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RESUMO Objetivo Verificar se o tratamento com os antivirais de ação direta para a hepatite C provocam efeitos adversos na audição. Métodos A casuística foi composta por 16 indivíduos portadores do vírus da hepatite C, de ambos os gêneros, com média de idade de 51 anos. Foram excluídos do grupo indivíduos com perda auditiva do tipo condutiva ou mista e que apresentassem fatores de risco para perda auditiva. A avaliação foi realizada em dois momentos: antes do uso dos antivirais de ação direta e após o término do tratamento de três meses. Incluiu os seguintes procedimentos: anamnese, inspeção do meato acústico externo, audiometria tonal liminar, limiar de recepção de fala, índice de reconhecimento de fala, medidas de imitância acústica e emissões otoacústicas evocadas por estímulo transiente e produto de distorção. Resultados: Houve baixa ocorrência de zumbido e vertigem. Não houve diferença estatisticamente significativa entre os resultados da avaliação pré-tratamento e pós-tratamento. Conclusão O tratamento com antivirais de ação direta contra o vírus da hepatite C não provocou efeitos adversos na função auditiva.

Introduction and objectives: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. Materials and methods: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). Results: 3939 patients (60% males, mean age 58 ± 10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. Conclusion: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.

Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. Trial Registration: ClinicalTrials.gov NCT03219216.

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.

Introduction: A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients. Material and methods: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters. Results: A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p

The potential role of coffee as a hepatoprotective substance for chronic liver diseases has been widely discussed. Our main aim was to evaluate the effect of coffee intake regarding clinical, biochemical tests and liver biopsy data in treatment naïve patients with chronic hepatitis C. One hundred and thirty-six patients with chronic hepatitis C, diagnosed through liver biopsy, or by means of clinical, ultrasound or endoscopic signs of cirrhosis, were assessed by determination of biochemical tests, metabolic and morphological alterations. Food frequency was scrutinized by using a structured questionnaire. Coffee intake represented more than 90% of the total daily caffeine, and the 75th percentile was 4-Brazilian coffee-cup/day (≥255 mL/day or ≥123 mg caffeine/day). According to caffeine intake, patients were divided into two groups (< or ≥123 mg caffeine/day). Patients with higher ingestion of caffeine had lower serum levels of aspartate aminotransferase (× upper limit of normal) (1.8 ± 1.5 vs 2.3 ± 1.5, p = 0.04), lower frequencies of advanced (F3, F4) fibrosis (23.5% vs 54.5%, p

Background/aims: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Methods: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Results: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59–3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59–12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. Conclusion: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Keywords: Hepatitis C, Insulin resistance, Genotype, Sustained virologic response

CONTEXT: Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. OBJECTIVE: To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. METHODS: One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5. RESULTS: NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. CONCLUSION: HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.CONTEXTO: Pela sua boa correlação com o "clamp" glicêmico, o HOMA-IR tem sido largamente utilizado como índice de resistência insulínica em estudos clínicos e epidemiológicos em pacientes com doença hepática gordurosa não-alcoólica. Porém os valores utilizados para esse parâmetro têm sido muito variáveis. OBJETIVO: Identificar o valor de corte do HOMA-IR que melhor diferencie pacientes com doença hepática gordurosa não-alcoólica não-diabéticos, de um grupo controle. MÉTODOS: Foram estudados 116 pacientes com doença hepática gordurosa não-alcoólica, diagnosticados por critérios clínicos, bioquímicos e de imagem ou biopsia hepática e 88 indivíduos saudáveis, sem doença hepática e com teste de tolerância oral à glicose dentro da normalidade. Esses grupos não diferiam quanto à idade e gênero. Todos foram submetidos ao teste de tolerância oral à glicose e coletadas amostras de sangue para dosagem de glicemia e de insulina através de método imunofluorimétrico. Foi feito o cálculo do HOMA-IR de acordo com fórmula = insulina de jejum (µU/L) x glicemia de jejum (nmol/L)/22.5. RESULTADOS: Os pacientes com doença hepática gordurosa não-alcoólica apresentaram valores mais elevados de insulina, glicemia e HOMA-IR que o grupo controle, mesmo quando excluídos os pacientes com diagnóstico de intolerância à glicose ou de diabetes mellitus pela curva glicêmica. O percentil 75 para HOMA-IR no grupo controle foi de 1.78 e o melhor índice de área sob a curva foi obtido para os valores de HOMA-IR de 2,0 [ASC = 0,840 (0,781-0,899 IC95%), sensibilidade: 85%, especificidade: 83%] enquanto o valor de 2,5 foi o que apresentou melhor especificidade, sem perda importante de sensibilidade [ASC = 0,831 (0.773-0.888) sensibilidade: 72%, especificidade: 94%] . CONCLUSÃO: Valores de HOMA-IR acima ou iguais a 2.0 ou 2.5 mostram elevado valor diagnóstico na distinção entre os doentes com doença hepática gordurosa não-alcoólica e indivíduos do grupo controle.

CONTEXT: Experimental and clinical studies suggest that LOLA may have a favorable influence on hepatic encephalopathy due to the effect on the reduction of ammonia, and improvement of the symptoms and laboratory findings. OBJECTIVES: To evaluate and to critically analyze the efficacy and/or effectiveness results of the use of LOLA when compared to placebo in the treatment of hepatic encephalopathy. DATA SOURCES: LILACS, SciELO, MEDLINE, PubMed database and Cochrane Collaboration Register of Controlled Trials were searched from 1966 to September of 2006. The review has included all the randomized controlled double-blind clinical trials performed in humans in English language. RESULTS: Four studies published between 1993 and 2000 were selected and reviewed. LOLA was showed as being able to reduce hyperammonemia in patients with hepatic encephalopathy, when compared to patients in the placebo group. CONCLUSIONS: Although the trials have shown efficacy of LOLA in reducing hyperammonemia of hepatic encephalopathy, sufficient evidence of a significant beneficial effect of LOLA on patients with hepatic encephalopathy was not found. The studies performed in this area were small, with short follow-up periods and half of them showed low methodological quality.CONTEXTO: Estudos experimentais e clínicos sugerem que a L-ornitina-L-aspartato pode ter uma influência favorável na encefalopatia hepática em virtude do seu efeito na redução da amônia, e melhora dos sintomas e achados laboratoriais. OBJETIVOS: Avaliar e analisar criticamente os estudos de eficácia e/ou efetividade do uso de L-ornitina-L-aspartato quando comparado com placebo no tratamento da encefalopatia hepática. FONTES DE INFORMAÇÃO: Foram pesquisadas as bases de dados LILACS, SciELO, MEDLINE, PubMed e o Registro de Ensaios Controlados da Colaboração Cochrane no período de 1966 até setembro de 2006. A revisão incluiu todos os ensaios clínicos controlados randomizados, duplo-cego, em seres humanos, no idioma inglês. RESULTADOS: Foram selecionados e revisados quatro estudos publicados entre 1993 e 2000, que mostraram que a L-ornitina-L-aspartato foi capaz de reduzir a hiperamonemia em portadores de encefalopatia hepática, quando comparados ao grupo que utilizou placebo. CONCLUSÕES: Embora os estudos tenham demonstrado eficácia da L-ornitina-L-aspartato em reduzir a hiperamonemia da encefalopatia hepática, não foi encontrada evidência suficiente que a L-ornitina-L-aspartato tenha um efeito clínico benéfico significativo em pacientes com encefalopatia hepática. Os ensaios realizados neste campo foram pequenos com períodos curtos de acompanhamento e a metade deles com baixa qualidade metodológica.

OBJETIVO: Revisar a importância da resistência insulínica no desenvolvimento da hepatite C crônica e sua interferência na resposta ao tratamento antiviral de pacientes infectados pelo vírus da hepatite C. FONTE DE DADOS: Revisão bibliográfica de trabalhos publicados pelo MEDLINE e dados dos próprios autores. SÍNTESE DE DADOS: Nos últimos anos, grande número de publicações tem demonstrado importante associação entre resistência insulínica e hepatite C crônica. Aumento na prevalência de diabetes mellitus tipo 2, desenvolvimento de esteatose hepática (principalmente nos pacientes com infecção pelo genótipo não-3), progressão mais rápida da doença e redução na taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina, têm sido todos associados à presença de resistência insulínica nos pacientes infectados pelo vírus da hepatite C. A produção aumentada de fator de necrose tumoral pelo core do vírus da hepatite C é o principal mecanismo responsável pelo aparecimento da resistência insulínica. O fator de necrose tumoral afetaria a fosforilação do substrato do receptor de insulina diminuindo a captação de glicose e acarretando hiperinsulinemia compensatória. Aumento da siderose hepática e alterações dos níveis circulantes das adipocitocinas podem ter efeito adicional sobre a sensibilidade à insulina na hepatite C crônica. CONCLUSÕES: O diagnóstico e o tratamento da resistência insulínica nesses pacientes podem não só evitar o aparecimento das complicações, mas também prevenir a progressão da doença e, possivelmente, aumentar a taxa de resposta virológica sustentada ao tratamento com interferon peguilado e ribavirina.OBJECTIVE: To revise the importance of insulin resistance in the development of chronic hepatitis C and its interference in the response to the antiviral treatment of these patients. DATA SOURCE: Bibliographic revision of published papers in the MEDLINE and the authors’ data. DATA SYNTHESIS: In the last years several published papers have demonstrated an important relationship between insulin resistance and chronic hepatitis C. Increased prevalence of type 2 diabetes mellitus, the development of hepatic steatosis (specially in non-3 genotype), a more rapid progression of hepatic disease and reduction in the sustained virological response to treatment with pegylated interferon plus ribavirin have been associated with insulin resistance in patients infected with HCV. The mechanism implied in the insulin resistance is the enhanced production of tumor necrosis factor by the HCV core. Tumor necrosis factor affects insulin receptor substrate phosphorylation, resulting in decreased glucose uptake and compensatory hyperinsulinemia. Increased liver iron accumulation and modification in the levels of adipocytokinemia can have an additional effect on insulin sensitivity in chronic C hepatitis. CONCLUSIONS: Diagnosing and treating insulin resistance in patients with chronic hepatitis C could not only avoid complications but also prevent disease progression and increased the sustained virological rate to treatment with pegylated interferon plus ribavarin.

INTRODUCTION: The main extra-hepatic manifestation of hepatitis C is mixed cryoglobulinemia (MC). The aim of this study was to evaluate its prevalence among patients with chronic hepatitis C (CHC), to correlate its presence to host and virological variables and to the response to combined therapy with interferon-alpha and ribavirin. CASUISTIC AND METHODS: 202 CHC naive patients (136 with chronic hepatitis and 66 with cirrhosis) were consecutively evaluated for the presence of cryoglobulins. Cryoprecipitates were characterized by immunoelectrophoresis and classified according to the Brouet's criteria. RESULTS: The prevalence of MC was 27% (54/202), and 24% of them (13/54) showed major clinical manifestation of the disease. Even though type III MC was more frequent (78%), symptomatic MC was more common in type II MC. The presence of cirrhosis (RR = 2.073; IC95% = 1.029 - 4.179; p = 0.041), and age of the patients (RR = 1.035; IC95% = 1.008 - 1.062; p = 0.01) were independently associated with the presence of cryoglobulins. No relationship was found with viral load and genotype. 102 patients were treated with interferon alpha and ribavirin. Among these, 31 had MC. Sustained virological response (around 30%) was similar in patients with and without MC (p = 0.971). CONCLUSION: MC represents a prevalent complication in patients with CHC, specially older and cirrhotic patients. Only 24% of these patients show clinical manifestation of the disease, specially those with type II MC. The presence of MC did not affect the response to therapy.INTRODUÇÃO: A crioglobulinemia mista (CM) representa importante complicação extra-hepática da hepatite C. Nesse estudo avaliamos sua prevelência em pacientes com hepatite C crônica (HCC) e relacionamos sua presença com aspectos clínicos e resposta ao tratamento com interferon alfa e ribavirina. CASUÍSTICA E MÉTODOS: 202 pacientes consecutivos com HCC (136 com hepatite crônica e 66 com cirrose) foram avaliados para a presença de CM. Os crioprecipitados foram caracterizados por imunoeletroforese e classificados de acordo com BROUET et al. RESULTADOS: A prevalência de CM nessa população foi de 27% (54/202), e, desses, 24% (13/54) apresentaram manifestações clínicas maiores da doença. Embora MC tipo III tenha sido a forma mais freqüentemente encontrada, a doença sintomática foi mais comum entre os pacientes com MC tipo II. A presença de cirrose (RR = 2,073; IC95% = 1,029 - 4,179; p = 0,041) e a idade do paciente (RR = 1,035; IC95% = 1,008 - 1,062; p = 0,01) estiveram independentemente associadas à presença de CM. Não houve associação entre a presença de CM e genótipo ou carga viral do vírus C. No total, 102 pacientes foram tratados com interferon alfa e ribavirina. Desses, 31 apresentavam CM. A resposta virológica sustentada (em torno de 30%) não diferiu entre pacientes com e sem CM (p = 0,971). CONCLUSÃO: CM é uma freqüente complicação na HCC, especialmente em pacientes com idade avançada e com cirrose hepática. Apenas 24% desses pacientes apresentam manifestações clínicas da doença, sendo mais freqüentes entre portadores de CM tipo II. A presença de crioglobulinemia não afetou a resposta virológica ao tratamento com interferon alfa e ribavirina.

BACKGROUD: Protein-calorie malnutrition is a frequent finding in patients with chronic liver disease, but investigations of nutritional status have been rarely performed in individuals seen at outpatient clinics AIM: To evaluate the nutritional status of patients with alcoholic and nonalcoholic cirrhosis, attended for the first time at a reference outpatient clinic for liver diseases. PATIENTS AND METHODS: A total of 300 consecutive patients attended at the outpatient clinics of a reference center for liver diseases were investigated. Anthropometric evaluation was performed by the usual parameters: triceps skinfold, arm circumference and arm muscle circumference. Biochemical parameters included creatinine/height index, serum albumin and lymphocytes count. The nutritional diagnosis was based on the PCM score proposed by Mendenhall et al. Food intake was retrospectively evaluated using 24-hour dietary recall data. RESULTS: About 71% of the patients studied were chronic alcohol abusers, whereas in 29% cirrhosis was of nonalcoholic etiology. Independently of the disease etiology 75.3% of the patients showed some degree of protein-calorie malnutrition, which was moderate or severe in 38.3% of them. More advanced protein-calorie malnutrition degrees were associated with lower energy and protein intake. The prevalence of moderate or severe protein-calorie malnutrition was higher in patients classified as Child-Pugh C than in patients classified as Child-Pugh A (21% x 58%, respectively). Regarding sexual differences, fat reserves, evaluated by triceps skinfold, were more depleted in females than in males (48.6% x 26.6%) regardless of the etiology of the cirrhosis, whereas muscle reserves (arm muscle circumference) were more depleted in males (43.4% x 13.4%) regardless of the etiology of cirrhosis. In contrast, cirrhosis of alcoholic etiology was determinant in reducing arm muscle circumference in females (20% x 9.1%) CONCLUSIONS: These data highlight the high prevalence of protein-calorie malnutrition occurring early in the natural history of the disease and accompanying functional hepatic deterioration. In addition, attention should be paid to the different gender patterns of response to protein-calorie malnutrition in these patients.RACIONAL: A desnutrição calórica e protéica é achado freqüente em pacientes com doença hepática. Poucas investigações da desnutrição calórica e protéica têm sido realizadas em pacientes atendidos em ambulatório OBJETIVO: Avaliar o estado nutricional de pacientes com cirrose hepática (alcoolistas e não-alcoolistas), atendidos na primeira consulta em ambulatório de referência para doenças hepáticas. PACIENTES E MÉTODOS: Trezentos pacientes consecutivamente atendidos pela primeira vez em ambulatório de doenças hepáticas foram incluídos neste estudo. Os mesmos foram submetidos a avaliação nutricional que constou de antropometria: dobra cutânea do tríceps, circunferência do braço e circunferência muscular do braço, e bioquímica: índice creatinina/altura, albumina sérica e contagem total de linfócitos. O diagnóstico do estado nutricional foi baseado pelo escore de desnutrição calórica e protéica proposto por Mendenhall e colaboradores e a ingestão alimentar por recordatório de 24 h RESULTADOS: Setenta e um porcento dos pacientes cirróticos estudados foram de causa alcoólica e 29% não-alcoólica. Independentemente da causa, a prevalência de desnutrição calórica e protéica foi de 75,3%, sendo que 38.3% deles já a apresentavam moderada e grave. Os pacientes com desnutrição calórica e protéica moderada e grave apresentavam pior ingestão de proteína e energia. A prevalência de moderada e grave foi mais elevada nos pacientes classificados como Child-Pugh C do que nos pacientes classificados como Child-Pugh A (21% x 58%, respectivamente). Em função das variáveis sexo e causa, as reservas de gordura, avaliadas pela dobra cutânea do tríceps, estiveram mais depletadas em mulheres cirróticas que nos homens cirróticos (48,6% x 26,6%). Já as reservas musculares, avaliadas por circunferência muscular do braço, estiveram mais depletadas em homens cirróticos (43,4% x 13,4%), independentemente da causa da cirrose. Em contraste, mulheres cirróticas alcoólicas apresentaram maior redução de circunferência muscular do braço que nas mulheres não-alcoólicas (20% x 9,1%) CONCLUSÕES: Os pacientes cirróticos já apresentavam elevada prevalência de desnutrição calórica e protéica na primeira consulta em ambulatório, principalmente nos pacientes com piora da função hepática. A variável sexo é outro aspecto que deve ser enfocado pois influenciou aspectos antropométricos (circunferência muscular do braço e dobra cutânea do tríceps) nesses pacientes.

RACIONAL: O teste respiratório da metacetina marcada com carbono 13 (13C-metacetina) é método não-invasivo que permite examinar a função hepática microssomal, permitindo avaliação quantitativa da massa hepática funcional. OBJETIVO: Avaliar a utilidade clinica do teste respiratório da 13C-metacetina na avaliação de pacientes com doença crônica do fígado pelo vírus da hepatite C. CASUÍSTICA E MÉTODOS: Setenta e oito pacientes com hepatite crônica C e 13 indivíduos saudáveis pareados por sexo e idade foram estudados. Pacientes infectados cronicamente pelo vírus C foram classificados como portadores de hepatite crônica (n = 51) ou cirrose hepática (n = 27, sendo 7 deles classificados como descompensados pela presença de ascite, icterícia e/ou encefalopatia). Pacientes co-infectados HbsAg/HIV, em uso crônico de álcool, com outras doenças crônicas ou em uso de medicamentos que pudessem interferir com a atividade do citocromo P450, foram excluídos. O estádio e a atividade da doença nos fragmentos de biopsia foram determinados de acordo com os critérios da Sociedade Brasileira de Hepatologia. O teste respiratório da 13C-metacetina foi realizado com 75 mg de 13C-metacetina e a concentração de 13CO2 no ar expirado foi medido através de espectrometria infravermelha não dispersiva. Foram calculados o "delta over baseline" e o percentual de recuperação cumulativo do 13CO2 aos 40 (teste respiratório da 13C-metacetina 40 min) e aos 120 minutos (teste respiratório da 13C-metacetina 120 min). RESULTADOS: Os parâmetros do teste respiratório da 13C-metacetina se correlacionaram com avaliação estrutural histológica, mas não com a atividade necroinflamatória no tecido hepático, sendo que a melhor correlação foi obtida entre o grau de estádio e o teste respiratório da 13C-metacetina 120 min. Os valores médios do teste respiratório da 13C-metacetina 120 min foram significantemente mais reduzidos nos grupos cirróticos (19,2 ± 7,1% para cirróticos compensados e 14,7 ± 4,0% para os cirróticos descompensados) que nos grupos controle (29,9 ± 4,5%) e com hepatite crônica (27,8 ± 6,1%). A melhor acurácia no diagnóstico de cirrose entre os portadores de hepatite crônica C foi encontrada para o teste respiratório da 13C-metacetina 120 min com 81% de sensibilidade e 77% de especificidade. CONCLUSÃO: O teste respiratório da 13C-metacetina se correlaciona com alterações estruturais encontradas na hepatite crônica pelo vírus C e o percentual de recuperação de 13CO2 aos 120 minutos é um sensível parâmetro para identificar a presença de cirrose nesses pacientes.BACKGROUND: The 13C-methacetin breath test is a non-invasive method to evaluate hepatic microssomal function that allows a quantitative assessment of the functional hepatic mass. AIM: To evaluate the clinical usefulness of the 13C-methacetin breath test in patients with hepatitis C chronic liver disease. PATIENTS AND METHODS: Seventy eight patients with chronic hepatitis C and 13 matched healthy controls were studied. HCV patients were classified as having chronic hepatitis (n = 51), cirrhosis (n = 27), being seven with decompensated disease (presence of ascite, jaundice and/or encephalopathy). HbsAg/HIV co-infected patients, chronic alcohol drinker, having other chronic diseases and those using drugs that could interfere with hepatic cytochrome P450, were excluded. The disease stage and activity in biopsy fragments were determined according the Brazilian Society of Hepatology criteria. Breath test was performed with 75 mg of 13C-methacetin, and the 13CO2 in the expired air was measured through a nondispersive infra red spectrometry. The delta over baseline, and the cumulative recovery of 13CO2 at 40 (13C-methacetin breath test 40 min) and 120 minutes (13C-methacetin breath test 120 min) were calculated. RESULTS: 13C-methacetin breath test parameters correlate only with hepatic staging but not with necroinflammatory (activity) parameters, being the best correlation found between hepatic staging and the 13C-methacetin breath test 120 minutes. The mean values for 13C-methacetin breath test 120 min was significantly reduced in the cirrhotic groups (19.2 ± 7.1% for compensated and 14.7 ± 4.0% for decompensated cirrhotics) than in control (29.9 ± 4.5%) and chronic hepatitis (27.8 ± 6.1%) groups. The best diagnostic accuracy for the diagnosis of cirrhosis among HCV patients was found for 13C-methacetin breath test 120 min with 81% of sensibility and 77% of specificity. CONCLUSION: 13C-methacetin breath test is correlated with structural changes in HCV-related chronic hepatic diseases and the cumulative recovery at 120 minutes is a sensitive parameter to identify the presence of hepatic cirrhosis in these patients.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pa-thophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

ABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.

ABSTRACT Space-occupying lessions of the liver may be cystic or solid. Ultrasonography is an extremely useful method for initial screening, and suffices for diagnosis of simple hepatic cysts. Complex cysts and solid masses require computed tomography or magnetic resonance imaging for confirmation. Wide surgical excision is indicated in cystadenoma or cystadenocarcinoma. Clinical and epidemiological data are important, as nodules in noncirrhotic livers are more likely to be benign. Hemangiomas, the most common benign tumors, require no follow-up after diagnostic confirmation if they are small and asymptomatic. Patients with giant, symptomatic hemangiomas or compression of adjacent structures should be referred to hepatobiliary centers for potential surgery. The genetic heterogeneity of hepatocellular adenoms and their epidemiology and prognosis prompted classification of these tumors into four subtypes based on histology and immunohistochemistry. The major complications of hepatocellular adenoms are rupture with bleeding and malignant transformation. Rupture occurs in approximately 30% of cases. The main risk factors are tumors size >5 cm and inflammatory subtype. Hepatocellular adenoms may enlarge during pregnancy due to marked hormonal stimulation. As oral contraceptive pills and anabolic steroids have associated with hepatocellular adenoms growth, particularly of the hepatocyte nuclear factor-1 alfa subtype, these drugs should be discontinued. Focal nodular hyperplasia is the second most common benign tumor of hte liver. It is most frequent in women aged 20 to 60, and 70% to 90% of cases are asymptomatic. In the adsence of a central scar and/or other hallmarks of Focal nodular hyperplasia, with uncertainty between this diagnosis and hepatocellular adenoma, liver-specific contrast agentes are indicated.

ABSTRACT Survival rates of critically ill patients with liver disease has sharply increased in recent years due to several improvements in the management of decompensated cirrhosis and acute liver failure. This is ascribed to the incorporation of evidence-based strategies from clinical trials aiming to reduce mortality. In order to discuss the cutting-edge evidence regarding critical care of patients with liver disease, a joint single topic conference was recently sponsored by the Brazilian Society of Hepatology in cooperation with the Brazilian Society of Intensive Care Medicine and the Brazilian Association for Organ Transplantation. This paper summarizes the proceedings of the aforementioned meeting and it is intended to guide intensive care physicians, gastroenterologists and hepatologists in the care management of patients with liver disease.

The combined therapy with interferon alfa plus ribavirin (INF+RBV) is considered the most appropriate treatment for patients with chronic hepatitis C virus genotypes 2 and 3 in Brazil. However, wide variations in the rates of sustained viral response (SVR) have been reported among such patients. We evaluated, retrospectively, factors associated with SVR in subjects with chronic hepatitis C virus genotypes 2 and 3 and that received medication from the Health Secretariat of the state of São Paulo. One-hundred-seventy-seven consecutive patients with chronic hepatitis C were treated for 24 or 48 weeks according to the viral genotype. Patients co-infected with associated hepatic diseases or who had problems with alcohol abuse were excluded. The genotype of the HCV-RNA was identified through restriction analysis, the viral load through quantitative PCR (Amplicor, Roche) and the degree of hepatic fibrosis according to the Metavir score. Demographic, virological and histological parameters were submitted to binary logistic regression analysis to identify the variables associated with SVR. The overall rate of SVR was 36.4% for the 177 patients, and genotype 2 or 3 was the main parameter independently associated with SVR. Among the 77 patients with these viral genotypes, only the stage of fibrosis had a significant effect on the SVR (odds ratio (OR) = 3.035; 95% CI (confidence interval) = 1.196-7.699; p=0.019). The rate of SVR among the subjects with fibrosis at an advanced stage (F3-F4) was 38%, compared to 75% for patients with fibrosis at an initial stage (F0-F2). Consequently, other therapeutic options should be considered for patients with genotypes 2 and 3 who have advanced fibrosis.

ABSTRACT BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.

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.

BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. METHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCVRNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. RESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. CONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease worldwide. Approximately 20% of individuals with NAFLD develop nonalcoholic steatohepatitis (NASH), which is associated with increased risk of cirrhosis, portal hypertension, and hepatocellular carcinoma. Intestinal microflora, including small intestinal bacterial overgrowth (SIBO), appear to play an important role in the pathogenesis of the disease, as demonstrated in several clinical and experimental studies, by altering intestinal permeability and allowing bacterial endotoxins to enter the circulation. OBJECTIVE: To determine the relationship between SIBO and endotoxin serum levels with clinical, laboratory, and histopathological aspects of NAFLD and the relationship between SIBO and endotoxin serum levels before and after antibiotic therapy. METHODS: Adult patients with a histological diagnosis of NAFLD, without cirrhosis were included. A comprehensive biochemistry panel, lactulose breath test (for diagnosis of SIBO), and serum endotoxin measurement (chromogenic LAL assay) were performed. SIBO was treated with metronidazole 250 mg q8h for 10 days and refractory cases were given ciprofloxacin 500 mg q12h for 10 days. RESULTS: Overall, 42 patients with a histopathological diagnosis of NAFLD were examined. The prevalence of SIBO was 26.2%. Comparison of demographic and biochemical parameters between patients with SIBO and those without SIBO revealed no statistically significant differences, except for use of proton pump inhibitors, which was significantly more frequent in patients with positive breath testing. The presence of SIBO was also associated with greater severity of hepatocellular ballooning on liver biopsy. Although the sample, as a whole, have elevated circulating endotoxin levels, we found no significant differences in this parameter between the groups with and without SIBO. Endotoxin values before and after antibiotic treatment did not differ, even on paired analysis, suggesting absence of any relationship between these factors. Serum endotoxin levels were inversely correlated with HDL levels, and directly correlated with triglyceride levels. CONCLUSION: Serum endotoxin levels did not differ between patients with and without SIBO, nor did these levels change after antibacterial therapy, virtually ruling out the possibility that elevated endotoxinemia in non-cirrhotic patients with NAFLD is associated with SIBO. Presence of SIBO was associated with greater severity of ballooning degeneration on liver biopsy, but not with a significantly higher prevalence of NASH. Additional studies are needed to evaluate the reproducibility and importance of this finding in patients with NAFLD and SIBO.