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Hepatitis C:The Next Tsunami
Danny JenkinsCri-Help
Common Ground – The Westside HIV Community Center
We Write the Grants
www.wewritethegrants.com
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Prevalence and Transmission of HCV and HIV
Prevalence 1999
– World: 40-175 million
– USA: ~4 million (1.8%)
Primary Modes of Transmission
– Injection > sexual
– Occupational
– Perinatal
Prevalence 1999– World: 40 million– USA: ~1 million
(0.4%)Primary Modes of
Transmission– Sexual > injection– Occupational– Perinatal
HCV HIV
Lee W, et al. Drugs. 2004;64:693-700.
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HCV/HIV CoinfectedHIV Monoinfected
70%30%
Overall Prevalence of HCV Among HIV-Infected Persons in the
United States
Thomas D. Hepatology. 2002;36:S201-S209.
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Hospital Admissions Among HIV-Infected Patients
1995 1996 1997 1998 1999 2000
12
15
8 8 8 8
57
8 8
11
22
57
8
11
20
32
0
5
10
15
20
25
30
35
Opportunisticinfections
IDU-relatedcomplications
Liver-related complications
5-fold increase in liver complications from 1995 to 2000H
osp
ital
izat
ion
s P
er P
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Yea
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ollo
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Gebo K, et al. J Acquir Immune Defic Syndr. 2003;34:165-173.
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HCV/HIV Coinfected Patients and End-Stage Liver Disease
Clinical HCV is accelerated in HIV/HCV coinfection– Faster disease progression with an
increased risk of cirrhosis and decompensated liver disease
– More patients develop cirrhosis within given timeframe
– Alcohol has an additional aggravating effect
1. Graham C, et al. Clin Infect Dis. 2001;33:562-569.2. Lee W, et al. Drugs. 2004;64:693-700.
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HCV/HIV Coinfection:An Area of High Medical Need
One third of HIV patients are coinfected with HCV1
– Among HIV-infected IDU, this rises to 50%-90%2
HCV viral load higher in HCV/HIV vs. HCV patients3
HIV accelerates clinical course of HCV-related liver disease – Time to cirrhosis significantly reduced4
– Liver disease is now the leading cause of death in hospitalized AIDS patients5
HCV may also impact the course of HIV disease1. Thomas D. Hepatology. 2002;36:S201-S209. 2.Sulkowski M, et al. Ann Intern Med. 2003;138:197-207. 3. Soriano V, et al. J Hep. 2006:44;S44-S48. 4. Soto B, et al. J Hep. 1997:26;1-5. 5. Bica I, et al. Clin Infect Dis. 2001;32:492-497. 6. Sulkowski M, et al. Hepatology. 2002;35:182-189. 7. Greub G, et al. Lancet. 2000;356:1800-1805.
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Hepatitis C (HCV) Basics
Blood-borne virus (formerly non-A/non-B hepatitis)
Six major genotypes: 1a, 1b, 2a, 2b, 3, 4, 5 & 6
1a and 1b = most common in US & difficult to treat
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Hepatitis C (HCV) Basics
Enters body through direct blood exposure
Attacks liver -> multiples (replicates)
Causes liver inflammation and kills liver cells
9
Natural History of HCV Infection
ExposureExposure(Acute phase)(Acute phase)
ResolvedResolved ChronicChronic
CirrhosisCirrhosisStableStable
SlowlySlowlyProgressiveProgressive
Liver CancerLiver CancerTransplantTransplant
DeathDeath
20%
15% 85%
25%
80%
75%
HIVHIV
Alter MJ. Semin Liver Dis. 1995;15:5-14. Management of Hepatitis C NIH Consensus Statement 1997; March 24-26:15(3).
AlcoholAlcohol2-12 Wks
10-40 Yrs
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Transmission
Blood to bloodstream Syringes, cookers, tattooing, piercing,
razors, toothbrushes Sexual transmission (very) rare Perinatal 5%
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Typical Symptoms
Nausea Fatigue Fever Headaches Loss of appetite
Abdominal pain Muscle/joint pain Flu-like symptoms Jaundice Dark urine
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Some HCV Numbers
Likely that >4M Americans infected 8-10K Americans die annually This is expected to triple in 10-20 years Alcohol & drugs are like HCV fuel Hepatitis A & B Vaccines are a must
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Factors Associated with Disease Progression in HCV Infected Patients
Age > 50 years Duration of infection Male gender Iron overload Steatosis Alcohol Co-infection with HBV Co-infection with HIV
Not associated: HCV “viral load” HCV genotype Serum ALT ? Smoking
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HCV Tests
Antibody tests: Elisa & RIBA Viral Load
Predict Medical TX Response Measure Rx Effectiveness NOT to measure disease progression
Genotype Tests Liver Biochem/function Tests Biopsies – gold standard
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HCV Treatments
Pegylated Interferon + Ribavirin are only FDA approved Rx
– Interferon injected weekly
– Ribavirin boosts effect, daily pills Sustained Virological Response (SVR):
– Genotype 1: 40-50%
– Genotypes 2 & 3: 75+%
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“Follow the Leader”Themes in Which HCV Has Lagged
Significantly Behind HIV
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Unmet Needs and
Challenges
Hepatitis C Drug Development: 2005
Many others including immune stimulants
gene therapy
Sta
ge
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Protease InhibitorsExample: VX-950 or Telapravir
Recent US Study – 250 patients– 60% cleared virus (vs 40% standard TX only)– 67% on 1yr TX = no signs of infection– 2X “both” patients stopped TX -> side effects
Recent European Study – 334 Patients– After 6 mos, 69% “both” -> undetectable– (vs 46% on standard TX only)
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ConclusionsDespite advances in therapy, many needs remain unmet
– Hard-to-treat patients– Nonresponders– Patients excluded from current therapies
New antivirals with innovative mechanisms of action may help meet those needs
– Monotherapy– In combination with PEG IFN +/- RBV– In combination with new antivirals with different
targetsNow is the opportunity to develop pipeline therapies toward
these many unmet needs
Hepatitis C Task Forcefor Los Angeles County
www.hepctaskforcela.org