CDC PUBLIC HEALTH GRAND ROUNDS

The 25th Anniversary of the
Discovery of the Hepatitis C Virus
Looking Back to Look Forward

June 17, 2014
1

The Epidemiology of Hepatitis C
How Did We Get Here?

John W. Ward, MD
Director, Division of Viral Hepatitis
National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention

2

Key Contributors to the Discovery of HCV

Harvey Alter

3

Daniel Bradley

Discovery of Hepatitis C Virus (HCV)
 Discovered in 1989, RNA virus, family Flaviviridae

 9,600 nucleotide genome-single polyprotein





Structural proteins
Non-structural proteins - viral replication and targets of therapy
High genetic diversity leads to intra-host variants “quasispecies”
7 major genotypes that predict treatment response
 Genotype 1 accounts for ~ 70% of infections in US

 No vaccine candidates for licensure

Serine protease
RNA helicase
Lindenbach BD, Fields Virology 2001. Simmonds P, Hepatology 1995. Irshad M, Hepatogastroenterology 2010.
Manos MM, J Med Virol 2012.
4

Global Burden of HCV Infection, 2005

135 million persons living with HCV
500,000 deaths per year

HCV: Hepatitis C virus.
Estimated from: Hanafiah K, Hepatology 2012. Lozano R, Lancet 2012.
5

Prevalence of Current HCV Infection Among
Persons in the United States
 Prevalence in United States ~3 million
 NHANES prevalence estimate
 2.7 million individuals (2.2-3.2 million)
 1.0% (0.8%-1.2%)
 Civilian, non-institutionalized populations

 Non-NHANES prevalence estimate
 360,000-840,000
 22%-52% of those incarcerated
 Homeless or incarcerated persons

NHANES: National Health and Nutrition Examination Survey.
Denniston M, Ann Int Med 2014. Chak E, Liver Int 2011.
6

Impact of Prevention Measures
on HCV in United States
20
18

1986 Indirect blood screening for HCV
and HIV prevention measures

16
14
12
10
8
6
4

Anti-HCV test licensed
1992 1992199219
Needlestick Safety
Discovery
and Prevention Act
of HCV
2001
1 111989

2
0

Year

22,000 new cases reported in 2012
Jagger J, J Infect Dis Pub Health 2008. Ward JW. Clin Liver Dis, 2013. CDC.gov/hepatitis
7

Recent Increases in HCV Infection
 Between 2007 and 2012
 50% increase in case reporting
 200% increase in 17 states

 Risk factors
 ~ 70% persons who inject drugs
 Previous oral prescription
narcotic use
 Equally male to female
 Young, ages 18 to 29 years
 Rural and suburban
 White
PWID: Persons who inject drugs.
8

CDC unpublished data.

HCV Transmission Among
Persons Who Inject Drugs (PWID)
 Transmission risks
 Injection duration
 Injection frequency
 Equipment sharing,
not just sharing needles

HIV
HCV

 HCV prevalence
 27 to 51%

 Incidence declined in
response to harm reduction for HIV
(e.g., syringe access programs)
Burt, J Urban Health 2007. Garfein R, J Urban Health 2013. Keen L, Addict Behav 2014. Amon JJ, Clin Infect Dis 2008
Kwon J, AIDS 2009.
9

Other Modes of HCV Transmission
 Accidental needle stick in healthcare setting
 HCV risk is 1.3%, HIV risk is 0.3%
 18 healthcare-associated outbreaks from 2008 to 2013
 223 cases involving over 90,550 at-risk persons notified
 Non-injecting drug use (e.g., intranasal cocaine use)
 Perinatal-infants born to HCV infected mothers
 ~4% risk if mother infected with HCV
 ~25% risk if mother co-infected with HCV and HIV
 Sexual transmission is rare
 HIV infected MSM at highest risk
 Miscellaneous reported
 Unregulated tattooing
MSM: Men who have sex with men.

10

Scheinmann, Drug and Alcohol Dependence 2006. Weinbaum, MMWR 2003. Gough, BMC Public Health 2010. Mast, J Infect Dis, 2005.
Marincovich B, Sex Transm Infect 2003. Yaphe S, Sex Transm Inf 2012. Bottieau, Eurosurveillance 2010. Ackerman Z, J Viral Hepat 2000.
Tohme RA, CID 2012. MMWR 2001. CDC/hepatitis.gov

Natural History of HCV Infection
In 20 years, 15-30% progress to cirrhosis
Progression accelerated by HIV, HBV, alcohol use, and fatty liver
20 years
Liver
Transplant
or
Early
Death

HIV: Human immunodeficiency virus. HBV: Hepatitis B virus.
Hepatocellular carcinoma = Liver cancer. Decompensated Cirrhosis = End stage liver disease.
11

Ly KN, Clin Infect Dis. 2014. Mahajan R, CID 2014 .

Mortality from HCV is Increasing
 From 1999 to 2010, HCV deaths increased by 50%
 In 2010, 16,600 deaths
 Mean age at death was 59 years

 Two-fold increased mortality risk
 Black non-Hispanic
 American Indian/Alaskan Natives

 Mortality is under estimated
 Only 33% of liver-related deaths among HCV infected
persons are reported on Vital Records

 At least 45-60% are not aware of their HCV
infection
Ly KN, Clin Infect Dis 2014. Mahajan R, CID 2014 .
12

The Silent Growing Burden of Hepatitis C
in the United States

Number of People

 Of 2.7 million HCV-infected people from NHANES
 1.47 million will develop decompensated cirrhosis (DCC)
 350,000 will develop hepatocellular carcinoma (HCC)
 900,000 will die from HCV-related complications
40,000

Deaths

35,000
30,000

DCC

25,000

HCC

20,000
15,000

10,000
5,000
0

Year

NHANES: Nutritional Health DCC: Liver failure. HCC: Liver cancer.
13

Rein D, Dig Liver Dis 2010.

 Six-fold higher prevalence than
other US adults 3.39% vs 0.55%
 Of all HCV infected US adults,
81% were born in this cohort

 Of all HCV-related deaths in US,
73% were born in this cohort

1988–1994
1999–2002

7.0
6.0
5.0
4.0
3.0
2.0
1.0

0.0
0

10

20

30

40

50

7.0

1945

70

1965

6.0

1988–1994
1999–2002

5.0
4.0
3.0

2.0
1.0
0.0
1910

1920

1930

1940 1950 1960
Year of Birth

Smith, AASLD Liver Meeting 2011. Armstrong, Ann Int Med 2006. Kramer, Hepatology 2011. Ly, Ann Int Med 2012.
14

60

Age at Time of Survey, y

Proportion Anti-HCV-Positive, %

Historical high incidence

Proportion Anti-HCV-Positive, %

The Birth Cohort:
People Born during 1945 to 1965

1970

1980

1990

One time Testing for HCV for
Persons Born 1945-1965
 Recommended by CDC in 2012 and USPSTF in 2013
 Screening recommendation is solely based on year of
birth, not on risk factors
 Clinicians may be reluctant to ask about risks
 Patients may be reluctant to disclose or may not recall risks

 Persons found to be HCV infected need to link to care
and treatment

15

USPSTF: U.S. Preventive Services Task Force.
MMWR Aug 2012. Moyer VA, Ann Int Med 2013. Shehab TM, J Viral Hepat 2001. Shehab TM, Am J Gastroenterol 2003. Serrante JM,
Fam Med 2008. Shehab TM, Hepatology 1999. Roblin, Am J Man Care 2011. Spradling, Hepatology 2012. Zapata, Ann Hepatology 2010.
Napper, AIDS Behav 2010. Haley, Preven Med 2002. Torrone, AIDS Pat Care 2010. Rein D, Ann Int Med 2012. Eckman, CID, 2013.
McEwan, Hepatology 2013. McGarry, Hepatology 2012. Liu S, Plos One 2013.

Continued Risk-based Recommendations
for HCV Screening
 Risk-based screening
 Major risk-past or present injection drug use
 Other risks








Received blood/organs prior to June 1992
Received blood products made prior to 1987
Ever on chronic hemodialysis
Infants born to HCV-infected mothers
Intranasal drug use
Unregulated tattoo
History of incarceration

 Medical
 Persistently elevated ALT
 HIV
USPSTF: U. S. Preventive Services Task Force. ALT: Alanine transaminase.

16

MMWR Aug 2012. Moyer VA, Ann Int Med 2013.

Benefits of Birth Cohort Testing

 The Birth Cohort urgently needs to be identified to
allow them the opportunity to be diagnosed and treated
 Reduces risks of all-cause mortality by 50%
 Reduces risks of hepatocellular carcinoma by 70%

Rein D, Ann Int Med 2012. Eckman, CID, 2013. McEwan, Hepatology 2013. McGarry, Hepatology 2012. Liu S, Plos One 2013.
17

HCV Testing Cost Effectiveness

Cost per Quality Adjusted
Life Year Gained

60,000
50,000
40,000

HCV
Therapy 2014*

HCV
Therapy 2012

30,000
20,000
10,000
0

*CDC unpublished data. TVR: Telapravir.
http://www.prevent.org/National-Commission-on-Prevention-Priorities/Rankings-of-Preventive-Services-for-the-US-Population.aspx
Rein D, Ann Int. Med 2012.
18

Improving the Continuum of Care
for HCV Management
 ~ 3 million persons living with HCV in the United States
 Current cure rates need to improve
120%
100%
80%

50%

60%

38%
23%

40%

11%
20%

6%

0%
All HCV
infected

anti-HCV
tested

HCV care

SVR: Sustained viral response. Holmberg S, NEJM 2013.
19

HCV RNA

Treated

SVR

Where Are We Now?
 The burden of HCV-related disease is large
 Reports of new HCV infections are increasing
 CDC and USPSTF recommend HCV testing for persons
 Born during 1945 to 1965
 Who inject drugs, past or present
 Others at risk
 At least half of HCV-infected person are unaware of status
 Access to HCV testing, care, and treatment must improve for
patients to benefit from advances in therapy

20

Know More Hepatitis Campaign
Times Square, May 2014

21

Hepatitis C: The Curative Era

David Thomas, MD
Stanhope Bayne Jones Professor of Medicine
Chief of Infectious Diseases
Johns Hopkins School of Medicine

22

Hepatitis C Treatment Responses
Non-Response, Relapse, Sustained Viral Response

HCV RNA serum levels

Non-Response (Null)
Treatment
Non-Response (Partial)

Relapse
Interval

Sustained Viral Response (SVR)

Non-Response
Relapse

SVR

AASLD HCV Treatment Guidelines, www.aasld.org
23

SVR is Considered Cure
Reinfection is Uncommon
Percent with 5-year SVR

5-year estimate of continued
sustained viral response:
99.2% (95% CI 98.1%-99.7%)
N=636

SVR: Sustained viral response
Swain, Gastro 2010. Manns, J Viral Hep 2014.
24

SVR is Considered Cure
Reduction in Liver Failure

Van der Meer, JAMA 2012. Backus, Clin Gastro 2011. Imazeki, Hepatology 2003. Shiratori, Ann Intern Med 2005.
Veldt, Ann Intern Med 2007. Berenguer, Hepatology 2009.
25

SVR is Considered Cure
Reduction in Hepatocelluar Carcinoma

Van der Meer, JAMA 2012. Backus, Clin Gastro 2011. Imazeki, Hepatology 2003. Shiratori, Ann Intern Med 2005.
Veldt, Ann Intern Med 2007. Berenguer, Hepatology 2009.
26

SVR is Considered Cure
Reduction in All-Cause Mortality

Van der Meer, JAMA 2012. Backus, Clin Gastro 2011. Imazeki, Hepatology 2003. Shiratori, Ann Intern Med 2005.
Veldt, Ann Intern Med 2007. Berenguer, Hepatology 2009.
27

Key Therapeutic Milestones in Reaching the
Curative Era of HCV

 FDA Approval of HCV Treatments
 1991 Interferon (IFN)
 1998 IFN and ribavirin
 2001 Pegylated IFN
 2011 Boceprevir and telaprevir
 2013 Sofosbuvir and simeprevir

28

Thomas, Nat Med 2013.

High Rate of SVR
Sofosbuvir, PegIFN, and Ribavirin for 12 weeks

Percent maintaining SVR 12 weeks
after end of therapy

100

98

92

90

87

87

Non-CC

Black

91

80

80
70
60
50

40
30
20
10
0
F0-3

F4

IL28B CC

PegIFN; pegylated interferon. F0-3: Stages of liver fibrosis from none to moderate. F4: Severe liver fibrosis.
Non-CC: Individuals with either CT or TT IL28-genotype.
29

Lawitz, NEJM 2013.

Latino

High Rate of SVR for Genotype 1 HCV
Ledipasvir (LDV) and Sofosbuvir (SOF)
LDV/SOF naive F0-2, naive
SVR12

Non-VF

Relapse

100%
Percent maintaining SVR 12 weeks
after end of therapy

LDV/SOF prior treatment, 20% cirrhosis
SVR12

Non-VF

Relapse

100%

90%
80%

80%

70%
60%

60%

50%
40%

40%

30%
20%

20%

10%
0%

0%
LDV/SOF 8W,
215

LDV/SOF/R
8W, 216

LDV/SOF 12W,
216

LDV/SOF LDV/SOF/R LDV/SOF LDV/SOF/R
12W, 109 12W, 111 24W, 109 24W, 111

SVR12: Sustained Viral Response for 12 weeks. Non-VF: Non-virologic treatment failure. 8W: 8 weeks of therapy.
12W: 12 weeks of therapy. 24W: 24 weeks of therapy. R: Ribavirin.
30

Kowdley NEJM 2014. Afdhal, NEJM 2014.

SVR with 6 weeks of Sofosbuvir, Ledipasvir,
and GS-9669 or GS-9451
SVR12

Relapse

Percent maintaining SVR 12 weeks
after end of therapy

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
SOF/LDV 8W

N=20

SOF/LDV/9669 6W

N=20

SOF/LDV/9451 6W

N=20

SVR12: Sustained Viral Response at 12weeks. SOF: Sofosbuvir. LDV: Ledipasvir. 8W: 8 weeks. 6W: 6 weeks.
31

Kohli, Poster 27LB, Conference on Retroviruses and Opportunistic Infections 2014. NCT01431898. NCT01805882.

Fewer Adverse Events with Newer Therapies
Events

Telaprevir, Peg, R
n=292

Boceprevir, Peg, R
n=205

Serious adverse event (SAE)

132 (45%)

67 (33%)

Premature discontinuation

66 (23%)

54 (26%)

Discontinuation due to SAE

43 (15%)

15 (7%)

6 (2%)

6 (3%)

14 (5%)

0

LDV-SOF x 8 wk
n=215

LDV-SOF RBV x 8 wk
n=216

Serious adverse event (SAE)

4 (2%)

1 (<1%)

Discontinuation due to SAE

0

1 (<1%)

Hepatic decompensation

Serious rash

Events

Peg=Pegylated interferon. R=Ribavirin. LDV=Ledipasvir. SOF=Sofosbuvir.
32

Hezode J Hepatol 2013. Knowdley, NEJM 2014.

Rapid Progress in Interferon-sparing
HCV Treatment
 Genotype 1







*Simeprevir and sofosbuvir (not FDA approved, filed)
*Sofosbuvir and ribavirin (alternative)
Sofosbuvir and ledipasvir (filed)
ABT 450/r, ombitasvir, dasabuvir, +/- ribavirin (filed)
Daclatasvir and asunaprevir (filed)
MK5172, MK8742, +/- ribavirin (phase 3)

 Genotype 2 and 3
 *Sofosbuvir and ribavirin

*the individual components of these regimens are already available in June 2014.
33

Expert Guidelines for HCV Screening,
Management and Treatment

Copyright © 2014 by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.
34

Evaluating the Cost Effectiveness
of New Therapies
 In 2011, average wholesale acquisition costs of
drugs alone were $32,000 to over $100,000
 Quality adjusted life years for those regimens
considered reasonable
 New regimens are $100,000 to $175,000 in US
 Incremental cost benefits have been demonstrated
 Evaluating cost effectiveness of new regimens also
has to reflect the increased efficacy of the treatment
(cost/cure)

35

Rein Ann Intern Med 2012 and unpublished data. Younoussi, J Hepatol 2014. Hagan, Hepatology 2014. Linas, AIDS 2014.
Deuffic-Burban, J Hepatol 2014. Brogan, Plos One 2014 .

Steady Progress in Treatment Efficacy Has Increased
the Proportion of Persons Who Are Cured

All oral
PegIFN, RBV, and protease inhibitor
PegIFN and ribavirin
IFN and ribavirin

IFN

36

Thomas, Nat Med 2013.

Greater Uptake Will Maximize Potential
Global Impact
135 million
2013

% cured

2011

2004

Lack of expanded use in
infected people

1998

1991

% treated

37

Thomas, Nat Med 2013.

Conclusions: HCV Curative Era
 HCV can be cured
 Curing HCV reduces mortality and morbidity

 Curing HCV reduces the risk of HCV transmission
 Major challenges to global control are screening and
testing and lack of treatment access

38

Steps Toward Ending Hepatitis C in the US

Phillip Coffin, MD, MIA
Director of Substance Use Research
San Francisco Department of Public Health
University of California San Francisco

39

Essential Goals to Eliminate HCV
 Prevent sequelae of advancing liver disease in
those already infected
 Baby Boomers, born 1945-1965
 Many don’t know they are infected

 Prevent new or “incident” infections
 Persons who inject drugs (PWID)
 Unsafe healthcare practices
 Sexual exposures in immunocompromised individuals

40

Continuum of Care Model for HIV
Primary
Prevention

Screening
and Testing

Diagnosis

Management

Linkage

Treatment

Engagement /
Retention

Engagement /
Retention

Adapted from: Das M, Conference on Retroviruses and Opportunistic Infections 2014.
41

Virologic
Suppression

Long-term
Reduction
in
Prevalence
and
Incidence
of HIV

Continuum of Care Model for HCV
Primary Prevention – Syringe Exchange,
Condoms, Substance Use Treatment

Screening
and Testing

Diagnosis

Management

Linkage

Treatment

Engagement /
Retention

Cure

Engagement /
Retention

HCV screening test

 Screening tests would be opt-out
 EHR designed to have automated reminders
 Healthcare-level tracking to ensure baby boomers get screened

Adapted from: Das M, Conference on Retroviruses and Opportunistic Infections 2014.
42

Long-term
Decrease
in
Prevalence
and
Incidence
of HCV

Continuum of Care Model for HCV

Screening
and Testing

Diagnosis

Management

Linkage

Treatment

Engagement /
Retention

Cure

Engagement /
Retention

Long-term
Decrease in
Prevalence
and
Incidence
of HCV

RNA confirmatory testing
Staging of fibrosis






Simplify two-step process of screening then RNA confirmatory through reflexive testing
Healthcare level systems could match positive screens to ensure follow-up testing
Public health systems cannot track follow-up testing, negative test results not reportable
Evaluate effectiveness of screening efforts by comparing to stage of fibrosis at diagnosis

Adapted from: Das M, Conference on Retroviruses and Opportunistic Infections 2014.
43

Continuum of Care Model for HCV

Screening
and Testing

Diagnosis

Management

Linkage

Treatment

Engagement /
Retention

Cure

Engagement /
Retention

Long-term
Decrease in
Prevalence
and
Incidence
of HCV

Screening for syndemics, Vaccination, Risk-reduction counseling,
Evaluation for treatment including liver function, Genotyping

 Patient management should include referral to substance use disorder treatment and
brief alcohol interventions
 Healthcare-level systems could track serial ALT to ensure periodic evaluation is done

ALT: Alanine transaminase. Syndemic infections include Hepatitis A, Hepatitis B and HIV.
Adapted from: Das M, Conference on Retroviruses and Opportunistic Infections 2014.
44

Continuum of Care Model for HCV

Screening
and Testing

Diagnosis

Management

Linkage

Treatment

Engagement /
Retention

Cure

Engagement /
Retention

Long-term
Decrease in
Prevalence
and
Incidence
of HCV

Serial RNA measurements







Historically, treatment uptake was major barrier
New regimens should improve treatment uptake
New barriers such as cost and access may limit potential impact of new regimens
Interventions could address these new barriers
If negative RNA results were reportable, public health systems could track SVR
SVR: Sustained viral response.

45

Adapted from: Das M, Conference on Retroviruses and Opportunistic Infections 2014.

Continuum of Care Model for HCV

Screening
and Testing

Diagnosis

Management

Linkage

Treatment

Engagement /
Retention

 Sustained viral response (SVR) is monitored
through repeated negative RNA results over time
 Healthcare systems could track this data
 Public health systems cannot track unless negative
RNA results become reportable

Adapted from: Das M, Conference on Retroviruses and Opportunistic Infections 2014.
46

Cure

Engagement /
Retention

SVR vs. re-infection
monitoring through
RNA measurements

Long-term
Decrease in
Prevalence
and
Incidence
of HCV

Potential Reduction in HCV-Related Liver Deaths
from Expanded Screening and Treatment Regimens
Annual number of HCV-related liver
deaths / 2008 U.S. adult population

40000

Old regimens and old screening
Old regimens and new screening
New regimens and old screening
New regimens and new screening

35000
30000
25000
20000

15000
10000
2015
5

2020
10

2025
15

2030
20

2035
25

Years after intervention
Coffin, CID 2012 (modified for new treatment regimens, direct-acting agents).
47

2040
30

Potential Reduction in HCV-Related Liver Deaths
by Treatment Strategy based on Liver Fibrosis
Annual number of HCV-related liver
deaths / 2008 U.S. adult population

40000

Old regimens and old screening
New Rx limited to F4
New Rx limited to F3-4
New Rx limited to F2-4
New Rx all stages, new screening

35000
30000
25000
20000
15000
10000
2015
5

2020
10

2025
2030
2035
15
20
25
Years after intervention

F2-F4: Stages of liver fibrosis including moderate (F2), severe (F3), and cirrhosis (F4)
Coffin, CID 2012 (modified for novel direct-acting agents).
48

2040
30

Expanding Treatment in Primary Care
to Meet Demand
 New therapies are 8-12 weeks, all-oral, with minimal side effects
 HCV specialists
 2,335 US-based AASLD
members in 2010
 Only 5,200 unique prescribers of
HCV therapeutics for
January-March 2014
 Primary care & other providers
 209,000 practicing PCPs in 2010
 Similar SVR with ECHO support
for IFN-based Rx
 9,000 IDSA members in 2013

49

AASLD: American Association for the Study of Liver Diseases. IDSA: Infectious Diseases Society of America. IFN: Interferon.
ECHO: Extension for Community Healthcare Outcomes.
Rustgi, Hepatology 2008. Arora, NEJM 2011. Centers for Medicare and Medicaid.

Strategies to Prevent New Infections of HCV
 Major risk factor for new infections is IV drug use
 Largest numbers of new infections are in PWIDs
 Strategies to reduce HCV in PWIDs
 Syringe access programs and education programs
 Treatment as Prevention (TasP)

 Medication-assisted treatment for substance use disorder
 Low threshold methadone treatment programs

 Vaccine research
 Early Phase 2 stages
PWIDs: Persons who inject drugs
50

Syringe Access Programs Impact On HCV
Prevalence and Incidence
Impact on Prevalence

NSP: Needle & syringe program.
Kwon J, AIDS 2012.
51

Impact on Incidence

Treatment as Prevention (TasP) for HCV
 Interrupt Secondary Transmission
 Maximize Impact on Incidence
 Target active injectors
 Social network-based recruitment strategy

 PWID in high prevalence areas
 Optimize treatment delivery
 Patient navigation programs
 Conditional cash transfer programs
 Directly observed therapy

52

Potential Impact of Treatment as Prevention
based on Prevalence
 Prevalence in many
US cities falls close
to 50%-65%
 Treating just 8% of
active injectors per
year would reduce
prevalence by 50% to
90% in 15 years

MartinHepatology 2013.
53

Value of Comprehensive Prevention:
TasP, Syringe Access and Opioid Substitution

TasP: Treatment as prevention. OST: Opioid substitution treatment. HCNSP: Syringe access programming.
Martin, Clinical Infectious Diseases 2013.
54

Concerns and Research Needs for HCV TasP
 Acceptability of new treatments to PWIDs
 Impact of acute infection on treatment and transmission

 Drug resistance archiving
 Efficacy of behavioral interventions to reduce reinfection

55

To Reduce and Perhaps Eliminate HCV
 Increase priority – widen public recognition of urgency of action
 Increase screening – follow USPSTF recommended screening
 Improve testing algorithm – simplify HCV screening and diagnosis
 Enhance surveillance – change policies to improve utility of data

 Expand clinical workforce – allow for primary care management
 Increase treatment availability – modify treatment regimens

 Reduce payer restrictions – increase number of therapeutics

56

CDC PUBLIC HEALTH GRAND ROUNDS

The 25th Anniversary of the
Discovery of the Hepatitis C Virus
Looking Back to Look Forward

57