Desafios do processo de implantação dos medicamentos das hepatites virais B e C no componente estratégico da assistência farmacêutica no Estado do Rio de Janeiro / Challenges with the strategic pharmaceutical care program in the state of Rio de Janeiro's implementation of the viral hepatitis B and C medicines

O Brasil é signatário do documento da Organização Mundial da Saúde (OMS) para eliminação das hepatites virais até 2030. Uma das estratégias para eliminação das hepatites virais é aumentar o número de diagnósticos e tratamentos. A migração dos medicamentos de hepatites virais crônicas B e C do componente especializado para o componente estratégico da assistência farmacêutica foi regulamentado pela portaria 1537 do Ministério da Saúde de Junho de 2020 e normatizada pela Nota Técnica 319 de 2020. Para essa transição foi organizado um cronograma com as etapas do processo e implantação do Sistema de Controle Logístico de Medicamentos (SICLOM) nos estados. O SICLOM é um sistema de cadastro de usuário, dispensação dos medicamentos, controle de estoque, avaliação dos critérios para prescrição dos medicamentos, além de emitir relatórios sobre quantidade de medicamentos dispensados. Uma etapa fundamental do processo foi a pactuação das Unidade Dispensadoras Municipais (UDM) no âmbito das Comissões Intergestores Regionais (CIR) e, posteriormente, na Comissão Intergestores Bipartite (CIB) para deliberar que essas unidades iniciassem o processo como farmácias dispensadoras de medicamentos de hepatites B e C no componente estratégico, utilizando o sistema SICLOM, no Estado do Rio de Janeiro. O objetivo deste trabalho é descrever o processo e avaliar os resultados relacionados ao número de pontos de atendimento e o quantitativo de tratamentos dispensados no período de julho de 2021 a fevereiro de 2022 no Estado do Rio de Janeiro. A metodologia compreendeu uma revisão da literatura sobre o papel do tratamento como estratégia de eliminação das hepatites virais e a descrição das atividades previstas e realizadas na linha do tempo desde o início do processo após o embasamento legal e da publicação das normativas e a extração dos dados e informações sobre o número de tratamentos do SICLOM. A migração resultou em 1084 tratamentos de julho a dezembro de 2021, correspondendo a 56,4% do total dos 1922 tratamentos dispensados pelo Componente Especializado da Assistência Farmacêutica (CEAF) durante todo o ano de 2020. A migração transcorreu com sucesso, aumentou de 29 polos de dispensação especializados para 61 UDM que são as farmácias do componente estratégico, tornando a dispensação mais ágil do que a espera anterior. Apesar dos efeitos negativos provocados pela pandemia pode-se considerar que houve um grande avanço na política pública de assistência às hepatites virais.

Brazil is a signatory country to the World Health Organization (WHO) document for the elimination of viral hepatitis by 2030. One of the strategies to eliminate viral hepatitis is to increase the number of diagnoses and treatments. The migration of drugs for chronic viral hepatitis B and C from the specialized component to the strategic component of pharmaceutical care was regulated by ordinance 1537 of the Ministry of Health of June 2020 and standardized by Technical Note 319 of 2020. A schedule was organized for this transition with the steps of the process and implementation of the logistics and dispensing system (SICLOM) in the states. SICLOM is a user registration system, drug dispensing, inventory control, evaluation of drug prescription criteria, in addition to issuing reports on the quantity of drugs dispensed. A fundamental step in the process was the agreement between the Municipal Dispensing Units (UDM) within the scope of the Regional Inter-management Commissions (CIR) and, later, in the Bipartite Inter-management Commission (CIB) to decide that these units would start the process as pharmacies that dispense hepatitis drugs. B and C in the strategic component, using the SICLOM system, in the State of Rio de Janeiro. The objective of this work is to describe the process and evaluate the results related to the number of service points and quantitative of treatments dispensed from July/2021 to February/2022 in the State of Rio de Janeiro. The methodology included a literature review on the role of treatment as a strategy to eliminate viral hepatitis, and the description of the activities planned and carried out in the timeline since the beginning of the process after the legal basis and the publication of norms, and the extraction of data and information on the number of treatments from SICLOM. The migration resulted in 1084 treatments from July to December 2021, corresponding to 56.4% of the total 1922 treatments dispensed by the Specialized Pharmaceutical Assistance Component (CEAF) throughout 2020. The migration was successful, increasing from 29 specialized dispensing centers to 61 DMUs, which are the pharmacies of the strategic component, making dispensing more agile than the previous wait. Despite the negative effects caused by the pandemic, it can be considered that there was a great advance in the public policy of assistance to viral hepatitis.

Impact of Coronavirus Disease 2019 Pandemic on Viral Hepatitis Elimination: What Is the Price?

In 2016, the World Health Organization developed a plan for viral hepatitis elimination by 2030. Globally, control of hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most challenging aspects of viral hepatitis elimination. In many developed countries elimination of HBV could be targeted to special populations mostly immigrants from low resource settings. Elimination of HCV, however, remains a challenge globally. Barriers to HCV elimination include high cost of medications and the ability to engage specific at-risk populations as well as individuals who are out of medical care. In the context of the coronavirus disease 2019 (COVID-19) pandemic, treatment access and screening have been further negatively impacted by social distancing rules and COVID-19-related anxieties. This threatens to throw most countries off course in their elimination efforts. Before the pandemic, some states in the United States had scaled up their elimination efforts with plans to ramp up testing and treatment using Netflix-like payment models for HCV direct acting antiviral drugs. Most of these efforts have stalled on account of the health system's focus on COVID-19 control. To prevent further delays in achieving elimination targets, programs would need to explore new models of care that address COVID-19-related access hurdles. Systems that leverage technologies such as telemedicine and self-testing could help maintain treatment levels. Mathematical models estimate that COVID-19-related delays in 2020 could lead to 44,800 hepatocellular cancers and 72,300 liver-related deaths for the next decade.

CE: Viral Hepatitis: New U.S. Screening Recommendations, Assessment Tools, and Treatments.

OVERVIEW: Over the past 15 years, the incidences of hepatitis A and B virus infection in the United States have declined significantly. By contrast, the incidence of hepatitis C virus infection, formerly stable or in decline, has increased by 75% since 2010. Suboptimal therapies of the past, insufficient provider awareness, and low screening rates have hampered efforts to improve diagnosis, management, and treatment of viral hepatitis. New screening recommendations, innovations in assessment and treatment, and an updated action plan from the U.S. Department of Health and Human Services (HHS) seem likely to lead to significant progress in the coming years. This article reviews the epidemiology, natural history, and diagnosis of viral hepatitis; discusses new screening recommendations, assessment tools, and treatments; and outlines the HHS action plan, focusing on the role of nurses in prevention and treatment.

Significant reduction in end-stage liver diseases burden through the national viral hepatitis therapy program in Taiwan.

UNLABELLED: A national viral hepatitis therapy program was launched in Taiwan in October 2003. This study aimed to assess the impact of the program on reduction of end-stage liver disease (ESLD) burden. Profiles of national registries of households, cancers, and death certificates were used to derive incidence and mortality of ESLDs from 2000 to 2011. Age-gender-adjusted incidence and mortality rates of hepatocellular carcinoma (HCC) and chronic liver diseases (CLDs) and cirrhosis of adults ages 30-69 years were compared before and after launching the program using Poisson's regression models. A total of 157,570 and 61,823 patients (15%-25% of those eligible for reimbursed treatment) received therapy for chronic hepatitis B and C, respectively, by 2011. There were 42,526 CLDs and cirrhosis deaths, 47,392 HCC deaths, and 74,832 incident HCC cases occurred in 140,814,448 person-years from 2000 to 2011. Male gender and elder age were associated with a significantly increased risk of CLDs and cirrhosis and HCC. Mortality and incidence rates of ESLDs decreased continuously from 2000 to 2003 (before therapy program) through 2004-2007 to 2008-2011 in all age and gender groups. The age-gender-adjusted rate ratio (95% confidence interval; P value) in 2008-2011 was 0.78 (0.76-0.80; P < 0.001) for CLDs and cirrhosis mortality, 0.76 (0.75-0.78; P < 0.005) for HCC mortality, and 0.86 (0.85-0.88; P < 0.005) for HCC incidence using 2000-2003 as the reference period (rate ratio = 1.0). CONCLUSIONS: The national viral hepatitis therapy program has significantly reduced the mortality of CLDs and cirrhosis and incidence and mortality of HCC.

Forgotten, not neglected: viral hepatitis in resource-limited settings, recall for action.

In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries.

Report from a Viral Hepatitis Policy Forum on implementing the WHO Framework for Global Action on viral hepatitis in North Asia.

BACKGROUND & AIMS: The World Health Organisation (WHO) Prevention & Control of Viral Hepatitis Infection: Framework for Global Action offers a global vision for the prevention and control of viral hepatitis. In October 2012, the Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP) organised the North Asia Workshop on Viral Hepatitis in Taipei to discuss how to implement the WHO Framework in the North Asia region. This paper presents outcomes from this workshop. METHODS: Twenty-eight representatives from local liver associations, patient organisations, and centres of excellence in Hong Kong, Japan, Korea, and Taiwan participated in the workshop. FINDINGS: Priority areas for action were described along the four axes of the WHO Framework: (1) awareness, advocacy and resources; (2) evidence and data; (3) prevention of transmission; and (4) screening and treatment. Priorities included: axis 1: greater public and professional awareness, particularly among primary care physicians and local advocacy networks. Axis 2: better economic data and identifying barriers to screening and treatment uptake. Axis 3: monitoring of vaccination outcomes and targeted harm reduction strategies. Axis 4: strengthening links between hospitals and primary care providers, and secure funding of screening and treatment, including for hepatocellular carcinoma. CONCLUSIONS: The WHO Framework provides an opportunity to develop comprehensive and cohesive policies in North Asia and the broader region. A partnership between clinical specialists, primary care physicians, policy makers, and people with or at risk of viral hepatitis is essential in shaping future policies.

[Organizational characteristics of treatment for chronic hepatitis in Hungary: Hepatitis Registry and Priority Index]. / A krónikus vírushepatitisek hazai ellátási rendszerének sajátosságai: Hepatitisz Regiszter és a Prioritási Index.

Hepatitis Registry was developed by the Hepatology Section of the Hungarian Gastroenterology Society with the contribution of the Foundation for Liver Patients. The main task was to register all interferon based treatments of chronic hepatitis C and B and to facilitate the preauthorization process. The registry helped to clarify the number and characteristics of hepatitis C patients waiting for triple therapy; 3000 previously failed patients are still eligible for protease inhibitor therapy, 40% of them already developed cirrhosis stage and 40% are null responders to the previous therapy. As a file is created for treatment authorization, the system counts automatically the Priority Index according to the calculation set in the guideline. Priority Index reflects the urgency of treatment. The most prominent parameter of the Index is the degree of fibrosis, but it also takes into account the progression rate, prognostic factors, and special situations.

Mortality due to viral hepatitis in the Global Burden of Disease Study 2010: new evidence of an urgent global public health priority demanding action.

The recently published Global Burden of Disease Study 2010 (GBD 2010) contains accurate, contemporary estimates of human morbidity and mortality, with substantial changes in the patterns of illness observed over the last two decades. One of the most significant alterations to these estimates has been the recognition that viral hepatitis is a leading cause of human mortality, with an estimated 1.29 million deaths worldwide in 2010. The global community must act to address emerging health priorities identified by GBD 2010, including the need to provide treatment and care to people living with viral hepatitis, especially in resource-poor settings.

Financial stress is associated with reduced treatment adherence in HIV-infected adults in a resource-rich setting.

OBJECTIVES: Financial stress has been identified as a barrier to antiretroviral adherence, but only in resource- limited settings. Almost half of HIV-infected Australian adults earn no regular income and, despite highly subsidised antiretroviral therapy and universal health care, 3% of HIV-infected Australians cease antiretroviral therapy each year. We studied the relationship between financial stress and treatment adherence in a resource-rich setting. METHODS: Out-patients attending the HIV clinic at St Vincent's Hospital between November 2010 and May 2011 were invited to complete an anonymous survey including questions relating to costs and adherence. RESULTS: Of 335 HIV-infected patients (95.8% male; mean age 52 years; hepatitis coinfection 9.2%), 65 patients (19.6%) stated that it was difficult or very difficult to meet pharmacy dispensing costs, 49 (14.6%) reported that they had delayed purchasing medication because of pharmacy costs, and 30 (9.0%) reported that they had ceased medication because of pharmacy costs. Of the 65 patients with difficulties meeting pharmacy costs, 19 (29.2%) had ceased medication vs. 11 (4.1%) of the remaining 270 patients (P < 0.0001). In addition, 19 patients (5.7%) also stated that it was difficult or very difficult to meet travel costs to the clinic. Treatment cessation and interruption were both independently associated with difficulty meeting both pharmacy and clinic travel costs. Only 4.9% had been asked if they were having difficulty paying for medication. CONCLUSIONS: These are the first data to show that pharmacy dispensing and clinic travel costs may affect treatment adherence in a resource-rich setting. Patients should be asked if financial stress is limiting their treatment adherence.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Maraviroque para pacientes em terapia antirretroviral / Maraviroque for patients on antiretroviral therapy

INTRODUÇÃO: A política de acesso universal ao tratamento foi estabelecida em 1996, com a publicação da Lei Federal 9.313 que define como responsabilidade da União o acesso ao tratamento antirretroviral a pessoas que vivem com HIV/Aids (PVHA) no Brasil. Desde então, esta política vem determinando aumento da sobrevida e da qualidade de vida das PVHA no país. Atualmente, cerca de 217 mil pessoas estão submetidas ao tratamento antirretroviral (TARV) no País e cerca de 30 mil iniciam tratamento anualmente. Estudo realizado pelo Departamento de DST, Aids e Hepatites Virais (DDSTAIDSHV) da Secretaria de Vigilância em Saúde (SVS) demonstrou maior tempo de sobrevida entre PVHA cujo diagnóstico é estabelecido em períodos mais recentes. Aqueles com diagnóstico entre 1998 e 1999, apresentam média de sobrevida de 107 meses, bastante superior aos 58 meses daqueles com diagnóstico em 1996. Entre os determinantes de aumento da sobrevida inclui-se a introdução de antirretrovirais de terceira linha, especialmente novas classes de antirretrovirais. As recomendações de tratamento da multirresistência permitem obter supressão viral duradoura (carga viral indetectável), que está associada ao impacto favorável na mortalidade ao longo do tempo. O convívio com a replicação, resistência viral e falha terapêutica apresenta risco relativo de morte de 1,21 para cada 3 meses de atraso em realizar a mudança do tratamento , além de ocasionar desenvolvimento de multirresistência. MARAVIROQUE: DESCRIÇÃO DA TECNOLOGIA: Tropismo viral é a capacidade do vírus de penetrar e infectar células específicas do hospedeiro por meio de ligação a receptores. Essa habilidade de ligação à célula CD4 pode ocorrer pelo co-receptor CCR5 (vírus R5), co-receptor CXCR4 (vírus X4) ou por ambos os co-receptores (tropismo duplo). Antagonistas do co-receptor de quimiocina C-C tipo 5 (CCR5) inibem especificamente a entrada na célula CD4 e, portanto, bloqueiam a replicação da variante R5 do HIV após ligação ao co-receptor transmembrana CCR5. O inibidor do CCR5 disponível comercialmente é o maraviroque. OBJETIVOS DA INCORPORAÇÃO DO MARAVIROQUE: A introdução de novos ARV no país deve sempre buscar a redução da necessidade de indicação de enfuvirtida - devido a razões relacionadas a seu elevado custo, toxicidade e dificuldade de administração, que acarreta baixa adesão ao tratamento. O Departamento de DST, Aids e Hepatites Virais, com subsídio da Comissão Técnica Assessora para Terapia Antirretroviral em Adultos Infectados pelo HIV, reunida no ano de 2012 propõe a incorporação do maraviroque para pacientes multiexperimentados em terapia antirretroviral com os seguintes objetivos: -Oferecer nova classe de ARV para pacientes em uso de esquemas de terceira linha que apresentam falha virológica; -Reduzir a necessidade de novas indicações de enfuvirtida. DELIBERAÇÃO FINAL: Após discussão sobre as contribuições da consulta pública e não tendo sido apresentadas mais informações sobre o uso do medicamento, os membros da CONITEC deliberaram, por unanimidade, por recomendar a incorporação do medicamento maraviroque ao arsenal terapêutico nacional como uma opção adicional de resgate para pacientes com AIDS multiexperimentados que necessitam de terceira linha de tratamento, com a condição de que o custo diário desse medicamento não seja superior. DECISÃO: PORTARIA SCTIE-MS N.º 44, de 23 de outubro de 2012 - Torna pública a decisão de incorporar o medicamento maraviroque para pacientes em terapia antirretroviral no Sistema Único de Saúde (SUS).

[Assessment and reversibility of liver fibrosis in viral hepatitis]. / Evaluation et réversibilité de la fibrose hépatique au cours des hépatites virales.

The evaluation of liver fibrosis in chronic viral hepatitis is of paramount importance since secondary complications, including hepatocellular carcinoma, occur in patients with extensive fibrosis and cirrhosis. Clinical examination and some simple biological and morphological tests represent the first step to appraise liver fibrosis in viral hepatitis. Biochemical (Fibrotest, Hepascore, Fibrometre) or morphological (Fibroscan) methods have emerged over the past ten years to avoid--in more than half of patients--the systematic use of the liver biopsy to appraise liver fibrosis in chronic hepatitis C virus infection. The liver biopsy remains however essential in many situations--especially for demonstrating regression of cirrhosis after viral inactivation. Regression of cirrhosis is now a recognized concept, thanks to the next generation of antiviral treatments. Today, the inactivation of viral hepatitis is an achievable primary goal and regression of cirrhosis becomes a reasonable secondary goal.

Viral hepatitis in India.

Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies.

[Assessment of efficacy of the drug litovit as a novel pathogenetic modality in acute virus hepatitis].

AIM: To study clinical and laboratory parameters in patients with acute viral hepatitis (AVH) given basic therapy in combination with a novel pathogenetic drug litovit versus ursosan. MATERIAL AND METHODS: 155 patients with AVH were divided into three groups: 70 patients of group 1 received basic therapy plus litovit, 10 patients of group 2--basic therapy plus ursosan, 60 patients of group 3--basic treatment only. RESULTS: Litovit was well tolerated. Side effects were absent. Hospital stay and severity of clinical AVH symptoms were significantly less in patients of group 1. Less pronounced were also hyperbilirubinemia, cytolytic and mesenchymal-inflammatory syndromes. CONCLUSION: Clinical and laboratory parameters in AVH patients treated with adjuvant litovit improve quicker than in those with adjuvant ursosan or basic therapy. Litovit has enterosorptive and hepatoprotective activity. Low cost of vitovit therapy makes the drug applicable in wide practice.

Hepatic disease in injection drug users.

A wide variety of infectious diseases affect injection drug users. One of the most common is viral hepatitis. In the United States, hepatitis B affects 1.5 million people, and hepatitis C affects more than 4 million people, many of whom are past or current users of injected drugs. Although the treatment for chronic hepatitis B and hepatitis C has improved, protocols specifically designed for injection drug users, especially given their lifestyle and reportedly low compliance rates, are seriously lacking. These disorders can lead to cirrhosis, hepatocellular carcinoma, and the need for liver transplantation in a sizeable proportion of cases. Therefore, early intervention should be a top priority.