hcv & brazil: lessons learned. evaldo stanislau affonso de araújo,md, phd. hospital das...
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HCV & Brazil: lessons learned.
Evaldo Stanislau Affonso de Araújo,MD, PhD.
Hospital das Clínicas FMUSP(presented by Dr.Fábio Mesquita)
Who am I? Why I am not here ?
Who I am... Why I am not here?
Left to right: Prof.Mendonça, Qui-Lim Choo(the one who discovered HCV), Prof.Barone and me.
THE HEPATITIS C CHALLENGE
1989
The burden of HCV infection
CDC. MMWR Morb Mortal Wkly Rep. 1998;47;1-39. NIH Consensus Conference Statement. Avaiable at: http://consensus.nih.gov/2002/ 2002HepatitisC2002116html.htm. Acesso 19 de Agosto, 2008. Rustgi VK. J Gastroenterol. 2007;42:513-521.
• Aproximately 3.9 million infected in USA– 35.000 estimated new cases per year– 85% became chronic
• 10.000-20.000 deaths per year associated to HCV– Estimated to become 3 times larger in the next 10-20 years
• Principal cause of – Chronic liver disease– Cirrhosis– Liver cancer– Liver Transplantation
14/08/2005 - 09h51
Mortalidade por hepatite C é a que mais cresce no país.
FERNANDA BASSETTE
da Folha de S.Paulo
www.uol.com.br, access 08/25/2005.
Brazil headline: HCV associated mortality in Brazil is growing at the fastest rate
among all other causes.
http://189.28.128.100/portal/arquivos/pdf/coletiva_saude_061008.pdf, acesso em 11/11/08.
Health Ministry Death Report: 11/2008: Cirrhosis and Liver diseases 8th cause of death among men.
Brazil: GDPs & HCV care: it is the Economy “stupid”...
GDP ($Reais) -2007 (from darker to lighter) + 500,000 + 100,000 + 50,000 + 10,000 + 5,000 + 1,000
Source: IBGE 2009/ DATASUS.
“HCV Belt”
São Paulo State ~ 70% of all HCV production!(care &therapy)
IMPROVING HDI
IMPROVING SCIENCE ($$)
IMPROVING DISEASE BURDEN
Human DeveIopment Index: 1990 (“HCV First Year”)-2006.
(darker color= higher HDI)
HCV vs Brazilian responseHCV Field & Brazil
• Before 1989 – NANB hepatitis• Universities and HIV units• 1989 – HCV• Viral Hepatitis academic units• 1990-1999 – Serologic tests, PCR, IFN&RBV• HAART, Blood Banks control, IFN, 90`s-NGO`s• Cities,States Hepatitis Programs• 2000-RBV distribution, social care• 2001 Cities Laws for prevention• 2002 – PegIFN• March 2002 – First National NGOs (11) Meeting –
Letter from Santos• 2002 – National Hepatitis Program & first National
Guideline
• Forced by LAW: PegIFN&RBV• 2002 – PCR without quotes/limits• 2004 – Isention of Federal Tax for liver
diseases patients• 2005 – Protocol update (Peg); Federal Law
reconizes viral hepatitis as an issue• 2006 – Health Ministry established the
central trade of PegIFN• 2007- Protocol update• 2008 – Patients with a representant in the
Advisory Board at Health Ministry• 2009 – Hepatitis Program joins Aids
Program• More than 70 NGOs; 2 National
Moviments, WHA representative.
Timeline of actions (Summary)
Before HCV
AcademicInstitutions
1989 1990`s
Academic InstitutionsHIV assistance NetSocial Mobilizations (NGOs)Local laws on awareness and assistance
2002-PegIFN2009 & Beyond
(DAAs)
NationalPolicies Government
&NGOs
Brazilian Constitution-Law!
WHY US ?
Maybe because an example of partnership. But, what about results ?
Epidemiology of HCV infection in Brazil.
* poverty, unsafe injections,dental care, health associated, tattoo, etc.
** Blood supply safe since 90’s & NAT recently approved.
Anti-HCV prevalence
0,32
1,050,81
1,08 1,10
1,61
1,89
0,69
1,791,94
0
0,5
1
1,5
2
2,5
Pre
vale
nce
Capitals National household survey– 2004-2005. Brazilian Health Ministry/ PAHO.
%
Nor
th-E
ast
Cen
ter-W
est
Fede
ral D
istri
ct
South
east
South
10 a 19 years
20 a 69 years
North: pending data.
~ 1,5%/ 189,000,000 = 2,7 mi with Anti-HCV + !
Prevalence of HCV genotypes during 1990-1997 and 1999-2007 in a cohort of patients from São Paulo, Brazil.
Cavalheiro NP, Melo CE, Tengan F, Araujo ESA, Barone AA.HCV 2008 Conference, San Antonio, USA.
2,155 samples 1990-2007Gt 1: 1538 (71,4%)Gt 2: 114 (5,3%)Gt 3: 478 (22,2%)Gt 4: 12 (0,6%)Gt 5: 13 (0,6%)Gt 6: zero.
Age is an issue !
• São Paulo city: – overall prevalence of Anti-HCV: 1,4 %.– 50-59 years: 3,8%.
Poynard T et al. Lancet, 1997: 825.
Brazil: Liver Disease by Age Group
0
500
1.000
1.500
2.000
2.500
Menor 1 ano
1 a 4 anos
5 a 14 anos
15 a 24 anos
25 a 34 anos
35 a 44 anos
45 a 54 anos
55 a 64 anos
65 a 74 anos
75 anos e mais
... 022 Hepatite viral
. 036 Neopl malig do fígado e vias bil intrahepát
... 080.2 Fibrose e cirrose do fígado
Source: MS/SVS/DASIS - Sistema de Informações sobre Mortalidade – SIM (2006).
Viral HepatitisLiver CancerLiver Cirrhosis * Alcohol excluded
Pro-activity: intervention before the problem increase !
Brazil: Deaths by determined causes(CID10) & liver diseases associated : 2000-2006.
0
1.000
2.000
3.000
4.000
5.000
6.000
7.000
8.000
9.000
10.000
2000 2001 2002 2003 2004 2005 2006
... 022 Hepatite viral
. 036 Neopl malig do fígado e vias bil intrahepát
... 080.2 Fibrose e cirrose do fígado
Viral HepatitisLiver CancerLiver Cirrhosis
Source: MS/SVS/DASIS - Sistema de Informações sobre Mortalidade – SIM (2006).
* Alcohol excluded
Brazil: Inpatients Impacts of Liver Disease vs ALL others diseases (2007)
648,91
672,35
5,8
576,63
576,63
9,16
0 100 200 300 400 500 600 700 800
Mean AIH Value (R$)
Mean value by Episode (R$)
Length of stay (mean)
Brasil (Mean) (other than liver disease)
Liver disease associated (Mean)
Source: Ministério da Saúde - Sistema de Informações Hospitalares do SUS (SIH/SUS) .
Liver disease stay longer & spent too much !
Liver Transplantation from cadaveric donor (2002- june 2007)
Number of Procedures
525
644
757
759
804
374
0 100 200 300 400 500 600 700 800 900
2002
2003
2004
2005
2006
* 2007
Source: Sistema Nacional de Transplantes / MS.
Waiting list for liver transplantation-HCFMUSP/São Paulo/2009.
Anti-Rejection drugs expenses (2000-2007).
35,35
28,56
89,38
63,99
54,47
2,2211,16
20,13
62,49
43,21
27,20
61,52
29,6331,3229,60
32,99
0,800,541,640,00 0,00 0,00 0,16 0,50
0,00
10,00
20,00
30,00
40,00
50,00
60,00
70,00
80,00
90,00
100,00
2000 2001 2002 2003 2004 2005 2006 2007
Millions (R$)
Tacrolimus 1/5 mg cápsula
Ciclosporin 100mg sol.oral-10/25/50/100 mg por cápsula
Anti-Hep B Immunoglobulin - 100/1000 UI inj
Source: Ministério da Saúde - Sistema de Informações Ambulatoriais do SUS (SIA/SUS)
HEALTH ASSISTANCE & THERAPY
Sistema Único de Saúde - SUS
SVR among pivotal trials and real-life at HC-FMUSP*
Manns M, et al. Lancet. 2001;358:958-965. Fried MW, et al. N Engl J Med. 2002;347:975-982.
Why so hugedifference ????
*HCFMUSP: 91% GT 1.
*Stanislau Affonso de Araújo,E et al (2007) Pegylated Interferon for chronic HCV infection:is it that good for “real real-life”? 14th International Symposium on Hepatitis C Virus & Related Viruses, p P284.
Real Life – HCFMUSP 2003-2006. Multivariate analysis.
Aim compliance: interdisciplinar approach !
Stanislau Affonso de Araújo,E et al (2007) Pegylated Interferon for chronic HCV infection:is it that good for “real real-life”? 14th International Symposium on Hepatitis C Virus & Related Viruses, p P284.
PegIFN by region in SUS (2002-2007*)*jan-may
Estimated therapies with PegINF by region//Brazil 2002-2007 (may).
Estimativa de terapias PegPopulação Estimativa de HCV(1,4%) 2002 2003 2004 2005 2006 2007(até maio) Total
Norte 15.022.000 210.308 0 80 143 45 33 287 587 "0,28%"Nordeste 51.609.000 722.526 20 269 441 163 50 617 1.561 "0,22%"Sudeste 79.561.000 1.113.854 95 753 1.728 820 692 6.075 10.163 "0,91%"
Sul 27.308.000 382.312 13 127 317 121 79 711 1.366 "0,36%"Centro-Oeste 13.269.000 185.766 4 93 168 70 55 293 682 "0,37%"
Total 186.769.000 2.614.766 132 1.322 2.796 1.219 909 7.983 14.360"0,55%"
"30%"= 784.430 "1,83%"
2010 update ~15,000 therapies
PROBLEMS
• Personal expectatives ?• How many ?• Myths
–HCV is always complex–HCV is always expensive
Imbalance....
System organization: Assistance net Financing
Knowledge evolutionPatients needs (the best, now!)Disease burden
Personal expectatives...different angles...
Solution ?
To manage !
Local organization.Training on disease management and estabilish
routines;Spread of assistance;Fight miths:
It is expensive... It is complex... Every patients take medicines... I do not have what offer...
HCV: predictable disease!
Avoid traps:ex.liver biopsy !*
*use of new non-invasive markers(including the simple and inexpensive
PLATELET COUNT!!!!)
TIME!
Time to organize !Time to stratify risk !
Time to Harm Reduction (avoid coinfections)!Time to non-pharmacologic therapies!Time in HCV Natural History= YEARS !
Possible paths to follow.1.Recognize the
problem: impacts & prevalence.
2. Define as a priority issue.
3. Make a plan.3.1Consider Natural History as an allied
and Harm Reductions policies3.2 Join Medical and Patients societies3.3 Establish a broad Therapeutic Protocol
3.3.1 – Non pharmacological3.3.2 - Pharmacologic
Conclusions• Magnitude and virologic aspects similar to developed countries, p.ex. USA.• Liver disease (HCV related) is an important and increasing cause of death in
Brazil• Despite efforts, assistance still far from ideal
– Access– Lack of exams– Southeast/South axis– Free Rx but how to expand assistance ?– Economic impact: raising costs (Rx, Tx, Post-Tx Rx…)
• Future burden of retreatment (increase # of NR) & DAAs (costs, resistance, compliance…)
• Poor real-life results– Compliance issues ?– Genetic/racial issues ?
• To be evaluated – IL28B polymorphism!
Irving et al J Viral Hep 13, 2006
Among the universe of HCV carriers in the USA
for each 100 tested, only 49 were refered,
27 went to a medical consultation,
17 did a liver biopsy and only 10 were treated.
What about us?
Effectiveness of Hepatitis C Treatment with Pegylated Interferon and Ribavirin in Urban Minority Patients. (HEPATOLOGY 2010;51:1137-1143.
Paul Feuerstadt,1 Ari L. Bunim,1 Heriberto Garcia,2 Jordan J. Karlitz,3 Hatef Massoumi,4 Amar J. Thosani,4 Andrew Pellecchia,1 Allan W. Wolkoff,4 Paul J. Gaglio,4 and John F. Reinus4.
Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic).3.3% of 1,656 treatment-naïve, HIV antibody–negative individuals ultimatelyachieved SVR.Current hepatitis C therapies may sometimes be unavailable to, inappropriatefor, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients.
HCV Prevention, Screening, Diagnosis and Treatment – a Practical Country Case Study: Brazil.
• Prevention– HBV vaccination, educational
activities (ex.cosmetic clinics, laws, days and weeks of prevention)
– Harm reduction policies: still weak.
– Avoid co-infections !
• Screening– Serologic and Campaigns
(NGOs) with point-of-care tests (thousands of tests and counseling!!!)
• Diagnosis– Strengthen official laboratories.– Centralized offer of Biomolecular
Tests.– Liver biopsies – a big concern.
• Treatment– Official rules.– Treat who needs to be treated– Central buying medicines.– Use of Aids net– Direct observation therapies– Multidisciplinary approach– OBTAIN compliance !
Brazilian proposition to WHO.
Facts & Faces to remember:
Harvey Alter & Qui-Lim Chooat the 20th HCV Anniversary Symposia in Brazil (2009).
Jeová Fragoso and Carlos Varaldo two cornerstoneLeadership in the NGOs moviment at the 20th HCV Anniversary Symposia in Brazil (2009).
The first step The more advanced step The necessary step
The ultimate step: union to win !
Working together against HCV: physicians, researchers, government and NGOs/patients (picture took at the end of the HCV 20 years Symposia, Brazil2009).
