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
Page 1 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 2 of 18
Bruce A. Luxon, MD, PhD, FACG
HCV is a Systemic Disease
Acute Infection*Chronic
Infection75%-85%
Extra hepatic Manifestations
Cirrhosis10%-20%
over 20 years
HCC1%-4% per year
Decompensated Cirrhosis
5-yr survival rate 50%
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 3 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 4 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 5 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 6 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 7 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 8 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 9 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 10 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 11 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 12 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 13 of 18
Bruce A. Luxon, MD, PhD, FACG
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.”
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 14 of 18
Bruce A. Luxon, MD, PhD, FACG
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)
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 15 of 18
Bruce A. Luxon, MD, PhD, FACG
Not All anti-HCV (+) Patients Are Infected!
Acute Infection*Chronic
Infection75%-85%
Clearance of HCV RNA15%-25%
Cirrhosis10%-20% over 20 years
HCC1%-4% per year
Decompensated Cirrhosis
5-yr survival rate 50%
HISTOLOGIC STAGING
NO FIBROSIS
STAGE 0
PORTAL FIBROSIS
STAGE 1
FEW SEPTA
STAGE 2
NUMEROUS SEPTA
STAGE 3
CIRRHOSIS
STAGE 4 STOP Before Here
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 16 of 18
Bruce A. Luxon, MD, PhD, FACG
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
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 17 of 18
Bruce A. Luxon, MD, PhD, FACG
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!
ACG 2016 Washington, DC, Hepatitis School Copyright 2016 American College of Gastroenterology
Page 18 of 18