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1 What are the options in Latin America Carlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em Clínica Médica e Gastroenterologia Universidade Federal do Estado do Rio de Janeiro Universidade Federal do Rio de Janeiro

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Page 1: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

1

What are the options in Latin America

Carlos Eduardo Brandão, MD, PhD

Professor Associado de Clínica Médica

Livre Docente em Clínica Médica e Gastroenterologia

Universidade Federal do Estado do Rio de Janeiro

Universidade Federal do Rio de Janeiro

Page 2: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Approximately 170 million people chronically infected

About 500,000 deaths/year

300,000 liver failure200,000 HCC

Global burden of HCV infection

Lim, et al. Lancet 2012; 380: 2224–2260.

Page 3: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

HCV Viremic Infections(Prevalence & Total Infected)

3

Total Infected (Viremic)

200K-650K

650K-1.9M

0-200K

1.9M-3.5M

3.5M-9.2M

Prevalence(Viremic)

0.0%-0.6%

0.6%-0.8%

0.8%-1.3%

1.3%-2.9%

2.9%-7.8%

Gower, E., Estes C., Hindman, S., Razavi-Shearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014.

Page 4: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

Argentina

Brazil

Chile

Colombia

CubaDominican Republic

Mexico

Peru

Puerto Rico

Venezuela

HCV Prevalence and Genotype DistributionLatin America

4

Total Infected (Viremic)

200K-650K

650K-1.9M

0-200K

Prevalence(Viremic)

0.0%-0.6%

0.6%-0.8%

0.8%-1.3%

1.3%-2.9%

2.9%-7.8%

Gower, E., Estes C., Hindman, S., Razavi-Shearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014.

Page 5: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Global Burden of HCV infection

Prevalência da infecção pela Hepatite C e Genotipagem

Distribuição da Faixa etária da infecção

Proporção da população diagnosticada e tratada

No Brasil < 20% diagnosticada e < 1% tratada ao ano

Duração da infecção pelo HCV

Dos fatores de comorbidade

(Álcool, HIV, HBV, Síndrome Metabólica)

Introdução e sucesso das novas modalidades terapêuticas

Bruggmann P, Berg T, Ovrehus AL, et al.. J Viral Hepat 2014; 21 Suppl 1: 5-33

Page 6: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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2,12%2,12%

1,04%1,04%

1,19%1,19%

1,43%1,43%

0,65%0,65%

Sociedade Brasileira de Hepatologia. Revista GED 1999; 18:53-58.

1,173,406 blood donors

14,527 anti-HCV+(1,23%)

HCV in Brazil: studies in blood donors

Page 7: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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0,32

1,05 1,08 1,10

1,611,89 1,79

1,94

0

0,5

1

1,5

2

2,5

10 - 19 years old

20 - 69 years old

1,0

3,2

3

Pereira LMMB, et al. BMC Infectious Diseases 2013, 13:60

HCV in Brazilian Regions: population studyA

nti-H

CV

pos

itive

(%)

Overall anti-HCV+ prevalence: 1.38% ( 2.6 million people) Around 2.1 million viremics (PCR+

Page 8: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Distribuição etária da população infectada:

Bruggmann P, Berg T, Ovrehus AL, et al.. J Viral Hepat 2014; 21 Suppl 1: 5-33.

Epidemias ‘mais jovens’ (UDIV e migração; fibrose discreta) vs ‘mais idosas’ (nosocomial; fibrose avançada e cirrose)

No Brasil Fibrose significativa (F2-F4) (55%) e prevalência por UDIV (5%) e histórico deTransfusão (15%)

Page 9: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

Age Distribution, 2013 Brazil, Egypt, Australia and Turkey

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

% o

f Tot

al H

CV

Infe

ctio

ns (2

013)

Brazil Egypt Australia Turkey

9Razavi H, Waked I, Sarrazin C, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014; 21 Suppl 1: 34-59.

Page 10: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

Prevalência da Hepatite C no Brasil HCC, Cirrose Descompensada e Transplante, 1950-2030 Brasil

10Razavi H, Waked I, Sarrazin C, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014; 21 Suppl 1: 34-59.

Page 11: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

HCV Treatment Rate

11

Page 12: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

Total Viremic HCV InfectionsCountries Responsible for 80% of Global Infections

12Gower, E., Estes C., Hindman, S., Razavi-Shearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014.

Page 13: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

Treatment Rate by Country, 2013

13

Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014;21 Suppl 1:34-59.

Hatzakis A, Chulanov V, Gadano AC, Bergin C, Ben-Ari Z, Mossong J, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm – J Viral Hepat 2014. Submitted for publication 30 July 2014.

Page 14: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Taxa de tratamento e número de tratados

Gore et al., Journal of Viral Hepatitis, 2014, 21 (Suppl. 1), 1–4

Page 15: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

15Adapted from Dore GJ, et al. Journal of Viral Hepatitis, 2014, 21 (Suppl.

Estimated HCV prevalence, diagnosis and treatment rate for several countries (2013)

12,000/yr (0.6%)

300,000(15%)

1%

0.3%

70%

Trea

tmen

t rat

e pe

r yea

r

Percent of the infected population diagnosed

5.2%

Page 16: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Brazil: more than 2 million people with

chronic HCV infection

‒ Less than 15% diagnosed

‒ Less than 10% treated

‒ Less than 5% cured

‒ Less than 1% treatment rate

But to achieve an SVR, first you have to find and treat the infected patients

Bruggmann, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 5–33

Page 17: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Outcome 2013 2030 Variation (%)

Total no. of HCV 1.940.000 1.250.000 ↓ 35

HCC 9.710 18.900 ↑ 95

Liver related deaths 9.000 16.620 ↑ 85

Decompensation 27.500 45.000 ↑ 95

Compensated cirrhosis 222.000 323.000 ↑ 65

Razavi, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 34–59

Estimated HCV disease burden in Brazil: (2013 vs 2030)

Page 18: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Year People treated

2007 6,533

2008 8,626

2009 8,224

2010 11,628

2011 11,505

2012 12,491

2014 15645

2014* Telaprevir (2600)Boceprevir (840)

Source: Programa DST/AIDS/Hepatites - 2014

HCV treatments per year in Brazil (including re-treatment and co-infection)

Only about 0.5% of all HCV infected patients are treated every year

Page 19: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Terapia Tripla no Brasil PegIFN/RBV e TelaprevirSVR24 por histórico de tratamento anterior

Ferreira, P; Brandão-Mello et al., 2014

Sem tratamento anterior (n=19)

Recidivantes do tratamento

anterior (n=31)

Respondedores parciais prévios

(n=15)

Respondedores nulos prévios

(n=28)

Page 20: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

2020

Outcome 2004 2006 2021

Total no. of HCV 575600 586800 647600

HCV Incidence 13700 14302 18700

Liver related deaths 10700 11000 19000

Treated patients 600 900 ?

Treatment rate (%) 0.10 0.15 ?

Kershenobich, et al. Liver International, 2011

Estimated HCV disease burden in Argentina: (2004 vs 2021)

Page 21: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

212121

Outcome 2004 2006 2021

Total no. of HCV 982700 1002900 1227600

HCV Incidence 29000 31044 47700

Liver related deaths 24800 25300 37000

Treated patients 1400 3300 ?

Treatment rate (%) 0.14 0.33 ?

Kershenobich, et al. Liver International, 2011

Estimated HCV disease burden in Mexico: (2004 vs 2021)

Page 22: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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HCV Treatment Rate

How to implement better strategies to increase treatment rate?

How to increase screening?How to increase diagnose?

22

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Impact of 3 different ways to manage HCVEstimates for Brazilian pts.

Strategy 1(no change)

Strategy 2(IFN‐free: ↑ SVR & pts eligibility)

Strategy 3(Strategy 2 plus↑ no. of treated pts )

Patients treated/year 11,700 11,700 118,700 (2021)Treatment rate (%) 0.6 0.6 9.1

Mean SVR (%)  43 90  90

New cases diagnosed/year  10,000 10,000 119,000 (2020)

Treatment elegibility (%) 60 95% 95%

Age for treatment (years) 15‐69 15‐69 15‐74

Stage for treatment (Metavir) ≥F2(G1); ≥F1(G2,3)  ≥F2(G1); ≥F1(G2,3) ≥F0 (all genotypes)

Reduction in mortality rate ‐ 5% 70%Reduction in HCC cases ‐ 5%  75%Reduction in decompensation ‐ 10% 80%Reduction in HCV infections ‐ 5% 90%

Wedemeyer, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89

Page 24: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

24Wedemeyer, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89

Brazil: comparison among strategies 1, 2, 3 Reduction in HCV infections Reduction in liver-related deaths

Reduction in HCC Reduction in cirrhosis

Page 25: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Estratégia de rastreamento

Wedemeyer, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89

Page 26: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Estimated age related distribution of HCV in Brazil vs. selected countries in 2013

Razavi, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 34–59

Baby boomer strategyis not appropriate for Brazil

Page 27: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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Estimated age related distribution of HCV in Brazil vs. selected countries in 2013

Razavi, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 34–59

Baby boomer strategyis not appropriate for Brazil

Brazil should test people born between 1950 and 1980

Page 28: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

28Wedemeyer, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89

Birth-cohort testing strategy to detect >75% of HCV pts. in several countries

Page 29: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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What are the options in Latin America

Países de América Latina que utilizam boceprevir e telaprevir:

Argentina, Brasil, Colômbia, Peru, Venezuela

Países de América Latina que somente utilizam o telaprevir:

Costa Rica, México, Santo Domingo

Países de América Latina que analisam a introdução dos novos DAAs:

Argentina, Brasil, Chile, Cuba, México

Países de América Latina que possuem um programa para as hepatites:

Argentina, Brasil, Chile, Colômbia, Costa Rica, Cuba, México

http://hepato.com/p_geral/023_geral_port.php#sthash.thJ4Tmyc.dpuf

Page 30: Carlos Eduardo Brandão, MD, PhDregist2.virology-education.com/2015/4thLatam/09_Brandao.pdfCarlos Eduardo Brandão, MD, PhD Professor Associado de Clínica Médica Livre Docente em

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What are the options in Latin AmericaSummary

A Epidemiologia da infecção pelo HCV é diferente entre os países daAmérica Latina

A carga de doença varia consideravelmente entre os países, nadependência da faixa etária, duração da infecção pelo HCV, dosfatores de comorbidade e da estratégia de tratamento antiviral

O número de pacientes diagnosticados e tratados é baixa (<10%:<1%)

Vários fatores socioecônomicos contribuem para as taxas de RVScomo doença hepática avançada, falta de infraestrutura de acesso aodiagnóstico e tratamento;população marginalizada e efeitos colateraisdo atual tratamento

Estratégias que combinem o emprego de medicações de alta eficáciae segurança aliada ao aumento nas taxas de rastreamento, diagnósticoe tratamento são imperiosas para reduzir o impacto causado pela HCV

Wedemeyer, et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89