Alterações hepáticas em transplantados renais do maior centro de transplante do Brasil / Hepatic alterations in kidney transplant recipients from the largest kidney transplant center in brazil

ABSTRACT Background Kidney transplant is the treatment of choice for patients with end-stage renal disease and is associated with lower mortality when compared to dialysis methods. Brazil is the country with the second largest number of kidney transplants in the world and among these patients it has been observed that liver abnormalities are common. The frequency of liver abnormalities ranges from 20-50% post-transplantation, and have an important impact on the survival and quality of life of these patients. There are scarce data about the frequency, causes and characteristics of these alterations. Objective To determine the prevalence of the different causes of hepatic abnormalities in kidney transplant recipients, to associate the characteristics of these abnormalities with demographic, epidemiological and clinical variables, to compare the characteristics of hepatic alterations between different etiologies, and to evaluate possible changes in diagnosis over two different periods of time. Methods Descriptive, cross-sectional observational, epidemiological study was conducted at the outpatient "Hepato-Rim"clinic of Hospital São Paulo (EPM/UNIFESP), a center providing specialized care for patients with hepatic abnormalities and underlying kidney diseases. Results Five-hundred eighty-one transplant patients were evaluated. The most prevalent etiologies of liver abnormalities were hepatitis C and B, iron overload, nonalcoholic fatty liver disease (NAFLD), and drug-induced liver injury (DILI). The most common cause — hepatitis C — was analyzed in greater detail. Compared to the other causes, this infection was more frequent in older patients, female patients, and patients with a longer time since transplantation and hemodialysis. Analysis of the two periods showed that patients of period 1 (P1 — 1993 to 2005) were older and were more frequently referred because of positive serology; referral due to aminotransferases abnormalities predominated during period 2 (P2 — 2006 to 2018). The predominant diagnoses were hepatitis C and B during P1 and NAFLD and DILI during P2. Conclusion Assessment of the main hepatic alterations in kidney transplant recipients is important because it permits better management of these patients in terms of diagnostic investigation and treatment and contributes to the prevention of complications in this special population.

RESUMO Contexto O transplante renal é o tratamento de escolha para pacientes com doença renal terminal e está associado a menor mortalidade quando comparado aos métodos dialíticos. O Brasil é o país com o segundo maior número de transplantes renais do mundo e, entre esses pacientes, observa-se que as alterações hepáticas são comuns. A frequência das alterações hepáticas varia de 20 a 50% pós-transplante e tem importante impacto na sobrevida e qualidade de vida desses pacientes. Existem poucos dados sobre a frequência, causas e características dessas alterações. Objetivo Determinar a prevalência das diferentes causas de anormalidades hepáticas em receptores de transplante renal, associar as características dessas anormalidades a variáveis demográficas, epidemiológicas e clínicas, comparar as características das alterações hepáticas entre diferentes etiologias e avaliar possíveis alterações no diagnóstico em dois períodos diferentes de tempo. Métodos Estudo epidemiológico descritivo, transversal, observacional, realizado no ambulatório "Hepato-Rim" do Hospital São Paulo (EPM/UNIFESP), centro de atendimento especializado a pacientes com anormalidades hepáticas e doenças renais de base. Resultados Quinhentos e oitenta e um pacientes transplantados foram avaliados. As etiologias mais prevalentes de anormalidades hepáticas foram hepatite C e B, sobrecarga de ferro, doença hepática gordurosa não alcoólica e lesão hepática induzida por drogas. A causa mais comum — hepatite C — foi analisada em maiores detalhes. Em comparação com as outras causas, essa infecção foi a mais frequente em pacientes mais velhos, pacientes do sexo feminino e pacientes com mais tempo de transplante e hemodiálise. A análise dos dois períodos mostrou que os pacientes do período 1 (P1 — 1993 a 2005) eram mais velhos e encaminhados com maior frequência devido à sorologia positiva; encaminhamento devido a anormalidades de aminotransferases predominou durante o período 2 (P2 — 2006 a 2018). Os diagnósticos predominantes foram hepatite C e B durante P1 e doença hepática gordurosa não alcoólica e lesão hepática induzida por drogas durante P2. Conclusão A avaliação das principais alterações hepáticas em receptores de transplante renal é importante, pois permite melhor manejo desses pacientes na investigação diagnóstica e no tratamento e contribui para a prevenção de complicações nesta população especial.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV)

ABSTRACT Introduction: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. Methods: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. Results: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p= 0.022, Fisher's exact test). Conclusion: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Evaluation of a strategy for identification of hepatitis C virus carriers in outpatient and emergency units: contribution to the microelimination of hepatitis C in Brazil

ABSTRACT Introduction: Hepatitis C virus (HCV) infection continues to be an important public health problem worldwide. Despite the availability of drugs that promote the cure of infection in more than 95% of cases, the identification of HCV carriers remains a major challenge. Objective: To evaluate a strategy for identifying HCV carriers based on combined criteria: screening in emergency units and specialty outpatient clinics of a tertiary hospital and among older adults (≥45 years), both suggested as efficient in epidemiological studies. Methods: A cross-sectional, analytical and descriptive study was conducted on individuals of both sexes, aged 45 years and older, attending the emergency department and specialty outpatient clinics of a University Hospital in São Paulo, Brazil, from January 2016 to June 2018. After giving formal consent, the patients were submitted to a standardized interview and rapid testing for the identification of HCV antibodies (SD BIOLINE® anti-HCV). Results: A total of 606 adult patients (62% women and 37% men) were evaluated. The mean age was 62 ± 10 years. Four positive tests were identified, with confirmation by conventional serology and HCV-RNA determination. Thus, the prevalence of HCV identified in the sample was 0.66%. All patients had a history of risk factors for infection. Conclusion: The strategies of birth-cohort testing and screening in emergency medical services for the identification of HCV carries, both suggested in the literature as efficient for the diagnosis of hepatitis C, resulted in a low rate of HCV infection. These findings highlight the magnitude of the challenge of identifying asymptomatic HCV carriers in Brazil.

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

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

Tratamento da hepatite C em pacientes com doença renal crônica e pós-tranplante renal: eficácia e segurança dos esquemas de antivirais de ação direta contendo sofosbuvir / Hepatitis c treatment of renal transplant and chronic kidney disease patients: efficacy and safety of direct-acting antiviral regimens containing sofosbuvir

ABSTRACT BACKGROUND: Direct-acting antivirals have revolutionized hepatitis C treatment, also for patients with chronic kidney disease (CKD), but some controversy exists regarding the use of sofosbuvir (SOF) in patients with glomerular filtration rate (GFR) <30 mL/min. OBJECTIVE: To evaluate the efficacy and safety of these regimens for hepatitis C treatment of patients with CKD and after renal transplantation, as well as the impact of SOF on renal function in non-dialysis patients. METHODS: All patients with hepatitis C and CKD or renal transplant treated with direct-acting antivirals at a referral center in Brazil between January 2016 and August 2017 were included. Efficacy was evaluated based on viral load (HCV RNA) and a sustained virological response (SVR) consisting of undetectable RNA 12 and/or 24 weeks after the end of treatment (SVR12 and SVR24) was defined as cure. Safety was determined by adverse events and ribavirin, when combined, was administered in escalating doses to all patients with GFR <60 mL/min. The impact of SOF on renal function was determined by the measurement of baseline creatinine during and after the end of treatment and its increase was evaluated using the Acute Kidney Injury Network (AKIN) classification. RESULTS: A total of 241 patients (52.7% females) with a mean age of 60.72±10.47 years were included. The combination of SOF+daclatasvir was the predominant regimen in 75.6% of cases and anemia was present in 28% of patients who used ribavirin (P=0.04). The SVR12 and SVR24 rates were 99.3% and 97.1%, respectively. The treatment was well tolerated and there were no major clinically relevant adverse events, with the most prevalent being asthenia (57.7%), itching (41.1%), headache (40.7%), and irritability (40.2%). Among conservatively treated and renal transplant patients, oscillations of creatinine levels (AKIN I) were observed in 12.5% of cases during treatment and persisted in only 8.5% after the end of treatment. Of these, 2.0% had an initial GFR <30 mL/min and this percentage decreased to 1.1% after SOF use. Only 0.5% and 1.6% of the patients progressed to AKIN II and AKIN III elevation, respectively. CONCLUSION: The direct-acting antivirals were safe and efficacious in CKD patients treated with SOF-containing regimens, with the observation of high SVR rates, good tolerability and few severe adverse events. The combination with ribavirin increased the risk of anemia and the administration of escalating doses seems to be useful in patients with GFR <60 mL/min. In patients with GFR <30 mL/min, SOF had no significant renal impact, with serum creatinine returning to levels close to baseline after treatment.

RESUMO CONTEXTO: Os antivirais de ação direta revolucionaram o tratamento da hepatite C, inclusive para os pacientes com doença renal crônica (DRC), porém ainda há divergências no emprego do sofosbuvir (SOF) quando taxa de filtração glomerular (TFG) <30 mL/min. OBJETIVO: Avaliar a eficácia e segurança desses esquemas no tratamento da hepatite C em pacientes com DRC e pós-transplante renal, além de avaliar o impacto do SOF sobre a função renal dos não-dialíticos. MÉTODOS: Todos os pacientes com hepatite C e DRC ou transplante renal que realizaram tratamento com antivirais de ação direta em centro referenciado do Brasil no período de janeiro/2016 a agosto/2017 foram incluídos. A eficácia foi avaliada por meio da carga viral (HCV-RNA), considerando-se cura uma resposta virológica sustentada (RVS) com resultado indetectável após 12 e/ou 24 semanas do término do tratamento (RVS12 e RVS24). A segurança foi determinada pelos eventos adversos e a ribavirina, quando associada, foi introduzida de forma escalonada em todos os pacientes com TFG <60 mL/min. Para determinação do impacto do SOF sobre a função renal, foram observadas as dosagens de creatinina basal, durante e após término do tratamento com seu incremento avaliado por meio da classificação de AKIN (acute kidney injury network). RESULTADOS: Foram incluídos 241 pacientes, sendo 52,7% do sexo feminino, com média de idade de 60,72±10,47 anos. A associação de SOF+daclatasvir predominou em 75,6% dos casos e anemia esteve presente em 28% dos pacientes que utilizaram ribavirina (P=0,040). As taxas de RVS12 e RVS24 foram de 99,3% e 97,1%. O tratamento foi bem tolerado, com eventos adversos pouco relevantes, sendo os mais prevalentes: astenia (57,7%), prurido (41,1%), cefaleia (40,7%) e irritabilidade (40,2%). Entre os pacientes em tratamento conservador e transplantados renais, os valores de creatinina sofreram oscilações AKIN I em 12,5% dos casos, durante o tratamento, persistindo em apenas 8,5% da amostra após o término, dos quais 2,0% apresentavam TFG <30 mL/min inicialmente, com queda para 1,1% após uso do SOF. Apenas 0,5% e 1,6% evoluíram com elevação AKIN II e AKIN III. CONCLUSÃO: Os antivirais de ação direta foram seguros e eficazes em pacientes com DRC tratados com esquemas contendo SOF, apresentando altas taxas de RVS, boa tolerabilidade e poucos eventos adversos graves. A associação com ribavirina aumentou o risco de anemia, portanto sua introdução de forma escalonada parece ser útil nos pacientes com TFG <60 mL/min. Em pacientes com TFG <30 mL/min o SOF não apresentou impacto renal significativo, com creatinina sérica retornando a valores próximos ao basal após o tratamento.

Practical Considerations of Real Life of Hepatocellular Carcinoma in a Tertiary Center of Brazil

ABSTRACT Background. Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epidemiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC. Material and methods. Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question. Results. The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P < 0.001), TACE (P < 0.001), or any kind of treatment (P < 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1). Conclusion. Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.

Hematological and dermatological adverse events during hepatitis C treatment with peg-interferon and ribavirin / Eventos adversos hematológicos e dermatológicos durante o tratamento da hepatite C com interferon peguilado e ribavirina

Objective: To evaluate frequency and impact of adverse events, mainly the hematological and dermatological ones, on sustained virological response, and compliance to hepatitis C treatment. Methods: Patients were treated according to the guidelines of the Brazilian Ministry of Health. Variables associated with hematological and dermatological adverse events were: age, gender, stage of fibrosis, type of Pegylated interferon, dose reductions, temporary discontinuation and early interruption of treatment. Results: Two hundred and twenty two patients were studied (58% females; age 49±11 years). Dose reductions, temporary interruptions, and early discontinuations were observed in 21%, 8% and 9.5% of patients, respectively. The main adverse events were hematological (anemia, neutropenia and thrombocytopenia) and dermatological (pruritus and alopecia). Anemia (Hemoglobin <10g/dL) was associated with female gender (p<0.001), advanced fibrosis (p=0.047) and dose reductions (p<0.001); neutropenia with advanced fibrosis (p=0.003) and temporary discontinuation (p=0.002); thrombocytopenia with advanced fibrosis (p<0.001) and pegylated interferon α2a (p=0.05). Pruritus and alopecia were associated to female gender (p=0.008 and p=0.02) and treatment interruption (p=0.029 and p=0.02).Conclusion: Hematological and dermatological adverse events are frequent in hepatitis C patients treated with pegylated interferon and ribavirin. However, despite frequent dose reductions and interruptions, these adverse events did not affect the sustained virological response.

Objetivo: Avaliar a frequência e o impacto de eventos adversos, principalmente hematológicos e dermatológicos, na resposta virológica sustentada e na aderência ao tratamento para hepatite C. Métodos: Os pacientes foram tratados de acordo com diretriz do Ministério da Saúde. Variáveis associadas com eventos adversos hematológicos e dermatológicos foram: idade, sexo, grau de fibrose, tipo de interferon peguilado, reduções de dose, descontinuação temporária e interrupção precoce do tratamento. Resultados: Foram estudados 232 pacientes (58% mulheres; idade 49±11 anos). Reduções de dose, interrupções temporárias e descontinuações precoces foram observadas em 21%, 8% e 9,5% dos pacientes, respectivamente. Os principais eventos adversos foram hematológicos (anemia, neutropenia e plaquetopenia) e dermatológicos (prurido e alopecia). Anemia (hemoglobina <10g/dL) se associou a sexo feminino (p<0,001), fibrose avançada (p=0,047) e reduções de doses (p<0,001); neutropenia com fibrose avançada (p=0,003) e interrupção temporária (p=0,002); plaquetopenia com fibrose avançada (p<0,001) e interferon peguilado α2a (p=0,05). Prurido e alopecia se associaram ao sexo feminino (p=0,008 e p=0,02) e interrupção do tratamento (p=0,029 e p=0,02). Conclusão: Eventos adversos hematológicos e dermatológicos foram frequentes em pacientes tratados com interferon peguilado e ribavirina. Entretanto, a despeito de frequentes reduções de dose e interrupções, estes eventos adversos não afetaram a resposta virológica sustentada.

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.

ASSOCIATION OF THE NUTRITIONAL PROFILE WITH HISTOLOGICAL FINDINGS OF PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C INFECTION

Background - Different factors are responsible for the progression of hepatic fibrosis in chronic infection with hepatitis C virus, but the role of nutritional factors in the progression of the disease is not clearly defined. This study aimed to evaluate the nutritional status and dietary profile among patients with chronic hepatitis C who were candidates for treatment and its association with histopathological features. Methods - A crossectional study was conducted on treatment-naïve patients with chronic hepatitis C genotype 1, between 2011 and 2013. The following assessments were performed before treatment: liver biopsy, anthropometric measurements and qualitative/quantitative analysis of food intake. Results - Seventy patients were studied. The majority of patients was classified as obese (34%) or overweight (20%) according to body mass index [BMI] and as at risk for cardiovascular diseases by waist circumference (79%). Unhealthy food intake was presented by 59% according to qualitative parameters and several patients showed an insufficient intake of calories (59%), excessive intake of protein (36%) and of saturated fat (63%), according to quantitative analysis. With respect to histology, 68% presented activity grade ≥2, 65% had steatosis and 25% exhibited fibrosis stage >2. Comparative analysis between anthropometric parameters and histological features showed that elevated waist circumference was the only variable associated to hepatic steatosis ( P =0.05). There was no association between qualitative and quantitative food intake parameters with histological findings. Conclusion - In this study, most of the patients with hepatitis C presented inadequate qualitative food intake and excessive consumption of saturated fat; in addition, excess of abdominal fat was associated to hepatic steatosis. Therefore, nutritional guidance should be implemented prior to treatment in patients with chronic hepatitis C, in order to avoid nutritional disorders and negative impact on the management of patients.

Contexto - Diferentes fatores são responsáveis pela progressão da fibrose na infecção crônica pelo vírus da hepatite C, mas o papel dos fatores nutricionais na progressão da doença não está definido. Este estudo teve como objetivo avaliar o estado nutricional e o perfil dietético de pacientes com hepatite C crônica candidatos a tratamento e sua associação com achados histopatológicos. Métodos - Foi conduzido um estudo transversal em pacientes com hepatite C crônica genótipo 1 virgens de tratamento, entre 2011 e 2013. Foram analisados, antes do tratamento, os seguintes aspectos: biópsia hepática, medidas antropométricas e análise qualitativa e quantitativa do consumo alimentar. Resultados - Setenta pacientes foram estudados. A maioria dos pacientes apresentava obesidade (34%) ou sobrepeso (20%) de acordo com índice de massa corporal e risco para doenças cardiovasculares de acordo com a circunferência da cintura elevada (79%). Na análise qualitativa do consumo alimentar, 59% apresentavam uma dieta inadequada. Conforme análise quantitativa, 59% tinham consumo insuficiente de calorias, 36% consumo excessivo de proteínas e 63% consumo excessivo de gorduras saturadas. Com relação à histologia, 68% apresentavam grau de atividade inflamatória ≥2, 65% mostraram esteatose hepática e 25% possuíam grau de fibrose >2. Na análise comparativa entre as medidas antropométricas e achados histológicos, somente a circunferência da cintura elevada mostrou associação com esteatose hepática ( P =0,05). Não houve associação entre consumo alimentar qualitativo e quantitativo com parâmetros histológicos. Conclusão - A maioria dos pacientes apresentava consumo alimentar inadequado de acordo com parâmetros qualitativos e consumo excessivo de gordura saturada, além de excesso de gordura abdominal, que esteve associada à esteatose hepática. Portanto, aconselhamento nutricional deveria ser implementado em pacientes candidatos a tratamento para hepatite C crônica visando evitar distúrbios nutricionais que podem impactar negativamente no manejo dos pacientes.

Clinical and epidemiological profile of female blood donors with positive serology for viral hepatitis B

ABSTRACTINTRODUCTION:Since women are frequently the minority among blood donors worldwide, studies evaluating this population usually reflect male features. We assessed the features of female blood donors with positive serology for HBV and compared them with those of men.METHODS The study comprised consecutive blood donors referred to a specialized liver disease center to be evaluated due to HBsAg- and/or anti-HBc-positive tests.RESULTS: The study encompassed 1,273 individuals, 219 (17.2%) of whom were referred due to positive HBsAg test and 1,054 (82.8%) due to reactive anti-HBc test. Subjects' mean age was 36.8±10.9 years, and 28.7% were women. Female blood donors referred for positive HBsAg screening tests demonstrated higher prevalence of healthcare workers (9.3% vs 2.5%) and lower prevalence of sexual risk behaviors (15.1% vs 41.1%) and alcohol abuse (1.9% vs 19.8%) compared to men. Women had lower ALT (0.6 vs 0.8×ULN), AST (0.6 vs 0.8×ULN), direct bilirubin (0.2 vs 0.3mg/dL), and alkaline phosphatase (0.5 vs 0.6×ULN) levels and higher platelet count (223,380±50,293 vs 195,020±53,060/mm3). Women also had a higher prevalence of false-positive results (29.6% vs 17.0%). No differences were observed with respect to liver biopsies. Female blood donors referenced for reactive anti-HBc screening tests presented similar clinical, epidemiological, and biochemical characteristics to those reported for positive HBsAg screening tests and similarly had a higher prevalence of false-reactive results.CONCLUSIONS: Compared to men, female blood donors with positive HBsAg and/or anti-HBc screening tests demonstrated higher prevalence of professional risk and false-positive results and reduced alteration of liver chemistry.

Reativação de leishmaniose durante tratamento de hepatite b crônica com alfainterferona 2b / Leishmaniasis reactivation during treatment of chronic hepatitis B with interferon alpha 2b - case report

Descreve-se aqui um caso de reativação de leishmaniose cutaneomucosa durante o tratamento com alfainterferona 2b (IFN) para hepatite B crônica (HBV). Relato do caso: Paciente masculino, 52 anos, natural da Bahia, procedente de São Paulo onde vivia há 30 anos, encaminhado por HBV. Na história epidemiológica, referiu-se a uma viagem há cinco anos para Porto Seguro-BA, sem apresentar outros fatores de risco. No exame físico para admissão, não havia evidências de doença hepática crônica. Sorologias pré-tratamento: HBsAg e HBeAg positivos, biópsia A0F0 (Metavir). Foi submetido a tratamento com IFN 5 milhões de UI/dia por 24 semanas. No final, apresentava-se HBV DNA detectável, sem soroconversão de HBeAg, porém evoluiu no quarto mês de tratamento com perda ponderal de 10 kg, astenia, sinais e sintomas de sinusite sem melhora clínica após antibioticoterapia. Foi encaminhado para a otorrinolaringologia com rouquidão persistente, destruição de septo nasal, com áreas de crostas, necrose local, alargamento nasal e lesão em palato mole, cuja biópsia mostrou processo inflamatório granulomatoso com necrose caseosa, sugestivo de leishmaniose. Sorologia para leishmaniose IgG 1/80 (IFI) e intradermorreação de Montenegro de 30 mm. Indicado antimoniato de meglumina IV por 30 dias, obteve melhora da rouquidão e das lesões de palato. Conclusão: O quadro clínico sugere reativação da leishmaniose induzida pelo IFN. Acredita-se que este seja o primeiro relato na literatura de reativação de leishmaniose muco-cutânea por uso de IFN, semelhantemente ao que ocorre com a tuberculose. Screening para leishmaniose deve ser realizado em paciente de região endêmica no pré-tratamento com IFN diante da possibilidade de reativação de infecção latente

Acute exacerbation of chronic hepatitis B virus infection in renal transplant patients

Introduction: There is scarce information regarding clinical evolution of HBV infection in renal transplant patients. Aims: To evaluate the prevalence of acute exacerbation in HBV-infected renal transplant patients and its association with the time after transplantation, presence of viral replication, clinical evolution, and use of antiviral prophylaxis. Materials and methods: HBV infected renal transplant patients who underwent regular follow-up visits at 6-month intervals were included in the study. The criteria adopted to characterize exacerbation were: ALT >5 × ULN and/or >3 × baseline level. Predictive factors of exacerbation evaluated were age, gender, time on dialysis, type of donor, post-transplant time, ALT, HBeAg, HBV-DNA, HCV-RNA, immunosuppressive therapy, and use of antiviral prophylaxis. Results: 140 HBV-infected renal transplant patients were included (71% males; age 46 ±10 years; post-renal transplant time 8 ±5 years). During follow-up, 25% (35/140) of the patients presented exacerbation within 3.4 ±3 years after renal transplant. Viral replication was observed in all patients with exacerbation. Clinical and/or laboratory signs of hepatic insufficiency were present in 17% (6/35) of the patients. Three patients died as a consequence of liver failure. In univariate analysis variables associated with exacerbation were less frequent use of prophylactic/preemptive lamivudine and of mycophenolate mofetil. Lamivudine use was the only variable independently associated with exacerbation, with a protective effect. Conclusions: Acute exacerbation was a frequent and severe event in HBV-infected renal transplant patients. Prophylactic/preemptive therapy with antiviral drugs should be indicated for all HBsAg-positive renal transplant patients. .

Acute pancreatitis associated with boceprevir: a case report

Approximately 170 million people are infected with hepatitis C, and the sustained virological response rate to treatment with pegylated interferon and ribavirin is 30-50%. In an attempt to improve the chances of cure, boceprevir is being added to therapy, but it is associated with an increased incidence of adverse events. We herein report a case of acute pancreatitis developed during treatment with pegylated interferon, ribavirin and boceprevir. Boceprevir was the most likely cause of drug-associated pancreatitis after the most common causes were ruled out, since this adverse event had not occurred when the patient had previously been exposed to pegylated interferon and ribavirin and there was no recurrence of the episode of pancreatitis when these two drugs were reintroduced. Acute pancreatitis is a rare adverse event associated with boceprevir therapy, but a potentially fatal event. Sequential determination of pancreatic enzymes should be considered during hepatitis C treatment with boceprevir.

Do differences exist between chronic hepatitis C genotypes 2 and 3?

Introduction Six genotypes of the hepatitis C virus (HCV) have been identified thus far, and their distribution is well defined. Genotype 1, which is the most prevalent worldwide, is always compared to genotypes 2 and 3, particularly in terms of treatment response. However, little is known about the differences between genotypes 2 and 3 because these genotypes are analyzed together in most studies. Therefore, the aim of this study was to evaluate differences in the clinical, epidemiological, laboratory, and histological parameters between HCV-2 and HCV-3. Methods Patients with chronic hepatitis C infected with genotypes 2 and 3 were studied retrospectively and compared according to clinical, laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV-RNA) was analyzed quantitatively by TaqMan® real-time PCR, and the HCV genotype was determined by sequencing the 5′-untranslated region. Results A total of 306 patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients infected with HCV-2 and HCV-3, respectively. The mean age was 47 ± 10 years, and there was a predominance of men in the group studied (61%). Comparative analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in patients with HCV-3 (p=0.001). After multivariate regression analysis, all the variables, except serum albumin, remained as variables associated with HCV-3 in the final model. Conclusions Clinical and histological differences exist between HCV-2 and HVC-3, which suggests the need for separate analyses of these genotypes. .

Clinical characteristics associated with hepatic steatosis on ultrasonography in patients with elevated alanine aminotransferase / Características clínicas associadas a esteatose hepática à ultrassonografia em pacientes com alanina aminotransferase elevada

CONTEXT AND OBJECTIVE: The main causes of hepatic steatosis (HS) are alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD). Although liver biopsy is the gold standard for NAFLD diagnosis, the finding of abnormal aminotransferases in abstinent individuals, without known liver disease, suggests the diagnosis of NAFLD in 80-90 percent of the cases. Identification of clinical factors associated with HS on abdominal ultrasound may enable diagnoses of fatty liver non-invasively and cost-effectively. The aim here was to identify clinical variables associated with HS in individuals with elevated alanine aminotransferase (ALT) levels. DESIGN AND SETTING: Cross-sectional study in a single tertiary care center. METHODS: Individuals with elevated ALT, serologically negative for hepatitis B and C, were evaluated by reviewing medical files. Patients who did not undergo abdominal ultrasonography were excluded. RESULTS: Among 94 individuals included, 40 percent presented HS on ultrasonography. Compared with individuals without HS, those with fatty liver were older (P = 0.043), with higher body mass index (BMI) (P = 0.003), diabetes prevalence (P = 0.024), fasting glucose levels (P = 0.001) and triglycerides (P = 0.003). Multivariate analysis showed that BMI (odds ratio, OR = 1.186; 95 percent confidence interval, CI: 1.049-1.341; P = 0.006) and diabetes mellitus (OR = 12.721; 95 percent CI: 1.380-117.247; P = 0.025) were independently associated with HS. CONCLUSIONS: Simple clinical findings such as history of diabetes and high BMI may predict the presence of HS on ultrasonography in individuals with elevated ALT and negative serological tests for hepatitis.

CONTEXTO E OBJETIVO: Doença hepática alcoólica e doença hepática esteatótica não alcoólica (DHENA) são as principais causas de esteatose hepática (EH). Apesar de a biópsia hepática ser o método de escolha para diagnóstico DHENA, o achado de aminotransferases elevadas em indivíduos abstêmios, sem doença hepática conhecida, sugere o diagnóstico de DHENA em 80-90 por cento dos casos. A identificação de variáveis clínicas associadas à EH na ultrassonografia abdominal pode permitir o diagnóstico de DHENA de forma não invasiva e custo-efetiva. O objetivo foi identificar variáveis clínicas associadas à EH em indivíduos com níveis elevados de alanina aminotransferase (ALT). TIPO DE ESTUDO E LOCAL: Estudo transversal em um único centro de atendimento terciário. MÉTODOS: Indivíduos com ALT elevada e sorologias negativas para os vírus de hepatite B e C foram avaliados por meio de revisão de prontuários. Os pacientes não submetidos à ultrassonografia foram excluídos. RESULTADOS: Foram incluídos 94 indivíduos, 40 por cento deles com EH à ultrassonografia. Quando comparados aos indivíduos sem EH, aqueles com EH apresentaram maior prevalência de diabetes (P = 0,024), maiores idade (P = 0,043) e índice de massa corpórea (IMC) (P = 0,003), glicemia de jejum mais elevada (P = 0,001) e triglicerídeos mais elevados (P = 0,003). A análise multivariada evidenciou que o IMC (odds ratio, OR = 1,186, 95 por cento intervalo de confiança, IC 1,049-1,341, P = 0,006) e o diabetes mellitus (OR = 12,721, 95 por cento IC 1,380-117,247, P = 0,025) foram associadas independentemente à EH. CONCLUSÕES: Achados clínicos simples como história de diabetes e o IMC elevado podem predizer a presença de EH à ultrassonografia de indivíduos com ALT elevada e sorologias negativas para hepatite.

Gender influence on treatment of chronic hepatitis C genotype 1 / Influência do gênero no tratamento da hepatite C crônica genótipo 1

INTRODUCTION: Although various studies have been published regarding the treatment of chronic hepatitis C (CHC) with peginterferon (Peg-IFN) and ribavirin, little is known regarding the real impact of gender on the characteristics that influence the effectiveness and safety of antiviral treatment for CHC patients. The objective of this study was to evaluate the influence of gender on HCV treatment outcomes. METHODS: A retrospective analytical study was conducted among selected carriers of CHC genotype 1, who were treated with Peg-IFN α-2b at a dose of 1.5 μg/kg or Peg-IFN α-2a at a dose of 180 μg/week plus a ribavirin dose of 1,000-1,250 mg/day, according to weight, between 2001 and 2007. RESULTS: Among 181 patients undergoing treatment, the mean age was 46.4 ± 11.0 years and 46 percent were women. At baseline, 32 percent of the patients had advanced fibrosis (F3-F4 Scheuer), and 83 percent of the subjects had viral load > 400,000 IU/ml, without significant difference between the genders (p = 0.428 and p = 0.452, respectively). When compared with men, women had higher incidence of many adverse events such as anemia (p < 0.001) and higher need for dose reduction, for both Peg-IFN (p = 0.004) and ribavirin (p = 0.006). However, the rate of sustained virological response (SVR) did not differ between the genders: 45 percent (female) vs 41 percent (male); p=0.464. CONCLUSIONS: This study suggests that women and men react differently to combined therapy, especially in relation to the incidence of adverse events and the need for dose modification. Nevertheless, these differences do not influence the SVR rate.

INTRODUÇÃO: Apesar dos vários estudos publicados a respeito do tratamento da hepatite C crônica (CHC) com Peg-Interferon (Peg-IFN) e ribavirina, se desconhece o real impacto do gênero sobre as características que influenciam a eficácia e a segurança da terapia antiviral em portadores de CHC. O objetivo deste estudo foi avaliar a influência do gênero no tratamento da CHC. MÉTODOS: Foi realizado um estudo analítico retrospectivo de portadores de CHC genótipo 1 tratados com Peg-IFN α-2b na dose de 1,5μg/kg ou Peg-IFN α-2a na dose de180μg/sem associado à ribavirina 1.000-1.250 mg/dia, de acordo com o peso, entre 2001 e 2007. RESULTADOS: Entre 181 pacientes submetidos ao tratamento, a média de idade foi de 46,4±11,0 anos e 46 por cento eram mulheres. No pré-tratamento, 32 por cento dos pacientes apresentavam fibrose avançada (F3-F4 Scheuer), e 83 por cento dos indivíduos apresentavam carga viral >400.000IU/mL, sem diferença significativa entre os gêneros (p=0,428 e p=0,452, respectivamente). Quando comparadas aos homens, as mulheres exibiram maior incidência de eventos adversos como anemia (p<0,001) e maior necessidade de redução de dose tanto do Peg-IFN (p=0,004) quanto da ribavirina (p=0,006). Entretanto, as taxas de resposta virológica sustentada (RVS) não diferiram entre os gêneros (45 por cento (mulheres) . vs 41 por cento (homens); p=0,464). CONCLUSÕES: Este estudo sugere que homens e mulheres reagem à terapia combinada de forma diferente, especialmente com relação aos eventos adversos e à necessidade de modificação de dose. No entanto, essas diferenças não influenciam as taxas de RVS.

Cerebral venous thrombosis and hepatitis: case report / Trombose venosa cerebral e hepatite: relato de caso

Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been regarded as a rare associated condition. We report on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.

Dentre as várias causas infecciosas de trombose venosa cerebral (TVC), a hepatite viral tem sido reconhecida como causa rara de TVC. Relatamos sobre um homem de 56 anos com TVC associada a coinfecção pelos vírus B e C da hepatite, ressaltando possíveis mecanismos patogênicos. Sugerimos que sorologia para vírus da hepatite B e C deveria ser solicitado em todos os casos de TVC de origem indeterminada.

Hemorragia digestiva alta / Upper gastrointestinal bleeding

Hemorragia digestiva alta é uma condição grave e potencialmente fatal associada com muitas doenças sistêmicas e gastrointestinais. Embora a mortalidade varia de acordo com a etiologia do sangramento, em geral, é cerca de 10%. Metade desses pacientes têm mais de 60 anos de idade, e neste grupo etário de mortalidade é ainda maior. que podem ser provenientes de várias fontes, principalmente: úlcera péptica, hypertesion portal, anomalias vasculares e neoplasias. Avaliação inicial inclui a estabilização do quadro hemodinâmico e de reposição de sangue sempre que necessário. Endoscopia desempenha um papel importante no diagnóstico e tratamento da maioria das condições de sangramento. O tratamento farmacológico inclui agentes anti-secretores octreotide, e vasopressina. A cirurgia é eventualmente necessário.

Upper gastrointestinal bleeding is a serious and potentially life threatening condition associated with many systemic and gastrointestinal diseases. Although mortality varies according to the etiology of the bleeding, in general, it is around 10%.Half of these patients are over 60 years of age, and in this age group mortality is even higher. it may originate from a number of sources, mainly: peptic ulcer disease, portal hypertesion, vascular anomalies and neoplasms. Initial evaluation includes stabilization of the hemodynamic status and blood replacement whenever necessary. Endoscopy plays an important role in diagnosis and treatment of most bleeding conditions. Pharmacological treatment includes anti-secretory agents, octreotide and vasopressin. Surgery is eventually necessary.

Hemocromatose hereditária: relato de caso e revisão da literatura / Hereditary hemochromatosis: case report and review of the literature

BACKGROUND: HFE-associated hemochromatosis is one of the most common inherited liver disease in Caucasian populations and refers to the association of increased iron stores with tissue damage (e.g., cirrhosis, diabetes, cardiomyopathy), which is progressive when diagnosis and treatment are delayed. AIMS: Description of a case of hereditary hemochromatosis in an asymptomatic 44-years-old patient, whose diagnosis was made through casual identification of abnormal iron markers. We will also present a brief review of the literature about the topic. CONCLUSIONS: Hereditary hemochromatosis is an ideal disease for primary prevention since the disease can be detected well before serious complications develop. This intervention has been shown to prevent the manifestations of the disease, altering its natural history

Correlaçäo entre marcadores séricos e a gravidade histológica da hepatopatia crônica pelo virus C / Correlation between laboratory parameters and histological severity in chronic hepatitis C

O objetivo do estudo foi estabelecer uma possível correlaçäo entre um escore modificado formado por três parâmetros laboratoriais com fibrose avançada e cirrose em pacientes com evidência de hepatite crônica pelo vírus C. Materiais e Métodos: Material obtido por biopsia hepática de 120 pacientes foi estudado. Conforme as alteraçöes histológicas, alocou-se os pacientes em três grupos: aqueles com alteraçöes discretas, com alteraçöes moderadas e com alteraçöes graves. Os três parâmetros laboratoriais foram: plaquetas, razäo ALT/AST e atividades de protombina, os quais foram comparados com resultados da histologia. Resultados: Evidenciou-se uma associaçäo entre o escore e a gravidade histológica na biópsia hepática (p<0,05). Hepatite crônica ativa acentuada e cirrose foram diagnosticadas com 70 por cento de sensibilidade e 95,5 por cento de especificidade utilizando-se como corte 7 pontos. Conclusöes: concluiu-se que o escore formado por três variáveis laboratoriais foi útil para identificar pacientes com hepatite crônica acentuada ou cirrose. Pacientes com valores menores que 7 requerem biópsia hepática para determinar a presença ou näo de cirrose.