HCV_Brazil_2010 by 9e8U70u

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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
 • 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


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.
    Brazil headline: HCV associated mortality
      in Brazil is growing at the fastest rate
             among all other causes.
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.
   Health Ministry Death Report: 11/2008: Cirrhosis and
      Liver diseases 8th cause of death among men.




http://189.28.128.100/portal/arquivos/pdf/coletiva_saude_061008.pdf, acesso em 11/11/08.
              Brazil: GDPs & HCV care: it is the
                      Economy “stupid”...

                              “HCV Belt”




GDP ($Reais) -2007               São Paulo State ~ 70% of all HCV production!
(from darker to lighter)                       (care &therapy)
 + 500,000
 + 100,000
 + 50,000
 + 10,000
 + 5,000
 + 1,000

Source: IBGE 2009/ DATASUS.
                             Human DeveIopment Index:
                             1990 (“HCV First Year”)-2006.




(darker color= higher HDI)


                                      IMPROVING HDI


                                       IMPROVING SCIENCE ($$)


                                             IMPROVING DISEASE BURDEN
                     HCV vs Brazilian response
     HCV Field & Brazil
•   Before 1989 – NANB hepatitis                •   Forced by LAW: PegIFN&RBV
•   Universities and HIV units                  •   2002 – PCR without quotes/limits
•   1989 – HCV                                  •   2004 – Isention of Federal Tax for
•   Viral Hepatitis academic units                  liver diseases patients
•   1990-1999 – Serologic tests, PCR, IFN&RBV   •   2005 – Protocol update (Peg); Federal
•   HAART, Blood Banks control, IFN, 90`s-          Law reconizes viral hepatitis as an
    NGO`s                                           issue
•   Cities,States Hepatitis Programs            •   2006 – Health Ministry established
                                                    the central trade of PegIFN
•   2000-RBV distribution, social care
                                                •   2007- Protocol update
•   2001 Cities Laws for prevention
                                                •   2008 – Patients with a representant
•   2002 – PegIFN                                   in the Advisory Board at Health
•   March 2002 – First National NGOs (11)           Ministry
    Meeting – Letter from Santos                •   2009 – Hepatitis Program joins Aids
•   2002 – National Hepatitis Program & first       Program
    National Guideline                          •   More than 70 NGOs; 2 National
                                                    Moviments, WHA representative.
      Timeline of actions (Summary)

                                                              2009 & Beyond
Before HCV     1989        1990`s             2002-PegIFN        (DAAs)

                                                  Brazilian Constitution
                                                          -Law!
Academic              Academic Institutions       National
Institutions          HIV assistance Net          Policies      Government
                      Social Mobilizations (NGOs)                   &
                      Local laws on awareness                     NGOs
                      and assistance
WHY US ?
    Maybe because an example of
partnership. But, what about results ?
      Epidemiology of HCV infection in Brazil.


                                               ** Blood supply safe since 90’s &
                                                     NAT recently approved.




       * poverty, unsafe injections,
dental care, health associated, tattoo, etc.
              Capitals National household survey– 2004-2005.
                       Brazilian Health Ministry/ PAHO.

                              Anti-HCV prevalence
~ 1,5%/ 189,000,000 = 2,7 mi with Anti-HCV + !
                                                                               10 a 19 years
                   %
             2,5                                                               20 a 69 years


              2                             1,89                                      1,94
                                                                        1,79
                              1,61
Prevalence




             1,5
                                     1,05                        1,08          1,10
              1                                    0,81
                                                          0,69
             0,5       0,32

              0




                                                                         North: pending data.
   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 1990-2007
Gt 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
       2.500      Pro-activity: intervention before the problem increase !

       2.000


       1.500


       1.000


         500


           0
               Menor 1   1a4     5 a 14    15 a 24    25 a 34   35 a 44     45 a 54   55 a 64   65 a 74   75 anos
                ano      anos    anos       anos       anos      anos        anos      anos      anos      e mais

                                    ... 022 Hepatite viral
                                     Viral Hepatitis
                                    . 036 Neopl malig do fígado e vias bil intrahepát
                                     Liver Cancer
                                    ... 080.2 Fibrose e cirrose do fígado
                                     Liver Cirrhosis                                    * Alcohol excluded

Source: MS/SVS/DASIS - Sistema de Informações sobre Mortalidade – SIM (2006).
Brazil: Deaths by determined causes(CID10) & liver diseases
                  associated : 2000-2006.

           10.000

            9.000

            8.000

            7.000

            6.000

            5.000

            4.000

            3.000

            2.000

            1.000

                    0

                        2000     2001             2002           2003            2004   2005    2006


                                     Viral Hepatitis
                                  ... 022 Hepatite viral

                                     Liver Cancer
                                  . 036 Neopl malig do fígado e vias bil intrahepát
                                  ... 080.2 Fibrose e cirrose do fígado
                                     Liver Cirrhosis                                    * Alcohol excluded
Source: MS/SVS/DASIS - Sistema de Informações sobre Mortalidade – SIM (2006).
       Brazil: Inpatients Impacts of Liver Disease vs
                 ALL others diseases (2007)


                                      9,16
              Length of stay                       Liver disease stay longer & spent too much !
               (mean)                 5,8



                                                                                       576,63
               Mean value by
               Episode (R$)                                                                     672,35



                                                                                       576,63
                Mean AIH
                Value (R$)                                                                   648,91


                                  0          100      200   300     400     500        600      700      800



                   Brasil (Mean) Liver disease associated (Mean)
                   (other than liver disease)
Source: Ministério da Saúde - Sistema de Informações Hospitalares do SUS (SIH/SUS) .
                 Liver Transplantation from cadaveric
                        donor (2002- june 2007)

                                Number of Procedures


* 2007                                    374



  2006                                                                                  804



  2005                                                                          759



  2004                                                                          757



  2003                                                              644



  2002                                                  525




         0        100     200    300      400     500         600         700     800         900




             Source: Sistema Nacional de Transplantes / MS.
 Wa i t i n g l i st fo r l i ve r t ra n s p l a ntat i o n -
          H C F M U S P/ S ã o Pa u l o / 2 0 0 9 .


                    1%
               2% 1% 1%
          7%
                                               HCV
  10%                                          ALCOHOL
                                               HBV
                                               CRIPTOGENETIC
                          HCV                  AUTOIMMUNE
10%                                51%         PBC
                                               HBV+HCV (1%)
                                               HBV+HDV (1%)
                                               SBC
        17%
                  Anti-Rejection drugs expenses (2000-2007).

Millions (R$)

100,00
                                                                                                             89,38
 90,00

 80,00

 70,00                         62,49                                                              63,99
                       61,52
 60,00                                                                                  54,47

                                                  43,21
 50,00
                                                                                35,35
 40,00                                                            32,99

 30,00
                                              20,13                             29,60     31,32      29,63
                                                                 28,56                                       27,20
 20,00
                                 11,16
 10,00                 2,22
                                                                                0,50    1,64                 0,80
                                                 0,00          0,16                                 0,54
                0,00             0,00
   0,00

                       2000     2001            2002             2003           2004       2005      2006    2007


                               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*
     *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.
                                                                                                              Why so huge
                                                                                                             difference ????




Manns M, et al. Lancet. 2001;358:958-965.
Fried MW, et al. N Engl J Med. 2002;347:975-982.                               *HCFMUSP: 91% GT 1.
                       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).
                                                2010 update ~15,000 therapies

                                                 Estimativa de terapias Peg
             População    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%"

    R$ 275.712.000,00/ ~ 140,000,000,00 US dollars (PegINF)
But only 0,5 a 1,8% of the patients needing care...and what is the SVR ?
            PROBLEMS
• Personal expectatives ?
• How many ?
• Myths
 –HCV is always complex
 –HCV is always expensive
                       Imbalance....
                                  Knowledge evolution
                                  Patients needs (the best, now!)
                                  Disease burden




System organization:
      Assistance net
          Financing
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!

                              Inclusion:
                           Basic assistance:
                        Time to organize !
             Advisory/ Non-pharmacological approach/ Harm
                     reduction/ Serological testing. !
                       Time to stratify risk
        Time to Harm Reduction (avoid coinfections)!
TIME!




                    Clinical & Laboratory
           Time to non-pharmacologic therapies!
                          evaluation.
           Time in HCV Natural History= YEARS !
                    Avoid traps:ex.liver biopsy !*



                                                 *use of new non-invasive markers
                              Therapy          (including the simple and inexpensive
                                                       PLATELET COUNT!!!!)
                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 policies
                          3.2 Join Medical and Patients societies
                          3.3 Establish a broad Therapeutic Protocol
                                    3.3.1 – Non pharmacological
                                    3.3.2 - 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!
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?


Irving et al J Viral Hep 13, 2006
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 ultimately
achieved SVR.
Current hepatitis C therapies may sometimes be unavailable to, inappropriate
for, 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                    • Diagnosis
   – HBV vaccination,            – Strengthen official laboratories.
     educational activities      – Centralized offer of Biomolecular
     (ex.cosmetic clinics, laws,   Tests.
     days and weeks of           – Liver biopsies – a big concern.
     prevention)
   – Harm reduction policies: • Treatment
     still weak.                 – Official rules.
   – Avoid co-infections !       – Treat who needs to be treated
• Screening                      – Central buying medicines.
   – Serologic and Campaigns     – Use of Aids net
     (NGOs) with point-of-care   – Direct observation therapies
     tests (thousands of tests   – Multidisciplinary approach
     and counseling!!!)          – OBTAIN compliance !
Brazilian proposition to WHO.
          Facts & Faces to remember:




Harvey Alter & Qui-Lim Choo   Jeová Fragoso and Carlos Varaldo two cornerstone
at the 20th HCV Anniversary   Leadership in the NGOs moviment at the 20th HCV
Symposia in Brazil (2009).    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).
Thanks for your attention !



contact: evaldostanislau@uol.com.br

								
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