Transcript Armstrong, Annals Intern Med 2006

HEPATITIS WEB STUDY
Hepatitis C Screening: An Urgent Priority
H. Nina Kim, MD MSc
Assistant Professor of Medicine
Division of Allergy & Infectious Diseases
University of Washington
April 24, 2012
No financial conflicts of interest
Hepatitis
web study
Hepatitis
web study
Burden of Chronic Hepatitis C
• Most common bloodborne chronic viral infection.
- Chronic viral hepatitis is 3-5 X more frequent than HIV
• No vaccine for hepatitis C.
•
- Up to 4 million* Americans live with HCV infection
- 80% of these have chronic persistent infection
- Highest HCV prevalence:
•
•
•
•
Aged 40-59
Blacks, Hispanics
Poverty level or below
Incarcerated, homeless, immigrant, active IDUs
Armstrong, Annals Intern Med 2006; 144:705.
www.cdc.gov/hepatitis/HCV
Hepatitis
web study
Subgroups with High HCV Seroprevalence
Armstrong, Annals Intern Med 2006; 144:705.
Dominitz, Hepatology. 2005;41(1):88-96.
Weinbaum, MMWR. 2003 Jan 24;52(RR-1):1-36.
Hepatitis
web study
HCV Seroprevalence by Age group
NHANES
Armstrong, Ann Intern Med. 2006;144(10):705-14.
Hepatitis
web study
Natural History of Hepatitis C
Exposure
(Acute phase)
5-25% symptoms
Accelerants:
HIV & Alcohol
80%
Resolved
Chronic
Stable
* in 20-30 yrs
** per year
5-20%*
Cirrhosis
Slowly Progressive
1-5%**
ESLD, HCC
Transplant
Death
Hepatitis
web study
Silent Nature of Chronic Hepatitis C
• Majority of those infected not yet diagnosed
- Asymptomatic – many unaware they are infected with HCV until
they have symptoms of cirrhosis or liver cancer
- Screening not being done
• Only a small minority (0.5 million) in US have been treated
• HCV is leading indication for liver transplantation in U.S.
- $30 billion health costs per year
• HCV is leading cause of death from liver disease in U.S.
- Now up to 12,000 deaths annually
Institute of Medicine Report 2010 on Chronic Viral Hepatitis.
www.cdc.gov/hepatitis/HCV
Hepatitis
web study
Trends in Health Care Resources for HCV in US
Grant, et. al. Hepatology 2005; 42(6):1406-1413.
Hepatitis
web study
Trends in Health Care Resources for HCV in US
Grant, et. al. Hepatology 2005; 42(6):1406-1413.
Hepatitis
web study
HCV Disease Progression
in an Aging Population
Davis, Gastroenterology. 2010;138(2):513-21.
Hepatitis
web study
Mortality for HCV now exceeds that of HIV
US, 1999-2007
Ly et. al. Annals of Intern Med 2012;156:271-278.
Hepatitis
web study
So how did we get here?
Hepatitis
web study
Gaps in Awareness & Understanding
among those at highest risk
• Drug User Intervention Trial enrolled 3,004 young injection drug users
(IDUs) in 5 U.S. cities – 34% found to be HCV-positive
- 72% of HCV-positive not aware of their status or thought they were negative
- More likely to be aware if hx drug treatment or needle exchange
• Among 150 patients seeking substance-use treatment at VA medical
center
- 90% of those HCV-infected were not aware of their status
- 41% IDUs did not know or were unsure of how HCV was spread or what
complications can develop
• Australian study: 42% of IDUs believed being antibody positive for HCV
meant you were immune
Hagan, Public Health Reports 2006;121(6):713-19.
Dhopesh, Am J Drug Alc Abuse 2000;26:703.
O’Brien, Addictive Behav 2008;33(12):1602-05.
Hepatitis
web study
Lack of Public
Awareness
Lack of Provider
Awareness
Lack of Public Resource
Allocation
• At-risk people do not know that they’re at risk or how to prevent getting infected
• At-risk people may not have access to preventive services
• Chronically infected people do not know that they are infected
• Many medical providers do not screen or know how to manage those infected
• Infected people often have inadequate access to testing & medical care
• Inadequate disease-surveillance systems both underreport acute/chronic HCV
Improved Provider &
Community Education
Integration & Enhancement
of Viral Hepatitis Services
Institute of Medicine Report 2010 on Chronic Viral Hepatitis.
Improved Disease
Surveillance
Hepatitis
web study
Goals for Healthy People 2020:
 Reduce by 25% number of new hep C cases
 Increase awareness of hep C infection from
45% to 66% among those infected
http://www.hhs.gov/ash/initiatives/hepatitis/
Hepatitis
web study
This alarming trend in hep C can be reversed…
We know HCV treatment can save lives and
permanently clear HCV virus…
Hepatitis
web study
Sustained Virologic Response (SVR)
Goal of HCV Treatment
Sustained Virologic Response (SVR)
HCV RNA Log10 IU/ml
7
HCV RNA negative 24 weeks after cessation of treatment
6
Sustained Virologic
Response (SVR)
5
4
End of Treatment
3
24 Weeks
2
1
Undetectable
0
-8
-4
-2
0
4
8
12
16
20
24
32
40
48
52
60
72
Weeks After Start of Therapy
Modified From: Ghany MG, et. al. Hepatology. 2009;49:1335-74.
Hepatitis
Hepatitis
web study
web study
www.hepwebstudy.org
HCV Patients with Advanced Fibrosis:
SVR Reduces Mortality & Morbidity
Liver Failure
50
50
40
40
Liver Failure
(%)
Liver-Related Death
(%)
Liver-Related Death
30
20
10
0
30
20
10
0
0
1
2
3
4 5
Year
6
7
8
5-yr occurrence
SVR: 4.4% (CI: 0% to 12.9%)
No SVR: 12.9% (CI: 7.7% to 18.0%)
P = .024 (log likelihood)
Veldt BJ, et al. Ann Intern Med. 2007;147:677-684.
0
1
2
3
4 5
Year
6
7
8
5-yr occurrence
SVR: 0%
No SVR: 13.3% (CI: 8.4% to 18.2%)
P = .001 (log likelihood)
Hepatitis
web study
Sustained Virologic Response
Clinical Outcomes in HIV-HCV Patients
Incidence per 100 person-yrs
5
4
Hepatic decompensation
3
2
1
0
Liver-related Death
Non-SVR
Hepatic
decompensation
SVR
Berengeur et. al. Hepatology 2009; 50:407-413.
Hepatitis
web study
Therapy for Hepatitis C: Historical Milestones
Timeline
1986
Source: Ghany MG, et. al. Hepatology. 2009;49:1335-74.
1998
2001
2002
Hepatitis
web study
Hepatitis
web study
Therapy for Hepatitis C: Historical Milestones
Timeline
1986
1998
2001
2002
2011
70
Hepatitis
web study
Direct-Acting Antivirals
A New Era of HCV Therapy
• New standard of care for HCV genotype 1 infection
- HCV protease inhibitor + pegIFN / ribavirin  “triple therapy”
- Higher SVR rates observed across all patient groups including
“difficult to treat” groups (prior tx failures, AA, cirrhotics).
• Challenges remain:
- Access & tolerability still limited by Peg-IFN + RBV
- Pill burden, q8h dosing + meal
- Additional side effects
- Drug interactions
- Resistance?
- Cost!
• IFN-free era in horizon?
Hepatitis
web study
Hepatitis C Virus
Classes of Direct-Acting Antivirals
NS3/4A protease inhibitor
Hepatitis C Proteins
Structural Proteins
C
E1
Nucleocapsid
Envelope
Glycoprotein
Nonstructural (NS) Proteins
E2
p7
Envelope
Glycoprotein
NS2
Cysteine
Protease
Vioporin
NS4
A
NS3
NS4B
Serine Protease
Cofactors
Serine
RNA
Protease Helicase
NS5A
NS5B
RNA binding and assembly
recognition complex
Membranous
Web Induction
RNA-Dependent
RNA
Polymerase
NS5A polymerase inhibitor
NS5B polymerase inhibitors
- Nucleoside analogues
- Non-nucleoside inhibitors
Hepatitis
web study
Hep C Screening is the First Step…
Cure
Assessment
Testing
Treatment
Counseling
Screening
Hepatitis
web study
Comprehensive Strategy to Prevent & Control HCV
Primary Prevention
•
•
•
•
•
Screen & test blood, plasma, organ, tissue donors
Sterilize plasma-derived products
Infection control practices
Risk reduction & counseling services
Drug treatment & safe syringe/needle access
Secondary Prevention
• Identify, counsel & test persons at risk
• Medical management of infected persons
Hepatitis
web study
What is Recommended for Hep C Screening?
Centers for Disease Control, 1998:
Yes: “Testing should be offered routinely to persons most likely to be
infected with HCV… and be accompanied by appropriate counseling &
medical follow-up.”
American Association for Study of Liver Diseases, 2009:
Yes: “as part of a comprehensive health evaluation, all persons should be
screened for behaviors that place them at high risk for HCV infection.”
US Preventive Services Task Force, 2004:
Not really: “USPSTF found insufficient evidence to recommend for or
against routine screening for HCV infection in adults at high risk for
infection.”
Hepatitis
web study
Who Should be Screened for Hepatitis C?
CDC Guidelines, 1998
• Ever injected illegal drugs
• Received clotting factors made
before 1987
• Received blood/organs before July
1992
• Ever on chronic hemodialysis
• Evidence of liver disease (elevated
liver enzymes)
• Infants born to HCV-infected
mothers
• HIV infection
• After HCV exposure (needlestick
injury)
Hepatitis
web study
Where Should Screening for Hepatitis C Take
Place?
CDC Guidelines, 1998
Screen at these venues:
 Correctional institutions
 HIV counseling & testing sites
 Drug treatment facilities
 STD treatment programs
Screening must include:
 Counseling on
o What results mean
o Whether further testing needs
to be done
 Referral/linkage to medical care
Hepatitis
web study
Targeted Risk-Based Screening
Only as good as the asking…
• 4,000 primary care physicians mailed survey; 1,412
responded
• Most clinicians lack familiarity with HCV:
- 73% had < 5 hep C patients in the preceding year
- 44% had no experience with treatment of HCV
• Only 59% said they asked all patients about hep C risk
factors
McGinn, Arch Intern Med 2008;168(18):2009-2013.
Hepatitis
web study
Risk-based Screening
Limitations
• Patients uncertain of past exposure history
• Reticence to disclose sensitive risk behaviors
• Providers reluctant to ask about sensitive risk behaviors
• Inconsistent system-wide implementation
• Ultimately it has failed…
- 40-85% of HCV-infected still undiagnosed
McGinn, Arch Intern Med 2008;168(18):2009-2013.
Shehab, J Viral Hepat 2001;8(5):377-83.
Serrante, Fam Med 2008;40(5):345-51.
Hepatitis
web study
Birth Cohort Screening
CDC, 2012-2013
• We need enhanced easy-to-implement screening guidance
that works
• Remember: 80% HCV-infected persons born 1945-1965
• Birth cohort screening shown by modeling to be more costeffective than risk-based screening:
- Would identify additional 808,580 HCV cases & prevent 82,000
HCV-related deaths at a cost of $2874 per new case identified
• $15,700 per QALY saved assuming standard treatment and
$35,700 per QALY saved assuming addition of new antivirals.
• Revised CDC guidelines coming… stay tuned.
Rein, Annals of Intern Med 2012;156:263-270.
Hepatitis
web study
HCV Diagnostic Algorithm
Antibody Test
EIA for anti-HCV
Negative for HCV Infection
Additional Testing Recommended if:
• Acute HCV suspected
• Hemodialysis
• Immunocompromised
HCV RNA
Active HCV Infection
Medical Evaluation
RIBA
Resolved HCV Infection
CDC Guidelines on Hep C Dx, MMWR 2003;52(RR03):1-16.
False-Reactive EIA
Hepatitis
web study
Counseling the HCV-positive Patient
www.cdc.gov/hepatitis/HCV
Hepatitis
web study
Counseling the HCV-positive Patient
www.cdc.gov/hepatitis/HCV
Hepatitis
web study
Rapid Testing for HCV
FDA approved, June 2010
• Approved for whole blood, fingerstick
• Oral swab testing not yet approved
• Antibody test, similar to HIV rapid test
• Point-of-care – results x 20 min
• Preliminary “positive” – needs confirmatory testing
- Sensitivity 79-99%
- Specificity 80-100%
• Increased feasibility of testing in outreach settings
(needle exchange, STD clinics, methadone programs)
Smith BD, J Infect Dis. 2011;204(6):825-31.
Hepatitis
web study
May 19
National Hepatitis Testing Day
• Opportunity to remind health care providers and the
public who should be tested for chronic viral
hepatitis.
• Build collective voice around this urgent issue.
http://www.cdc.gov/hepatitis/KnowMoreHepatitis.htm
Hepatitis
web study
Meeting the Challenges of HCV
Parallels with HIV
• Both infections can carry stigma
- Disproportionate burden among marginalized
• Many undiagnosed & untreated
• Risk-based screening has proven inadequate in identifying
infected persons promptly
• Barriers to new life-saving treatments
- Increasing complexity of management
- Shortage of skilled clinicians
- Concerns re cost & reimbursement
• But HCV treatment is of limited duration & achieves a cure
• Like HIV, we can gain ground with advocacy & education
Hepatitis
web study
www.hepwebstudy.org
Hepatitis
web study
www.hepwebstudy.org
Hepatitis
web study
www.hepwebstudy.org
Hepatitis
web study
www.hepwebstudy.org
Hepatitis
web study
Questions?
Hepatitis
web study