Hepatitis C: Update on
Testing and Treatment
10/23/12
Karla Thornton, MD, MPH
Division of Infectious Diseases
Department of Internal Medicine
UNM Health Sciences Center
kthornton@salud.unm.edu
Learning Objectives
• Recognize the magnitude of the HCV epidemic
and the consequences of not addressing the
problem
• Understand the CDC’s new screening
guidelines for HCV
• Become familiar with the new drugs approved
for HCV and the future of HCV therapy
Hepatitis C Prevalence, U.S.
• Overall prevalence of anti-HCV in the U.S.
population from NHANES III (1988-1994)
3.9 million (1.8%)
• Prevalence of chronic infection
2.7 million (1.3%)
• Correcting for patient groups under-represented in
NHANES (incarcerated, homeless, hospitalized,
active duty military, and nursing home residents)
5 million (~2.4%)
• Infection is most prevalent among those born during
1945–1965
Alter et al. N Engl J Med. 1999;341(8):556-562.
Edlin, B. R. Hepatology 42, 213A (2005).
Source: National Notifiable Diseases Surveillance System (NNDSS)
HCV is a Neglected Disease
Edlin B. Nature 2011; 474:S18-19.
Prevalence of Anti-HCV, United States,
1999-2002 (NHANES)
Overall prevalence: 1.6% (4.1 million)
8%
Men
Prevalence of anti-HCV
7%
Women
6%
5%
4%
3%
2%
1%
Age Group (years)
Armstrong, et al, Ann Intern Med. 2006;144:705-714.
55+
50-54
45-49
40-44
35-39
20-34
6-19
0%
HCV in AI/AN Populations
Seroprevalence Studies
1. Alaska native population – estimated prevalence
0.8%
2. Pregnant women in Arizona 3%
3. Urban Native American Clinic in Nebraska 11.5%
1. McMahon, Epidemiology and Risk Factors for Hepatitis C in Alaska Natives, Hepatology,
February 2004. 2. Wilson, Hepatitis C Infection and Type 2 Diabetes in American-Indian
Women, Diabetes Care, September 2004. 3. Neumeister, Hepatitis C Prevalence in an
Urban Native-American Clinic, Journal of the National Medical Association, April 2007.
Source: National Notifiable Diseases Surveillance System (NNDSS)
Wise, et al. Changing Trends in Hepatitis C-Related Mortality in the United States, 1995-2004. Hepatology Vol.47,
No. 4, 2008.
Projected Morbidity and
Mortality
Forecasting HCV
Morbidity and Mortality
• Incident HCV infections peaked in the 1980’s
(300,000-400,000/year)
• Large cohort of currently asymptomatic patients
who are approaching the years when they will
develop complications
• Mathematical model which forecast future cases
of end-stage liver disease, transplants, and
deaths from 2010 to 2060.
Rein, DB, Wittenborn, JS, Weinbaum, CM Sabin, M, Smith, BD, Lesesne, SB. Forecasting the Mortality and Morbidity
Associated with Prevalent Cases of Pre-Cirrhotic Chronic Hepatitis C Infections in the United States. Journal of Digestive Liver
Diseases 2010.
Forecasting HCV
Morbidity and Mortality
• Of 2.7 M HCV infected persons in
primary care
— 1.47 M will develop cirrhosis
— 350,000 will develop liver cancer
— 897,000 will die from HCV-related complications
Rein, DB, Wittenborn, JS, Weinbaum, CM Sabin, M, Smith, BD, Lesesne, SB. Forecasting the Mortality and Morbidity
Associated with Prevalent Cases of Pre-Cirrhotic Chronic Hepatitis C Infections in the United States. Journal of Digestive Liver
Diseases 2010.
Forecasted Annual Incident Cases of Decompensated Cirrhosis (DCC), Hepatocellular
Carcinoma (HCC), Liver Transplants, and Deaths Associated with Persons with Chronic
Hepatitis C Infection and No Liver Cirrhosis in the United States in 2005
Rein, DB, Wittenborn, JS, Weinbaum, CM Sabin, M, Smith, BD, Lesesne, SB. Forecasting the Mortality and Morbidity
Associated with Prevalent Cases of Pre-Cirrhotic Chronic Hepatitis C Infections in the United States. Journal of Digestive
Liver Diseases 2010.
IOM Report and DHHS
Guidelines
Institute of Medicine : Hepatitis and Liver
Cancer A National Strategy for Prevention
and Control of Hepatitis B and C
•
Viral hepatitis “cause(s)
substantial morbidity
and mortality despite
being preventable and
treatable.”
Underlying Issues
that impede current efforts:
Lack of
Resources
Lack of
Public
Awareness
Lack of
Provider
Awareness
Current CDC Resource Allocation
$1 Billion Total
STD
15%
Domestic
HIV
69%
TB
14%
Viral
Hepatitis
2%
National Center for HIV/AIDS, Viral Hepatitis,
Sexually Transmitted Disease and Tuberculosis Prevention
Comparison of Viral Hepatitis and
HIV/AIDS disease Burden Burden
People
Prevalence
(millions infected)
Dollars
Undiagnosed
Infections
Annual
Deaths
Prevention
Care
Research
(CDC)
(HRSA)
(NIH)
(millions undiagnosed)
(thousands)
(millions of dollars)
(billions of dollars)
(billions of dollars)
5
16
800
4.5
4.5
14
700
4
4
5
3.5
3
3
10
2.5
2.5
8
2
2
6
300
1.5
1.5
4
200
0.5
0.5
0
0
3.0
600
3.5
1
3.5
2
12
1
2.5
500
2.5
1.5
2.0
400
2
100
0
0
HIV/AIDS
Hepatitis B
1
1.5
Hepatitis C
1.0
0.5
0.5
0
0
Edlin BR. Nature 2011; 474: S18-9
HHS Viral Hepatitis Action Plan
• Educate providers and
•
•
•
communities
Improve testing, care, and
treatment
Increase in the proportion of
persons who are aware of
their HCV infection
25%reduction in the number
of new HCV cases
May 12, 2011
Screening Strategies
Groups Recommended for HCV Testing by AASLD
• Recent/past injection drug users—even if only used once
• Groups with high HCV prevalence
– HIV-infected individuals
– Hemophiliacs treated with clotting factor concentrates before 1987
– Hemodialysis recipients
– Patients with unexplained aminotransferase abnormalities
• Recipients of transfusion or transplantation before July 1992
• Children born to women infected with HCV
• Healthcare, public safety, and emergency medical personnel following
needle injury or mucosal exposure to HCV-infected blood
• Current sexual partners of individuals infected with HCV
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47:1-39.
How good are we at identifying
people with HCV?
• Acute infection unrecognized
• Lack of testing – < 10% of patients asked
about HCV risk factors in initial visit to
PCP*
• Unpublished CDC data from large managed
care organization in the Southeast screening rate 0.5% general population
*Shehab, et al. Identification and Management of Hepatitis C
Patients in Primary Care Clinics, AJG, March 2003
Birth-Cohort Screening
Rationale for Considering Birth Cohort
Screening Recommendations
• 45%-85% of infected persons are undiagnosed
• Limitations of current risk-based strategies
• 75% of chronic infections are in persons born
from 1945-1965
• Without identifying and treating the estimated 2.8
million Americans with HCV in primary care
– 1.47 million will develop cirrhosis
– 350,000 will develop liver cancer
– 897,000 will die from complications of HCV
.
The Cost-Effectiveness of Birth-Cohort
Screening for Hepatitis C Antibody in U.S.
Primary Care Settings
• Objective: To estimate the cost-effectiveness of
birth-cohort screening
• Design: Cost-effectiveness simulation
• Data Sources: NHANES, U.S. Census, Medicare
• Target Population: Adults born from 1945-1965
with 1 or more visits to a PCP annually
• Intervention: One-time antibody test of 1945–
1965 birth cohort
The Cost Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary care
Settings. Rein DB, et al. Ann Intern Med, e-378, published ahead of print November 4, 2011.
Outcome Measures
• Numbers of cases that were identified and
treated and that achieved SVR
• Liver disease and death from HCV
• Medical and productivity costs
• Quality-adjusted life-years (QALYs)
The Cost Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary care
Settings. Rein DB, et al. Ann Intern Med, e-378, published ahead of print November 4, 2011.
Results
• Compared with the status quo, birthcohort screening identified 808,580
additional cases of chronic HCV
infection
• Screening cost of $2874 per case
identified
The Cost Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary care
Settings. Rein DB, et al. Ann Intern Med, e-378, published ahead of print November 4, 2011.
Discussion
• No universally accepted standard exists to determine
what level of cost-effectiveness justifies the
implementation of a new strategy
• Birth-cohort screening with PEG/RBV alone ranks
equivalently to colorectal cancer and hypertension
screening, influenza vaccination of adults age ≥ 50 yrs,
pneumococcal vaccination of adults age ≥65 yrs, and
vision screening of adults age ≥ 65 yrs
• Birth-cohort screening with DAA plus PEG/RBV
ranks equivalently to cervical cancer or cholesterol
screening
The Cost Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary care
Settings. Rein DB, et al. Ann Intern Med, e-378, published ahead of print November 4, 2011.
Summary
• The majority of persons infected with HCV remain
undiagnosed
• New screening strategies are desperately needed
• Birth-cohort screening appears to be a viable
screening strategy
• Birth-cohort screening appears to be as cost effective
as many common and recommended screening tests
• CDC is planning national education campaign called
Know More Hepatitis – target PCP’s as well as
persons born in the birth cohort
HCV Treatment
Key Points
• Antiviral therapy for HCV can cure an
estimated 70 %
• Those who are cured have a 60% reduction in
mortality
• Chance of cure and intensity of treatment
depends on viral genotype and host genetics
• Therapy is expensive and has side effects, but
neither of these hurdles are insurmountable
Slide courtesy of John Scott, MD
Treatment Evolution of Hepatitis C
Therapy
1998
2001-2004
2011
McHutchison J., et al., NEJM 1998;339:1485-92, Poynard T., et al., Lancet 1998;352:1426-32, Manns M., et al., Lancet 2001;358:958-65,
Fried MW., et al., NEJM 2002;347:975-82, Hadziyannis S., et al., Ann Intern Med 2004;14:346-55. Poordad F, et al. NEJM 2011;364:11951206.
Protease Inhibitors
•
•
•
•
•
•
•
Approved May 2011
Boceprevir (Victrelis) and Telaprevir (Incivek)
Potent
Still need pegylated interferon and ribavirin
Rapid antiviral resistance if used alone
More side effects, particularly rash and anemia
Major drug interactions Cyp3a/4
Slide courtesy of John Scott, MD
Boceprevir (VICTRELISTM)
• Merck
• Oral HCV protease
inhibitor for genotype 1
infections
• Approved by FDA on
May 13, 2011
• Combined with IFN/RBV
– Dosed 800 mg q8h
– Resistance develops
quickly if used alone
SPRINT-2: Overall SVR Rates
100
P < .001 for both treatment arms vs control
80
SVR (%)
63
66
60
38
40
20
n/N =
0
233/368
4-Wk PR +
Response-Guided
BOC/PR
Poordad F, et al. NEJM 2011;365:1195-1206
242/366
4-Wk PR +
44-Wk
BOC/PR
137/363
48-Wk PR
RESPOND-2: SVR in Prior Relapsers
and Prior Non-Responders
Prior Relapsers
n/N=
15
51
72
105
77
103
PR48 BOC BOC/
RGT PR48
Bacon B, et al. N Engl J Med. 2011;364(13):1207-1217.
Prior NonResponders
2
29
27
57
PR48 BOC
RGT
30
58
BOC/
PR48
Telaprevir (IncivekTM)
• Vertex Pharmaceuticals
• Oral HCV protease
inhibitor for genotype 1
infections
• FDA approved on May
23, 2011
• Combined with
IFN/RBV
– Dosed 750 mg q8h
– Resistance develops
quickly if used alone
ADVANCE: SVR and Relapse Rates
100
% of Patients
90
80
75
SVR
70
Relapse Rates
60
44
50
40
28
30
9
10
0
n/N=
271/363
27/314
158/361
T12PR
Data from Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
64/229
PR
REALIZE: SVR in Prior Relapsers, Prior Partial
Responders, and Prior Null Responders
Prior
Relapsers
100
Prior Partial
Responders
Prior Null
Responders
88
SVR (%)
80
54
60
40
33
24
15
20
5
0
n/N =
Pbo/
PR48
LI T12/
PR48
Pbo/
PR48
LI T12/
PR48
Pbo/
PR48
LI T12/
PR48
16/68
124/141
4/27
26/48
2/37
25/75
Data from Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.
What now?
• 800,000 new cases identified
• Newer therapies becoming
available
• Cure rate continues to increase
Expansion of Treatment
Project ECHO
Hepatitis C in New Mexico
 Number HCV cases 30,000
 In 2004 less than 5% had been treated
 2400 prisoners diagnosed in corrections
system– none treated before 2004
 Highest rate of chronic liver
disease/cirrhosis deaths in the nation
 32 of 33 counties Medically Underserved
Areas
 20% of doctors practice in rural areas
Goals

Develop capacity to safely and effectively
treat HCV in all areas of New Mexico and
to monitor outcomes
 Develop a model to treat complex
diseases in rural locations and
developing countries
Partners






University of New Mexico School of Medicine:
Departments of Internal Medicine, Telemedicine
and CME
NM Department of Corrections
NM Department of Health
Indian Health Service
Community Clinicians with an interest in HCV
Primary Care Association
Method




Use Technology (multipoint videconferencing and
internet) to leverage scarce healthcare resources
Disease Management Model focused on
improving outcomes by reducing variation in
processes of care and sharing “best practices”
Case based learning: Co-management of patients
with specialists (Learning by Doing)
HIPAA compliant centralized database to monitor
outcomes
Arora S, Geppert CM, Kalishman S, et al: Acad Med. 2007 Feb;82(2): 154-60.
Steps




Train physicians, mid-levels, nurses,
pharmacists, educators in HCV
Conduct telemedicine clinics – “Knowledge
Network”
Initiate co-management – “Learning loops”
Collect data and monitor outcomes centrally
Benefits to Clinicians





Diminishes professional isolation
Enhances professional satisfaction
No-cost CMEs and Nursing CEUs
A mix of work and learning
Access to specialty consultation with GI,
hepatology, psychiatry, infectious diseases,
addiction specialist, pharmacist, patient
educator
Arora S, Thornton K, et al. Hepatology. 2010 Sept; 52(3):1124-33.
How well has the model
worked for HCV?




>500 HCV Telehealth ECHO Clinics have been
conducted
>4500 patients entered into HCV disease
management program
>300 prisoners treated in the Corrections
Department
>6,000 CME/CE hours issues to ECHO
clinicians
Outcomes of Treatment for
Hepatitis C Virus Infection by
Primary Care Providers
Results of the HCV Outcomes
Study
Arora S, Thornton K, et al. N Engl J Med. 2011 Jun; 364:2199-207.
Objectives



To train primary care clinicians in rural areas
and prisons to deliver HCV treatment to rural
populations of New Mexico
To show that such care is as safe and effective
as that given in a University Clinic
To show that Project ECHO improves access to
HCV care for minorities
Arora S, Thornton K, et al.. N Engl J Med. 2011 Jun; 364:2199-207.
Results
Arora S, Thornton K, et al.. N Engl J Med. 2011 Jun; 364:2199-207.
SVR According to Genotype and
Site of Treatment
HCV Genotype
ECHO sites
UNM HCV
Clinic
P Value
All Genotypes
152/261 (58.2%)
84/146 (57.5%)
0.89
Genotype 1
73/147 (49.7%)
38/83 (45.8%)
0.57
Genotype 2 or 3
78/112 (69.6%)
42/59 (71.2%)
0.83
Arora S, Thornton K, et al.. N Engl J Med. 2011 Jun; 364:2199-207.
Conclusions


Rural primary care clinicians deliver HCV
care under the aegis of Project ECHO that
is as safe and effective as that given in a
university clinic
Project ECHO improves access to HCV
care for New Mexico minorities.
Arora S, Thornton K, et al.. N Engl J Med. 2011 Jun; 364:2199-207.
Summary
• HCV is a prevalent disease and 50-75% of
infected patients are undiagnosed
• The morbidity and mortality associated with
HCV will increase dramatically over the next 20
years
• Greater awareness and new screening strategies
are required in the primary care setting
• All persons born from 1945-1965 should be
screened for HCV
Summary
• Diagnosis can lead to potentially life saving
treatment
• Newer therapies will be available in 3-5
years that will cure almost all patients who
receive treatment
• There is a dire need to expand access to
HCV treatment
Questions?