Hepatitis C Update: key issues along the care continuum - PowerPoint Presentation

Slide1

Hepatitis C Update: key issues along the care continuum

Oluwatoyin ( Toyin) Adeyemi, MDDirector, CORE Viral hepatitis ClinicSenior director for HIV services, Cook County Health

Triple Threat 11: HIV, HCV &

Opiods

Dusable

Museum , June 25, 2019

Slide2

Treatment Cascade for People With Chronic HCV Infection

US 2003−2013

RNA, ribonucleic acid; SVR, sustained virologic response.

Yehia B.

PLoS One. 2014;9(7):e101554.

Identified Chronic

HCV-Infected Population, %

Slide3

Ruth M.

Rothstein CORE Center, Cook County Health

Multidisciplinary Hepatitis

clinic established at CORE in Sept

2001The CORE Center is 1 of 7 sites where we provide HIV care and 1 of 3 where we treat HCV.1st fibroscan in the state of Illinois in 2014.

HCV birth cohort (1945-1965) testing system-wide in October 2016. Reflex HCVRNA testing in late 2017.910 (another 40 to start)HCV patients treated at the CORE hepatitis clinic. SVR (cure) 96% to date

Slide4

Lecture Overview

EpidemiologyWho needs to be screened?How do you make the diagnosis? Assess severity?What are the treatment options and cure rates?After the cure, now what?

Slide5

1 slide Bottom line

Many with HCV infection don’t know.Simple blood test (or oral swab)*to diagnose HCV Untreated HCV can lead to liver failure, liver cancer and death in some patients.Effective , well tolerated oral agents available that can CURE HCV in over 95% of people.HCV cure reduces risk of liver decompensation by 90%, Liver cancer by 70% and improves overall quality of life.

We have the tools to eliminate HCV infection in the US

Slide6

Slide7

HCV Burden Is Higher in Marginalized Populations

Denniston M, et al.

Ann Int Med

. 2014;160(5):293–300; Edlin BR, et al.

Hepatology. 2015;62(5):1353–1363; Grebely J, et al. Inl J Drug Policy. 2015;26(10):1028–1038; Maier MM, et al. 2016;106(2):353–358; Galbraith JW, et al. Hepatology. 2015;61(3):776–782; Backus L, et al. Fed Pract. 2018;35(2):S8–S12.

Implementation of research strategies and interprofessional collaborative efforts are essential to target these populations

These populations experience:

High burden of comorbidities

Inconsistency of HCV testing Limited access to HCV care

Slide8

Baby boomers

represent

75%

of those living with HCV and

78% of deaths attributed to HCV. More than 15,000 deaths/year1

HCV

prevalence is

6.7%

among HIV+ MSM who do not inject drugs;

prevalence

is 40% among HIV+ MSM who inject drugs2

High Seroprevalence of HCV in

Certain Subpopulations

HCV prevalence among

PWID

is estimated to be

70%−77%

3

HCV prevalence in

corrections is estimated to be between

~10% and 45%

4,5

Among

migrants

from intermediate and high endemic countries, HCV seroprevalence of >2%

is reported: a level higher than that reported for most host populations6

PWID

MSM

Migrants

Baby Boomer

Birth Cohort

People in

Prisons

and Jails

Slide9

But the Face of HCV Is Changing

An Increasingly Bimodal Age Distribution

Newly Reported HCV Diagnoses in 2012 and 2016 by Year of Birth, Chicago

CDPH. Hepatitis C Surveillance Report ‒ Chicago, 2016. 2018. https://www.chicago.gov/content/dam/city/depts/cdph/CDPH/Healthy%20Chicago/2016ChicagoHCVReport_FINAL_07272018b.pdf. Accessed May 20, 2019.

Diagnoses, N

Year of Birth

180

160

140

120

100

80

60

40

20

0

1911

1915

1919

1922

1925

1928

1931

1934

1937

1940

1943

1946

1949

1952

1955

1958

1961

1964

1967

1970

1973

1976

1979

1982

1985

1988

1991

1994

1997

2000

2004

2007

Younger Adults:

Born Between

1975 and 1995

Baby Boomers:

Born Between

1945 and 1965

Diagnosis Year

2012

2016

Slide10

US Trends for Acute HCV Casesand Drug Overdose-Related Deaths

Centers for Disease Control and Prevention (CDC). Viral Hepatitis Surveillance – United States, 2016. https://www.cdc.gov/hepatitis/statistics/2016surveillance/pdfs/2016HepSurveillanceRpt.pdf. Accessed 5/8/2019; CDC. Drug Overdose Deaths in the United States, 1999–2017. https://www.cdc.gov/nchs/products/databriefs/db329.htm. Accessed 5/8/2019.

~69% of people with acute HCV infection reported injection-drug use

Reported Cases of

Acute HCV (2001–2016)Drug Overdose Death Rates (1999–2017)

Synthetic opioids other than methadone

Heroin

Deaths per 100,000 Standard Population

10

8

6

4

2

0

1999

2001

2003

2005

2007

2009

2011

2013

2015

2017

Number of Cases

3,500

3,000

2,500

2,000

1,500

1,000

500

0

2001

2004

2007

2010

2013

2016

Year

Year

Slide11

HCV is increasing in the younger population:

Incidence of acute hepatitis C, by age group — United States, 2000–2014

Source: CDC, National Notifiable Diseases Surveillance System (NNDSS)

Slide12

Circumstances and Risks Faced by PWIDRecognizing the Constellation

Prevailing backdrop

of economic, legal,

and social hardships:

Marginalization

1,2

Mental illness

3

Polysubstance

abuse

4

Intimate-partner

violence

(domestic abuse)

5

Transactional sex

6,7

Incarceration

8,9

Slide13

People Living With HCV in Chicago, 2016

Distribution and Socioeconomic Correlates

HCV Prevalence

Highest impacted communities

Southside: Fuller Park, Washington Park, Grand Boulevard, Englewood, Douglas, West Englewood, Oakland, Woodlawn, Greater Grand CrossingWestside: East Garfield Park, Near West Side, West Garfield Park, North Lawndale, Austin, Humboldt Park

Northside: UptownPer Healthy Chicago 2.0Higher rates of economic hardship, unemployment, blood lead levels among children, infant mortality, STIs, and

firearm‐related homicidesLower rates for child opportunity, high

school graduation, and life expectancySTI, sexually transmitted infection.Chicago Department of Public Health (CDPH). Hepatitis C Surveillance Report ‒ Chicago, 2016. 2018. https://www.chicago.gov/content/dam/city/depts/cdph/CDPH/Healthy%20Chicago/2016ChicagoHCVReport_FINAL_07272018b.pdf. Accessed May 27, 2019.

Cases per

100,000 Population

232.4-449.7

449.8-694.2

694.3-1034.5

1034.6-1357.1

1357.2-2260.1

Estimated 58,000 persons living with HCV in Illinois

Slide14

Other Demographic Characteristics and Prevalence of HCV

NHANES and Chicago DPH Data

NHANES: HCV Prevalence, by Demographic Characteristic, 2001‒2010

1

Chicago DPH: HCV Prevalence, by Selected Demographic Characteristic, 20162AI/AN, American Indian/Alaska Native; H, Hispanic; HIV, human immunodeficiency virus; NHB, non-Hispanic black; NHW, non-Hispanic white; Neg, negative; NHANES, National Health and Nutrition Examination Survey 2001 through 2010; PIR, poverty index ratio; Pos, positive.

1. Ditah I, et al. J Hepatol. 2014;60(6):691-698; 2. CDPH. 2018. https://www.chicago.gov/content/dam/city/depts/cdph/CDPH/Healthy%20Chicago/2016ChicagoHCVReport_FINAL_07272018b.pdf. Accessed May 27, 2019.

All Patients Identified as

Having HCV, %

Patient Characteristic

Demographic Characteristic

N

%

Rate/

100,000

Sex

Male

16,341

61.6

1,249.2

Female

10,060

37.9

725.0

Unknown

134

0.5

—

Race/ Ethnicity

AI/AN, NH

75

0.3

—

Asian, NH

303

1.1

—

Black, NH

7,447

28.1

—

Hispanic

1,737

6.5

—

Other, NH

382

1.4

—

White, NH

2,775

10.5

—

Unknown

13,816

52.1

—

Slide15

African Americans and HCV infection

Africans Americans comprise approximately 11% of the U.S. population, but represent 25% of people with chronic hepatitis C

infections

African Americans aged 20 to 59 are

1.6 times more likely to be chronically infected with hepatitis C compared to other races. African Americans aged 60 and older are 10 times more likely to be chronically infected with hepatitis C compared to other races.

Slide16

“The National Viral Hepatitis Action Plan 2017-2020

includes a focus on African Americans as one of the priority populations impacted by viral hepatitis. One of our national goals is to reduce health disparities in viral hepatitis, including reducing deaths among African Americans related to viral hepatitis infection. Only by working together and in the communities most impacted by viral hepatitis can we achieve this goal and improve the health and lives of people across the

nation”.

Goal 20 – Reduce STIs and viral hepatitis

        

Reduce the burden of sexually transmitted infections (STIs) and Viral Hepatitis, among people living with or vulnerable to HIV.

Strategy 66

–

Cure 50% of hepatitis C cases among people living with HIV.

GTZillinois.HIV

/plan

Slide17

Sexual transmission of Hepatitis C (HCV)

The risk of sexual transmission of HCV is low. Most studies: 0-3% risk of HCV through unprotected heterosexual intercourse with a long-term, monogamous HCV-positive partner. Health

Canada estimates

HCV transmission from

unprotected sex with a steady HCV-infected partner at 2.5% over 20 years.For monogamous couples, CDC does not recommend routine condom use to prevent hepatitis C transmission. Couples should avoid sharing razors, toothbrushes and nail clippers, and should also avoid having intercourse during menstruation.New research shows that gay men who are HIV-positive and have multiple sex partners may increase their risk for Hepatitis C.

Slide18

National Goals for HCV Elimination

National Academies of Sciences—Viral Hepatitis Elimination Goals by 2030

Department of Health and Human Services (DHHS).

National Viral Hepatitis Action Plan 2017–2020.

www.hhs.gov. Accessed 5/17/19; The National Academies of Sciences, Engineering, and Medicine. A National Strategy for the Elimination of Hepatitis B and C: Phase 2 Report. Washington, DC: The National Academies Press; 2017.DHHS—National Viral Hepatitis Elimination Goals by

2020

↓90

%

new HCV infections

↓65%

HCV-related deaths

↓60

%

New HCV infections

↓25%

HCV-related deaths

↑22

%

Persons aware of

HCV status

↓

Health disparities across HCV patient populations

Slide19

Deaths From Hepatitis C Have Surpassed Deaths From HIV Infection

Ly K.N et al., Annals of Int. Med, 2012: 157 (9)

Age-adjusted Mortality Rates of HIV and Hepatitis C: United States, 1999-2010

Slide20

Projected Cases of Hepatocellular Carcinoma and Decompensated Cirrhosis Due to HCV

Davis GL, et al.

Gastroenterology

. 2010;138(2):513-521

1950

1960

1970

1980

1990

2000

2010

2020

2030

Year

Number of cases

160,000

0

140,000

120,000

100,000

80,000

60,000

40,000

20,000

Decompensated cirrhosis

Hepatocellular cancer

Peak incidence:

145,000 cases/year in 2020

Peak incidence:

14,000 cases/year in 2019

Slide21

Complications of Cirrhosis

Ascites/Peritonitis

Variceal

Hemorrhage

Hepatocellular Carcinoma (HCC)

Hepatic Encephalopathy

Hepatic

Decompensation

Events

Primary

Liver

Cancer

Slide22

Pathogenesis of HIV/HCV Co-infection

Slide23

Screening for Hepatitis C

Slide24

2012 CDC Birth Cohort HCV Testing Recommendations

CDC now recommends:

Age-based testing: All adults born during

1945–1965

should have 1-time testing without prior ascertainment of HCV risk All persons identified with HCV should receive: Alcohol screeningIntervention as clinically indicated

Referral to appropriate carePost-test counseling

CDC = Centers for Disease Control and Prevention

.MMWR. 2012;61(RR04):1

–18.

Slide25

Who needs to get screened for HCV?

Slide26

Sometimes, providers need (a lot of)Help.

Figure I. Number of baby boomers screened for anti-HCV and percent increase, by site, pre- and post-

implemention

of

eCDS

, Cook County Health, August 2015 – September 2017

Slide27

How about Pregnancy?

Slide28

Slide29

Testing for HCV- simple blood test

Slide30

Linkage to care

Slide31

Chronic

HCV Counseling

Hepatitis A, B immunizations if

non-immune

Pneumococcal vaccination for cirrhoticsAnti-HBV treatment if HBV-coinfectedAbstain from alcohol

Maintain BMI <25 kg/m2Limit acetaminophen to <2 gm/day

Avoid

raw seafood (Vibrio infection)

www.hcvguidelines.org

Slide32

Counseling Recommendations forHCV-Infected Individuals

Avoid sharing toothbrushes and dental or shaving equipment

Prevent blood contact with others

Stop using illicit drugs; those who continue to inject drugs should take precautions to avoid viral transmission

Risk of sexual transmission is low, but practice

“

safe sex

”

Avoid alcohol consumption

Excess alcohol may lead to progressive liver disease, increased HCV RNA replication, and reduced response to treatment

Vaccinate

for hepatitis A and B

Get tested for HIV

Encourage family members to get screened

Additional Recommendations

To Prevent HCV Transmission

*If patient meets generally accepted indications for HCV treatment.

Adapted from Ghany MG, et al.

Hepatology

. 2009;49:1335-1374.

Slide33

How to Determine Liver Fibrosis Stage

Liver Biopsy

Serum Markers

Transient

Elastography

HCV FibroSure

age (years) x AST (U/L)

platelets (10

9

/L) x



ALT (U/L)

AST (U/L) / AST (upper limit normal)

platelets (10

9

/L)

FIB-4 =

APRI =

Ultrasound

Liver stiffness (kPa)

Liver fibrosis

Sterling RK.

Hepatology

2006;43:1317-25.

Kirk GD et al.

Clin Infect Dis

2009;48:963-72.

Chou R.

Ann Intern Med

2013;158:807-20.

X 100

Slide34

Transient

Elastography

Slide35

Transient

Elastography: HCV

Slide36

Fibrosis Staging in HCV

SVR = Sustained Viral ResponseGhany MG, et al.

Hepatology

. 2009;49(4):1335–1374;

AASLD/IDSA. Recommendations for Testing, Managing, and Treating HCV. www.hcvguidelines.org. Accessed 7/18/18. Images courtesy of Zachary Goodman, MD.

METAVIR Scale

Score

F0

F1

F2

F3

F4

Fibrosis (scarring)

No damage

Mild

Portal fibrosis without septa

Moderate

Portal fibrosis with rare septa

Advanced

Numerous septa, not cirrhosis

Severe

Cirrhosis

Determining fibrosis level is important as it may affect treatment regimen,

duration of treatment, and determines the need for HCC screening post-cure

AASLD/IDSA Guidance

Initiating therapy in patients with lower-stage fibrosis augments the benefits of SVR

Slide37

Risk Factors Associated with

Faster Fibrosis Progression in Chronic HCV

Poynard

A.

Antivir Ther.

2010;15(3):281-291; Poynard, et al. Lancet. 1997;349(9055):825-832.

HCC

Disease State Factors

Host/Viral Factors

Male gender

Age

Obesity

Diabetes

Metabolic syndrome

HIV, HBV co-infection

Immune system compromise

Steatosis

Iron overload

Genotype 3

Heavy alcohol consumption

Tobacco use

Lifestyle Factors

Fibrosis stage

Inflammation grade

Persistently elevated ALT

Cirrhosis

Normal Liver

Slide38

Strategies for Enhanced Linkage Patient-navigation models

Peer navigatorsTester/navigatorsNonpeer navigatorsCBO-based navigatorsClinic-based navigators

Embedded models; ie, care within SUD treatment programs

Nurse-led models

Physician-led modelsMobile care models Mixed modelsCBO, community-based organization; SUD, substance use disorder.

Bajis S, et al. Int J Drug Policy

.

2017;47:34-46

.

Slide39

Testing and Linkage to Care Protocol

PCP, primary care provider; PCR, polymerase chain reaction.

Protocol courtesy of Stacey Trooskin, MD, PhD. 2017.

Rapid HCV antibody test reactive

Blood draw for confirmatory HCV PCR

Insured with no known primary care provider

Patient navigator facilitates PCP acquisition

Insured with a primary care provider

PCP Visit

Obtain referral to subspecialist

Uninsured

Patient navigator facilitates appointment with clinical social worker

HCV RNA not detected

Patient navigator notifies patient and provides counseling

HCV RNA detected

Patient navigator notifies patient and provides counseling + insurance assessment

Slide40

Treatment and CURE

Slide41

Barriers to care and cure include

Psychosocial comorbiditiesSubstance use disorder (SUDs)

Untreated mental health issues

Transportation

Incarceration Homelessness or unstable housingDrug-drug interactionsComplicated prior-approval processes and denialsProviders’ lack of awareness of Ryan White ADAP coverage of HCV treatment and/or lifting of fibrosis restrictions

Slide42

Benefits of Achieving SVR (CURE)

SVR

Improved Hepatic

Outcomes

Viral EradicationImproved Extra-Hepatic

OutcomesImproved liver histologyReduced:

Decompensation/HCC/TransplantationLiver-related mortality

Decreased Transmission

Improved QOL/mental healthReduced Overall mortality Non-liver malignancy Diabetes/CVD/CKD

QOL = Quality of Life; CVD = Cardiovascular Disease; CKD = Chronic Kidney Disease.

Yoshida EM, et al.

Hepatology

. 2015;61(1):41

–

45; Thorlund K, et al.

Clin Epidemiol

. 2014;6:49

–58; van der Meer AJ, et al.

JAMA. 2012;308(24):2584–

2593; Smith-Palmer J, et al. BCM Infect Dis. 2015;15:19; Negro F, et al. Gastroenterology

. 2015:149(6):1345–1360; Arase Y, et al.

Hepatology. 2009;49(3):739–744; Arase Y, et al. J Med Virol

. 2014;86(1):169–

175; Hsu YC, et al. Hepatology

. 2014;59(4):1293–1302.

Slide43

HCV Life Cycle and DAA Targets

Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6(12):991-1000.

Slide44

HCV DAAs Target Steps of HCV Life Cycle

1. McCauley JA, et al.

Curr

Opin

Pharmacol

. 2016;30:84-92.

2.

Eltahla

AA, et al. Viruses. 2015;7:5206-5224.

3.

Gitto

S, et al. J Viral Hepat. 2017;24:180-186.

Inhibitor Class

Suffix

Examples

Targeting HCV Protein Processing

NS3/4

Pr

otease

[1]

-

PR

EVIR

Glecaprevir

, grazoprevir,

paritaprevir

,

simeprevir

,

voxilaprevir

Targeting HCV Protein Processing

NS5

B

Polymerase

[2]

-

B

UVIR

Nucleotide: sofosbuvir

Nonnucleoside: dasabuvir

NS5

A

[3]

-

A

SVIR

Daclatasvir, elbasvir, ledipasvir,

ombitasvir

,

pibrentasvir

,

velpatasvir

Slide credit:

clinicaloptions.com

Slide45

SVR12 (CURE) rates! We have come a long way….

Slide46

History and Evolving Landscape of HCV Therapy

Discovery

of HCV

(Chiron)

HCV

Antibody

Testing

Approval

Ribavirin

Approval

pegIFN-alfa-2b

Genotype-Specific

RGT

Approval

Telaprevir

Boceprevir

Approval

Simeprevir

Sofosbuvir

1989

1992

2005

1998

2011

2014

6%

20%

40%

54%

65–75%

>90%

12%

SVR:

pegIFN-alfa 2b = Peg-Interferon Alfa-2b; RGT = Response-Guided Therapy; OBV/PTV-R + DAS =

Ombitasvir/Paritaprevir and Ritonavir+Dasabuvir (or 3D).

Houghton M.

Liver Int

. 2009;29(Suppl 1):82–88; Carithers RL, et al.

Hepatology

. 1997;26(3 Suppl 1):S83

–

S88; Zeuzem S, et al.

N Engl J Med

. 2000;343(23): 1666

–

1672; Poynard T, et al.

Lancet

. 1998;352(9138):1426

–

1432; McHutchison JG, et al.

N Engl J Med

. 1998;339(21):1485

–

1492; Lindsay KL, et al.

Hepatology

. 2001;34(2):395

–

403; Fried MW, et al.

N Engl J Med. 2002;347(13):975–982; Manns MP, et al. Lancet

. 2001;58(9286):958–965; Poordad F, et al. N Engl J Med. 2011;364(13):1195–1206; Jacobson IM, et al. N Engl J Med. 2011;364(25):2405–2416; Lawitz E, et al. N Engl J Med. 2013;368(20):1878–

1887;

Jacobson IM, et al.

Lancet

. 2014;384(9941):403

–

413;

Afdhal N, et al.

N Engl J Med

. 2014;370(20):1889

–

1898; Nelson DR, et al.

Hepatology. 2015;61(4):1127–1135; Zeusem S, et al. Ann Intern Med. 2015;163(1):1–13; Feld JJ, et al. N Engl J Med. 2015;373(27):2599–2607; Foster GR, et al. N Engl J Med. 2015;373(27):2608–2617; Drygs@FDA: FDA Approved Drug products. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 5/9/2019. 2013ApprovalLedipasvir/Sofosbuvir OBV/PTV-R + DAS ApprovalDaclatasvir20152016ApprovalGrazoprevir/ElbasvirSofosbuvir/Velpatasvir2017ApprovalSofosbuvir/Velpatasvir/

VoxilaprevirApprovalGlecaprevir/Pibrentasvir1997

Slide47

Factors to Consider in

Selection of a DAA Regimen

HCV genotype: determines selection of DAA

Cirrhosis: duration of treatment

Drug-drug interactions: statins, PPI, ART(boosted/TDF)Renal impairment: Mavyret and Zepatier(PI/NS5A) can be used safely

Prior treatment experience (Interferon, Ribavirin, DAAs): Resistance testing may be neededSVR rates >95% among existing regimines Insurance

 Which DAA is on formulary?

Slide48

CORE hepatitis Clinic data (DAA experience 2015- through June 2019)

923 HCV infected individuals treated (on rx/completed/SVR12)350 HIV/HCV co-infected733 have reached SVR with 96% SVR (cure)Rapid increase in starts since 2019 ( Medicaid restrictions removed)

Slide49

After the Cure

Slide50

HCV Care Continues Past Achievement of SVR

Falade-Nwulia O, J

Hepatol

, 2017

.

Diagnosis

Linkage

to care

Treatment

Cure

Persons at risk for infection:

Counseling

Harm reduction

(injection and sex practices)

Surveillance for reinfection

Persons with advanced

fibrosis (stage 3/4)

Counseling

Harm reduction

(alcohol and obesity)

Surveillance for HCC

Slide51

Harm Reduction

Recommendations for Testing and Prevention of HCV Infection in Men Who Have Sex With Men (MSM)

RECOMMENDED

RATING 

Annual HCV testing is recommended for sexually active HIV-infected adolescent and adult MSM. Depending on the presence of high-risk sexual or drug use practices, more frequent testing may be warranted.

IIa, C

HCV testing at HIV pre-exposure prophylaxis (

PrEP

) initiation and at least annually thereafter (while on

PrEP

) is recommended in HIV-uninfected MSM. Depending on sexual or drug use risk practices, more frequent testing may be warranted.

IIa, C

All MSM should be counseled about the risk of sexual HCV transmission with high-risk sexual and drug use practices, and educated about measures to prevent HCV infection or transmission.

IIa

, C

www.hcvguidelines.org

Slide52

Take home points

Rise in new cases in the under 30 year olds due to opioid use.All baby boomers (born 1945-1965)- No additional risk factors required to

trigger

testing

.Pregnant women should be screened for HCVImportant to assess severity of fibrosis before treatment initiatedHCV diagnosis an opportunity for vaccination, health counselingEffective, safe treatment with cure rates over 95%People with advanced disease require follow up and screening post cureCounsel on re-infection post cureVisit and benchmark hcvguidelines.org

Slide53

To make a difference in the HCV epidemic we must:

Educate and raise awareness- community, providers, systemsScreen for HCV in clinical and community settings- age, risk based, pregnancyPut in prompts/reminders /reflex testing to improve testing and linkage Provide support after testing through linkage to treatment to cureOptimize and expand the pool of MAT providers and services

Continue to advocate for access, support

Empower our patients to advocate for themselves

Be creative in our models of service delivery- where/how/who/whenShare our successes and best practices