Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach

ABSTRACT Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

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.

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.

Resultado do inquérito nacional sobre condutas no acompanhamento e no tratamento da recurrência da hepatite C em portadores de vírus C submetidos a transplante de fígado / National survey about management and treatment options of hepatitis C recurrence after liver transplantation

RACIONAL: A recurrência da hepatite C no período pós-operatório do transplante hepático é um dos principais desafios atualmente enfrentados pela comunidade transplantadora. O tratamento com interferon peguilado e ribavirina tem sido associado à resposta virológica sustentada em 21 por cento a 45 por cento dos casos e constitui a única conduta eficaz, até o momento, para mudar o curso da progressão acelerada da doença no período pós-operatório do transplante hepático, que pode levar à perda do enxerto e à necessidade de retransplante. No entanto, a portaria n° 863 do Ministério da Saúde não disponibiliza esse tratamento para pacientes com recidiva da hepatite C após o transplante hepático. OBJETIVOS: Avaliar as condutas de acompanhamento e tratamento de pacientes com vírus C submetidos a transplante hepático em diferentes centros nacionais. MÉTODOS: Foram enviados questionários à maioria dos centros de transplante hepático nacionais de adultos sobre condutas acerca de acompanhamento e/ou tratamento de pacientes com hepatite C. RESULTADOS: Dezenove centros nacionais que congregam mais de 2 800 pacientes (51 por cento com hepatite C) submetidos a transplante hepático responderam o questionário. A maioria (53 por cento) usa tacrolimus e prednisona como esquema de indução e 32 por cento usam esquemas diferenciados para hepatite C. Treze centros fazem biopsia protocolar para seguimento, sendo empregados diferentes critérios histológicos para diagnóstico de recurrência. Todos os centros indicam tratamento com interferon peguilado e ribavirina apenas na recurrência histológica da hepatite C e 46 por cento empregam estádios de fibrose inferiores a F2 de acordo com a classificação METAVIR, mais leves do que aqueles preconizados para tratamento de pacientes não transplantados. A duração do tratamento é de 1 ano em 32 por cento dos centros, baseada no genótipo em 21 por cento e a la carte em 47 por cento. A maioria dos centros (84 por cento)...

BACKGROUND: Recurrence of hepatitis C after orthotopic liver transplantation is one of the major clinical challenges faced by the liver transplantation community. Treatment of hepatitis C recurrence with peguilated interferon and ribavirin has been associated with sustained virological response in 21 percent to 45 percent of treated patients. Furthermore, it has been shown to halt disease progression after orthotopic liver transplantation and to prevent graft failure and the need for retransplantation at least in those subjects with sustained virological response. However, treatment of hepatitis C recurrence after orthotopic liver transplantation in Brazil was not recommended according to ministerial Law number 863. AIMS: To assess the management and treatment options of hepatitis C recurrence after orthotopic liver transplantation in different liver transplantation centers in Brazil. METHODS: Inquiries were sent to active liver transplantation centers throughout the country. RESULTS: Nineteen centers accepted to participate and answered the questionnaire. Altogether they transplanted around 2,800 subjects, half of them with hepatitis C. Immunosuppressive regimen is comprised by tacrolimus and short-term prednisone in 53 percent of the centers. One third of them claim to use different schedules for hepatitis C patients. Protocol biopsies for diagnosis of recurrence are employed by 13 centers. Different histological criteria are used for the either diagnosis or decision for treatment in most of the centers. Approximately half of them (42 percent) indicate treatment in subjects with less severe stages of fibrosis (less than F2 according to METAVIR classification). All centers are referring patients for treatment with peguilated interferon and ribavirin, for 1 year, for 6 months or 1 year based on the genotype, or a la carte based on response, respectively, in 32 percent, 21 percent and 47 percent of the centers. Most of them (84 percent)...

Hepatite colestática associada ao vírus da hepatite C pós-transplante hepático: estudo virológico, histopatológico e imuno-histoquímico / Severe recurrent cholestatic hepatitis after liver transplantation: virological, histological and immuno-histochemical evaluation

A evolução da recorrência da hepatie C pós-transplante hepático pode ter um curso bastante variável. Raramente a doença pode progredir para uma forma conhecida como hepatite recorrente colestática grave, cuja patogenia ainda não é bem conhecida. Nós estudamos nesse trabalho alguns aspectos virológicos, histológicos e imunohistoquímicos de seis pacientes com essa forma rara de recorrência da doença, tendo como comparação um grupo pareado de seis pacientes transplantados com a forma leve de hepatite C recorrente, e como controle imunocompetente, cinco pacientes não transplantados com hepatite crônica pelo vírus C. Foram avaliados como possíveis fatores preditivos de gravidade da progressão da recorrência: viremia do VHC, evolução de quasispécies, parâmetros histopatológicos, e imunoreatividade para o antígeno core do VHC.Following liver transplantation (OLT) HCV-related disease severity is highly variable, with a minority of cases progressing to an extremely severe form of cholestatic hepatitis, in which the pathogenesis is not yet understood. We aim to compare virological, histological and immunohistological changes in patients developing mild and severe post-OLT HCV recurrence. Twelve patients with recurrent HCV infection were studied (6 with severe and 6 with mild disease). Five HCV-infected immunocompetent patients were used as controls. We looked at viral load, quasispecies evolution of HCV, several histological parameters and immuno-reactivity of core antigens at three time-points (pre-OLT, early post-OLT and late post-OLT) as predictors of severity of recurrence post-OLT...

Transplante hepático: política de captação, alocação e distribuição de órgão no Brasil / Liver transplant: organ procurement, allocation, and distribution policies in Brazil

Embora o primeiro transplante hepático da fase pós-experimental tenha sida realizado no Brasil em 1985, na realidade, os números atuais atestam quadro dramático para os brasileiros portadores de doença hepática terminal. Projeção para atendimento da demanda das listas de espera atesta a ineficiência do sistema de captação, bem como enorme distócia e injustiça nos critérios de distribuição dos órgãos captados. O número de novos casos registrados em listas de espera tem aumentado dramaticamente. Assim, nos Estados Unidos, o número de registros elevou-se de 616 em 1988 para 14.088 em 1999. No Brasil, não somente em função da falta de conscientização da sociedade e da classe média, mas agravado pela precariedade do Sistema de Saúde, o número de candidatos ao transplante hepático é insignificante frente à estimativa de uma população de quase 157 milhões de habitantes (3.200 transplante/ano). Este artigo aborda a política vigente do Ministério e da secretaria de Estado da Saúde de São Paulo, onde a grave distorção provocada pelo critério exclusivamente cronológico em detrimento da gravidade clínica de cada caso tem levado a índices de mortalidade inaceitáveis nas listas de espera das equipes transplantadoras. Discute, também, possíveis soluções para o quadro atual, considerado dramático

Transplante hepático nas hepatites virais / Liver transplantation on viral hepatitis

O transplante de fígado alterou o prognóstico dos portadores de hepatopatias em fase terminal inclusive aquelas produzidas por vírus. Cirrose devida a hepatite crônica de etiologia nao-A, nao B é a indicaçao mais comum para o transplante. Tais doenças, contudo, sao passíveis de recidiva. As taxas de reinfecçao e recidiva da doença sao às vezes tao elevadas que tornam a indicaçao motivo de sérias controvérsias. O objetivo deste artigo é rever os dados mais atuais no que diz respeito à indicaçao do transplante de fígado para doenças hepáticas de etiologia viral. Tem sido observado que o tratamento de fígado portadores do vírus B, apesar da alta incidência de recidiva da infecçao e da doença, vem sendo realizado em diversos centros. Em relaçao à infecçao pelo vírus Delta, o transplante vem demonstrando resultados surpreendentes melhores, uma vez que a recidiva da doença somente se desenvolve na dependência da expressao dos marcadores do vírus B. Quanto ao vírus C, transplante hepático é realizado rotineiramente com bons resultados. Embora haja incidência de recidiva, a intensidade da doença hepática é, na maioria dos casos bastante discreta. É importante enfatizar que nao há métodos profiláticos ou terapêuticos eficazes para estas infecçoes no que diz respeito ao pós-transplante.

Hepatite crônica näo-A, näo-B: estudo clínico e morfológico / Chronic hepatitis non-A, non-B: clinical and morphologic study

Tendo em vista a grande freqüência mundial da hepatite crônica näo-A, näo-B (HCNANB) e a escassez de dados nacionais sobre a doença, realizamos estudo retrospectivo de 85 pacientes, atendidos até dezembro de1987. Foram divididos em quatro grupos: I: pós transfusional (PT), 35 pacientes (41,2%); II: de risco (GR), incluindo profissionais da saúde e toxicômanos, 11 (12,9%); III: esporádico com início bem definido (EBD), 19 (22,4%) e IV: esporádico com início näo definido (END), 20 (23,5%). A média de idade no grupo I foi significativamente maior que nos grupos II e III. O padräo polifásico das transaminases foi observado nos quatro grupos. Histologicamente, a freqüência das formas graves foi semelhante nos quatro grupos mas a HC lobular predominou no grupo III. Concluiu-se que a maneira como foi adquirida a infecçäo aguda näo tem implicaçöes prognósticas