BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA.

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.

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.

Choosing wisely recommendations regarding the top five list of procedures to avoid in the treatment of viral hepatitis: A position statement from the Brazilian Society of Hepatology endorsed by the Latin American Association for the Study of the liver.

INTRODUCTION AND OBJECTIVES: The Choosing Wisely (CW) initiative aims to improve daily practice supported by evidence concerning unnecessary medical tests, procedures, and treatments. This philosophy is essential in managing viral hepatitis (VH), which primary care physicians increasingly carry out. It is also essential to achieving disease elimination. Thus, the aim of our study was to propose evidence-based CW recommendations in VH. MATERIALS AND METHODS: The Brazilian Society of Hepatology (SBH) formed a panel of experts in VH who selected evidence-based CW recommendations, which were subsequently scrutinized and ranked by all members of SBH using a web-based approach. RESULTS: Five recommendations were chosen in order of importance: 1) do not order anti-HCV testing after achieving sustained virological response; 2) do not request serial HCV viral load to evaluate HCV progression, 3) do not add ribavirin to direct-acting antivirals in non-cirrhotic, naïve HCV patients; 4) do not screen for hepatocellular carcinoma in HCV patients with none to moderate fibrosis (≤ F2); 5) do not request anti-HBs after HBV vaccination, except for children born to HBV-infected mothers, hemodialysis patients, healthcare professionals, people who have had sexual contact with chronic HBV carriers, HIV-positive persons and immunocompromised individuals (hematopoietic stem-cell transplant recipients or persons receiving chemotherapy). CONCLUSIONS: CW recommendations may help general practitioners adopt a more rational and cost-effective approach in managing patients with VH in Brazil and Latin America, leading to lesser waste or harm to patients.

Combined liver transplantation with sleeve gastrectomy: a pioneer case series from Brazil.

The association of a bariatric operation during liver transplantation may benefit patients with liver failure and obesity and sleeve gastrectomy emerges as the procedure of choice. The aim of this study is to present our experience with combined liver transplantation and sleeve gastrectomy. During an 18-month period, seven patients were submitted to simultaneous liver transplant and sleeve gastrectomy (LTSG). There were four male and three female, and the mean recipient age was 60.5 years, mean BMI was 38.2 kg/m2, and mean MELD score was 25 points. The indication for liver transplantation was nonalcoholic steatohepatitis (NASH) with hepatocellular carcinoma (HCC) in four cases, hepatitis C with HCC in one case, pure NASH in one case and alcoholic cirrhosis with HCC in one case. Six patients are alive with normal allograft function. There were no biliary complications.

Portomesenteric vein thrombosis after bariatric surgery: a case series. / Trombose venosa portomesentérica após cirurgia bariátrica: série de casos.

OBJECTIVE: Portomesenteric vein thrombosis (PMVT) is a potentially severe complication that can occur after bariatric surgery. PMVT has gained importance because of the increasing number of bariatric surgeries being performed. to report a rare and severe complication after bariatric surgery, which is difficult to manage. To try to identify common characteristics among the cases and discuss potential causes comparing our data to the available literature. METHODS: We describe six cases of PMVT in young women with different presentations. RESULTS: All six cases occurred in young women 29-41 years old with obesity - body mass index - BMI: 36-39) and weighing 105-121 kg. The patients had few comorbidities (all of which were related to metabolic syndrome) and moderate hepatic steatosis with no sign of cirrhosis. Five patients used oral contraceptives until a few days before the operation. One patient tested positive for thrombophilia. Five patients underwent a laparoscopic sleeve gastrectomy and one underwent a gastric bypass with no complications during the operation (median operating time: 61.3 min, range 52-91 min). The mean duration of follow-up after hospitalization was 12.3 months (range: 7-18 months) and to-date only one patient has had no recanalization. CONCLUSION: The frequency of PMVT appears to be increased in woman and after sleeve gastrectomy. Our findings indicate that patients with abdominal pain weeks after bariatric surgery must be investigated.

OBJETIVO: A trombose portomesentérica (TPM) é uma complicação potencialmente grave que pode ocorrer após a cirurgia bariátrica. A TPM ganhou importância devido ao crescente número de cirurgias bariátricas sendo realizadas. Relatar complicação rara após cirurgia bariátrica, porém grave e de difícil manejo. Tentar identificar algumas características comuns aos pacientes e discutir possíveis causas, comparando a pouca literatura disponível. MÉTODOS: Descrevemos seis casos de TPM em mulheres jovens com diferentes apresentações. RESULTADOS: Todos os seis casos ocorreram em mulheres jovens de 29 a 41 anos sem obesidade grave - índice de massa corporal - IMC: 36 a 39 e com peso que variou de 105 a 121 kg. As pacientes apresentavam poucas comorbidades (todas relacionadas à síndrome metabólica) e esteatose hepática moderada, sem sinais de cirrose. Cinco pacientes usavam contraceptivos orais até dias antes da cirurgia. Uma paciente apresentou resultado positivo para trombofilia. Cinco pacientes foram submetidas a gastrectomia vertical e apenas uma submetida ao bypass gástrico sem complicações durante a cirurgia (tempo médio de operação: 61,3 min, variando de 52 a 91 min). A duração média do seguimento após a hospitalização foi de 12,3 meses (variação: 7 a 18 meses) e até o momento apenas uma paciente não teve recanalização. CONCLUSÃO: A frequência da TPM parece ser maior em mulheres e após gastrectomia vertical. Nossos achados indicam que pacientes com dor abdominal semanas após a cirurgia bariátrica devem ser investigados.

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.

Fibrosis assessment using FibroMeter combined to first generation tests in hepatitis C.

AIM: To evaluate the performance of FibroMeterVirus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC). METHODS: First generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C. RESULTS: Seven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeterVirus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3). CONCLUSION: The stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.

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.

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 decompensated (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...

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.

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.

Hepatitis B virus prevalence and transmission risk factors in inflammatory bowel disease patients at Clementino Fraga Filho university hospital.

AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBD patients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%).

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...

HBV-DNA levels in HBsAg-positive blood donors and its relationship with liver histology.

INTRODUCTION AND OBJECTIVES: The clinical meaning of viremia, especially at low levels, in chronic hepatitis B virus (HBV)-infected patients remains unknown. The objective of the present study was to determine serum HBV-DNA levels and its relationship with liver histology in HBsAg-positive blood donors. METHODS: A cross-sectional study was conducted on 78 blood donors, with alanine aminotransferase (ALT) and HBeAg evaluation and quantitative determination of HBV-DNA by polymerase chain reaction (Amplicor, HBV Monitor, Roche; lower limit of sensitivity 1,000 copies/mL). Liver biopsy was obtained from all patients with detectable viremia irrespective of ALT and HBV-DNA levels. RESULTS: Among 78 blood donors, serum HBV-DNA was detected in 47 (60%) patients; 39 (83%) were males; mean age 37.6+/-10.4 years; 31 (66%) were HBeAg-negative, and ALT was elevated in 26 (55%). The median of HBV-DNA levels was 24,000 copies/mL and 31 (40%) subjects had no detectable serum HBV-DNA. Although the histologic lesions were mild in the majority of patients, HBV-DNA levels were significantly higher in patients with chronic hepatitis or cirrhosis when compared with patients without histologic liver disease (25,260,000 vs. 9480 copies/mL; P<0.001). There was a significant correlation between HBV-DNA levels and necroinflammatory score (r=0.59) and fibrosis (r=0.50); however, in the subset of HBeAg-negative patients with HBV-DNA levels below 30,000 copies/mL, 25% presented histologic disease related to HBV. CONCLUSIONS: Most HBsAg-positive blood donors show low viral load. There is a significant association between viral replication and liver damage; however, low HBV-DNA levels do not exclude the presence of histologic disease.

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.