Hepatitis C: Update on Testing and Treatment - PowerPoint Presentation

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Hepatitis C: Update on Testing and Treatment10/23/12

Karla Thornton, MD, MPH

Division of Infectious Diseases

Department of Internal Medicine

UNM Health Sciences Center

kthornton@salud.unm.eduSlide2

Learning ObjectivesRecognize the magnitude of the HCV epidemic and the consequences of not addressing the problemUnderstand the CDC’s new screening guidelines for HCVBecome familiar with the new drugs approved for HCV and the future of HCV therapySlide3
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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).

Hepatitis C Prevalence, U.S.Slide5

Figure 4.2. Incidence of acute hepatitis

C,

by age group — United States,

2000–2010

Source: National

Notifiable

Diseases Surveillance System (NNDSS)Slide6
Slide7

HCV is a Neglected Disease

Edlin B. Nature 2011; 474:S18-19.Slide8

Prevalence of Anti-HCV, United States, 1999-2002 (NHANES)

Armstrong, et al,

Ann Intern Med.

2006;144:705-714.

Overall prevalence: 1.6% (4.1 million)Slide9

HCV in AI/AN PopulationsSeroprevalence 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.Slide10

Figure 4.4. Incidence of acute hepatitis

C,

by race/ethnicity — United States,

2000–2010

Source: National

Notifiable

Diseases Surveillance System (NNDSS)Slide11

Wise, et al. Changing Trends in Hepatitis C-Related Mortality in the United States, 1995-2004. Hepatology Vol.47, No. 4, 2008.Slide12

Projected Morbidity and MortalitySlide13

Forecasting HCV Morbidity and MortalityIncident 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

.Slide14

Forecasting HCV Morbidity and MortalityOf 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.Slide15

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.Slide16

IOM Report and DHHS GuidelinesSlide17

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.

”Slide18

Lack of Resources

Underlying Issues

that impede current efforts:

Lack of Provider

Awareness

Lack of Public

AwarenessSlide19

Current CDC Resource Allocation

$1 Billion Total

National Center for HIV/AIDS, Viral Hepatitis,

Sexually Transmitted Disease and Tuberculosis PreventionSlide20

Comparison of Viral Hepatitis and HIV/AIDS disease Burden Burden

Undiagnosed

Infections

(millions undiagnosed)

Prevalence

(millions infected)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

People

0

0.5

1

1.5

2

2.5

0

100

200

300

400

500

600

700

800

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

HIV/AIDS

Hepatitis B

Hepatitis C

Dollars

Care

(HRSA)

(billions of dollars)

Prevention

(CDC)

(millions of dollars)

Research

(NIH)

(billions of dollars)

Annual

Deaths

(thousands)

0

2

4

6

8

10

12

14

16

Edlin BR. Nature 2011; 474: S18-9Slide21

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, 2011Slide22

Screening StrategiesSlide23

Ghany MG, et al. Hepatology. 2009;49:1335-1374. Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47:1-39.

Groups

Reco

mmended for HCV Testing by AASLD

Recent/past injection drug users

—even if only used onceGroups with high HCV prevalenceHIV-infected individualsHemophiliacs treated with clotting factor concentrates before 1987

Hemodialysis recipientsPatients with unexplained aminotransferase abnormalitiesRecipients of transfusion or transplantation before July 1992Children 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 HCVSlide24

How good are we at identifying people with HCV?Acute infection unrecognizedLack 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 2003Slide25

Birth-Cohort Screening Slide26

45%-85% of infected persons are undiagnosedLimitations 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

Rationale for Considering Birth Cohort Screening Recommendations.Slide27

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

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.Slide28

Numbers of cases that were identified and treated and that achieved SVRLiver disease and death from HCV Medical and productivity costs Quality-adjusted life-years (QALYs)Outcome Measures

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.Slide29

ResultsCompared with the status quo, birth-cohort screening identified 808,580 additional cases of chronic HCV infectionScreening 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.Slide30

DiscussionNo universally accepted standard exists to determine what level of cost-effectiveness justifies the implementation of a new strategyBirth-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.Slide31
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SummaryThe majority of persons infected with HCV remain undiagnosedNew screening strategies are desperately neededBirth-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 cohortSlide36
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HCV TreatmentSlide38

Key PointsAntiviral 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, MDSlide39

Treatment Evolution of Hepatitis C Therapy

1998

2001-2004

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;364:1195-1206.

2011Slide40
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Protease InhibitorsApproved May 2011Boceprevir (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, MDSlide42

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 aloneSlide43

SPRINT-2: Overall SVR Rates

0

20

40

60

80

100

4-Wk PR + Response-Guided BOC/PR

SVR (%)

63

4-Wk PR + 44-Wk BOC/PR

48-Wk PR

66

38

P

< .001 for both treatment arms vs control

Poordad F, et al. NEJM 2011;365:1195-1206

n/N =

233/368

242/366

137/363Slide44

RESPOND-2: SVR in Prior Relapsers and Prior Non-RespondersBacon B, et al.

N Engl J Med

. 2011;364(13):1207

-

1217.

72

1051551

77

103

27

57

30

58

Prior Relapsers

Prior Non-Responders

BOC

RGT

BOC/

PR48

PR48

BOC

RGT

BOC/

PR48

PR48

n/N=

2

29Slide45

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 aloneSlide46

ADVANCE: SVR and Relapse Rates Data from Jacobson IM, et al. N Engl J Med

. 2011;364:2405-2416.

100

90

80

70

60

50

40

30

10

0

271/363

75

44

158/361

27/314

9

28

64/229

SVR

Relapse Rates

% of Patients

n/N=

T12PR

PRSlide47

REALIZE: SVR in Prior Relapsers, Prior Partial Responders, and Prior Null RespondersSVR (%)

Prior

Relapsers

Prior Partial

Responders

Pbo/

PR484/27

LI T12/

PR48

26/48

n/N =

Pbo/

PR48

2/37

LI T12/

PR48

25/75

Pbo/

PR48

16/68

LI T12/

PR48

124/141

Prior Null

Responders

Data from Zeuzem S, et al.

N Engl J Med.

2011;364:2417-2428.Slide48
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What now?800,000 new cases identifiedNewer therapies becoming availableCure rate continues to increaseSlide53

Expansion of Treatment

Project ECHOSlide54

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 areasSlide55

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 countriesSlide56

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 Slide57

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.Slide58

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 centrallySlide59
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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.Slide62

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 cliniciansSlide63

Outcomes of Treatment for Hepatitis C Virus Infection by Primary Care ProvidersResults of the HCV Outcomes Study

Arora S, Thornton K, et al. N Engl J Med. 2011 Jun; 364:2199-207.Slide64

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.Slide65

Results

Arora S, Thornton K, et al.. N Engl J Med. 2011 Jun; 364:2199-207.Slide66

SVR According to Genotype and Site of Treatment

Arora S, Thornton K, et al.. N Engl J Med. 2011 Jun; 364:2199-207.

HCV Genotype

ECHO sites

UNM HCV Clinic

P

V

alue

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%)

0.83Slide67

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.Slide68

SummaryHCV is a prevalent disease and 50-75% of infected patients are undiagnosedThe morbidity and mortality associated with HCV will increase dramatically over the next 20 yearsGreater awareness and new screening strategies are required in the primary care setting

All persons born from 1945-1965 should be screened for HCVSlide69

SummaryDiagnosis can lead to potentially life saving treatmentNewer therapies will be available in 3-5 years that will cure almost all patients who receive treatmentThere is a dire need to expand access to HCV treatmentSlide70

Questions?