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Hepatitis C – A Primer

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					NIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2002
                                   2
          Developed countries



                                               Americas + Western Europe
       South Africa
                           5
                                                   1
Middle East
North Africa
                4



                  IVDU
                            3
                                          6 Asia
Simmonds P, Journal of Hepatology, 1999
                                   170 Million Carriers Worldwide, 3 - 4 MM new cases/year
                                   3% of World Population




                                           EAST
        CANADA 300,000          WEST                          FAR EAST ASIA
                                           MEDITERRANEAN
                                EUROPE     20M                60 M
             U.S.A.             9M
             4M                                        SOUTH EAST ASIA
                                                       30 M
                                         AFRICA
                                         32 M


                      SOUTH
                      AMERICA
                      10 M                                       AUSTRALIA
                                                                 0.2 M




SOURCE, WHO 1999
1. Zou S et al. Canada Communicable Disease Report. Sept 2001; 2753.
Wong Am J Pub Health 2000
90,000

80,000

70,000

60,000

50,000

40,000

30,000

20,000

10,000

    0
    1992   1994   1996   1998   2000   2002   2004   2006
IDU           Ex-IDU
20%            34%


                       Transfusion
      Other                11%
      35%




                        Hemophilia
                          0.3%
                  Factors Which Might Influence The
                  Outcome Of Hepatitis C

                                                         Host
                 Virus                          -   Sex
           - Load                               -   Age
           - Genotype                           -   Race
           - Quasispecies                       -   Genetics
                                                -   Immune response



                                 Environment
                                  - Alcohol
                                  - HBV
                                  - HIV
                                  - Drugs
                                  - Steatosis
                                  - Iron
                                  - TREATMENT
Alberti, J of Hepatology, 1999
               RELATIONSHIP BETWEEN CIRRHOSIS AND YEARS AFTER EXPOSURE

              100
                                                          85
              80
% CIRRHOSIS




                                                64
                                      58
              60                                                  HCV
                                                     40
              40                           31                     HCV+ALC
                         18
              20                 12
                     6
               0
                      10          20        30        40
                              YEARS AFTER EXPOSURE
                                                      Wiley et al.
                                                      Hepatology, 1998
Are you sure he said we
can only have one?
Haematological                                       Ocular
• Mixed cryoglobulinemia                             • Corneal ulcer
• Aplastic anaemia                                   • Uveitis
• Thrombocytopenia
• Non-Hodgkin’s b-cell lymphoma
                                                     Vascular
Dermatological                                       • Necrotising vasculitis
                                                     • Polyarteritis nodosa
• Porphyria cutanea tarda
                                                     • Pulmonary fibrosis
• Lichen planus
• Cutaneous necrotising                               Neuromuscular
  vasculitis                                          • Weakness/myalgia
Renal                                                 • Peripheral neuropathy
• Glomerulonephritis                                  • Arthritis/arthralgia
• Nephrotic syndrome                                 Autoimmune
Endocrine                                            Phenomena
• Anti-thyroid antibodies                            •CREST syndrome
• Diabetes mellitus                                  •Granuloma
                                                     •Autoantibodies
Salivary
• Sialadenitis                Hadziyannis. J Eur Acad Dermatol Venereol. 1998.
                                                                       Assess severity of
                                                                          fibrosis and
                                                                      necroinflammation1,2



Associated risks:
                                                                               Can aid decision
 bleeding <1%
                                                                                   making
death 0.01 – 1%3



       Evaluate possible
                                                                                    Assess
     concomitant disease
                                                                                 therapeutic
  processes (eg, alcoholic liver
                                                                                intervention1
       disease, NASH)1,2

     1. NIH Consensus Statement Online. Management of hepatitis C. 2. British Liver Trust Information Service.
                                               A guide to liver function tests. 3. Canadian Liver Foundation.
                Liver Damage in Chronic HCV Infection:
                    ‘Normal’ vs Elevated Serum ALT

               Portal                      Bridging
                26%                          16%                 Cirrhosis
                          Bridging                                 22%
                             6%
   No                      Cirrhosis
fibrosis                               Portal
                              6%
  23%                                   24%
                                                                       Mild
                                                                       19%

                          Mild                 No
                          39%               fibrosis
                                              19%

           ‘NORMAL’ ALT                         ELEVATED ALT
                                                  Shiffman et al. J Infect Dis. 2000.
                              Secondary objective = delay/prevent

                              • Reduce progression of fibrosis1

                              • Reduce progression to cirrhosis2

                              • Prevent decompensation

                              • Prevent HCC2




1. Worman. Hepatitis C: Sourcebook 2002. 2. Peters et al. Medscape HIV/AIDS eJournal. 2002;8(1).
Continued next slide
Treatment        Peginterferon alfa-2a sc 180 µg/week, plus oral
options          ribavirin 1000 (if <75 kg) or 1200 mg/day (≥75 kg)
                         or
                 Peginterferon alfa-2b sc 1.5 µg/kg/week,
                 plus oral ribavirin 800–1200 mg/day
                 (depending on patient weight)
Duration        48 weeks

Criteria for     No EVR (week 12)
discontinuation  Viremia after week 24
     Treatment              Peginterferon alfa-2a sc 180 µg/week,
     options                plus oral ribavirin 800 mg/day
                                   or
                            Peginterferon alfa-2b sc 1.5 µg/kg/week,
                            plus WBD oral ribavirin1
     Duration of            24 weeks
     treatment


1Unconvincing  evidence that ribavirin doses >800 mg/day
 are required for genotype 2/3
   Time-point                                                   HCV RNA status
Week 4                         RVR Negative (<50 IU/mL)
                               EVR ≥2-log10 decline or negative (<50 IU/mL)
Week 12                        EVC Negative (<50 IU/mL)
                               PVR Positive (≥2-log10 decline)
24 weeks after                 SVR Negative (<50 IU/mL)
EOT

  EOT= end of treatment; EVC = early virologic clearance (also known as aviremic EVR); EVR = early virologic response;
  PVR = partial virologic response (also known as viremic EVR); RVR = rapid virologic response; SVR = sustained virologic
  response
                100%
                                       79%
                                                  72%
                80%                                           66%


                60%
        SVR %




                             42%

                40%


                20%


                 0%
                       G1 n=1078   G2 n=276   G3 n=389   Other n=41


AASLD, 2007 Abstract # 254
               100%
                                           P<0.001
                         66%
               75%
                                     56%
       SVR %




                                                     40%
               50%
                                                                29%


               25%



                0%
                      F1, n=250   F2, n=318     F3, n=206   F4, n=172



AASLD, 2007 Abstract # 254
                    • Alopecia
                    • Injection-site reaction
                    • Leukopenia
                    • Thyroiditis
                    • Autoimmunity
                    • Thrombocytopenia




INTRON® A. PDR . 56th ed. 2002. ROFERON®-A. PDR . 56th ed.
                                                    2002.
REBETOL®. PDR. 56th ed. 2002. Chutaputti. J Gastroenterol Hepatol. 2000 (suppl).

				
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