HCV Epidemiology, Screening, and Natural...

Bruce A. Luxon, MD, PhD, FACG

HCV Epidemiology, Screening, and Natural HistoryBRUCE A. LUXON, MD, PHD, FACG

A N TON A N D M A RGAR ET F UI S Z C H A I R I N M ED I C I N E

P R O F E S S O R A N D C H A I R M A N

D E PA R T M E N T O F M E D I C I N E

G EO R G E TO W N U N I V E R S I T Y

Hepatitis C In the U.S.

5.1 million estimated true

prevalence

3.9 million CDC estimate

http://ww.cdc.gov/hepatitis/statistics/index.htm Chak E, et al. Liv Int 2011;31:1090-1101

IncarceratedHomeless

Nursing homesHospitalized

Active Military25%

Diagnosed

Large reservoir of infected patients who

are undiagnosed

Why Should You Care?

And Untreated

ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology

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Natural History of HCV

Acute Infection*Chronic

Infection75%-85%

Cirrhosis10%-20%

over 20 years

HCC1%-4% per year

Decompensated Cirrhosis

5-yr survival rate 50%

AsymptomaticMost Americans infected >35 yAdditional impact of:

AlcoholObesityOlder age*Most have minimal symptoms

Consequences of Under-Diagnosis of HCV Infection33% of undiagnosed Americans have advanced fibrosis/cirrhosis

McGarry LJ, et al. Hepatology 2012;55:1344-1355Davis G, et al. Gastroenterology 2010;138(2):513-521.

Now


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HCV is a Systemic Disease


Infection75%-85%

Extra hepatic Manifestations

Cirrhosis10%-20%

over 20 years

HCC1%-4% per year



Extrahepatic Manifestations of HCV

Mixed cryoglobulinemia Sjögren (sicca) syndrome Lymphoproliferative

disorders Porphyria cutanea tarda Neuropathy Membranoproliferative

glomerulonephritis Cryoglobulinemic vasculitis

Corneal ulcers (Mooren ulcers) Thyroid disease Lichen planus Pulmonary fibrosis Type 2 diabetes Systemic vasculitis

(polyarteritis nodosa, microscopic polyangiitis) Arthralgias, myalgias,

inflammatory polyarthritis Autoimmune

thrombocytopenia

Adapted from Ali A, Zein NN. Cleve Clin J Med. 2005;72:1005-1008.

Strongly associated Possibly associated


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HCV Infection Increases Risk of Chronic Kidney Disease – REVEAL-HCV Study

HCV (+), High VL

HCV (+), Low VL

HCV (-)

Lai TS, et al. AASLD 2014, Abstract #172

N=23,785; 1,313 seropositive for HCV

HCV Infection is Associated with Increased All Cause Mortality “Reveal-C”

Follow-Up (Years)

20

18

16

14

12

10

2

00 2 4 6 8 10 12 14 16 18 20

8

6

4

Follow-Up (Years)

12

10

8

6

4

2

00 2 4 6 8 10 12 14 16 18 20

All Causes(n=2394)

Liver Cancer(n=115)

Extrahepatic Diseases(n=2199)

Cum

ulat

ive

Mor

talit

y (%

)

Anti-HCV+, HCV RNA detectable Anti-HCV (–)

Follow-Up (Years)

35

30

25

20

15

10

5

00 2 4 6 8 10 12 14 16 18 20

30.1%*

12.8%12.4%

10.4%*

1.6%

0.3%

19.8%*

12.2%11.0%

Lee M-H, et al. J Infect Dis 2012;206:469-477

23,800 adults, 16.2 y f/u


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Increasing Healthcare Costs Associated with the Aging HCV Population

Prevalence(95% CI)

Health Care Cost(95% CI)

Pre

vale

nce

(M

illio

n)

Razavi H, et al. Hepatology 2013;57:2164-2170

Expensive to have end stage liver disease

We Can Make A Difference!

P<.001

Non-SVR

SVR

Time (years)

Perc

ent

0

10

20

30

0 1 2 3 4 5 6 7 8 9 10

All-Cause Mortality

Van der Meer AJ, et al. JAMA 2012;308:2584-2593


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SVR Improves Long-Term Liver Outcomes

Per

cen

t

Cumulative Incidence of Any Liver-Related Outcome Among Patients With Bridging Fibrosis or Cirrhosis

Morgan TR, et al. Hepatology 2010;52:833-844

Outcome After SVR in Advanced Fibrosis (HALT-C)

NR = non response; BT/R= Breakthrough/relapse; SVR = Sustained response

Morgan TR, et al. Hepatology 2010;52:833-844


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How Do You Get Hepatitis C?

1998 CDC Risk Based HCV Screening Recommendations

• Ever injected illegal drugs

• Received blood, organs, or clotting factors prior to 1992

• Have ever been on hemodialysis

• Have elevated ALT

• Born to HCV-infected mothers

• Have HIV infection

• Percutaneous or mucosal exposure to HCV positive blood

CDC. MMWR 1998;47(RR-19):1-39


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Risk-Based Screening Does Not Work

• Primary care setting, U.S. – 2005-2010• 17,464 tested for HCV◦ 6.4% positive

• Odds ratios for positive anti-HCV◦ IVDU: 6.3◦ 1945-1965 birth cohort: 4.4◦ Elevated ALT: 4.8

• Risk based screening missed 4 out of 5 HCV positive adults

Yartel AK, et al. AASLD 2013; abstract #24

HCV in the US – 2001-2010Milliman Study: Based on NHANES and Claim Forms

82% aged 44-63 years

http://publications.milliman.com/research/health-rr/pdf/consequences-hepatitis-c-virus-RR05-18-09.pdf


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HCV in the U.S.8,810 Americans with hepatitis C infectionDanville PA, Detroit MI, Portland OR, Honolulu HI

7.20%

42%

33.30%

8.20%4.60% 1.40%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

1935-1944 1945-1954 1955-1964 1965-1974 1975-1984 1985-1990

Distribution by Birth Year

Moorman AC, et al. CID 2013;56:40-50

75% born between 1945-1964

Baby Boomer EpidemicAnti-HCV Prevalence by Birth

Year, NHANES 1999-2008

Smith BD, et al. AASLD 2011, abstract 241


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Birth Year 1945 – 1965Baby BoomersWoodstock Festival 1969“Share Love and Hep C”

Not Only the Boomer’s Fault…

• Hepatitis C was not on the radar• Blood supply was contaminated• No universal precautions in healthcare settings• No way to screen organs or blood products


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2012 CDC Recommendations for Birth Cohort Screening (1945 - 1965)Recommendation #1◦Adults born from 1945-1965 should receive one-time

testing for HCV.

Recommendation #2◦HCV (+) individuals ◦Brief alcohol screening and intervention◦Referral to appropriate care for HCV

Smith BD, et al. Ann Intern Med 2012;157;817-822

2013 USPSTF HCV Screening Recommendations1. Those at high risk for HCV infection2. Those born from 1945 to 1965◦ Grade B recommendation – high certainty that the net benefit

is moderate to substantial

The Affordable Care Act◦ Requires insurance plans to provide Grade A or B

recommendations without cost sharing

USPSTF = United States Preventive Services Task Force

Moyer VA - on behalf of the USPSTF. Ann Intern Med 2013;159:349-357


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Baby Boomers in the VA Population

Birth Year % screened Anti-HCV (+) HCV-RNA (+)

<1945 42% 2.9% 1.7%

1945-1965 64% 13.1% 9.9%

>1965 58% 1.9% 1.1%

VA Screening program; 5.5 million eligible for screen

Backus L, et al. AASLD 2013; Abstract #21

Is it Effective?3 Randomized Controlled Trials

Compared to “standard of care”◦ Testing for HCV in persons born 1945-1965 with

no prior testing◦Was 5 times more effective in identifying

persons with current or prior infection

Smith BD, et al. AASLD 2014, Abstract #194


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For “Non-Baby Boomers”

Risk based screening◦ IVDU – single or multiple◦ Intranasal cocaine use◦Getting an unregulated tattoo and other

percutaneous exposures◦Blood or blood product transfusion before 1992◦Born to an HCV-infected mother◦ Incarceration

Moyer VA - on behalf of the USPSTF. Ann Intern Med 2013;159:349-357

Transmission of HCVRoute Hepatitis C

IV drug use

Transfusion

Hemodialysis

Intra-institutional

Sexual

Household

Mother-to-newborn

Oral-oral contact

Food-borne

Fecal (oral)

Water-borne

Raw shellfish

Common Infrequent Never

Generates Questions

in my Clinic


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HCV Is Not Going Away!

You Want Your Doctor to AvoidThese Mistakes

“Liver tests are normal, not much can be going on.”

“Hepatitis C does not damage the liver unless alcohol is involved.”

“I discussed vaccinating patient vs. HCV & patient declined.”

“There is nothing to do about treating hepatitis C.”

“Treatment of hepatitis C is worse than the disease.”


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0

500

1,000

1,500

2,000

2,500

3,000

3,500N

umbe

r of c

ases

Year

Source: National Notifiable Diseases Surveillance System (NNDSS)

0

0.5

1

1.5

2

2.5

3

Repo

rted

cas

es/1

00,0

00 p

opul

atio

n

Year

0–19 yrs

20–29 yrs

30–39 yrs

40–49 yrs

50–59 yrs

≥60 yrs

Source: National Notifiable Diseases Surveillance System (NNDSS)


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Not All anti-HCV (+) Patients Are Infected!


Infection75%-85%

Clearance of HCV RNA15%-25%

Cirrhosis10%-20% over 20 years

HCC1%-4% per year



HISTOLOGIC STAGING

NO FIBROSIS

STAGE 0

PORTAL FIBROSIS

STAGE 1

FEW SEPTA

STAGE 2

NUMEROUS SEPTA

STAGE 3

CIRRHOSIS

STAGE 4 STOP Before Here


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Importance of Confirming Viremia

Anti-HCV Antibody HCV RNA

No Further Testing

No Active Disease

Positive Positive

Negative Negative

HCV Genotype Consider Liver Biopsy

Vaccinate for HAV / HBV*

Benefits of Diagnosis

PREVENT TRANSMISSION

Avoid sharing objects with blood

Stop illicit drugs or sharing needles

Discuss risk of sexual transmission with “unsafe sex”

OTHER RECOMMENDATIONSAvoid alcohol consumption

Discuss available treatments

Vaccinate for hepatitis A and B

Test for HBV, HIV

Consider family member screening


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HCV Epidemiology, Screening and Natural History - Summary

1. Most HCV patients remain undiagnosed2. 75% of them were born from 1945-19653. 33% of them have advanced fibrosis “ticking time bombs” waiting to explode (bleed) on a Friday at midnight

when you are on call

4. Therapy is more effective and safer5. It’s time to incorporate screening into your

practice!


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HCV Epidemiology, Screening, and Natural...

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