global ai- hcv talk
TRANSCRIPT
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Hepatitis CEpidemiology, Diagnosis,
& Current treatment options
Amir Butt, MDAssistant Professor
Medical Director Pancreatico-biliary ServiceDivision of Gastroenterology, Hepatology, & Nutrition
Brody School of Medicine
East Carolina University
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Disclosures
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Objectives
Hepatitis C: Prevalence, transmission &symptoms
Making the diagnosis
Current treatment options
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Help
While suturing a HCV infected patient at 8pm on aSaturday evening, a surgical resident receives a needlestick injury. He shows up to occupational health onMonday morning and after lab work, he is told to be HCV
Ab positive. That afternoon he is in your clinic.
Which of the following is the most appropriate response?
A. Almost all surgeons get HCV Ab sometime in their life
B. You have contracted HCV from the needle stick
C. HCV infection not entirely curable
D. You should have stuck to Internal Medicine
E. You have Hepatitis C from a prior exposure
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Epidemiology
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NANB - Hepatitis
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Hepatitis C virus: The major causative agentof viral non-A, non-B hepatitis
A blind recombinant immunoscreening approach,of general
application to studies of infectious diseases, was used to cloneand identify the genome of the previously uncharacterizednon-A, non-B hepatitis (NANB) virus. This agent is a positive-strandedRNA virus that appears to be distantly related to theflaviviridae family. Data obtained usingthis assay indicate thatthis agent, termed the hepatitis Cvirus (HCV), is the majorcause of post-transfusion, community-acquiredand
cryptogenic, NANB.
QL Choo, et al. Chiron Corporation, Emeryville California, USA - 1990
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Hepatitis C Virus
Single stranded, positive sense, RNA Flaviviridae family
Spherical, enveloped
Great genetic diversity Six genotypes: 1 through 6
Multiple subtypes: a, b, c, etc
Viral sequences can be used to track acommon source of infection
~ 50 nm
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HCV: Magnitude of the Problem
Nearly 4 million persons in United States infected Approximately 35,000 new cases yearly 85% of new cases become chronic
Leading cause of Chronic liver disease Cirrhosis Liver cancer Liver transplantation
Centers for Disease Control and Prevention. Hepatitis C fact sheet. February 1, 2006.
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Advanced Liver Disease in ChronicHCV-Infected US Population, 2009-2028
The total number of patients with advanced liver disease in 20 yrs isprojected to be > 4-fold greater than it is today
The Milliman Report. Consequences of Hepatitis C Virus (HCV): May 2009.
Assuming No Changes in SOC
0
50,000
100,000
150,000
200,000
250,000
Individuals
2009 2012 2015 2018 2021 2024 2027Year
Hepatocellularcarcinoma
Decompensatedcirrhosis
Liver transplant
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Annual US Medical Costs for ChronicHCV Infection From 2009-2028
Total medical costs for patients with HCV infection are expected to more thandouble, from $30 billion to more than $85 billion USD over the next 20 yrs
The Milliman Report. Consequences of Hepatitis C Virus (HCV): May 2009.
0
60
100
USD$,
Billions 80
40
20
2009 2012 2015 2018 2021 2024 2027
MedicareUninsuredVAMedicaidCommercial
Assuming No Changes in SOC
Year
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Hepatitis C: A Worldwide Epidemic
Estimated ~ 170 million (3.1%) globally (2003)
1, 2, 31
1, 3
1,3
1
Worldwide: 6
3
4
44
4,5
Asia: 63
Europe8.9 million
(1.03%)
The Americas13.1 million
(1.7%)
Africa31.9 million
(5.3%)
Southeast Asia32.3 million
(2.15%)
Western Pacific62.2 million
(3.9%)
EasternMediterranean21.3 million
(4.6%)
Common Genotype
World Health Organization. Hepatitis C: global prevalence: update. 2003. Farci P, et al. Semin LiverDis. 2000;20:103-126. Wasley A, et al. Semin Liver Dis. 2000;20:1-16.
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HCV: Genotypes in the USA
All others
1%
Type 3
10%
Type 2
17%
Type 1
72%
McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.
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Determination of HCV GenotypeINNOLiPA Assay
HCV genotype
Best pretreatment predictor ofresponse
Determines duration of
therapy
All patients should havegenotype determined priorto initiating therapy
PCR1a
1b
3a3b
4
2b
2a
5
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Large Population Underscreened andHCV Patients Under diagnosed
Current screening practices fail to identify a largeproportion of patients with chronic HCV infection[1]
As few as 25% of patients are diagnosed
Survey of 4000 primary care physicians[2]
Only 59% of 1412 respondents asked all patients aboutHCV risk factors
AASLD recommends that as part of acomprehensive health evaluation, all personsshould be screened for behaviors that place themat high risk for HCV infection[3]
1. Kim WR. Hepatology. 2002;36:S30-S34.2. Shehab TM, et al. J Viral Hepat. 2001;8:377-383.3. Ghany MG, et al. Hepatology. 2009;49:1335-1374.
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HCV Infection: High-Risk Populations inWhich Screening Is Indicated
Injection drug use
Nasal inhalation ofcocaine
Chronic renal failure ondialysis
Incarceration
Multiple sexual partners,MSM, HIV positive
Transplantation ortransfusion of bloodproducts before 1992
Occupational exposure toblood products
Body piercing andpossibly tattoo
Children born to HCV-positive women
Centers for Disease Control and Prevention. April 10, 2007. Verucchi G, et al. Infection.2004;32:33-46.
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High Prevalence of HCV Among IDUs
89
80
67
64
74
0 20 40 60 80 100
HCV (%)
Bulgaria
New Zealand
Russia
Amsterdam
Baltimore
63New York
Thomas DL, et al. Medicine (Baltimore). 1995;74:212-220. Des Jarlais DC, et al. AIDS. 2005;19(suppl 3):S20-S25.
Vassilev ZP, et al. Int J STD AIDS. 2006;17:621-626. Kemp R, et al. N Z Med J. 1998;111:50-53.
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Reasons for High HCV Risk Among Injection
Drug Users Contaminated needles
Contaminated works Syringes, cookers, cottons, rinse water
Old (infected) mentor transmits to young initiate
Villano SA, et al. J Clin Microbiol. 1997;35:3274-3277. Garfein RS, et al.J Acquir Immune Defic Syndr Hum Retrovirol. 1998;18(suppl 1):S11-S19. Thorpe LE, et al.Am J Epidemiol. 2002;155:645-653. Hagan H, et al. Public Health Rep. 2006;121:710-719.
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Modes of HCV Transmission
HCV can probably survive on environmental surfaces atroom temperature for 16-72 hours
Do not exchange blood Razors, toothbrushes, nail clippers
Sexual transmission rate is low Condoms recommended for multiple sexual partners
Not transmitted by casual contact (eg, hugging)
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HCV Prevalence
Sex
0
1.0
2.0
3.0
4.0
All W B H M FRace
A
nti-HCVPosit
ive(%)
Alter MJ, et al. N Eng J Med. 1999;341:556-562.
1.8%
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Prevalence in 2006
0
1
2
3
4
5
6
78
9
10
6-19 20-29 30-39 40-49 50-59 60-69 70+
Age group
PercentAnti-HCV
Po
sitive
NH White NH Black Mex Amer
Armstrong GL, Ann Intern Med 2006;144:705-714
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Prevalence rates of HCV - 2008
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Diagnosis
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Making the diagnosis
Natural History - Acute Infection
Symptoms
Are uncommon (body aches, flu-like symptoms, etc)
On average, appear 6 to 7 weeks after infection.
Testing
6 to 8 weeks: Average time antibodies can be detected.
1 to 3 weeks: Average time virus can be detected.
4 to 12 weeks: Often elevation in ALT
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Serologic Pattern of Acute HCV Infectionwith Recovery
Symptoms +/-
Time after Exposure
Titer
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
HCV RNA
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Chronic HCV Symptoms
Asymptomatic
Symptomatic
Cirrhosis
0
20
40
60
80
100
Fatigue
Perce
ntageofPatients37%
7%
56%
Unpublished data from MCV Hepatitis Program, 1995.
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Serologic Pattern of Acute HCV Infectionwith Progression to Chronic Infection
Symptoms +/-
Time after Exposure
Titer
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
HCV RNA
anti-HCV
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0
50
100
150
200
0 6 12 18 24
Month
ALT(IU/l)
Resolution
Chronic
HCV RNA+/- + -
HCV Response: Acute vs Chronic
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Hepatitis C Virus Diagnostic Testing
Diagnostic Test Type
Specifications Serologic VirologicMode of detection Antibodies Virus
Sensitivity > 95% > 98%
Specificity Variable > 98%
Detection postexposure 2-6 months 2-6 weeks
Use Screening Confirmation
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Hepatitis C VirusHost Production of HCV Antibodies
HCV infects cell
HCV proteins expressedon surface ofhepatocytes
Antibodies to HCVproteins produced byhost
HCV antibodies doNOTconfer immunity YYY
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Natural History
Stable75% to 95%
HCC orDecompensation
1% to 3%/yr
Stable97% to 99%/yr
Resolved15%
Acute HCV
Cirrhosis5% to 25%
Chronic HCV85%
Thomas DL, et al. Clin Liver Dis. 2005;9:383-398 Strader DB, et al. Eur J Gastroenterol Hepatol. 1996;8:324-328.Seeff LB, et al. Hepatology. 2002;36(suppl):S1-S2. Seeff LB, et al. Hepatology. 2002;36(suppl):S35-S46. Liang TJ, et
al. Ann Intern Med. 2000;132:296-305. Fattovich G, et al. Gastroenterology. 1997;112:463-472.
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Are laboratory data helpful?
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Serum HCV RNA Level
Stability Over Time
Patient
Limit of detection
0
2
4
6
8
Baseline 1 2 3 4
Time (Years)
LogHCVR
NA
(IU/mL)
1
23
4
5
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
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HCV RNA effect on Liver Histology & Fibrosis
Genotype
NoFibrosis
PortalFibrosis
BridgingFibrosis
Cirrhosis
Serum HCV RNA does not correlate with level of fibrosis
0
2
4
6
8
L
ogHCVRNA
(copies/mL)
1
2
3
4
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
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HCV RNA effect on Liver Histology &Inflammation
Genotype
Serum HCV RNA does not correlate with level ofinflammation
0
2
4
6
8
0 2 4 6 8 10 12
Inflammation Score
LogHCVRNA
(copies/mL)
1
2
3
4
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
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Chronic HCV Infection
Normal vs Elevated Serum ALT
Normal ALT Elevated ALT
Portal
26%
No
fibrosis
23%
Mild39%
Cirrhosis
6%
Bridging
6%Portal
20%
No
fibrosis
16% Mild
33%
Cirrhosis
18%
Bridging
13%
Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.
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HCV Infection - Liver Biopsy
Only test that can accurately assess Severity of inflammation
Degree of fibrosis
Determines the following Risk for developing cirrhosis in future
Need for therapy
Need for ongoing therapy when initial treatment has failed
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Is Liver Biopsy Necessary?
NO
Patient wants treatment evenif no fibrosis
Patient does not wanttreatment or treatmentcontraindicated even ifadvanced fibrosis
Labs and radiographic studiesdo not suggest cirrhosis
Patient achieves SVR
YES
Patient would only accepttreatment if advanced fibrosis
Labs or radiographic studiessuggest cirrhosis may bepresent
Patient fails to achieve SVRand no recent biopsyavailable
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Chronic HCV: Progression to Cirrhosis
0
20
40
60
80
100
0 5 10 15 20
Time (Years)
Bridging
Portal
None
Approxim
atePercenta
geof
PatientsWithCirrho
sis
Yano M, et al. Hepatology. 1996;23:1334-1340.
Proportion of Patients Developing CirrhosisAccording to Initial Level of Fibrosis
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I hope I dont have
Hepatitis C
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HCV and Alcohol
Excessive alcohol intake characterized as > 40 g/day for women and > 60 g/day for men.
0
20
40
60
80
100
10 20 30 40
Years Following Exposure
Cirrhosis
(%)
HCV
HCV + alcohol
Wiley TE, et al. Hepatology. 1998:28:805-809.
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< 10 11-20 21-30 31-40 > 40
Duration of Infection (Years)
FibrosisSc
ore
4.0
3.0
2.0
1.0
0
Poynard T, et al. Lancet. 1997;349:825-832.
HCV Fibrosis Progression: Effect of Age
Age at time
of infection> 40 years< 40 years
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Viral Kinetics
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Response Definition
RVR HCV RNA negative (< 50 IU/mL) at Wk 4
EVR
Complete
EVR
HCV RNA positive at Wk 4 but negative at Wk 12
PartialEVR
HCV RNA positive at WK 4 and 12 but 2 log10 IU/mLdrop from baseline at Wk 12
Non-EVR < 2 log10 IU/mL drop from baseline at Wk 12
Definitions of On-Treatment Response
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SVR Holy Grail
SVR Sustained virologic response Undetectable viral load measured at 24 weeks after
completing therapy
Patients achieving SVR are considered Cured
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RVR
Achieving RVR is highly predictive of SVR[1] Independent of genotype and treatment regimen
RVR achieved by 15% to 20% with genotype 1; 66% withgenotypes 2/3[1,2]
1. Ferenci P, et al. J Hepatol. 2005;43:425-433.2. Shiffman ML, et al. N Engl J Med. 2007;357:124-134.
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SVR in Patients Who Achieved an RVR
90 282 257 9
GT 1 GT 2 GT 3 GT 4
100
868688
Patients With an RVR
RVR: HCV RNA negative (< 50 IU/mL) at Wk 4
Fried MW, et al. EASL 2008.
0
20
40
60
80
100
SVR(%)
n =
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EVR as Predictor of SVR in Genotype 1Patients
Failure to achieve EVR strongly correlates withnonresponse[1,2] 97% to 100% who do notachieve EVR also fail to achieve SVR
Patients without EVR can discontinue therapy
Achieving EVR is less accurate in predicting SVR[3] 65% to 72% of patients withEVR go on to achieve SVR
cEVR is a better predictor of SVR than pEVR[3] 83% vs 21%, respectively, achieved SVR[2]
1. Fried MW, et al. N Engl J Med. 2002;347:975-982. 2. Davis GL, et al. Hepatology. 2003;38:645-652.3. Ghany MG, et al. Hepatology. 2009;49:1335-1374.
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Viral Kinetics and Outcome Importance of RapidVirologic Response
Wk 4Wk 12Wk 24
Neg
Neg
Neg
> 2 log
Neg
Neg
< 2 log
Neg
Neg
> 2 log
> 2 log
Neg
< 2 log
> 2 log
Neg
Any
Pos
Pos
VirologicResponse(%)
91
72
60
4843
20
20
40
60
80
100
EOT response
SVR
9194
9086
90
13
PegIFN alfa-2a+ RBV (N = 453)
HCV RNA Status
Ferenci P, et al, Predicting sustained virological responses in chronic hepatitis C patients treatedwith peginterferon alfa-2a (40 KD)/ribavirin, 425-433, 2005.
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Factors Associated With Increased SVRRates
Useful for advising patients on their likelihood of an SVR
Absence of favorable factors should not be used to deny therapy
1. Manns MP, et al. Lancet. 2001;358:958-965. 2. Fried MW, et al. N Engl J Med. 2002;347:975-982.3. Hadziyannis SJ, et al. Ann Intern Med. 2004;140:346-355. 4. Nguyen MH, et al. Am J Gastroenterol.
2008;103:1131-1135.
Less Consistently Reported[1,2,4]
Dose of pegIFN (1.5 vs 0.5 g/kg/wk) Lower body weight ( 75 kg)
Dose of RBV (> 10.6 mg/kg) Absence of insulin resistance
Female sex Elevated ALT levels (3 x ULN)Younger age (younger than 40 yrs) Absence of bridging fibrosis or cirrhosis
Nonblack race
Major Predictors[1-3]
Viral genotype (nongenotype 1) Pretreatment HCV RNA( 600,000 IU/mL)
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Current Treatment
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Recommended Regimens for Initial HCVTreatment
Optimal duration of treatment should be based on the viral genotype
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
Genotype 1 PegIFN alfa-2a PegIFN alfa-2b
PegIFN dose (weekly) 180 g 1.5 g/kg
RBV dose (daily) 1000 mg if 75 kg1200 mg if > 75 kg
800 mg if 65 kg1000 mg if > 65 to 85 kg1200 mg if > 85 to 105 kg
1400 mg if >105 kg
Planned duration 48 wks 48 wks
Genotype 2/3 PegIFN alfa-2a PegIFN alfa-2b
PegIFN dose (weekly) 180 g 1.5 g/kg
RBV dose (daily) 800 mg 800 mg
Planned duration 24 wks 24 wks
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The Future is now
Before 2011
PegIFN/RBV constituted standard of care for patientsinfected with all major HCV genotypes until 2011
Genotypes 1 and 4: 48 wks of therapy
Genotypes 2 and 3: 24 wks of therapy
2011
Patients with genotype 1 HCV have new options with theFDA approval of 2 protease inhibitors: telaprevir and
boceprevir Each agent used in combination with pegIFN/RBV
Patients with genotype 2, 3, or 4 HCV continue to receivepegIFN/RBV
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Treatment of Chronic HCV:
Peginterferon and Ribavirin this was then
0
20
40
60
80
100
1 2-3
Genotype
SustainedVir
ologic
Response(%)
PegIFN-2a/RBV
PegIFN-2b/RBV
Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.
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GT1 SVR Whites vs Blacks this was then
SVR
(%)
0
20
40
60
80
100
PegIFN alfa-2b 1.5 g/kg/wk+ RBV 800-1000 mg/day[1]
Non-Hispanic whites
Blacks
n =
52
19
P< .001
100100
52
28
P< .0001
SVR
(%)
0
20
40
60
80
100
196205
PegIFN alfa-2a 180 g/wk +RBV 1000-1200 mg/day[2]
n =
1. Muir AJ, et al. N Engl J Med. 2004;350:2265-2271.2. Conjeevaram H, et al. Gastroenterology. 2006;131:470-477.
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Boceprevir and Telaprevir
Boceprevir, a potent inhibitor of HCV NS3 protease
Telaprevir, a potent inhibitor of HCV NS3/4A protease
Both agents are to be used in combination with current standard-of-care
(peginterferon alfa-2/ ribavirin)
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Trials reported at AASLD 2010
Boceprevir
SPRINT-III: naive GT1 patients
RESPOND-2: nonresponder GT1 patients
Telaprevir ADVANCE: naive GT1 patients
Ph III SPRINT 2 B i
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Phase III SPRINT-2: Boceprevir +PegIFN/RBV in GT1 Tx-Naive Patients
Treatment-naivepatients withgenotype 1
HCV(2 cohorts:
N = 938nonblack and159 black)
PR*
(n = 316,
52)
PR*
(n = 311 nonblack, 52 black)
Wk 72Wk 48
Follow-up
Follow-up
Wk 28
Follow-up
Wk 4
BOC + PR*
(n = 316 nonblack,
52 black)
BOC + PR*
(n = 311 nonblack, 55 black)
PR*
(n = 311,55)
PR*
*BOC 800 mg q8h; pegIFN alfa-2b 1.5 g/kg/wk; weight-based RBV 600-1400 mg/day.Undetectable HCV RNA at Wk 4 of BOC treatment (ie, at Wk 8) and at all subsequent assays.
Poordad F, et al. AASLD 2010.
Follow-upRVR
NoRV
R
Randomized, placebo-controlled trial
SPRINT 2 R R t A di
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SPRINT-2: Response Rates Accordingto Race
0
20
40
60
80
100
Patients(%)
SVR Relapse
4-wk PR + 44 weeks BOC + PR4-wk PR + response-guided BOC + PR 48-wk PR
67 68
40
8
23
9
0
20
40
60
80
100
Patients(%)
SVR Relapse
42
53
2317 1412
Nonblack Patients Black Patients
P< .0001P= .044
P= .004
Poordad F, et al. AASLD 2010.
n =211 213 125 21 18 37 22 29 12 3 6 2
Ph III ADVANCE T l i
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Phase III ADVANCE: Telaprevir +PegIFN/RBV in GT1 Tx-Naive Patients
Treatment-naivepatients with
genotype1HCV
(N = 1088)
Wk 12
TVR + PR*
(n = 364)
TVR + PR*
(n = 363)
PR*
(n = 361)
eRVR: PR*
Wk 72Wk 48Wk 8
Follow-up
Follow-up
Follow-up
*TVR 750 mg q8h; pegIFN alfa-2a 180 g/wk; weight-based RBV 1000-1200 mg/day.eRVR: extended rapid virologic response = undetectable HCV RNA at Wks 4 and 12.
Jacobson IM, et al. AASLD 2010.
Wk 24
PR*
eRVR: PR*
PR*
Follow-up
Follow-up
Randomized, placebo-controlled trial
ADVANCE O ll SVR d R l
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ADVANCE: Overall SVR and RelapseRates
0
20
40
60
80
100
Patients(%)
69
SVR
75
44
P< .0001 for both treatmentarms vs control
12-wk TVR + PR + 12/36-wk PR (n = 363)
48-wk PR (n = 361)
8-wk TVR + PR + 16/40-wk PR (n = 364)
n = 250 271 158
Relapse
9 9
28
n = 28 27 64
Jacobson IM, et al. AASLD 2010.
ADVANCE: SVR with Telaprevir
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ADVANCE: SVR with Telapreviraccording to Race & Ethnicity
SVR(%)
Race/Ethnicity
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
Phase III: genotype 1, treatment naive
75
62
74 75
70
58
66 69
46
25
3944
0
20
40
60
80
100
White Black Latino Non-Latino
325n = 315 318 26 40 28 35 44 38 328 320 323
T12PR
T8PR
PR48
Phase III RESPOND 2: Boceprevir in
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Phase III RESPOND-2: Boceprevir inGT1 Prior Nonresponders to PegIFN/RBV
PR*(n = 80)
PR*(n = 161)
BOC + PR*
BOC + PR*PR*
(n = 162)
BOC+ PR*If detectable
at Wk 8 PR*
Bacon BR, et al. AASLD 2010. Abstract 216.
Treatment-experiencedpatients with
GT1 HCV
(N = 403)
Wk 48Wk 8 Wk 36
Follow-up
Follow-up
Follow-up
Follow-up
*BOC 800 mg TID; pegIFN alfa-2b 1.5 g/kg/wk; weight-based RBV 600-1400 mg/day.Follow-up for 24 wks after completion of therapy.
RESPOND 2: SVR Rates According to
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RESPOND-2: SVR Rates According toTreatment Arm and Prior Response
0
20
40
60
80
100
Overall
SVR(%)
4-wk PR + 44-wkBOC + PR (n = 161)
59*
PreviousNonresponders
PreviousRelapsers
48-wk PR (n = 80)
4-wk PR + response-guidedBOC + PR (n = 162)
66
21
40
52
7
75
29
69
P
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PegIFN adverse effects
AE Occurring in > 20% of Pts, % PegIFN alfa-2a/RBV (n = 1035) PegIFN alfa-2b/RBV (n = 1019)
Fatigue/insomnia 64/41 67/38
Headache 41 50
Nausea 34 40
Anemia 34 35
Rash 34 29
Neutropenia 31 26
Irritability/depression 25/20 25/25
Chills 23 39
Injection-site reactions 23 34
Myalgia/arthralgia 22/22 27/21
Dyspnea 22 21
Pyrexia 21 35
Anorexia 21 29
Alopecia 17 23
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RBV adverse effects
Adverse events occurring more frequently whenRBV added to pegIFN vs pegIFN alone
Hemolytic anemia
Headache
Cough/SOB
Gastrointestinal upset
Rash
Insomnia Teratogenicity
Adverse Events Reported More Frequently
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Adverse Events Reported More FrequentlyWith TVR and BOC vs PegIFN/RBV
Adverse Event, % TVR-Containing Arms(n = 727)
PegIFN/RBV Arm(n = 361)
Pruritus 45-50 36
Nausea 40-43 31
Rash 35-37 24
Anemia 37-39 19
Diarrhea 28-32 22
Adverse Event, % BOC-Containing Arms(n = 734)
PegIFN/RBV Arm(n = 363)
Anemia 49 29
Dysgeusia 37-43 18
Telaprevir[1]
Boceprevir[2]
1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB4.
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Everyone is special !!!
Probabilit
yof
Achievinga
nSVR
100
80
60
40
20
0
89
74
5236
1914
7
Cirrhosis No No No No No No No Yes
ALT quotient 7 2 2 2 2 2 1 1
Age in years 20 20 43 43 43 60 60 60
BMI 20 20 26 26 26 30 30 30
HCV RNA, IU/mL x 103 40 40 40 1200 9000 9000 9000 9000
97
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HCV and Renal Disease
Description GFR,mL/min*1.73 m2
Recommended Treatment
Kidney damage withnormal or increased GFR
90 Routine combination therapy
Kidney damage with mildlydecreased GFR 60-90
Moderately decreased GFR 30-59 PegIFN alfa-2b 1 g/kg/wk or pegIFNalfa-2a 135 g/wk + RBV 200-800 mg/day(starting with lowest dose and increasing
if adverse effects manageable)
Severely decreased GFR 15-29
Kidney failure < 15
Dialysis Standard IFN 3 mU 3x/wk or pegIFNalfa-2b 1 g/kg/wk or pegIFN alfa-2a
135 g/wk markedly reduceddaily RBV dose*
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
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HCV and Renal Disease
HCV treatment not recommended for patients who haveundergone kidney transplantation, unless fibrosingcholestatic hepatitis develops
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
R l Di IFN i IFN
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Renal Disease: pegIFN not superior to IFN
78 hemodialysis patients treated with pegIFN alfa-2a 135g/wk[1]
SVR obtained in 14% of patients
Adverse events reported in 83% of patients (flu-like syndrome,mild to moderate thrombocytopenia, leukopenia, and anemia)
32% of patients noncompliant
Randomized trial of 16 patients receiving pegIFN alfa-2b1.0 or 0.5 g/kg/wk discontinued due to adverse eventsand modifications[2]
56% of patients in 1 g/kg/wk group and 28% in 0.5 g/kg/wkexperienced serious adverse events requiring therapydiscontinuation
1. Covic A, et al. J Nephrol 2006;19:794-801.2. Russo MW, et al. Nephrol Dial Transplant. 2006;21:437-443.
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IFN Monotherapy in Dialysis Patients
100
80
60
40
20
0
SVR(%)
2027
21 20 19
56 58
68
33
Russo MW, et al. Am J Gastroenterol. 2003;98:1610-1615.
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Current Contraindications to Treatment
CharacteristicsMajor uncontrolled depressive illness
Most solid organ transplantation (renal, heart, or lung)
Autoimmune hepatitis or other autoimmune condition known to beexacerbated by peginterferon and ribavirin
Untreated thyroid disease
Pregnant or unwilling to comply with adequate contraception
Severe concurrent medical disease such as Severe hypertension, heart failure, significant coronary heart disease,
poorly controlled diabetes, chronic obstructive pulmonary disease
Younger than 2 yrs of age
Known hypersensitivity to drugs used to treat HCV
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
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Summary
Chronic HCV infection leads to cirrhosis and liverfailure in a large number of persons
Health care providers must recognize that chronic
HCV is common in IDU and high risk behaviors
Effective treatment of chronic HCV can preventfibrosis progression and reduce complications
New treatment modalities in genotype 1 patientsshow improved SVR
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Thank youEmail: [email protected]