Transcript Chronic hepatitis C: Latest CDC, USPSTF screening recommendations and update on treatment Mumtaz Niazi MD Assistant Professor of Medicine Avera Center For Liver Disease Avera McKennan Hospital&

Chronic hepatitis C:
Latest CDC, USPSTF screening
recommendations
and update on treatment
Mumtaz Niazi MD
Assistant Professor of Medicine
Avera Center For Liver Disease
Avera McKennan Hospital& University Health Center
Sioux Falls, South Dakota
Prevalence
Prevalence
Worldwide
170 million ( 3%)
United States
Anti-HCV positive
HCV RNA positive
3.9 million (1.8%)
2.7 million (1.4%)
Alter MJ et al., New Engl J Med 1999; 341:556
Lavanchy D & McMahon B, In: Liang TJ & Hoofnagle JH (eds.)
Hepatitis C. New York: Academic Press, 2000:185
Prevalence
Prevalence
Worldwide
170 million ( 3%)
United States
Anti-HCV positive
3.9 million (1.8%)
If born during 1945-1965 : incidence 3.25%
HCV RNA positive
2.7 million (1.4%)
Alter MJ et al., New Engl J Med 1999; 341:556
Lavanchy D & McMahon B, In: Liang TJ & Hoofnagle JH (eds.)
Hepatitis C. New York: Academic Press, 2000:185
Smith BD et al, Abstract. AASLD 11,6, 2011. San Francisco, CA
Prevalence of HCV antibody
by year of Birth
5X higher
Prevalence of HCV
antibody in adults
born between 1945
and 1965 vs adults
born in other years
National Health and Nutrition Examination Survey, United
States, 1988–1994 and 1999–2002
Screening recommendations
by CDC
 Clotting Factor
Treatment Prior
to 1987
Long-Term
Hemodialysis
 Multiple
Sexual Partners
 Blood
Transfusion
Or Organ Transplant
Prior to 1992
Risk Factors
for Hepatitis C
Abnormal LFTs
Needle sticks
Tattoos
CDC. MMWR 1998;47(No. RR–19)
 IV Drug Use
even once
 Intranasal
Cocaine
 Birth from
Infected Mother
Risk Factors for Hepatitis C
Screening recommendations by CDC
 HIV-infected patients should be tested
routinely for evidence of chronic HCV
infection.
 Initial testing for HCV should be performed
using the most sensitive immunoassays
licensed for detection of antibody to HCV
(anti-HCV) in blood.
CDC. Guidelines for prevention and treatment of opportunistic infections in HIV-infected
adults and adolescents: Recommendations from CDC, the National Institutes of Health,
and the HIV Medicine Association of the Infectious Diseases Society of America.
MMWR 2009;58(No. RR–4).
Screening recommendations
by CDC
Recommendations for the Identification of Chronic
Hepatitis C Virus Infection Among Persons Born
during 1945–1965*
 Adults born during 1945–1965 should receive one-time
testing for HCV without prior ascertainment of HCV risk.
 All HCV infected individuals should receive a brief
alcohol screening and intervention as clinically indicated,
followed by referral to appropriate care and treatment
services for HCV infection and related conditions.
CDC. Recommendations for the identification of chronic hepatitis C virus infection
among persons born during 1945–1965. MMWR 2012;61(No. RR–4)
2013 Updated USPSTF HCV Screening
Recommendations
 Those at high risk for HCV infection:
 Most important risk factor is past or current injection
drug use
 Additional risk factors include:
•
•
•
•
•
•
Receiving a blood transfusion before 1992
Long-term hemodialysis
Being born to an HCV-infected mother
Incarceration
Intranasal drug use
Getting an unregulated tattoo, and other percutaneous
exposures
 Adults born between 1945 and 1965 (“Baby
Boomers”)
Moyer VA; on behalf of the USPSTF. Ann Intern Med. Jun 11, 2013
Why Need For Birth Yr Based Screening
Recommendations
 Out of 2.7-3.9 million HCV infected persons in
US, 45%-85% are not aware of their infection
 According to data from national health survey,
55% HCV infected persons reported exposure risk,
45% reported no risk factors
 Barriers to HCV testing:
 Inadequate health insurance
 Accuracy of pts to recall of risk factors decreases over time
 Providers lack of knowledge about hepatitis serology and
treatments
Why Baby Boomers Need to be Tested
 It is estimated that this “birth cohort” screening
strategy would:
Identify >800,000 more cases of HCV than would
be identified through risk-based screening alone
Approximately 416,000 more patients will receive
treatment
Reduce the number of future cases of
decompensated cirrhosis by approximately 64,000
Reduce the number of HCV-related deaths by
approximately 121,000
Mortality From HCV and HIV Infection in the US
Mortality Rate (per 100,000
Persons)
7
6
DEATH
HIV
5
HCV :15106
4
HCV
HIV :12734
3
2
1
0
Year
99
00
01
02
03
04
05
06
07
Ly KN, et al. Ann Intern Med. 2012;156:271-278.
Hepatitis C Infection
Outcome Following Hepatitis C Infection
Acute hepatitis C
55 - 85%
Chronic infection
70%
Chronic hepatitis
20%
1 - 4%/yr
HCC
Cirrhosis
Time
(yr)
4 - 5%/yr
10
20
Decompensation
30
HCV–Infected US Population: 2009-2028
Assuming no changes in standard of care
Individuals
250,000
Liver
transplantation
Hepatocellular
carcinoma
Decompensated
cirrhosis
200,000
150,000
100,000
50,000
0
2009
2012
2015
2018
2021
2024
2027
Yr
Total number of patients with advanced liver disease in 20 yrs projected to be >
4-fold higher than today
Milliman, Inc. Consequences of HCV: costs of a baby boomer epidemic, 2009.
HCV Viremia Was Associated With Increased
Mortality in a Prospective Taiwanese Cohort Study
Anti-HCV+, HCV RNA detectable
All Causes
Liver Cancer
n=115
Anti-HCV–
Extrahepatic Diseases
n=2199
Cumulative Mortality (%)
n=2394
Anti-HCV+, HCV RNA undetectable
Follow-Up (Years)
REVEAL HCV: Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (1991-2008).
Lee M-H, et al. J Infect Dis. 2012;206:469-477.
Liver Cancer Has the Fastest Growing
Death Rate in the United States
Trends in US Cancer Mortality Rates
All Other Cancers
(Average)
Corpus & Uterus, NOS
Testis
Lung & Bronchus (Female)
Esophagus
Thyroid
Liver
-2
-1.5
-1
-0.5
0
0.5
1
Annual Percent Change (1994–2003)
1.5
2
National Cancer Institute. Seer Summary Figures and Tables. Available at:
http://seer.cancer.gov/csr/1975_2003/results_merged/topic_graph_trends.pdf. Accessed on April 17,
Health Care Cost
(95% CI)
Prevalence
Million)
Prevalence
(95% CI)
Health Care
Cost (Billion)
Increasing Health Care Costs Associated With Progressive
Liver Disease in the Aging HCV-Infected Population
While the prevalence of HCV infection is declining from its peak, the incidence of
advanced liver disease and associated health care costs continue to rise
Razavi H, et al. Hepatology. 2013. Epub ahead of print.
SVR Reduced HCC and Liver-Related Complications
in Patients With Bridging Fibrosis or Cirrhosis
HCC
(n=307)
Cumulative Incidence (%)
Cumulative Incidence (%)
Liver-Related Complications*
(n=307)
Follow-Up (years)
Follow-Up (years)
Cardoso A-C, et al. J Hepatol. 2010;52:652-657.
SVR Reduced Risk of All-Cause Mortality in a
Retrospective VA Study
Genotype 2
(n=2904)
Genotype 1
(n=12,166)
Cumulative Mortality (%)
SVR rate:
35%
Years
SVR rate:
72%
Years
Genotype 3
(n=1794)
SVR rate:
62%
Years
Backus LI, et al. Clin Gastroenterol Hepatol. 2011;9:509-516.
SVR Was Associated With Reduced Long-Term Risk of
All-Cause Mortality in an International, Multicenter Study
Percent
All-Cause Mortality
Time (years)
International, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe
and Canada. Patients with chronic HCV infection started an interferon-based treatment regimen
between 1990 and 2003 (n=530).
van der Meer AJ, et al. JAMA. 2012;308:2584-2593.
Factors Associated With Fibrosis
Factors Associated With Fibrosis
 Duration of infection
 Alcohol > 50 gm per day
 Age > 40 years at infection
 Male gender
Poynard T, et al., Lancet 1997; 349:825
Alcohol Consumption Increases Risk
of Cirrhosis in HCV Patients
100
Cirrhosis (%)
80
P < .01
P < .01
64
58
60
P < .01
85
40
40
20
0
HCV
HCV + alcohol*
31
18
12
6
10
20
30
Years Following Exposure†
40
*Excessive alcohol intake characterized as > 40 g/day for women and > 60 g/day for men.
†Duration of exposure defined as either first blood transfusion before 1990 or from the year of initial
intravenous drug use.
Wiley TE, et al. Hepatology. 1998:28:805-809.
Initial evaluation of high risk patient for hepatitis C
HCV - Diagnosis
Initial Evaluation
Risk
factors for
HCV
Clotting factor treatment
prior to 1987
Injecting drug use
Long-term hemodialysis
Parenteral transmission prior to universal
precautions
Initial evaluation of patients at risk for hepatitis C
HCV - Diagnosis
Pretreatment Evaluation
Risk
factors for
HCV
Elevated
ALT
Test for HCV
antibody
Initial evaluation of patients at risk for hepatitis C
HCV - Diagnosis
Pretreatment Evaluation
Risk
factors for
HCV
Elevated
ALT
Baby Boomers
Test for HCV
antibody
Initial evaluation of a patient with a positive antibody test for HCV
HCV - Diagnosis
Pretreatment Evaluation
HCV antibody
positive
HCV RNA level
Genotype
liver biopsy
Anti-HCV Antibody Testing
ELISA screening tests
 Detect circulating HCV antibodies
 Sensitivity: 97% to 100%
 Positive predictive value
– 95% with risk factors and elevated ALT
– 50% without risk factors and normal ALT
False Positives More Likely in:
False Negatives More Likely in:
Patients with low risk of HCV infection
Severely immunosuppressed patients
Transplantation recipients
Patients with chronic renal failure on
dialysis
HIV-positive patients
NIH Consensus Statement. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html.htm.
Accessed May 7, 2009. Carithers RL Jr, et al. Semin Liver Dis. 2000;20:159-171.
Pawlotsky JM. Hepatology. 2002;36(suppl 1):S65-S73.
HCV - Diagnosis
Quantitative HCV RNA (PCR)
 Confirms diagnosis of HCV infection
 Useful in the early diagnosis of acute
hepatitis C
 Demonstrates the presence of active
infection
 “Gold standard” for documenting
response to treatment
CDC Analytic Framework for Guiding HCV Testing Among
Persons Born During 1945–1965
HCV-infected
Testing persons born 1945–1965
for HCV infection
(Anti-HCV antibody)
Brief alcohol
Screening &
counseling
Referral for
treatment
Antiviral
Treatment
provided
No Antiviral
Treatment
provided
Fewer complications from
Cirrhosis and
decompensated cirrhosis
More complications from
cirrhosis and
decompensated cirrhosis
 Fewer liver transplants
 Fewer incidents of HCC
 Less mortality
 Decreased HCV transmission
 Higher quality of life
 More liver transplants
 More incidents of HCC
 More mortality
 Increased H CV transmission
 Lower quality of life
Not
HCV-infected
Reassurance
of testing
negative
CDC: MMWR
August 17, 2012
Vol. 61 / No. 4
AASLD Counseling Guidelines
 Avoid sharing dental or shaving equipment
 Cover bleeding wounds to prevent contact with others
 Discontinue illicit injection drug use; if injection drug use continues:
– Avoid reusing/sharing needles/syringes
– Clean injection site with fresh alcohol swab
 Do not donate blood, organs, tissue, or semen
 Due to low sexual transmission rate, barrier protection not needed in
monogamous relationships; otherwise, safe sex practices warranted
 No Alcohol
 HAV and HBV vaccinations.
 Hepatitis C does is not spread by kissing, hugging, sneezing,
coughing, or sharing food, eating utensils or glasses.
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
Goals of Hepatitis C
Treatment
Primary
 Eradicate the virus
Secondary
 Prevent progression to cirrhosis
 Reduce incidence of HCC
 Reduce need for transplantation
 Enhance survival
Hepatitis C Virus
Genotypes in the USA
Type 2
17%
Type 1
72%
Type 3
10%
All others
1%
McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.
New Standard of Care for HCV in
2013/2014
Boceprevir or
Telaprevir +
P/R
Interferon +
Ribavirin
1991
Standard
Interferon
1998
GT1
2011
Simeprevir or
Sofosbuvir +
P/R
2013
2001
Peginterferon/
Ribavirin
GT2/3
2013
Sofosbuvir +
Ribavirin
First-line Treatment for Genotype 1
HCV
Simeprevir
or
Sofosbuvir
PegIFN-α
Ribavirin
SVR is 90+ in treatment naive and relapsers
First-line Treatment for Genotype 2&3
HCV
Sofosbuvir Ribavirin
SVR is > 90% in Genotype 2
SVR is > 80% in Genotype 3
First-line Treatment for Genotype 4
HCV
Sofosbuvir
PegIFN-α
Ribavirin
SVR is 90+ in treatment naive and relapsers
SVR Equivalent to Viral Cure
Patients With SVR (%)
Nearly 100% of patients who achieve SVR remain undetectable during
long-term follow-up[1-4]
100
99[1]
99[2]
100[3]
100[4]
80
60
40
20
0
3.9 yrs
(mean)
3.4 yrs
3.3 yrs
(median)
(median)
Duration of Follow-up
5.4 yrs
(median)
1. Swain MG, et al. Gastroenterology. 2010;139:1593-1601. 2. Giannini EG, et al. Aliment Pharmacol Ther.
2010;31:502-508. 3. Maylin S, et al. Gastroenterology. 2008;135:821-829. 4. George SL, et al. Hepatology.
2009;49:729-738.
SVR Associated With Improved Outcome
SVR Associated With Improved
Outcome
SVR
 Durable
 Leads to improved histology
 Leads to clinical benefits
 Decreases decompensation
 Prevents de novo esophageal varices
 Decreases risk of hepatocellular carcinoma
 Decreases mortality
Bruno S, et al. Hepatology. 2010;51:2069-2076. Veldt BJ, et al. Ann Intern Med. 2007;147:677-684.
Maylin S, et al. Gastroenterology. 2008;135:821-829.
Conclusions
Chronic Hepatitis C is a major liver disease worldwide
and in the US
Identifying patients at risk and proper screening are
essential
Adults born during 1945–1965 should receive one-time
testing for HCV without prior ascertainment of HCV risk.
Treatment for hepatitis C is much better
HCC screening is recommended for all cirrhotics and
hepatitis B infected non-cirrhotics
Therapy success has definite great impact on patients’
survival
Hepatitis C is a curable disease