Hepatitis C New Treatments, New Challenges Christopher Murphy MD, Ellis Family Medicine Residency RFMC, Sept. 8 th , 2012
Hepatitis C
New Treatments, New Challenges
Christopher Murphy MD, Ellis Family Medicine Residency
RFMC, Sept. 8th, 2012
Hepatitis C: A Global Health Problem~200 Million (M) Carriers Worldwide
World Health Organization. Weekly epidemiological record. 1999;74:421-428.
United States 3-4 M
Americas12-15 M
Africa 30-40
M
Southeast Asia30-35 M
Australia0.2 M
Western Europe
5 M
Eastern Europe
10 M
Far East Asia60 M
HEP C IN THE UNITED STATES
● Incidence: ~ 17,000 new cases / yr.
● 4 million HCV-
infected in U.S.
● Prevalence: General pop. 1% IVDUs 80-90% Incarcerated 15% HIV-infected 30%
● Prevalence of Cirrhosis
9.0% in 1996.18.5% in 2006.
● Prevalence of liver cancer
0.1% in 1996. 1.3% in 2006.
● ~12,000 deaths each year.
HEP C IN THE UNITED STATES
MOST
CASES ARE
NOT YET
DIAGNOSED
LIVER DISEASE IN THE UNITED STATES
Chronic Hepatitis C
The Economic Cost
Hepatitis C: Risk Factors
Sexual Transmission of HCV
• 895 monogamous heterosexual discordant couples, Italy– Yearly HCV antibody testing– Follow-up – 10 years (8,060 persons-yrs)– Average exposure, 1.8 per week, no condoms
• Three spouses – acquired HCV infection• 1 discordant genotype, other 2 –sequence
analysis – not from the partner – Intra-spousal transmission – no cases
Vandelli C et al. Am J Gastroenterol 2004
Single-stranded RNA virus
Class: Flaviviridae 6 genotypes >90 subtypes
~70% are type 1 in US 1a > 1b (57% vs. 16%)
30% are type 2 or 3
HCV RNA
Symptoms +/-
Time after Exposure
Tite
r
Anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
Serologic Pattern of Acute HCV Infection with Recovery
Source: Centers of Disease Control & Prevention, Hepatitis C, Division of Viral Hepatitis, 1/17/03, http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/hep_c/hcv_epi_for_distrib_000925.pdf
Serologic Pattern of Acute HCV Followed By Chronic
Infection
•Symptoms +/-
•Time after Exposure
• Tit
er
•Anti-HCV Ab
•ALT
•Normal
•0 •1 •2 •3 •4 •5 •6 •1 •2 •3 •4•Years•Months
•HCV RNA
•//
NORMAL
Natural History of HCV Infection
100 People
Resolve (15)
15%
Chronic (85)
85%
Cirrhosis (17)
Stable (68)
80%
75%
Stable (13)Death (4)
25%
20% Leading Indication for Liver Transplant
Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention, MMWR, 1998 Oct 16;47(RR-19):1-39.
Hepatocyte
Stellate Cell
Kupffer cell in sinusoidal lumen
Collagen
Endothelial Cell
CD8+ CD4+
Cytokines(IL-2, IFN-TNF-a, TGF-PDGF)Cell killing
Kupffer cell
Hepatocytes
Hepatic stellate cells
TGF-Activation
Fibrosis
Death
Hepatitis C Disease Pathogenesis
Stage 1Portalfibrosis
Stage 2Periportalfibrosis
Stage 3Septalfibrosis
Stage 4Cirrhosis
fibrosi
s
F-1: @ the portal triadF-2: Periportal areaF-3 Bridging from one portal to anotherF-4 Complete encircling of the triads
F-4 pts have a lower response rate to TxAND
a higher rate of complications to Tx.
Metavir Scoring System
Evolution of HCV Therapy
2001
PegIFN/RBV
Pegylated-interferon alfa-2a + RBV: SVR in Genotype 1, High Viral Load
0
10
20
30
40
50
16
26
36
47
n = 50 n = 47 n = 190 n = 186
SV
R (
%)
24 Weeks 48 Weeks
RBV800 mg/day
RBV1000-1200 mg/day
RBV800 mg/day
RBV1000-1200 mg/day
PEG-IFN2a 180 µg SC QW + RBV
Hadziyannis et al. Ann Intern Med 2004;140:370-381
160
47
24
23
113
14
3failed
7 DNF
10
2 DNF
1 failed
9
1 failed
1 in treatment
SVREOTREVRGT 1 pts
37.5% SVR
Evolution of HCV Therapy
2001 2011
PegIFN/RBVProtease inhibitor
Important Dates in the History of Hepatitis C
Sustained virologic response= SVR = cure
Evolution of HCV Therapy
2001 2011 Beyond
PegIFN/RBVProtease inhibitor
Nucleos(t)ide polymerase inhibitorNonnucleoside polymerase inhibitor
NS5A inhibitor
Chronic Hepatitis C
Reverse fibrosis, delay decompensation, and reduce deaths
Viral clearance
Prevent HCC
Prevent cirrhosis and HCV recurrence afterliver transplantation
Goals of Antiviral Therapy
Prevent cirrhosis
Assessing Severity of Hepatitis C Estimate prognosis. Guide to aggressiveness of therapy.
Standard labs and Scans•AST / ALT•T.BILI, Albumin, INR•Platelet count•Ultrasound
Liver Fibrosis Markers
Hepascore® Fibrosure
Liver Biopsy•inflammation•fibrosis
Fibro-elastography FibroScan®
Assessing Severity of Hepatitis C
P-33
Liver Biopsy Gold standard for grading and staging disease However, not necessary to treat HCV! Invasive, expensive Needle liver biopsy samples < 1/50,000th of the
liver Incorrect staging of 1 stage in 10% to 20% of
cases Dependent on
Length of biopsy—25 mm optimal (16%)Number of biopsies performed Type of biopsy needle usedEtiology of liver disease
Bedossa P, et al. Hepatology. 2003;38:1449-1457. Reproduced with permission.
Potential for Sampling Error in Liver Biopsies
Chronic Hepatitis C
FDA-Approved TherapiesPrevious Standard of Care:• Pegylated interferon alfa-2a with ribavirin• Pegylated interferon alfa-2b with ribavirin
HCV Standard of Care Prior to May 2011
PegIFN alfa-2b 1.5 µg/kg/wk + RBV 800 mg/day for 48 Wks[1]
PegIFN alfa-2a 180 µg/wk + Weight-Based RBV (1000 or 1200 mg/day) for 48 Wks[2]
1. Manns MP, et al. Lancet. 2001;358:958-965. 2. Fried MW, et al. N Engl J Med. 2002;347:975-982.
46
76
56
Overall GT1 GT2/3
298 140453
42
82
100
80
60
40
20
0
54
Overall GT1 GT2/3
SV
R (
%)
348 147511
100
80
60
40
20
0n = n =
GT1 (most common in US, Europe) least responsive to pegIFN/RBV
HCV treatment definitions:
Definitions of Virologic ResponseResponse Definition
SVR HCV RNA undetectable by sensitive assay 24 wks after treatment end
RVR HCV RNA undetectable at Wk 4
EVR > 2 log10 IU/mL reduction in HCV RNA at Wk 12
cEVR HCV RNA detectable at Wk 4, but undetectable at Wk 12
Null response HCV RNA decline < 2 log10 IU/mL from baseline at Wk 12
Partial response HCV RNA decline > 2 log10 IU/mL from baseline at Wk 12, but HCV RNA detectable at Wks 12 and 24
Viral breakthrough HCV RNA detectable at any time during treatment after being undetectable
Relapse HCV RNA detectable after withdrawing treatment in a patient who was undetectable at end of treatment
New response categories with PI-based therapy
eRVR with boceprevir HCV RNA undetectable at Wks 8 and 24 of therapy
eRVR with telaprevir HCV RNA undetectable at Wks 4 and 12 of triple therapy
Week 8 response Among boceprevir-treated patients, HCV RNA undetectable at Wk 8 of the overall treatment course (ie, after 4 wks of pegIFN/RBV lead-in and 4 wks of triple therapy)
Lead-in RVR HCV RNA undetectable at Wk 4 for patients who had a pegIFN/RBV lead-in phase of therapy
• Genotype 1 • African-American ethnicity • High HCV RNA levels• Failure to achieve early (12-week) response• Presence of advanced fibrosis, steatosis or
cirrhosis • Long duration of disease• Older age at time of treatment (>45 y)• Higher body weight/BMI • Male gender
Chronic Hepatitis CNegative Predictive Factors for SVR
C allele is associated with SVR
Ge, Nature, 2009
HCV Life Cycle and DAA Targets
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
Receptor bindingand endocytosis
Fusion and
uncoating
Transportand release
(+) RNA
Translation and
polyprotein processing
RNA replication
Virionassembly
Membranousweb
ER lumen
LD
LDER lumen
LD
NS3/4 protease inhibitors
NS5B polymerase inhibitors
Nucleoside/nucleotideNonnucleoside
*Role in HCV life cycle not well defined
NS5A* inhibitors
HCV-specific Enzymes: Targets for the Future
NS5B RNA-dependent
RNA polymeraseNS3 Protease
domain
NS3 Helicase domain
NS3 Bifunctionalprotease/helicase
NS3NS3CC E1E1 E2E2 NS2NS2 NS4BNS4B NS5ANS5A NS5BNS5BNS4ANS4AP7P7
5’ UTR5’ UTR 3’ UTR3’ UTR
IRES
Phase III Protease Inhibitor Studies
Telaprevir Treatment-naive
ADVANCE[1]
ILLUMINATE[2]
Treatment-experienced
REALIZE[3]
Boceprevir Treatment-naïve
– SPRINT-2[4]
Treatment-experienced
– RESPOND-2[5]
1. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 2. Sherman KE, et al. N Engl J Med. 2011;365:1014-1024. 3. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. 4. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 5. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.
Schematic of Study Design International, multicenter, randomized, double-blind, placebo-controlled
phase III trial
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
Treatment-naive patients with genotype 1
HCV infection
(N = 1088)
T12PR:Telaprevir 750 mg q8h
+ PegIFN/RBV†
(n = 363)
T8PR:Telaprevir
750 mg q8h +PegIFN/RBV†
(n = 364)
PR:Placebo +
PegIFN/RBV†
(n = 361)
Wk 8
PegIFN/RBV†‡
eRVR: follow-upNo eRVR: pegIFN/RBV†
eRVR: follow-upNo eRVR: pegIFN/RBV†
Wk 12 Wk 24* Wk 48*Stratified by genotype 1 subtype and HCV RNA level
*SVR determined after 24 wks of follow-up. †PegIFN alfa-2a 180 µg/wk + RBV 1000-1200 mg/day. ‡Placebo given with pegIFN//RBV from Wks 8-12.
PegIFN/RBV†
PegIFN/RBV†
Main Findings of ADVANCE (TVR)
Response, % T8PR (n = 364)
T12PR(n = 363)
PR(n = 361)
SVR 69* 75* 44
RVR 66 68 9
eRVR 57 58 8
Undetectable HCV RNA at end of treatment
81 87 63
Undetectable HCV RNA 72 wks after starting treatment
67* 73* 44
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
*P < .001 vs pegIFN/RBV control arm.
Main Findings
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
Patients who attained eRVR had higher SVR rates than those without eRVR across all arms
83
SV
R (
%)
100
80
60
40
20
0PRT12PRT8PR
50
89
54
97
39
eRVRNo eRVR
SVR Rates With BOC + PegIFN/RBV in Genotype 1 Treatment-Naive Patients
P < .001
P < .001
Nonblack Patients
P = .04
P = .004
Black Patients
125/311
211/316
213/311
12/52
22/52
29/55
Pat
ient
s (%
)
PR 48 BOC RGT
100
80
60
40
20
0BOC/PR48
40
67 68
Pat
ient
s (%
)
PR 48 BOC RGT
100
80
60
40
20
0BOC/PR48
23
4253
n/N=
n/N=
Poordad F, et al. N Engl J Med. 2011;364:1195-1206.
SPRINT-2
Response-Guided Therapy With TVR in Tx-Naive Pts in 2 Studies
65% of patients eligible for shortened therapy[1]
58% of patients eligible for shortened therapy[2]
92 88
ILLUMINATE: Response-Guided TVR + PegIFN/RBV in
Treatment-Naive Genotype 1
T12PR24 T12PR48
SV
R in
Pts
Ach
ievi
ng e
RV
R (
%) 100
80
60
40
20
0
149/162
140/160
n/N=
1. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 2. Sherman KE, et al. N Engl J Med. 2011;365:1014-1024.
ADVANCE: TVR + PegIFN/RBV in Treatment-Naive Genotype 1
8997
T12PR24 PR
SV
R in
Pts
Ach
ievi
ng e
RV
R (
%) 100
80
60
40
20
0
189/212
28/29
n/N=
100
0
60
SV
R (
%)
80
40
REALIZE: SVR in Previous Relapsers, Partial Responders, Null Responders
Previous Relapsers Previous Partial Responders
n/N=
Previous Null Responders
*P < .001 vs PR48.
20121/145
124/141
83*88*
16/68
24
29/49 26/48
59*54*
4/27
15
21/72 25/75
29*33*
2/37
5
T12/PR48PR48 LI T12/PR48
Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.
SVR by Response at Wk 4 in Lead-in Arm With BOC and
TVR
1. Foster G, et al. EASL 2011. Abstract 6. 2. Bronowicki JP, et al. EASL 2012. Abstract 11.
Partial NRRelapsers Null NR
N/A
56†64
72
36
55
0
20
40
60
80
100
SV
R (
%)
< 1 log ≥ 1 log
PROVIDE (BOC)
n/N =
14/22
13/36
5/9
36/50
6/11
*Excludes 4 pts who dropped out during lead-in phase and 8 who were direct enrollers (ie no pegIFN/RBV lead-in).†Majority of prior relapsers still receiving treatment.
REALIZE (TVR)
62
94
56
59
15
54
0
20
40
60
80
100
SV
R (
%)
< 1 log ≥ 1 log
8/13 10/18
106/113 16/2
715/2
86/41
Current Standard-of-Care Therapy Is Complex
Adherence to pegIFN/RBV therapy decreases over time
Triple therapy has greatly increased treatment complexity, involves multiple daily pills plus injection drug BOC TID: 12 pills/day TVR TID: 6 pills/day RBV BID: 4-6 pills/day PegIFN: QW injection
Increased risks with nonadherence to triple therapy include potential for resistance
Lo Re V 3rd, et al. Ann Intern Med. 2011;155:353-360.
Treatment Wk
(N = 5706)
100
80
60
40
20
0PegIFN RBV
1000-1213-2425-3637-48
959589
978684
76
Mean A
dhere
nce
(%
)
Futility Rules for BOC or TVR + PegIFN/RBV in Tx-Naive
Patients
1. Boceprevir [package insert]. May 2011. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.3. Telaprevir [package insert]. May 2011.
Recommendation: All therapy should be discontinued in patients with the following:
Assay should have a lower limit of HCV RNA quantification of ≤ 25 IU/mL and a limit of HCV RNA detection of approximately 10-15 IU/mL.
BOC[1,2]
Time Point Criteria Action
Wk 12 HCV RNA ≥ 100 IU/mL Discontinue all therapy
Wk 24 HCV RNA detectable Discontinue all therapy
TVR[1,3]
Time Point Criteria Action
Wk 4 or 12 HCV RNA > 1000 IU/mL Discontinue all therapy
Wk 24 HCV RNA detectable Discontinue pegIFN/RBV
Factors for Considering Treatment Candidacy for PI-Based Therapy
Factor Role
Genotype Boceprevir and telaprevir licensed only for patients with genotype 1 HCV
Fibrosis stage
Individuals with mild or moderate fibrosis have better rates of SVR with PI-based triple therapy than those with advanced fibrosis or cirrhosis
SVR rates for individuals with cirrhosis are markedly improved with PI-based therapy vs pegIFN/RBV alone, but SVR rates are still lower than for individuals with F0-F3 fibrosis
Treatment experience
Treatment-naive patients and previous relapsers or partial responders to IFN-based therapy have excellent response rates with PI-based therapy
Both previous partial responders and previous null responders have lower SVR rates with triple therapy than treatment-naive patients or relapsers. Previous null responders have the lowest SVR rates with triple therapy
Combination of fibrosis stage and treatment experience
The highest expected SVR rates with triple therapy are for treatment-naive patients or previous relapsers with minimal fibrosis
The lowest expected SVR rates with triple therapy are for those with cirrhosis who were previous null responders to IFN-based therapy
Treat
Pros and Cons of Treating vs Deferring Therapy with PIs
Protease inhibitors substantially increase chance of SVR
Successful treatment may arrest progression of liver disease (including potential for cirrhosis, HCC, etc)
Many patients already “warehoused” awaiting DAAs, but when is the right time to exit the warehouse?
Current regimens complex, challenging adverse events
Potential for better treatment options in future, eg, better response rates, fewer adverse events, shorter duration
Risk of resistance if therapy fails; impact on future options?
Defer
152/213
118/149
100
0
50
1b 1aGenotype
79
71
< 800,000 ≥ 800,000HCV RNA (IU/mL)
7874
F0-2 F3-F4Fibrosis
62
78
SV
R (
%)
75
25
ADVANCE: Influence of Baseline Patient and Virus
Factors on SVR Data from T12PR arm only
207/281
64/82
45/73
226/290
Marcellin P, et al. EASL 2011. Abstract 451.
n/N =
Similarities and Differences in Phase III Studies of TVR and BOC in GT1 Naive Pts
Parameter TVR[1] BOC[2]
PR lead-in? No Yes: 4 wks
PegIFN alfa formulation 2a 2b
PI dosing requirements TID; administer with fatty meal TID
Duration of PI triple therapy 8-12 wks followed by 12-40 wks PR
24-44 wks after 4 wks PR lead-in
Qualification for shortened therapy (response guided)
Undetectable HCV RNA until Wk 12 of triple therapy
Undetectable HCV RNA until Wk 24 of triple
therapy
Qualified for shortened therapy, % 58 (24 wks) 44 (28 wks)
SVR, % 69-75 63-66
Relapse, % 9 9
Adverse events more frequent in PI arms
Rash, anemia, pruritus, nausea Anemia, dysgeusia
1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB-4.
Drugs Contraindicated With Boceprevir and Telaprevir
1. Boceprevir [package insert]. May 2011. 2. Telaprevir [package insert]. May 2011.
Drug Class Contraindicated With Boceprevir[1] Contraindicated With Telaprevir[2]
Alpha 1-adrenoreceptor antagonist
Alfuzosin Alfuzosin
Anticonvulsants Carbamazepine, phenobarbital, phenytoin N/A
Antimycobacterials Rifampin Rifampin
Ergot derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine
Dihydroergotamine, ergonovine, ergotamine, methylergonovine
GI motility agents Cisapride Cisapride
Herbal products Hypericum perforatum (St John’s wort) Hypericum perforatum
HMG CoA reductase inhibitors Lovastatin, simvastatin Atorvastatin, lovastatin, simvastatin
Oral contraceptives Drospirenone N/A
Neuroleptic Pimozide Pimozide
PDE5 inhibitor Sildenafil or tadalafil when used for treatment of pulmonary arterial hypertension
Sildenafil or tadalafil when used for treatment of pulmonary arterial hypertension
Sedatives/hypnotics Triazolam; orally administered midazolam Orally administered midazolam, triazolam
Common AEs of DAAs in Naive PtsAgent AEs More Frequent in
Experimental Arm vs PRDiscontinuations
due to AEs, % (Wk)
Boceprevir[1] Anemia, dysgeusia 14 (48)
Telaprevir[2] Rash, anemia, pruritus, nausea 10 (48)
ANA598[3] Rash incidence and severity increased with 400-mg dose 2 (12)
BI 201335[4] Gastrointestinal events, jaundice, and rash* 5 (12)
BMS-790052[5] None reported 8 (12)
Danoprevir[6] ALT elevation, neutropenia, nausea diarrhea 4 (12)
Filibuvir[7] None reported 0 (4)
RG7128[8] None reported 2 (12)
TMC435[9] Mild bilirubin increases in first 2 wks of therapy 7 (24)
Vaniprevir[10] Vomiting with 600-mg dose 0 (6)
1. Poordad F, et al. AASLD 2010. Abstract LB-4. 2. Jacobson IM, et al. AASLD 2010. Abstract 211. 3.Lawitz E, et al. AASLD 2010. Abstract 31. 4. Sulkowski M, et al. EASL 2010. Abstract 1190. 5. Pol S, et al. EASL 2010. Abstract 1189. 6. Terrault N, et al. AASLD 2010. Abstract 32. 7. Jacobson I, et al. EASL 2010. Abstract 2088. 8. Jensen DM, et al. AASLD 2010. Abstract 81. 9. Fried M, et al. AASLD 2010. Abstract LB-5. 10. Manns MP, et al. AASLD 2010. Abstract 82.
*Higher in BID dosing than QD.
Treatment of Chronic Hepatitis C
1991 20010
20
40
60
80
100
8-12
SV
R (
%)
15-20
38-43
25-30
50-60
1995 1998
Standard interferon (6 mos)[1]
Standardinterferon
(12-18 mos)[2,3]
Interferon/ribavirin
(6-12 mos)[3,4] PegIFNmonotherapy(6-12 mos)[5,6]
PegIFN/ribavirin(6-12 mos)[6,7]
2011
70-75
PI + PegIFN/RBV(6-12 mos)[8-10]
1. Carithers RL Jr., et al. Hepatology. 1997;26(3 suppl 1):83S-88S. 2. Zeuzem S, et al. N Engl J Med. 2000;343:1666-1672. 3. Poynard T, et al. Lancet. 1998;352:1426-1432. 4. McHutchison JG, et al. N Engl J Med. 1998;339:1485-1492. 5. Lindsay KL, et al. Hepatology. 2001;34:395-403. 6. Fried MW, et al. N Engl J Med. 2002;347:975-982. 7. Manns MP, et al. Lancet. 2001;358:958-965. 8. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 9. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 10. Sherman KE, et al. N Engl J Med. 2011;365:1014-1024.
HCV Life Cycle and DAA Targets
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
Receptor bindingand endocytosis
Fusion and
uncoating
Transportand release
(+) RNA
Translation and
polyprotein processing
RNA replication
Virionassembly
Membranousweb
ER lumen
LD
LDER lumen
LD
NS3/4 protease inhibitors
NS5B polymerase inhibitors
Nucleoside/nucleotideNonnucleoside
*Role in HCV life cycle not well defined
NS5A* inhibitors
Investigational Agents for HCV
Class Drugs
Interferons Peginterferon lambda-1a
Cyclophilin inhibitor Alisporivir
Nucleos(t)ide analogue polymerase inhibitor GS-7977Mericitabine
Nonnucleoside polymerase inhibitor ABT-072ABT-333BI 207127 Tegobuvir
Protease inhibitor ABT-450AsunaprevirBI 201335 DanoprevirGS-9451Simeprevir (TMC435)
NS5A inhibitor DaclatasvirGS-5885
New Testing Recommendations from the
CDC
HCV Testing Recommended Based on increased risk for infection
Ever injected illegal drugs Received clotting factors made before
1987 Received blood/organs before July 1992 Ever on chronic hemodialysis Evidence of liver disease High risk sexual activity
Based on need for exposure management Healthcare, emergency, public safety
workers after needle stick/mucosal exposures to blood
Children born to HCV-positive women
Large Population Underscreened and HCV Patients Underdiagnosed
Current screening practices fail to identify a large proportion 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 about HCV risk factors
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.
Large and Growing Population of Nonresponders
Based on the assumption that there will be no changes in SOC and 40-50% of treatment naive patients will not achieve SVR
Year
Pati
ents
2009 2012 2015 2018 2021 2024 2027
Nonresponder Pool
Naive Patients Treated
HCV Screening Is the First Step on the Road to a Cure
Screening
Counseling
Testing
AssessmentCure
Treatment
Harm Reduction for People with HCV
Central to identifying factors that will affect treatment Obesity and NASH HIV and other medical co-morbidities Drugs Alcohol Social issues Psychiatric issues
… To Summarize• Screening
– For ALL patients • Risk assessment and risk reduction plan
• Testing – For those at risk…and Boomers… & everyone else?
• Staging – For those who are infected
• Treatment – For those for whom benefits outweigh risks
• Education– For ALL patients
• Transmission risk reduction counseling
– For already infected• Disease progression harm reduction counseling