Hepatitis C:
The Next Tsunami
Danny Jenkins
Cri-Help
Common Ground – The Westside HIV Community Center
We Write the Grants
www.wewritethegrants.com
Prevalence and Transmission of HCV
and HIV
HCV


Prevalence 1999
– World: 40-175 million
– USA: ~4 million
(1.8%)
Primary Modes of
Transmission
– Injection > sexual
– Occupational
– Perinatal
Lee W, et al. Drugs. 2004;64:693-700.
HIV
Prevalence 1999
– World: 40 million
– USA: ~1 million
(0.4%)
 Primary Modes of
Transmission
– Sexual > injection
– Occupational
– Perinatal

2
Overall Prevalence of HCV Among
HIV-Infected Persons in the
United States
HIV Monoinfected
HCV/HIV Coinfected
30%
70%
Thomas D. Hepatology. 2002;36:S201-S209.
3
Hospital Admissions Among
HIV-Infected Patients
Hospitalizations Per Patient-Year Follow-Up
5-fold increase in liver complications from 1995 to 2000
Opportunistic
infections
35
IDU-related
complications
Liver-related
complications
32
30
25
22
20
20
15
15
12
11
10
5
7 7
8 8 8
8 8
1997
1998
11
8
8
5 5
0
1995
1996
1999
2000
Gebo K, et al. J Acquir Immune Defic Syndr. 2003;34:165-173.
4
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.
5
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

1.
HCV may also impact the course of HIV disease
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.
6
2000;356:1800-1805.
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
7
Hepatitis C (HCV) Basics

Enters body through direct blood exposure

Attacks liver -> multiples (replicates)

Causes liver inflammation and kills liver cells
8
Natural History of HCV Infection
Exposure
(Acute phase)
15%
Resolved
85%
Chronic
HIV
2-12 Wks
20%
80%
Stable
Alcohol
Cirrhosis
75%
Slowly
Progressive
10-40 Yrs
25%
Liver Cancer
Transplant
Death
Alter MJ. Semin Liver Dis. 1995;15:5-14.
Management of Hepatitis C NIH Consensus Statement 1997; March 24-26:15(3).
9
Transmission




Blood to bloodstream
Syringes, cookers, tattooing, piercing,
razors, toothbrushes
Sexual transmission (very) rare
Perinatal 5%
10
Typical Symptoms





Nausea
Fatigue
Fever
Headaches
Loss of appetite





Abdominal pain
Muscle/joint pain
Flu-like symptoms
Jaundice
Dark urine
11
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
12
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
13
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
14
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+%
15
“Follow the Leader”
Themes in Which HCV Has Lagged
Significantly Behind HIV
16
Unmet Needs
and
Challenges
17
Stage
Hepatitis C Drug Development: 2005
Many others including
immune stimulants
gene therapy
Protease Inhibitors
Example: 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)
19
Conclusions
 Despite
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
targets
 Now
is the opportunity to develop pipeline therapies toward
these many unmet needs
20
Hepatitis C Task Force
for Los Angeles County
www.hepctaskforcela.org