Abstract OBJECTIVE: Hepatitis B is an important public health concern. Currently, the COVID-19 pandemic is a major challenge for health systems, and the access to pharmacologic and non-pharmacologic treatment of chronic diseases, such as hepatitis B, may have been affected due to the contingency measures. This study aimed to evaluate the access to antiviral therapy during the ongoing pandemic. METHODS: This was a descriptive analysis of the access to treatment for chronic hepatitis B at a tertiary-level university hospital in São Paulo, integrated with the Brazilian health system. The study was conducted from April to December 2020. RESULTS: Access to antiviral therapy for 225 patients was assessed. The majority of the population was male (59%). The main type of service was the Programa Medicamento em Casa (Home Medication Delivery Program), which was availed by 144 (64%) patients. Women had poorer access to antiviral therapy (56%, p<0.05), and patients registered in the HMDP (68%, p<0.05) had better access. The age group of >48 years represented 70% of the group without access to antiviral therapy. Twenty-two pharmaceutical appointments were conducted through phone calls with patients without access to antiviral therapy. CONCLUSION: This study contributes to the rationalization of efforts in a public health crisis through the identification of groups with the highest risk of poor access to antiviral therapy and the demonstration of the benefits of a medication delivery system.

RESUMO Contexto: O carcinoma hepatocelular (CHC) é o tumor maligno hepático mais comum, e a cirrose é o principal fator de risco para o seu desenvolvimento. Objetivo: Avaliar o papel da medição da rigidez hepática por elastografia transitória (ET) como fator de risco para ocorrência de CHC em uma coorte prospectiva de pacientes brasileiros com cirrose por vírus da hepatite C (VHC). Métodos: Um total de 99 pacientes com VHC e medida de rigidez hepática ≥12 kilopascals (kPa) foram incluídos consecutivamente, entre 2011 e 2016. As variáveis do baseline foram avaliadas e a ocorrência de CHC foi documentada. Os testes de Kaplan-Meier e log-rank, além das análises uni e multivariadas de Cox avaliaram a associação entre as variáveis e os resultados clínicos. Resultados: A média de idade foi de 57,8±10,6 anos. Vinte (20,2%) pacientes desenvolveram CHC, num período médio de seguimento de 3,3 anos. Na análise de regressão logística univariada, as variáveis associadas à ocorrência de CHC foram: contagem de plaquetas mais baixa (P=0,0446), valores séricos mais elevados de alfa-fetoproteína (P=0,0041) e de bilirrubina (P=0,0008), maior pontuação do escore MELD (P=0,0068) e valores mais altos de rigidez hepática por ET (P=0,0354). A medição da rigidez hepática por ET foi independentemente associada ao desenvolvimento de CHC, e o melhor valor de corte para maior risco de CHC foi >21,1kPa (HR: 5,548; IC95%: 1,244-24,766; P=0,025). Conclusão: Um alto valor de rigidez hepática está relacionado substancialmente a um risco aumentado de ocorrência de CHC em pacientes brasileiros com cirrose por HCV.

ABSTRACT Background: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. Methods: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. Results: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). Conclusion: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.

OBJECTIVES: A good health care does not only depend on good medical practice, but also needs great management of its resources, which are generally short. In this sense, PROAHSA has been training new health managers since 1972. With the arrival of the COVID-19 pandemic, it was clear that medicine will go through a new phase, where telehealth will be present in this “Improved Normal”. This report is about how a pilot teleconsultation study was carried out for HCFMUSP patients through the Scrum-like framework. It is to deploy a pilot of remote assistance involving a doctor and a patient in the Ambulatory of Hepatology and Liver Transplantation of HCFMUSP. METHODS: We applied the Scrum-like framework to carry out this work with an interdisciplinary multifunctionality team. RESULTS: A full telemedicine service flow was implemented within eight weeks using existing infrastructure and resources implementing the Scrum methodology. Twenty-three teleconsultations were scheduled and eight guides built. CONCLUSION: Scrum framework has a great potential to improve the training of students and to conclude pilot projects.

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

Resumo Introdução: A hepatite B é um importante problema de saúde pública no mundo e uma das formas de contágio seria através da transmissão vertical. O diagnóstico precoce possibilita a adoção de medidas de profilaxia, o que resulta na prevenção em mais de 90% dos casos. Objetivo: Descrever as prevalências de transmissão vertical e comparar duas gerações (mãe/paciente e paciente/filho). Método: Trata-se de um estudo transversal, que incluiu 101 pacientes. As entrevistas foram realizadas por meio da aplicação do instrumento de coleta de dados e informações do prontuário físico antes da consulta médica. Resultados: A média ± DP de idade foi de 50,9 ± 13,1 anos, houve predomínio do gênero masculino, com 56,4% dos pacientes, e predominou a cor branca, com 43,6%. A transmissão vertical entre mãe do paciente/paciente ocorreu em 17,8% e entre paciente/filho, em 7,9%. Em todos os oito casos de transmissão vertical, o diagnóstico foi posterior ao nascimento dos filhos infectados por HBV; em 3/8 (37,5%), houve mais de um caso de infecção por esse mecanismo por paciente, totalizando 13 filhos com a doença. Conclusão: Houve uma redução na transmissão vertical, mostrando que as medidas preventivas foram efetivas.

Summary Introduction: Hepatitis B is an important public health problem in the world and one of the forms of contagion would be through vertical transmission. Precose diagnosis allows the adoption of prophylaxis measures, which results in prevention in more than 90% of cases. Objective: To describe the prevalences of vertical transmission and compare two generations (mother/patient and patient/child). Method: This was a cross-sectional study, which included 101 patients. The interviews were performed through the application of the instrument of data collection and information of the physical file before the medical consultation. Results: The mean ± SD of age was 50.9 ± 13.1 years, the male gender predominated, with 56.4% of the patients, and the predominance was white, with 43.6%. Vertical transmission between mother and patient occurred in 17.8% and between patient and child, in 7.9%. In all of the eight cases of vertical transmission, the diagnosis was after the birth of children infected with HBV, and in 3/8 (37.5%), there was more than one case of infection by this mechanism per patient, totaling 13 children with the disease. Conclusion: There was a reduction in vertical transmission, showing that preventive measures were effective.

OBJECTIVES: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R) and 11 non-refractory ascites (NR)]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034). The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively). Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262). CONCLUSION: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

Resumo Desde 2010, a Divisão de Gastroenterologia e Hepatologia Clínica do Instituto Central do HC-FMUSP tem desenvolvido atividades assistenciais eletivas especializadas em Hepatologia no Ambulatório de Especialidades Nível Secundário de São Paulo no Estado de São Paulo NGA-63 Várzea do Carmo. O objetivo do estudo é analisar o perfil farmacoterapêutico dos pacientes. Trata-se de um estudo transversal e retrospectivo, no qual pacientes foram atendidos pelo setor de Hepatologia e os dados encontrados foram submetidos à estatística descritiva. Os resultados demonstraram que 492 pacientes foram atendidos nesse ambulatório durante o período do estudo com a média de idade de 58,9 anos, frequência de 61,2% do sexo feminino e 74,8% residindo na capital paulista. Essa população foi atendida por outras diferentes especialidades médicas (cardiologia e endócrino, entre outras), e os principais diagnósticos hepáticos foram hepatite crônica B e C e esteatose hepática. Também foram identificadas comorbidades como diabetes, hipertensão arterial e dislipidemia. Boa parte da população tende a retirar a sua medicação nas Unidades Básicas de Saúde. Foi verificado que 30% dos pacientes fazem uso de mais de cinco medicamentos, sendo os mais prescritos o omeprazol (208; 42,3%), metformina (132; 26,8%) e losartana (80; 16,3%). Por se tratar de uma população adulta/idosa, com diversas comorbidades e com polimedicação, é importante estar atento ao uso racional do medicamento. O atendimento da equipe multiprofissional é importante para aplicar tomadas de condutas corretas para a segurança no uso de medicamentos e diminuir a oneração em gastos em saúde, melhorando a qualidade de vida do paciente.

Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym) has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others) and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as diabetes, hypertension and dyslipidemia. Most patients took their medication in the Basic Health Units. We found that 30% of patients use of more than five medications and the most prescribed were omeprazole 208 (42.3%), metformin 132 (26.8%) and losartan 80 (16.3%). Because it is an adult/elderly population, with several comorbidities and polymedication, it is important to be aware of the rational use of medication. The multidisciplinary team is important in applying correct conducts for the safe use of medicines, to reduce the burden on health spending and improving the quality of life of patients.

O advento de novas tecnologias na saúde causou impacto nos indicadores clínicos e econômicos. Os métodos de pesquisa que incorporam conceitos da economia da saúde e epidemiologia clínica permitem avaliar a eficiência de novas tecnologias, por exemplo, através da análise de custo-efetividade. Este é um instrumento de análise de valor das intervenções em saúde. A metodologia, análise de custo-efetividade, é condição determinante da moderna prática de cuidados à saúde, pois as opções terapêuticas hoje disponíveis no Sistema Único de Saúde (SUS) ou no sistema de saúde suplementar do Brasil passam necessariamente por tal análise, logo o sistema de saúde bem como os profissionais da saúde são levados a reexaminar os benefícios e custos de suas ações para assegurar que haja incorporação das tecnologias mais eficientes. Neste segundo artigo sobre avaliação de tecnologia em saúde reviram-se os conceitos de análise de custo-efetividade, os passos envolvidos na sua execução e o método para a análise crítica dos resultados.

New health technologies have made an impact in clinical and economic outcomes. Therefore, research methodologies that allow to evaluate the efficiency of these new technologies such as cost-effectiveness analysis are necessary. Cost-effectiveness analysis assess the value of health care interventions or drugs, the technology. Cost-effectiveness analysis is also deemed a determinant of modern health care practice, because the therapeutic options available at public (SUS) or private health care system must go through a formal health technology assessment in Brazil; thus, both the health care system and the health care professionals have to reevaluate the clinical consequences and costs of their actions to assure that the most efficient technologies are the one used in the practice. In this second article about health technology assessment we review the concepts of cost-effectiveness analysis, the steps involved in performing such analysis, and the criteria most frequently used to critically review the results.

Existe, atualmente, grande demanda para se aumentar a eficiência do ato médico e isto pode ser alcançado através de pesquisas de avaliação de tecnologia em saúde, a ATS. Esta visa, por um lado, determinar a melhor evidência de eficácia ou efetividade de um dado tratamento em saúde, por outro, determinar os custos associados com tal tratamento médico. Somente as alternativas com custo e efetividade comprovados, ou seja, que sejam eficientes, serão adotados doravante nos hospitais e sistemas de saúde público e privados. Exemplo são os custos crescentes de tratamentos com biológicos, por exemplo, em doença inflamatória intestinal ou hepatites virais, ou mesmo em oncologia. Há necessidade de se desenvolver pesquisas em ATS para a identificação não somente dos tratamentos que funcionam dos que não funcionam, mas também se os custos a eles associados compensam o seu uso. Este artigo introduz esta terminologia e os métodos para se desenvolver esses estudos.

Currently it is expected a higher efficiency of health care and this can be achieved by health technology assessment . This aims, for one side, to determine the best evidence of efficacy or effectiveness of a given treatment, and, on the other side, to determine the costs associated with this treatment. Only cost-effective alternatives, in other words, efficients, should be adopted in hospitals or public or private health care system. For instances, the increasing costs of biologics treatments in inflammatory bowel disease or hepatology or oncology. There is a need to increase the number of health technology assessment research not only to identify those treatment that works from those does not, but also whether the costs associated with each treatment compensate its use. This young researcher forum article introduce the concepts and basic methods used in health technology assessment studies.

INTRODUÇÃO: A quantificação do AgHBe sérico não é habitualmente utilizada para monitorizar a resposta viral ao tratamento da hepatite crônica B. MÉTODOS: Neste estudo, 21 pacientes sob tratamento com diferentes terapias foram acompanhados e a resposta viral monitorizada pela quantificação concomitante da carga viral e do AgHBe a fim de investigar o significado e a cinética de ambos os parâmetros. RESULTADOS: Distinguiram-se três diferentes padrões de resposta viral. O primeiro caracterizou-se pela redução simultânea do HBV DNA e AgHBe séricos. O segundo padrão caracterizou-se por uma redução do AgHBe porém com detecção persistente do HBV DNA. O terceiro padrão caracterizou-se por HBV DNA indetectável com positividade persistente do AgHBe, sugerindo ausência de resposta (Padrão III-B), exceto quando os níveis de AgHBe mostraram uma queda lenta porém persistente, caracterizando um "respondedor lento" (Padrão III-A). CONCLUSÕES: O primeiro padrão é compatível com resposta viral. Uma seropositividade prolongada do AgHBe porém com uma redução lenta e persistente (Padrão III-A) é também compatível com resposta viral, sugerindo o prolongamento do tratamento anti-viral.

BACKGROUND: The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. METHODS: In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. RESULTS: It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a "slow responder" patient (Pattern III-A). CONCLUSIONS: The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Pattern III-A) is also compatible with a viral response and calls for a prolongation of anti-viral treatment.

O carcinoma hepatocelular (CHC) é um importante tipo de câncer relacionado etiologicamente a alguns vírus, carcinógenos químicos e outros fatores ambientais que causam danos crônicos ao fígado em humanos. A freqüência de mutação do gene p53 em CHC é altamente heterogênea (0-52%) nos diversos países. OBJETIVO: O objetivo deste estudo foi determinar, imuno-histologicamente, a freqüência da expressão anômala de p53 em CHCs em pacientes cirróticos versus não-cirróticos, bem como em displasia hepática e hiperplasia adenomatosa. Para isso, foram estudados 84 pacientes com carcinoma hepatocelular ou cirrose. RESULTADOS: Foram detectadas expressões do p53 alterado em 58,3% dos pacientes com CHC graus III-IV, contrastando com os 22,2% dos pacientes com CHC graus I-II (p = 0,02). Áreas não tumorais, tanto nas proximidades do CHC como nos 30 casos de cirrose não mostraram expressão nuclear alterada do p53, mesmo nas displasias ou hiperplasias adenomatosas. Quando se considerou HBV, HCV ou alcoolismo nos casos estudados, não se encontrou diferença significativa. CONCLUSÃO: A elevada freqüência de imuno-expressão de p53 nesta população é próxima à relatada na China e África, tornando necessárias outras pesquisas para explicar as diferenças com os CHC estudados na Europa e na América do Norte.

Hepatocellular carcinoma (HCC) is an important type of cancer etiologically related to some viruses, chemical carcinogens and other host or environmental factors associated to chronic liver injury in humans. The tumor suppressor gene p53 is mutated in highly variable levels (0-52%) of HCC in different countries. OBJECTIVE: The objective of the present study was to compare the frequency of aberrant immunohistochemical expression of p53 in HCC occurring in cirrhotic or in non-cirrhotic patients as well as in liver cell dysplasia and in adenomatous hyperplasia. We studied 84 patients with HCC or cirrhosis. RESULTS: We detected p53 altered immuno-expression in 58.3% of patients in Grade III-IV contrasting to 22.2% of patients in Grade I-II (p = 0.02). Nontumorous areas either in the vicinity of HCC or in the 30 purely cirrhotic cases showed no nuclear p53 altered expression, even in foci of dysplasia or adenomatous hyperplasia. No significant difference was found among cases related to HBV, HCV or alcohol. CONCLUSION: The high frequency of p53 immunoexpression in this population is closer to those reported in China and Africa, demanding further studies to explain the differences with European and North American reports.

Agentes exógenos correlacionados com o carcinoma hepatocelular (HCC) têm sido identificados e bem caracterizados. Esses agentes, entre os quais se incluem os diferentes vírus que causam hepatite e cirrose hepática, podem provocar o aparecimento de nódulos regenerativos e nódulos displásicos/hiperplasia adenomatosa. Essas condições associadas com diversas alterações moleculares do hepatócito podem culminar com o aparecimento do HCC. Recentemente, grandes progressos têm ocorrido na identificação de mutações somáticas ou germinativas que estariam correlacionadas com o desenvolvimento do HCC, justificando ampla revisão do tema. Procuramos discutir nesta revisão os fatores envolvidos no processo de carcinogênese hepática, tal como a infecção pelos vírus das hepatites B e C, com ênfase nas alterações moleculares descritas nos últimos anos, assinalando áreas em que potenciais avanços na abordagem clínica poderão surgir em futuro próximo.

Exogenous agents correlated with hepatocellular carcinoma (HCC) have been identified and well characterized. These agents, including the different viruses that cause chronic hepatitis and cirrhosis, can lead to regenerative nodules and dysplastic nodules/adenomatous hyperplasia. These conditions associated with several molecular alterations of hepatocyte ultimately culminate in hepatocellular carcinoma. Recently, there has been a great progress in the identification of somatic and germinative mutations that may be correlated with the development of HCC, justifying a review on the subject. Hence, the factors involved in the process of hepatic carcinogenesis, such as infection by the hepatitis B and C viruses, with a special focus in the molecular alterations described in recent years are discussed herein, pointing out areas potentially relevant for clinical development.