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

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

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

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

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.

Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. 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 containing the recommendations of the Brazilian Society of Hepatology.

RESUMO O carcinoma hepatocelular é uma neoplasia de importância global e associada a altos índices de mortalidade. Recentes avanços no diagnóstico e tratamento da doença tornaram necessárias que se atualizassem as recomendações sobre o manejo da doença. Para definir as recomendações sobre o diagnóstico e tratamento do carcinoma hepatocelular, a Sociedade Brasileira de Hepatologia organizou uma reunião monotemática em João Pessoa (PB). Todos expositores foram solicitados a fazer uma revisão sistemática da literatura e apresentar os temas relacionados a fatores de risco para o desenvolvimento de carcinoma hepatocelular, métodos para rastreamento, diagnóstico radiológico e sistemas de estadiamento da doença, tratamentos curativos e paliativos e carcinoma hepatocelular em fígado não cirrótico. Após o encontro, todos os expositores se reuniram para discussão dos tópico e elaboração dessas recomendações. O texto resultante foi ainda submetido a avaliação e aprovação por todos membros da Sociedade através de sua homepage. O documento atual é a versão final que contêm as recomendações da Sociedade Brasileira de Hepatologia.

Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.

Disease burden of chronic hepatitis C in Brazil

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective.Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2).Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n= 325,900) and decompen- sated (n= 45,000) cirrhosis; hepatocellular carcinoma (n= 19,100); and liver-related deaths (n= 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively.Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

Efeito da terapia com interferon peguilado e ribavirina sobre o estado nutricional de pacientes com infecção crônica pelo vírus C / Effect of therapy with pegylated interferon and ribavirin on the nutritional status of patients with chronic hepatitis C virus infection

Introdução: A hepatite C afeta cerca 3% da população mundial. No Brasil este percentual varia entre 1% e 2%. O tratamento com melhor resposta é realizado através da terapia combinada de interferon peguilado (PegINF) e ribavirina (RBV). Aproximadamente 10% a 20% desses pacientes apresentam os efeitos adversos da terapia. O estado nutricional tem sido reconhecido como um indicador com valor prognóstico para estes pacientes. Objetivo: O objetivo do trabalho foi avaliar o estado nutricional de pacientes com infecção crônica pelo vírus C submetidos à terapia antiviral combinada de PegINF e RBV. Métodos: A amostra foi constituída de 29 pacientes com idade entre 18 e 70 anos, ambos os sexos, com diagnóstico de hepatite C, em tratamento com PegINF e RBV, sendo acompanhados em ambulatório. Os parâmetros para avaliação nutricional foram: avaliação subjetiva global adaptada para hepatopatas, antropometria (peso, estatura, IMC, dobra cutânea tricipital, circunferência do braço e circunferência muscular do braço) e parâmetros bioquímicos (glicose e hemoglobina). Resultados: Durante a terapia 93,1% dos pacientes perderam peso. Quanto à reserva adiposa 100% dos pacientes do sexo masculino eram eutróficos, já no sexo feminino 25% apresentavam desnutrição. Quanto ao compartimento proteico somático 84,6% dos pacientes do sexo masculino apresentavam desnutrição, enquanto no sexo feminino 37,5%. Observou-se perda de peso maior nos pacientes com depressão e náuseas. Conclusão: Considerando o estado nutricional destes pacientes é importante estimular o diagnóstico e tratamento nutricional visando diminuir a frequência e/ou gravidade dos efeitos colaterais e melhora da resposta ao tratamento...

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

A single nucleotide polymorphism, rs129679860, in the IL28B locus is associated with the viral kinetics and a sustained virological response in a chronic, monoinfected hepatitis C virus genotype-1 Brazilian population treated with pegylated interferon-ribavirin

Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been associated with a sustained virological response (SVR) in interferon-ribavirin (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European and African populations. In this study, the genotype frequency of two IL28B SNPs (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in Brazil was evaluated and the SNP sufficient to predict the treatment response outcome was determined. A total of 66 naïve genotype-1 chronic HCV-infected patients were genotyped and the associated viral kinetics and SVR were assessed. The overall SVR was 38%. Both the viral kinetics and SVR were associated with rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However, rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG = 18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860, successfully predicts SVR in the IFN-RBV treatment of HCV.

Hepatitis B virus genotypes in Southeast Brazil and its relationship with histological features

Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.

Encefalopatia hepática: relatório da 1ª reunião monotemática da Sociedade Brasileira de Hepatologia / Hepatic encephalopathy: report 1st monothematic meeting of the Brazilian Society

A encefalopatia hepática (EH) é um distúrbio funcional do sistema nervoso central (SNC) associado à insufi ciência hepática, de fisiopatologia multifatorial e complexa. Devido aos avanços no conhecimento sobre o manejo da EH na cirrose e na insuficiência hepática aguda (IHA), a diretoria da Sociedade Brasileira de Hepatologia (SBH) promoveu uma reunião monotemática acerca da fi siopatologia, diagnóstico e tratamento da EH, abordando aspectos controversos relacionados ao tema. Com a utilização de sistemática da medicina baseada em evidências, foram abordados o manejo da EH e da hipertensão intracraniana na IHA, o manejo da EH episódica na cirrose, as controvérsias no manejo da EH e a abordagem da EH mínima. O objetivo desta revisão é resumir os principais tópicos discutidos na reunião monotemática e apresentar recomendações sobre o manejo da síndrome votadas pelo painel de expertos da SBH.

Hepatic encephalopathy (HE) is a functional disorder of the central nervous system (CNS) associated with liver failure, either end-stage chronic liver disease or fulminant hepatic failure. Its pathogenesis remains complex and poorly understood. In view of recent advances in the management of HE, the Brazilian Society of Hepatology endorsed a monothematic meetingregarding HE in order to gather experts in the to discuss related data and to draw evidence-based recommendations concerning: management of HE and intracranial hypertension in FHF, treatment of episodic HE in cirrhosis, controversies in the management of EH including difficult to treat cases and diagnostic and treatment challenges for minimal HE. The purpose of this review is to summarize the lectures and recommendations made by the panel of experts of the Brazilian Society of Hepatology.

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

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

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

Gastroesophageal reflux in cirrhotic patients with esophageal varices without endoscopic treatment

BACKGROUND: Portal hypertension in patients with liver cirrhosis causes manifestations such as esophageal varices, ascites and edema. Some studies have been conducted about the role of esophageal varices in the development of esophageal motor disorders and abnormal gastroesophageal reflux in these patients. Ascites could be a factor promoting gastroesophageal reflux and it has been questioned whether reflux would favor the rupture of varices. However there are a few studies using ambulatory esophageal pH recording in the evaluation of these patients. AIMS: Evaluate gastroesophageal reflux by pH recording in cirrhotic patients with esophageal varices and possible predictors. METHODS: Fifty one patients (28 men, 23 women, mean age of 54 years) with liver cirrhosis, diagnosed by clinical, laboratorial, image and histological findings were prospectively evaluated. All patients had esophageal varices confirmed by endoscopy and were submitted to a questionnaire about typical gastroesophageal reflux disease symptoms (heartburn and or acid regurgitation). pH recording was performed with the probe placed 5 cm above the superior lower esophageal sphincter limit, as determined by manometry. Abnormal reflux ( percent total time with pH < 4 >4.5 percent) was related to the size of varices, congestive gastropathy, ascites, severity of cirrhosis and typical gastroesophageal reflux disease symptoms. RESULTS: The caliber of the varices was considered to be small in 30 patients (59 percent), medium in 17 (33 percent) and large in 4 (8 percent), 21 (41 percent) congestive gastropathy. Ascites was observed in 17 (33 percent), 32 patients (63 percent) were classified as Child-Pugh A, 17 (33 percent) Child-Pugh B and 2 (4 percent) Child-Pugh C. Twenty seven patients (53 percent) presented with typical gastroesophageal reflux disease symptoms. Abnormal reflux at pH recording was found in 19 patients (37 percent). One of them presented with erosive esophagitis...

RACIONAL: A hipertensão porta que acomete os pacientes com cirrose hepática é causa de varizes de esôfago, ascite e edema. Alguns estudos têm sido realizados para avaliar a importância das varizes de esôfago no desenvolvimento dos distúrbios motores esofagianos e do refluxo gastroesofágico anormal neste grupo de pacientes. A ascite pode ser um fator promotor de refluxo gastroesofágico e tem sido questionado se o refluxo anormal poderia favorecer a rotura das varizes de esôfago. Entretanto, são poucos os estudos que utilizam a pHmetria esofagiana prolongada ambulatorial na avaliação destes pacientes. OBJETIVO: Avaliar a presença de refluxo anormal a pHmetria esofagiana prolongada ambulatorial em pacientes cirróticos com varizes de esôfago e seus possíveis fatores preditivos. MÉTODOS: Cinqüenta e um pacientes (28 homens, 23 mulheres, média de idade de 54 anos) com cirrose hepática diagnosticada por métodos clínicos, laboratoriais, de imagem e histopatológicos foram avaliados de forma prospectiva. Todos os pacientes apresentavam varizes de esôfago à endoscopia digestiva alta e foram submetidos a um questionário para avaliação da presença de sintomas típicos da doença do refluxo gastroesofágico (pirose e/ou regurgitação ßcida). pHmetria esofagiana prolongada ambulatorial foi realizada posicionando-se o cateter 5 cm acima do limite superior do esfíncter esofagiano inferior, determinado previamente pela esofagomanometria. Refluxo anormal ( por cento tempo total com pH < 4 >4,5 por cento) foi relacionado com o tamanho das varizes, gastropatia congestiva, ascite, gravidade da cirrose e presença de sintomas típicos da doença do refluxo gastroesofágico. RESULTADOS: O calibre das varizes foi considerado pequeno em 30 pacientes (59 por cento), médio em 17 (33 por cento) e grosso em 4 (8 por cento), 21 (41 por cento) gastropatia congestiva. Ascite foi observada em 17 (33 por cento); 32 pacientes (63 por cento) foram classificados com Child-Pugh...

Weight-based combination therapy with peginterferon alpha-2b and ribavirin for Naïve, relapser and non-responder patients with chronic hepatitis C

Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54 percent for naïve, 62 percent for relapser and 38 percent for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67 percent) compared to those with genotype 1 (45 percent). In relapsers and non-responders, SVR was, respectively, 69 percent and 24 percent in patients with genotype 1 and 43 percent and 73 percent in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (< 65 kg, 65-85 kg and > 85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78 percent, 81 percent and 58 percent of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63 percent, 67 percent and 61 percent, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13 percent of the patients, due to loss to follow-up, hematological abnormalities or depression.

Vitamin A metabolic aspects and alcoholic liver disease

The liver is a strategic organ in the metabolism of macro and micronutrients; when its functioning is compromised, it may cause some change in the nutritional status of vitamin A. The purpose of this article is to review scientific evidence in literature on the liver metabolism of vitamin A, the role of ethanol and retinol interactions on hepatic morphology, besides the alterations in the metabolism of this vitamin in alcoholic liver disease. Data were collected from Medline database. The liver is the main organ responsible for the storage, metabolism and distribution of vitamin A to peripheral tissues. This organ uses retinol for its normal functioning such as cell proliferation and differentiation. This way, vitamin A deficiency seems to alter liver morphology. Patients with alcoholic liver disease have been found to have low hepatic levels of retinol in all stages of their disease. In alcoholic liver disease, vitamin A deficiency may result from decreased ingestion or absorption, reduction in retinoic acid synthesis or increased degradation. Long-term alcohol intake results in reduced levels of retinoic acid, which may promote the development of liver tumor. So, in chronic alcoholic subjects, vitamin A status needs to be closely monitored to avoid its deficiency and clinical effects, however its supplementation must be done with caution since the usual dose may be toxic for those who consume ethanol.

O fígado é um órgão estratégico no metabolismo de macro e de micronutrientes e, portanto, é de esperar que o comprometimento de sua função seja acompanhado de alterações no estado nutricional de vitamina A. O objetivo deste artigo é revisar na literatura evidências científicas sobre o metabolismo hepático da vitamina A, o efeito das interações entre a vitamina A e o etanol sobre a morfologia hepática, além das alterações do metabolismo dessa vitamina na doença hepática alcoólica. Os dados foram selecionados na base de dados Medline no período de 1979 a 2005. O fígado é o principal órgão responsável pelo armazenamento, metabolismo e distribuição da vitamina A para os tecidos periféricos. Esse órgão utiliza retinol para seu funcionamento normal como proliferação e diferenciação celular. Dessa forma, a deficiência dessa vitamina parece alterar a morfologia hepática. Baixos níveis de retinol hepático têm sido encontrados em todos os estágios da doença hepática alcoólica. A deficiência de vitamina A na doença hepática alcoólica pode resultar da diminuição da sua ingestão ou absorção, na redução da síntese de ácido retinóico ou na diminuição da sua degradação. A ingestão crônica de álcool resulta em níveis reduzidos de ácido retinóico, o que favorece a formação de tumor hepático. Logo, em etilistas crônicos o estado nutricional de vitamina A deve ser monitorado, para evitar sua deficiência e seus sintomas clínicos, embora a suplementação deva ser feita com cautela, pois doses comumente usadas podem ser tóxicas para aqueles que consomem etanol.

Hepatites / Hepatitis

É um estudo aprofundado das hepatites virais, em sua epidemiologia, clínica e no diagnóstico e tratamento das formas agudas e crônicas. As hepatites virais B e C são abordadas também em situações especiais, como no paciente renal crônico, no pós-transplante, nas co-infecções HIV-VHC, HIV-VHB e nas hepatites agudas com evolução para formas fulminantes. Questões relevantes e atuais sobre a esteatoepatite não-alcoólica, hepatites medicamentosas, hepatites alcoólica e auto-imune, que podem ter evolução para formas graves, com desenvolvimento de cirrose hepática, são relevantes nesta obra. Em capítulo especial é analisado o carcinoma hepatocelular, visto sua elevada frequência e relação com as hepatites virais (VHB e VHC).

Alterações da motilidade esofagiana em pacientes cirróticos com varizes de esôfago não submetidos a tratamento endoscópico / Esophageal motor disorders in cirrhotic patients with esophageal varices non-submitted to endoscopic treatment

RACIONAL: A cirrose hepática apresenta como uma das principais causas de morbimortalidade, a hipertensão porta com o desenvolvimento de varizes esofagianas, possibilidade de hemorragia digestiva alta e agravamento da insuficiência hepática. É importante identificar fatores preditivos causais ou agravantes desta condição e se possível, preveni-los. Nos últimos anos tem se observado a associação de distúrbios motores de esôfago e de refluxo gastroesofágico em pacientes cirróticos com varizes de esôfago. OBJETIVOS: Estudar a prevalência dos distúrbios de motilidade esofagiana e, entre eles, da motilidade esofagiana ineficaz, neste grupo de pacientes e seus possíveis fatores preditivos. MÉTODOS: Avaliaram-se de maneira prospectiva, 74 pacientes com cirrose hepática e varizes esofagianas diagnosticadas por endoscopia digestiva alta, virgens de tratamento endoscópico terapêutico. Todos foram submetidos a um protocolo de investigação clínica, a esofagomanometria e 55 pacientes também realizaram pHmetria esofagiana ambulatorial. RESULTADOS: Alterações da motilidade esofagiana foram observadas em 44 pacientes (60 por cento), sendo a mais prevalente a motilidade esofagiana ineficaz, verificada em 28 por cento. Refluxo anormal foi encontrado em 35 por cento dos pacientes. Não houve correlação entre anormalidade manométrica em geral e motilidade esofagiana ineficaz, em particular, e a presença de sintomas esofagianos ou típicos de doença do refluxo, refluxo anormal, a gravidade da doença, a presença de ascite e o calibre das varizes. CONCLUSÕES: A maioria dos cirróticos com varizes esofagianas não submetidos a tratamento endoscópico apresenta distúrbios motores do esôfago, sem fatores preditivos identificáveis. A importância clínica desses achados necessita de maior aprofundamento na questão, para elucidar seu papel definitivo.

Prevalence of hepatitis C virus and evaluation of associated risk factors in a group of Braziliam patients with inflammatory bowel disease

Objective: To evaluate the prevalence of the hepatitis C virus (HCV) infection and associated risk factors in patients with inflammatory bowel disease followed at the University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro (HUCFF-UFRJ). Methods: A total of 146 patients were studied, 58 with Crohn's disease and 88 with ulcerative colitis, with a mean age of 40 years. The results were correlated with the following variables: time elapsed since diagnosis, endoscopic exams, surgeries, use of intravenous drugs, blood transfusion and immunosuppressor therapy. Results: The prevalence of anti-HCV was 4,8por cento(7/146). Both univariate and multivariate analysis showed blood transfusion as the only risk factor significantly associated with HCV infection (rr= 5.71; 95por cento confidence interval: 1.04-10.37; p= 0.023). Conclusion: The prevalence of HCV infection in patients with inflammatory bowel disease was higher thanthat observed among blood donors of the same region and the only risk factor associated with this infection was blood transfusion

Tratamento da hepatite C com fator promotor do crescimento do hepatócito (phgf) / Treatment of hepatitis C with promoting hepatocyte growth factor

Em 1987, pesquisadores chineses do Hospital da Força Aérea,localizado em Guangzhou, China, extraíram do fígado de porco recém-nato uma substância denominada promoting hepatocyte growth factor (phgf), que funcionaria como um estimulador do crescimento do hepatócito. Para tanto, agiria no DNA do hepatócito, promovendo síntese e divisão celular, com efeitos antifibrose e antiinflamatório. Investigações recentes sugerem que o phgf possa agir no tratamento das hepatites virais. Desenvolveu-se estudo randomizado e controlado do uso intravenoso do phgf em 18 pacientes com diagnóstico histólogico de hepatite crônica ativa ou cirrose hepática em atividade e RNA-VHC positivo. Todos os pacietes apresentavam aumento da ALT por um período mínimo de 12 meses. Outras causas de hepatopatia foram afastadas (viral, auto-imune, medicamentosa, metabólica e alcoólica). O estudo foi aprovado pela Comissão de Ética do Hospital Universitário Clementino Fraga Filho, Rio de Janeiro. O tratamento foi instituído durante três meses e, mensalmente, eram tomadas amostras de sangue para análise do hemograma, leucograma, contagem de plaquetas, TAP e dosagem da ALT. Determinações de carga viral antes e no final do tratamento foram feitas pelo teste Amplicor HCV Monitor-Roche. Todos os pacientes finalizaram o tratamento, sem a ocorrência de efeitos colaterais atribuíveis à medicação. Em três pacientes a ALT normalizou-se durante o uso de phgf(16,9por cento), com retorno aos valores basais pré-tratamento após a sua interrupção. Porém, em relação ao grupo controle, os valores da ALT diminuiram sensivelmente no grupo tratado, com significância estatística. Apesar de a análise média da carga viral ter mostrado nítica diminuição, estatisticamente significativa no grupo que utilizou o phgf, nenhum paciente tratado apresentou negativação do RNA-VHC. Os resultados mostram que a ação do phgf se fez no processo inflamatório sem influir na replicação viral, sugerindo efeito um pouco semelhante ao da ribavirina

Detecção imunoistoquímica das oncoproteínas p21ras, c-myc E p53 no carcinoma hepatocelular e no tecido hepático não-neoplásico / Immunohistochemical detection of p21ras, c-myc and p53 oncoproteins in hepatocellular carcinoma and in non-neoplastic liver tissue

RACIONAL: A hepatocarcinogênese é um processo no qual as alterações genéticas e epigenéticas são bem conhecidas em modelos animais, mas carece de estudos no homem. OBJETIVOS: Analisar a freqüência das oncoproteínas p21ras, c-myc e p53 no carcinoma hepatocelular e no fígado não-neoplásico. Verificar ainda a associação destas oncoproteínas com os padrões e graus histológicos, assim como com as infecções pelos vírus das hepatites B e C. MÉTODOS: Foi analisada por método imunoistoquímico a detecção das oncoproteínas p21ras, c-myc e p53 em 47 casos de carcinoma hepatocelular e no tecido não-neoplásico circunjacente ao tumor (40 casos). RESULTADOS: As oncoproteínas p21ras, c-myc e p53 foram detectadas, respectivamente, em 44,7 por cento, 53,2 por cento e 36,2 por cento dos casos de carcinoma hepatocelular. A imunorreatividade do p21ras e c-myc mostrou uma associação significativa. Contudo, não houve associação significativa entre a detecção do p21ras, c-myc e p53 com os diferentes graus e padrões histológicos, nem tampouco com as infecções pelos vírus das hepatites B e C. A mesma associação significativa entre o p21ras e c-myc foi encontrada no tecido não-neoplásico dos casos de cirrose em relação aos que não apresentaram cirrose, enquanto que o p53 foi negativo em todos os casos. CONCLUSÕES: A imunorreatividade das oncoproteínas p21ras, c-myc e p53 corrobora evidências prévias de sua detecção no carcinoma hepatocelular, o que sugere poder haver participação destas proteínas na hepatocarcinogênese humana. A significativa associação entre as proteínas p21ras, c-myc e p53 no carcinoma hepatocelular e na cirrose pode apontar uma interação entre as mesmas, sobretudo na hepatocarcinogênese pela via da cirrose.