) ou invasão vascular (P=0,26666). CONCLUSÃO: Encontramos diferença na imunoexpressão da proteína B-Raf em fígados normais, nas áreas de cirrose por HCV e no hepatocarcinoma. Não encontramos associação entre a expressão de B-Raf e marcadores histopatológicos de progressão tumoral. Nossos dados sugerem que o B-Raf pode desempenhar um papel importante na carcinogênese inicial do CHC. Estudos maiores são necessários para validar essas observações.

Consumption of fructose rich industrialized beverages in patients with biopsy-proven non-alcoholic fatty liver disease: a cross-sectional study

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and liver fibrosis. Recently, consumption of high fructose corn syrup (HFCS) has been associated with NAFLD development. OBJECTIVE: The aim of this study was to investigate the relationship between consumption of HFCS and NAFLD associated metabolic factors and disease progression. METHODS: This cross-sectional study included 51 patients with biopsy-proven NAFLD who underwent biochemical tests, anthropometrical assessment and full-day dietary evaluation including industrialized beverages quantification. RESULTS: Individuals were 80% female, with 54 ± 12 years old, 96% with central obesity, 75% with insulin resistance or diabetes mellitus and were separated according to industrialized beverage intake: < 7 and ≥ 7 coups/week (i.e., daily). Daily consumption of HFCS was associated with obesity (P = 0.04), hypertriglyceridemia (P = 0.05), higher serum triglycerides (P = 0.03) and VLDL (P = 0.01). There was a significant correlation (R = 0.29; P = 0.04) between consumption of industrialized beverages and increased serum triglycerides. We found no association between daily HFCS intake and NASH diagnosis or presence of fibrosis. CONCLUSION: Excessive consumption of HFCS in industrialized beverages was associated with obesity, hypertriglyceridemia and high levels of blood triglycerides in patients with NAFLD

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Nonalcoholic fatty liver disease in women with polycystic ovary syndrome: associated factors and noninvasive fibrosis staging in a single Brazilian center

ABSTRACT Objective Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. Subjects and methods Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. Results A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. Conclusion Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42

Current management of non-alcoholic fatty liver disease / Atualidades no tratamento da doença hepática gordurosa não alcoólica

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic inflammation and fibrosis. Lifestyle modification involving diet and enhanced physical activity associated with the treatment of underlying metabolic are the main stain in the current management of NAFLD. Insulin-sensitizing agents and antioxidants, especially thiazolidinediones and vitamin E, seem to be the most promising pharmacologic treatment for non-alcoholic steatohepatitis, but further long-term multicenter studies to assess safety are recommended.

RESUMO A doença hepática gordurosa não alcoólica (DHGNA) é caracterizada pela deposição significativa de lipídios nos hepatócitos de pacientes que não apresentam história de ingestão alcoólica significativa. É a doença do fígado mais prevalente em populações ocidentais e existe forte associação da DHGNA com a resistência à insulina (RI) e com a síndrome metabólica. O tratamento objetiva reduzir a RI, o estresse oxidativo, a obesidade, a dislipidemia bem como a inflamação e a fibrose hepáticas. O tratamento atual baseia-se principalmente em modificações do estilo de vida, que incluem dieta e prática regular de exercícios físicos, associadas ao tratamento de todos os componentes da síndrome metabólica. Quanto ao tratamento medicamentoso da esteato-hepatite não alcoólica, os agentes insulino-sensibilizantes e os antioxidantes parecem os mais promissores, especialmente as tiazolidinodionas e a vitamina E, mas faltam estudos multicêntricos avaliando sua segurança a longo prazo.

Nonalcoholic fatty liver disease: a cohort study focusing on treatment response to nutritional counseling / A doença hepática gordurosa não-alcoólica: um estudo de coorte com foco na resposta ao tratamento com orientação nutricional

BACKGROUND: Nonalcoholic fatty liver disease is the leading cause of liver pathology. The mainstay of management is weight loss. Our aim was to evaluate responses to nutritional counseling in long-term patients with this condition. METHODS: A prospective cohort study with consecutive inclusion of 105 subjects with nonalcoholic fatty liver disease who received individualized low-calories diet counseling (1400 to 1600 kcal/day according to gender) every three months for 24 months. Weight loss of 5% or more was considered as a therapeutic response. RESULTS: Out of 105 patients, 45 (42.9%) did not return for a second evaluation. Mean age was 55 ± 9 years, 81.6% were women and mean body mass index was 31.9 (23.8-44.9) kg/m2. Follow-up time was 6.5 (3.2-26.9) months and median appointment number was 3 (2-11). Metabolic syndrome and hypercholesterolemia were more common in women. The number of subjects who lost more than 5% weight was: 5/20 (25%) at 6-months; 3/15 (33%) at 12 months; 3/18 (17%) at 18 months and 4/13 (31%) at the end of follow up. The median body weight loss at 6, 12, 18 and 24 months decreased significantly. CONCLUSIONS: Adherence to nutritional counseling is poor in patients with nonalcoholic fatty liver disease. Only a very small proportion of patients reached the targeted body loss of weight on long term.

RESUMO OBJETIVOS: A doença hepática gordurosa não alcoólica éa principal causa de patologia hepática. Essencial para seu manejo éa perda de peso. Nosso objetivo foi avaliar as respostas a aconselhamento nutricional em pacientes crônicos com esta condição. METODOS: Estudo prospectivo de coorte com inclusão consecutiva de 105 indivíduos com doenca hepática gordurosa não alcoólica que receberam dieta individualizada de baixa caloria (1400-1600kcal/dia, de acordo com o sexo) e aconselhamento a cada 3 meses, durante 24 meses. A perda de peso de 5% ou mais foi considerada como resposta terapêutica adequada. RESULTADOS: Dos 105 pacientes, 45 (42,9%) não voltaram para uma segunda avaliação. A média de idade foi de 55 ± 9 anos, 81,6% eram mulheres e o índice de massa corporal foi de 31,9 (23,8-44,9) kg/m2. O tempo de seguimento foi de 6,5 (3,2-26,9) meses e número médio de entrevistas foi de 3 (2-11). A síndrome metabólica e a hipercolesterolemia foram mais comuns em mulheres. O número de indivíduos que perderam mais de 5% em peso foi: 5/20 (25%) em 6 meses; 3/15 (33%) aos 12 meses; 3/18 (17%) e aos 18 meses 4/13 (31%) no final do seguimento. A perda de peso corporal média aos 6, 12, 18 e 24 meses diminuiu significativamente. CONCLUSÕES: A adesão ao aconselhamento nutricional épobre em pacientes com doenca hepática gordurosa não alcoólica. Apenas uma pequena proporcão de pacientes que atingiu a perda de peso corporal programada a longo prazo.

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

RESUMO Para definir as recomendações baseadas em evidências científicas sobre o diagnóstico e tratamento das doenças autoimnus do fígado, a Sociedade Brasileira de Hepatologia organizou em Outubro de 2014, encontro monotemático em São Paulo. Um Comitê organizador de sete investigadores foi selecionado pela Diretoria da Sociedade para organizar a agenda científica, assim como para selecionar vinte debatedores para fazer uma revisão sistemática e apresentar tópicos relacionados à hepatite autoimune, colangite esclerosante primária, cirrose biliar primária e suas síndromes de superposição (overlap). O texto inicial do submetidoo a apreciação e aprovação da Sociedade Brasileira de Hepatologia através de consulta a todos associados através da home page da Sociedade, O trabalho apresentado representa a versão final do trabalho original, devidamente revisado e organizado em tópicos, segundo as recomendações da Sociedade Brasileira de Hepatologia.

Dietary patterns in Brazilian patients with nonalcoholic fatty liver disease: a cross-sectional study

OBJECTIVE: Recent evidence suggests that non-alcoholic fatty liver disease is associated with diet. Our aim was to investigate the dietary patterns of a Brazilian population with this condition and compare them with the recommended diet. METHODS: A cross-sectional study was conducted on 96 non-alcoholic fatty liver disease patients before any dietetic counseling. All patients underwent abdominal ultrasound, biochemical tests, dietary evaluations, and anthropometric evaluations. Their food intake was assessed by a semi-quantitative food-frequency questionnaire and 24-hour food recall. RESULTS: The median patient age was 53 years, and 77% of the individuals were women. Most (67.7%) participants were obese, and a large waist circumference was observed in 80.2% subjects. Almost 70% of the participants had metabolic syndrome, and 62.3% presented evidence of either insulin resistance or overt diabetes. Most patients (51.5, 58.5, and 61.7%, respectively) exceeded the recommendations for energy intake, as well as total and saturated fat. All patients consumed less than the amount of recommended monounsaturated fatty acids, and 52.1 and 76.6% of them consumed less polyunsaturated fatty acids and fiber, respectively, than recommended. In most patients, the calcium, sodium, potassium, pyridoxine, and vitamin C intake did not meet the recommendations, and in 10.5-15.5% of individuals, the tolerable upper limit intake for sodium was exceeded. The patients presented a significantly high intake of meats, fats, sugars, legumes (beans), and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations. CONCLUSIONS: Although patients with non-alcoholic fatty liver disease exhibited high energy and lipid consumption, most of them had inadequate intake of some micronutrients. The possible role of nutrient-deficient intake in the development of non-alcoholic fatty liver disease warrants investigation.

Epidemiologicalaaspects of hepatocellular carcioma in a referral center of minnas gerais, Brazil / Aspectos epidemiologicos do carcinoma hepatocelular em centro de referencia de Minas Gerais

Context Studies on epidemiology of hepatocellular carcinoma and modalities of therapy used to treat this condition are scarce in Brazil. Our aim was to characterize hepatocellular carcinoma according to etiology of the underlying chronic liver disease, and treatment modalities, in a referral center in Brazil. Methods All cases of hepatocellular carcinoma registered in the Department of Pathology during a 12-year period (1998-2010) were included. Demographic data, etiology of the underlying liver disease and treatment performed were collected. Results This case series included 215 patients, mean age 57.3 (± 14.1) years, 164 (76.2 %) male. Virus C and virus B infection were detected in 88 (43%) and 47 (23%) patients, respectively. Ethanol abuse alone or combined with other etiologies was identified in 64 (32%) individuals. Schistosomiasis was found in 18 (9%) patients. Liver transplantation was the treatment of choice in 112 (51%) patients. This procedure was more frequently performed in hepatitis C virus-related hepatocellular carcinoma (70%) than B virus-related hepatocellular carcinoma (17%). Tumor resection was performed in 40 (18%) individuals, ethanol injection or thermo ablation in 18 (14%), and chemoembolization in 14 (7%). In 40 (19.4%) patients no treatment was performed and this percentage remained constant over the years. Conclusions Chronic hepatitis C, followed by ethanol abuse and chronic hepatitis B were the leading causes of underlying chronic liver disease associated with hepatocellular carcinoma. The results show a trend of increasing incidence of hepatocellular carcinoma; however, the proportion of untreated patients remained constant over the analyzed period. .

Contexto Estudos sobre epidemiologia do carcinoma hepatocelular e terapias utilizadas em seu tratamento são escassos no Brasil. O objetivo foi caracterizar o carcinoma hepatocelular quanto à etiologia da hepatopatia crônica subjacente e modalidades terapêuticas empregadas, em um centro de referência no Brasil. Método Todos os casos de carcinoma hepatocelular registrados no Departamento de Patologia em período de 12 anos (1998-2010) foram incluídos. Dados demográficos, etiologia da hepatopatia crônica e tipo de tratamento realizado foram coletados dos prontuários. Resultado Esta série de casos incluiu 215 pacientes, com média de idade 57,3 (± 14,1) anos, 164 (76,2%) do sexo masculino. Infecções virais C e B foram detectadas em 88 (43%) e 47 (23%), respectivamente. Abuso de etanol isoladamente ou associado a outras causas foi identificado em 64 (32%) indivíduos. Esquistossomose foi encontrada em 18 (9%) indivíduos. Transplante hepático foi o tratamento de escolha em 112 (51%) pacientes. Esse procedimento foi mais frequentemente realizado em carcinoma hepatocelular relacionado com hepatite C (70%) do que hepatite B (17%). Ressecção cirúrgica foi realizada em 40 (18%) indivíduos, alcoolização ou termo-ablação em 18 (14%) e quimioembolização em 14 (7%). Em 40 (19,4%) pacientes nenhum tratamento foi empregado e esta porcentagem permaneceu constante ao longo dos anos do estudo. Conclusões Hepatite viral C seguida de abuso de etanol e hepatite viral B foram as causas de hepatopatia crônica mais frequentemente associadas ao carcinoma hepatocelular. Os resultados mostram tendência a aumento da incidência do carcinoma hepatocelular; no entanto, a proporção de pacientes não-tratados permaneceu constante ...

Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis

BACKGROUND: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). AIMS: To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our cohort, nine (47 percent) patients were homozygous for the C282Y mutation, two (11 percent) were heterozygous for the H63D mutation, and one each (5 percent) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. CONCLUSIONS: One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.

Análise ecocardiográfica da função diastólica do ventrículo esquerdo após infarto do miocárdio em ratos / Echocardiographyc analysis of the ventricular diastolic function after myocardial infarction in rats

Objetivo: Avaliar a função ventricular diastólica do ventrículo esquerdo(VE)pelo ecocardiograma(ECO)uma e três semanas pós infarto agudo do miocárdio(IAM).Método: Utilizaram-se 19 ratas Wistar com peso médio de 209 gramas. Os animais foram distribuídos em: grupo A, controle(n=7)submetido a ECO e não infartado; grupo B, infartado(n=9), submetido a ECO após uma semana(grupo B1, n=9) e 3 semanas(grupo B3, n=8) do IAM. Três animais morreram no transoperatório e um após o primeiro ECO. Realizou-se anestesia com cetamina(50 mg/Kg/peso) e xilazina(10 mg/kg/peso)intraperitoneal, intubação e ventilação. O IAM foi induzido por ligadura da artéria descendente anterior após toracotomia esquerda. Avaliou-se a função cardíaca por ECO modelo 21275A HP Sonos 1500 com transdutor de 7,5/5,5 MHz e a função diastólica pelo Doppler transmitral com avaliação das ondas A e E, e volume atrial esquerdo(VAE). O IAM foi confirmado por análise histopatológica na terceira semana.Resultados: Não houve diferença significativa na velocidade das ondas E(A=62 cm/s, B1=65 cm/s, B3=69 cm/s) e onda(A=43 cm/s, B1=40 cm/s, B3=41 cm/s)entre os grupos. Observou-se aumento significativo no VAE grupo A vs B1 e grupo A vs B3(A= 0,05 ml vs B1=0,15 ml, p=0,04 e A vs B3=0,14 ml, p=0,01). Todos os animais apresentaram IAM na terceira semana.Conclusões: VAE parece ser útil para definição diastólica do VE pós-IAM. O VAE pode refletir aumento da pressão diastólica final do VE, secundário à disfunção sistólica e/ou diastólica

Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B

BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 + or - 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT

Whipple's disease. Report of five cases with different clinical features

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up

Transplante celular: nova perspectiva para o tratamento da insuficiência cardíaca / Cell transplantation: a new perspective to heart failure treatment

A despeito da expectativa de alguns autores, o tratamento convencional da insuficiência cardíaca não proporciona regeneração miocárdica. Para isso, o transplante celular ou cardiomioplastia celular poderia representar nova opção de tratamento da insuficiência cardíaca e doença coronária. Células transplantadas em área isquêmica, bem como em cicatrizes de infarto prévio, melhoram a disfunção miocárdica. São necessários novos trabalhos para confirmar esses resultados, entretanto, os resultados disponíveis são promissores. O futuro próximo sinaliza como terapêutica a reconstrução do miocárdio lesado por replicação de cardiomiócitos, transplante ou ativação de células-tronco. O implante local de células da medula óssea autóloga induz angiogênese e melhora áreas isquémicas do miocardio, prevenindo o remodelamento ventricular e melhorando a função cardíaca.

Possibilidade de uma hermenêutica na relação entre o psicoterapeuta e o seu confidente / The possibility of hermeneuthics practices along the relation between psychotherapist and his confident

A hermenêutica é um prática interpretativa de leitura. Das leituras sagradas à procura de Dilthey, chega-se a uma hermenêutica emergente da filosofia de Heidegger: o Dasein. A partir da experiência do ser no ente que o acolhe e dele depende para viver, possibilita um intermezzo entre pessoas, como o analista e o seu paciente? Fenomenologicamente, como decorreria esse processo? A inquirição hermenêutica é essencialmente interativa e implica a autocompreensão do intérprete no processo de compreensão do outro