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.

Hepatite C no sistema público de saúde brasileiro: impacto da doença / Hepatitis c in the brazilian public health care system: burden of disease

ABSTRACT BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é uma das principais causas de hepatite C crônica e provoca implicações graves para pacientes, familiares e sistema de saúde. OBJETIVO: Os objetivos deste estudo foram: analisar a gravidade da fibrose hepática, comorbidades e complicações da hepatite C; examinar a qualidade de vida relacionada à saúde (QVRS), a perda de produtividade e o uso de recursos e custos no sistema público por pacientes brasileiros com hepatite C crônica, genótipo tipo 1. MÉTODOS: Foi realizado um estudo transversal, multicêntrico em pacientes com hepatite C crônica genótipo-1 para avaliar a carga da doença no sistema público de saúde brasileiro entre novembro de 2014 e março de 2015. Os pacientes foram submetidos a uma elastografia hepática transitória (FibroScan) para avaliar a fibrose e a uma entrevista composta por um questionário desenvolvido para o estudo e cinco questionários padronizados: EQ-5D-3L, HCV-PRO, e WPAI:HepC. RESULTADOS: Foram recrutados 313 pacientes. A amostra foi composta predominantemente por mulheres (50,8%), caucasianos/brancos (55,9%) e indivíduos empregados (39,9%). A média de idade foi 56 (DP=10,4) anos. Em média, os pacientes com HCV esperaram 40,6 (DP=49,6) meses entre o diagnóstico e o primeiro tratamento. Ademais, 42,8% dos pacientes que realizaram o FibroScan tinham cirrose; a comorbidade mais frequente foi doença cardiovascular (62,6%) e a complicação mais comum as varizes esofágicas (54,5%). Os resultados também mostraram que "dor e desconforto" foi a dimensão de QVRS mais afetada (55,0% dos pacientes relataram alguns problemas) e que a média do escore do HCV-PRO foi 69,1 (DP=24,2). Em relação à perda de produtividade, o componente do WPAI:HepC mais afetado foi atividade diária (23,5%) e entre os pacientes empregados, presenteísmo foi mais frequente do que absenteísmo (18,5% vs 6,5%). Os custos diretos médicos totais com essa amostra foi de 12.305,72USD por paciente em um período de dois anos; o tratamento medicamentoso representou 95% desse total. CONCLUSÃO Esse estudo mostrou a maioria dos pacientes possui cirrose, apresenta alta prevalência de doenças cardiometabolicas e varizes esofágicas, QVRS reduzida principalmente em termos de dor/desconforto e dano na produtividade, especialmente presenteísmo. Adicionalmente, nós demonstramos que o HCV impõe uma carga econômica no sistema de saúde brasileiro e que os medicamentos correspondem à maioria dos custos.

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.

Characteristics of an outpatient chronic hepatitis B virus infection cohort / Caracterização de uma coorte ambulatorial de pacientes com infecção por vírus da hepatite B crônica

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. .

RESUMO Objetivo: Caracterizar uma coorte de pacientes com hepatite B crônica, segundo parâmetros iniciais e evolutivos. Métodos: Análise retrospectiva e descritiva dos dados clínicos e laboratoriais de portadores crônicos adultos do HBsAg, sem HIV, virgens de tratamento, com ao menos duas consultas ambulatoriais entre fevereiro de 2006 a novembro de 2012. Empregaram-se os testes exato de Fisher, χ², Wilcoxon, Spearman, Kappa e comparações múltiplas, o nível de significância estatística adotado foi de 5% e intervalo de confiança de 95%. Resultados: Foram incluídos 175 pacientes com média de idade de 42,95±12,53 anos, 93 (53,1%) do sexo masculino, 152 (86,9%) não reagentes para o antígeno e (HBeAg), 3 (1,7%) coinfectados com hepatite C, 15 (8,6%) cirróticos e 2 (1,1%) com carcinoma hepatocelular. Predominou o genótipo A. Constataram-se hepatite ativa em 66 pacientes (37,7%), imunotolerância em 6 (3,4%), estado de portador inativo em 38 (21,7%), exacerbações e/ou escapes virais em 16 (9,1%). Em 32 (18,3%), havia DNA viral persistentemente elevado e alanina aminotransferase normal; em 17 (9,7%), carga viral constantemente baixa e alanina aminotransferase alterada. Se fossem considerados apenas transaminases e DNA viral iniciais, 15 casos de hepatite ativa não teriam sido evidenciados. Fibrose avançada foi mais prevalente em HBeAg reagentes e associou-se direta e significativamente ao DNA do vírus da hepatite, idade e transaminases. Conclusão: Grande parte dos pacientes apresentou hepatite ativa. Porém, aproximadamente um quarto (todos pertencentes ao grupo HBeAg não reagente) foram identificados somente em função da análise conjunta das mensurações sequenciais de DNA do vírus da hepatite e transaminases, por vezes aliada a dados histológicos, após seguimento. .

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

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