Factors Associated with Insulin Resistance in Patients with Chronic HCV Genotype 1 Infection without Obesity or Type 2 Diabetes.

OBJECTIVE: To investigate the prevalence of insulin resistance (IR) and its association with clinical parameters in patients with hepatitis C virus (HCV) genotype 1 without obesity or type 2 diabetes. METHODS: One hundred and twenty-seven HCV-infected patients admitted to the Nutrition and Hepatology Clinic were included. Statistical analysis was performed using the Mann-Whitney test, Fisher's exact test, and Poisson regression analysis. RESULTS: The prevalence of IR (homeostasis model assessment [HOMA]-IR ≥ 3.0) was 37.0%. The independent predictors for IR included the following: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper normal limit (odds ratio [PR] = 2.06, 95% CI, 1.16-3.66; PR = 2.32, 95% CI, 1.26-4.49, respectively); gamma glutamyl transferase (γGT) ≥ 85 U/L (PR = 2.09, 95% CI, 1.12-4.12); increased waist circumference (PR = 2.24, 95% CI, 1.25-4.17); increased waist : hip ratio (PR = 2.24, 95% CI, 1.11-5.17); increased body fat percentage (PR = 2.21, 95% CI, 1.01-5.79); overweight (PR = 2.54, 95% CI, 1.40-4.82); and metabolic syndrome (PR = 3.05, 95% CI, 1.69-5.44). High ALT levels and anthropometric parameters remained in the model of multivariate regression analysis. CONCLUSIONS: Our findings showed a significantly high prevalence of insulin resistance in nondiabetic, nonobese patients with hepatitis C genotype 1. High ALT levels and anthropometric parameters were significantly associated with IR after multivariate regression analysis. Our data show the importance of monitoring IR, weight, and body composition in patients with chronic hepatitis C. Nutritional management seems to be important in the control of comorbidities related to excess weight and the enhancement of therapeutic responses.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.

OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. CONCLUSION: Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.

Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. CONCLUSION: Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus ...

Effect of soy protein supplementation in patients with chronic hepatitis C: a randomized clinical trial.

AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk. RESULTS: Patients' baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients.

Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes.

OBJECTIVE: The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus-infected patients who are not obese and do not have type 2 diabetes. METHODS: This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients. RESULTS: Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2% were overweight, 48.1% had a high waist circumference, 85.2% had an increased body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95% CI: 1.09-6.25), elevated gamma-glutamyl transferase (γGT) (OR 2.63; 95% CI: 1.04-7.29), elevated fasting glucose (OR 8.05; 95% CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95% CI: 1.07-7.16), hypertriglyceridemia (OR 7.91; 95% CI: 2.88-22.71), elevated waist circumference (OR 10.33; 95% CI: 3.72-30.67), overweight (OR 11.33; 95% CI: 3.97-41.07), and increased body fat percentage (OR 8.34; 95% CI: 2.94-30.08) were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63-44.41) and total body fat percentage (OR 8.73; 95% CI: 2.33-42.34). However, metabolic syndrome risk was also high for those with blood glucose >5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64-76.35; OR 7.23; 95% CI: 1.86-32.63, respectively). CONCLUSION: Metabolic syndrome is highly prevalent among hepatitis C virus-infected patients without type 2 diabetes or obesity. Metabolic syndrome was significantly associated with hypertension, insulin resistance, increased abdominal fat, and overweight.

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.

BACKGROUND: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. AIMS: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. METHODS: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. RESULTS: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group. CONCLUSION: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes

OBJECTIVE: The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus-infected patients who are not obese and do not have type 2 diabetes. METHODS: This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients. RESULTS: Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2% were overweight, 48.1% had a high waist circumference, 85.2% had an increased body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95% CI: 1.09-6.25), elevated gamma-glutamyl transferase (γGT) (OR 2.63; 95% CI: 1.04-7.29), elevated fasting glucose (OR 8.05; 95% CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95% CI: 1.07-7.16), hypertriglyceridemia (OR 7.91; 95% CI: 2.88-22.71), elevated waist circumference (OR 10.33; 95% CI: 3.72-30.67), overweight (OR 11.33; 95% CI: 3.97-41.07), and increased body fat percentage (OR 8.34; 95% CI: 2.94-30.08) were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63-44.41) and total body fat percentage (OR 8.73; 95% CI: 2.33-42.34). However, metabolic syndrome risk was also high for those with blood glucose >5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64-76.35; OR 7.23; 95% CI: 1.86-32.63, respectively). CONCLUSION: Metabolic syndrome is highly prevalent among hepatitis C virus-infected patients without type 2 diabetes or obesity. Metabolic syndrome was significantly associated with hypertension, insulin resistance, increased abdominal fat, and overweight.

Hemorragia digestiva alta varicosa: relatório do 1º consenso da Sociedade Brasileira de Hepatologia / Varicel bleeding: consensus meeting report from the brazilian society of hepatology

Nas últimas duas décadas, foi observada redução importante na mortalidade associada ao primeiro sangramento varicoso, que vem sendo atribuída à melhoria na assistência ao paciente cirrótico e à abordagem multidisciplinar do paciente com hemorragia digestiva alta varicosa (HDAV), particularmente por emergencistas, hepatologistas, gastroenterologistas, endoscopistas e intensivistas. Visando estabelecer recomendações para o manejo da HDAV, a Sociedade Brasileira de Hepatologia (SBH) realizou reunião de consenso para elaboração de documento a ser utilizado como orientação de conduta médica. Dentro da sistemática utilizada, foi criada pela SBH uma comissão organizadora composta por quatro membros que escolheram 27 pesquisadores, representando as diversas regiões do país, para serem moderadores ou expositores dos tópicos relacionados à prevenção, diagnóstico e tratamento da HDAV. Todos os tópicos foram abordados de acordo com o grau de evidência científica disponível. As recomendações foram elaboradas em reunião após ampla discussão com os membros da comissão organizadora, expositores, moderadores e participantes da reunião do consenso, ficando a cargo da comissão organizadora a redação do documento final. A reunião do consenso ocorreu em Salvador em 06 de maio de 2009 e esta publicação exibe as principais conclusões do consenso organizadas sob a forma de resumo da literatura médica seguido pelas recomendações da SBH.

In the last decades, several improvements in the management of variceal bleeding have resulted in a significant decrease in morbidity and mortality of cirrhotis with bleeding varices. Progress in the multidisciplinary approach to the patient with variceal blleding has led to a better management of this disease by critical care physicians, hepatologists, gastroenterologists, endoscopists, radiologists and surgeons. In this respect, the Brazilian Society of Hepatology has, recently, sponsored a consensus meeting in order to draw evidence-based recommendations on the management of these difficult-totreat subjects. An organizing committee comprised of four people was elected by the Governing Board and was responsible to invite 27 researchers from distinct regions of the country to make a systematic review of the subject and to present topics related to variceal bleeding, including prevention, diagnosis, management and treatment, accoding to evidence-based medicine. After the meeting, all participants were held together for discussion of the topics and the elaboration of the aforementioned recommendations. The organizing committee was responsible for writing the final document. The meeting was held at Salvador, May 6th, 2009 and the present manucrispt is the summary of the systematic review that was presented during the meeting organized in topics followed by the reccomendations of the Brazilian Society of Hepatology.

Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders.

BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.

Curso de atualização em emergências médicas: aula 18: insuficiência hepatica aguda / Course of updating in medical emergencies: class 18: acute hepatic failure

A insuficiência hepática aguda (IHA) é uma síndrome clínica extremamente grave, de diagnóstico precoce difícil, evolução rápida e alta mortalidade. Nesta revisão buscamos reunir as informações mais atuais sobre classificação, etiologia, diagnóstico e tratamento, discutindo as diversas controvérsias sobre o tema. O diagnóstico da IHA é difícil e engloba o quadro clínico e laboratorial de hepatite aguda (grave), tempo de protrombina alargado, com qualquer alteração do sensório, além de pesquisa cuidadosa na história do paciente, incluindo o uso de medicações ou ervas e presença de diagnóstico prévio de hepatopatia. O diagnóstico etiólogico inclui infecções virais, medicamentos e toxinas, causas cardíacas e vasculares, metabólicas, além da hepatite autoimune, doenças de Wilson e neoplasias. O tratamento da IHA é dado em duas etapas, sendo a primeira constituída pelas medidas de suporte, prevenção e tratamento das complicações, que devem ser oferecidas a todos os pacientes, e a segunda pelas medidas específicas, que serão direcionadas dependendo da etiologia. O transplante hepático é a única terapia definitiva para os pacientes que não conseguem o restabelimento da função hepática.

Acute hepatic failure (AHF) is one extremely serious clinical syndrome of difficult pre-emptive diagnosis, rapid evolution and high mortality. In this review we summarized the current information regarding its classification, etiology, diagnosis and treatment, and discussed the controversies about the issue. The diagnosis of the AHF is difficult and includes laboratorial and clinical findings of severe acute hepatitis, increased prothrombin time and presence of hepatic encephalopathy. It is necessary that a careful history of the patient be obtained especially with respect to utilization of medications, herbs as well as the presence of previous diagnosis of liver disease. The possible etiologies include viral infections, cardiac and vascular affections, medications and toxins, metabolic causes, auto-immune hepatitis, Wilson's disease and neoplasm. The treatment of AHF requires support measures, prevention and treatment of complications that must be offered all patients and specific measures which should be offered according to the etiology of AHF. Liver transplant is the only definitive therapy for patients who do not recover the hepatic function.

Hepatite crônica B / Chronic hepatitis B

A infecção pelo vírus da hepatite B (VHB) é um importante problema de saúde pública, associado a significante morbidade e mortalidade por doença crônica do fígado. Em pacientes com infecção crônica pelo VHB as lesões hepáticas são imunomediadas, através de citocinas, expressando a tentativa do sistema imune de destruir o agente viral. O ccDNA, entretanto, persiste na célula infectada, caracterizando não haver a cura da infecção viral mesmo quando há evidência sorológica de "clearence viral" e a viremia está indetectável.

Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study.

AIM: This randomized controlled study evaluated the effect of autologous infusion of bone marrow cells (BMC) in patients with hepatic cirrhosis. METHODS: Thirty patients on the liver transplant waiting list were randomly assigned to receive BMC therapy or no treatment. They were followed up for 1 year. The study was nonblinded. Autologous mononuclear-enriched BMC were infused into the hepatic artery; liver function scores/tests were chosen as endpoints to assess efficacy. Statistical analysis calculated mean relative changes (RC) from baseline and fitted a random-effects model. RESULTS: Mean age, baseline model for end-stage liver disease, and Child-Pugh score were similar in both groups. Child-Pugh score improved in the first 90 days in the cell therapy group compared with controls (P = 0.017, BMC group RC = -8%, controls RC = +5%). The model for end-stage liver disease score remained stable in the treated patients (RC -2 to +6%), whereas it increased during follow-up in the control group (RC +6 to +18%). Albumin levels improved in the treatment arm, whereas they remained stable among controls in the first 90 days (P = 0.034; BMC group RC = +16%, control group RC = +2%). Bilirubin levels increased among controls, whereas they decreased in the therapy arm during the first 60 days; INR RC differences between groups reached up to 10%. The changes observed did not persist beyond 90 days. CONCLUSION: Transplantation of autologous BMC into the hepatic artery improved liver function in patients with advanced cirrhosis in the first 90 days. However, larger studies are necessary to define the role of BMC therapy in cirrhotic patients. Repeated autologous BMC infusions or combination therapy with granulocyte-colony-stimulating factor might improve or sustain the treatment response.

Current status of stem cell therapy for liver diseases.

Liver failure is one of the main causes of death worldwide and is a growing health problem. Since the discovery of stem cell populations capable of differentiating into specialized cell types, including hepatocytes, the possibility of their utilization in the regeneration of the damaged liver has been a focus of intense investigation. A variety of cell types were tested both in vitro and in vivo, but the definition of a more suitable cell preparation for therapeutic use in each type of liver lesions is yet to be determined. Here we review the protocols described for differentiation of stem cells into hepatocytes, the results of cell therapy in animal models of liver diseases, as well as the available data of the clinical trials in patients with advanced chronic liver disease.

Crohn's disease in one mixed-race population in Brazil.

AIM: To evaluate the classification and severity of Crohn's disease in different racial groups. METHODS: Patients with Crohn's disease from the outpatient clinic of the University Hospital Prof. Edgard Santos were enrolled in the study. This hospital is a reference centre for inflammatory bowel disease. Race was determined using self-identification. The Vienna's classification was applied for all subjects. The severity of Crohn's disease was determined according to the number of surgical procedures, hospital admissions in the last year and treatment with steroids and immunosuppressors. Statistical analysis was calculated using t test for means, chi2 or F for proportions. A P value < 0.05 was considered to be significant. RESULTS: Sixty-five patients were enrolled. Non-white patients were more frequently diagnosed with Crohn's disease in the age less than 40 years than white patients. The behaviour of disease was similar in both groups with a high frequency of the penetrating form. There was a tendency for non-white patients to have a greater frequency of hospital admissions in the last year compared to white subjects. Non-whites also had a higher rate of colonic and upper gastrointestinal involvement, and were also more frequently on treatment with immunossupressors than white patients although this difference was not statistically significant. CONCLUSION: Non-white patients with Crohn's disease had an earlier diagnosis and appeared to have had a more severe disease presentation than white patients.

Frequency of celiac disease and its serological markers in patients with autoimmune hepatitis

Transglutaminase (anti-tTG) and anti-endomysial (AEA) antibodies were reported to occur in patients with autoimmune hepatitis (AIH) as well as in subjects with advanced cirrhosis, but the prevalence of celiac disease (CD) in patients with AIH is either negligible or unknown. The frequency of IgA anti-tTG and IgA AEA was determined in 64 patients (54 females, mean age 19[5-67] years ) with AIH diagnosed according to international criteria. Patients with positive or intermediate results for those antibodies were submitted to duodenal biopsy and HLA-DQ2 or DQ8 typing. Anti-tTG and AEA were detected in 6 (9 por cento) and one patient (1.6 por cento) with AIH, respectively. Positive and borderline results for IgA anti-tTG were detected, respectively, in two (3 por cento) and four (6 por cento) patients. Only one patient with HLA-DQ2 and IgA anti-tTG and IgA AEA had CD on duodenal biopsy. Two patients with either positive or borderline results for IgA anti-tTG antibody and HLA-DQ2 had normal histology on duodenal biopsy. IgA anti-tTG antibody and/or AEA were observed in 9% of AIH patients, but CD was confirmed in only one of them. The occurrence of IgA anti-tTG antibody in the other patients could be ascribed to the presence of chronic liver disease or to latent or potential CD.

Tolerância à sulfassalazina em pacientes com retocolite ulcerativa (RCUI) em Salvador-Bahia / Sulphasalazine tolerability in patients with ulcerative colitis in Salvador-Bahia

A sulfassalazina (SSZ) é amplamente utilizada para tratamento da retocolite ulcerativa idiopática. Estudos relatam frequência de efeitos colaterais em torno de 20-45%, os quais em geral são dose-dependentes e relacionados com altos n¡veis séricos de sulfapiridina, ocorrendo principalmente nos pacientes com baixa capacidade genética de acetilação hepática da medicação. Embora seja droga utilizada há muito tempo, a escassez de dados em nosso meio motivou a realização de um levantamento da tolerância desse medicamento em pacientes do Programa Estadual de Medicamentos de Alto Custo da Secretaria de Saúde da Bahia. Métodos: Estudo retrospectivo com avaliação de prontuários de pacientes em acompanhamento ambulatorial que fizeram uso de SSZ. Foram levantados dados epidemiológicos, dados sobre a extensão da doença, exames laboratoriais, dose, tempo de uso e suspensão da SSZ, relatos de queixas espontâneas dos pacientes com relação a eventos adversos gastrointestinais, hematológicos, dermatológicos, neurológicos e urinários. Resultados: Foram avaliados 100 pacientes com média de idade de 44,1 anos (13-87), sendo 73% do sexo feminino. Apresentaram efeitos colaterais 37% dos pacientes, havendo necessidade de suspensão da medicação em 47,4% (18/37) dos casos, redução da dose em 18,4% (7/37) e hospitalização em 7,8% (3/37). Os efeitos colaterais mais frequentes nos pacientes com colite distal, predominando cefaléia (11 %), epigastralgia (11 %) e náuseas em 9% dos pacientes. Conclusões: A frequência de eventos adversos foi semelhante … relatada em outros estudos, com baixa frequência de reações adversas graves. Não foi observada relação entre a frequência e gravidade dos efeitos colaterais e a extensão da doença.

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease.

AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 +/- 0.9) and 4 mo (2.10 +/- 1.0) after cell transplantation that baseline levels (2.78 +/- 1.2). Albumin levels 4 mo after BMC infusion (3.73 +/- 0.5) were higher than baseline levels (3.47 +/- 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

Daily interferon induction regimen using different manufactured interferons (alpha-2a or alpha-2b) in combination with ribavirin for treatment of chronic hepatitis C: a prospective randomized study

BACKGROUD: Studies on hepatitis C virus kinetics showed that serum levels of interferon fall 48 h after drug administration, when viral load is increasing again. Previously to the availability of pegylated interferon, daily induction therapy with standard interferon was under evaluation. AIMS: To evaluate the safety and efficacy of interferon alpha daily induction regimen in combination with ribavirin. PATIENTS AND METHODS: A randomized trial including 93 patients with chronic hepatitis C was carried out. On satisfying all eligibility criteria, patients were randomly allocated to two different treatment groups: 44 individuals in treatment arm A: IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily for 48 weeks (IFN TIW) and 49 individuals in treatment arm B: IFN 3 MU daily + ribavirin 1.0-1.2 g daily for 12 weeks followed by IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily, until completion of 48 weeks of therapy (IFN QD). HCV genotyping was obtained in 85 subjects. A negative HCV-RNA 6 months after cessation of therapy was considered a sustained virological response RESULTS: Eighty three patients completed treatment, five dropped out (one from IFN TIW and four from IFN QD) and in five patients therapy was discontinued due to medical request (two from IFN TIW and three from IFN QD). There was no statistically significant difference between groups with respect to therapy interruption. The frequency of cirrhosis was 29 percent, similar in both groups. In the "intention to treat" analysis the overall sustained virological response was 39.8 percent. There was no significant difference in sustained virological response rate between both treatment strategies (36.4 percent IFN TIW vs 42.9 percent IFN QD). In the 83 patients who finished the trial, sustained virological response was 44.6 percent. Among subjects with HCV genotype-1, the sustained virological response was 42 percent (40.9 percent IFN TIW vs 42.9 percent IFN QD) and among patients...

RACIONAL: Estudos em cinética viral na hepatite C demonstraram que há uma queda dos níveis séricos de interferon 48 h após a sua administração, quando a carga viral do vírus C volta a se elevar. Antes da disponibilidade do interferon peguilado, diversos ensaios clínicos investigaram a terapia de indução com interferon standard OBJETIVOS: Avaliar a segurança e eficácia do esquema de indução diário com interferon alfa associado à ribavirina. PACIENTES E MÉTODOS: Noventa e três pacientes com hepatite crônica C foram incluídos. Através de randomização, foram alocados em um de dois braços terapêuticos: 44 indivíduos no grupo A: IFN 3MU três vezes por semana + ribavirina 1,0-1,2 g diariamente por 48 semanas e 49 indivíduos no grupo B: IFN 3MU diariamente por 12 semanas, seguindo-se por IFN 3MU três vezes por semana até completar 48 semanas + ribavirina 1,0-1,2 g diariamente por 48 semanas. A genotipagem do vírus C foi realizada em 85 indivíduos. Considerou-se resposta virológica sustentada a persistência do HCV-RNA negativo 6 meses após o término da terapia RESULTADOS: Oitenta e três pacientes completaram o tratamento. Houve cinco abandonos (um do grupo A e quatro do grupo B) e em cinco pacientes a terapia foi retirada devido a efeitos adversos (dois do grupo A e três do grupo B). Não houve diferença estatisticamente significante entre os grupos quanto à interrupção do tratamento. A freqüência de cirrose foi 29 por cento, semelhante entre os grupos. Na análise "intention to treat" a resposta virológica sustentada foi 39,8 por cento. Não houve diferença estatística na taxa de resposta virológica sustentada entre ambas as estratégias terapêuticas (36,4 por cento grupo A vs 42,9 por cento grupo B). Nos 83 pacientes que finalizaram o estudo, a resposta virológica sustentada foi 44,6 por cento. Entre os pacientes com genótipo 1, a resposta virológica sustentada foi 42 por cento (40,9 por cento grupo A vs 42,9 por cento grupo B) e entre os pacientes...

Distribution of hepatitis B virus genotypes among patients with chronic infection.

UNLABELLED: Hepatitis B virus (HBV) can be classified into at least eight genotypes, A-H. We evaluated the distribution HBV genotypes among patients with chronic infection. METHODS: We consecutively evaluated adult patients with chronic HBV infection from Salvador, Brazil. Patients were classified according to HBV infection chronic phases based on HBV-DNA levels and presence of serum HBV markers. HBV-DNA was qualitatively and quantitatively detected in serum by polymerised chain reaction (PCR). Isolates were genotyped by comparison of amino acid mutations and phylogenetic analysis. RESULTS: One-hundred and fourteen patients were evaluated. HBV-DNA was positive in 96 samples. HBV genotype was done in 76. Mean age was 36 +/- 11.3. In 61 of 76 cases subjects were classified as inactive HBsAg carriers. Their mean HBV serum level was 1760 copies/ml and 53 of 61 were infected with HBV genotype A, seven with HBV genotype F and one with genotype B. Twelve of the 76 patients had detectable hepatitis B e-antigen (HBeAg) in serum. Ten were infected with HBV genotype A and two with genotype F; most had increased alanine aminotransferase and high HBV-DNA levels. Three patients were in the immunotolerant phase, two were infected with HBV genotype A and one with genotype F. HBV subtyping showed subtypes adw2 and adw4. CONCLUSIONS: HBV genotype A adw2 and genotype F adw4 were the most prevalent isolates found. We could not find differences in genotype distribution according to HBV clinical phases and DNA levels. We did not detect HBV genotype D in contrast to a previous study in our center with acute hepatitis B. All inactive HBsAg carriers had low HBV-DNA levels.