Transcript Management of Patients with Chronic Hepatitis C: The Route

Sameh W. Boktor, MD, MPH
Medical Epidemiologist
Pennsylvania Department of Health
Harrisburg, Pennsylvania
Sameh Boktor, MD, has no financial
interests/relationships or affiliations in relation to this
activity.
This activity was independently peer-reviewed by CME
Peer Review. Neither of the independent reviewers had
relevant financial relationships to disclose.
Off-label and/or investigational use of pharmaceuticals may be discussed in
the presentation. This disclosure is to ensure participants in the activity may
formulate their own judgments regarding the presentation.
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Evaluate the most recent clinical guidelines to
improve screening for and diagnosis of infection
with hepatitis C virus (HCV)
Optimize current evidence-based components
of chronic HCV therapy based on patient status,
HCV genotype, comorbidities, and concomitant
therapies
Integrate methods to minimize toxicities and
adequately manage treatment-related adverse
effects
Evaluate the utility of investigational therapies
for the treatment of HCV
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About 5.2 million infected individuals in the United
States currently (~2% of the population)
Leading cause for liver transplant and liver cancer
Number of patients with morbidity and mortality from
chronic HCV increasing
Approximately 1.76 million persons with untreated
chronic HCV infection will develop cirrhosis over the
next 40 to 50 years
The projected incidence peak of end-stage liver disease
will occur in 2030, with about 38,600 cases per year
Transplants are expected to peak in 2032 to 2033 at level
of 3200 HCV-related transplants per year
Rein et al. Dig Liver Dis 2011;43:66-72. Zalesak et al. PLOS ONE 2013;8(5):e63959.
Chronic hepatitis
occurs in 75-85% of
infected individuals
and can lead to
fibrous scar within
the liver
Over time,
fibrosis can
lead to severe
scarring or
cirrhosis in 1020% patients
Davis et al. Gastroenterology 2009;138(2):513-521.
Huffman et al. JABFM 2014;27(2):284-291.
In 1-4% patients,
cancer of the liver
will develop
Decompensated cirrhosis (5-year survival rate of 50%):
• Ascites
• Jaundice
• Hepatic encephalopathy
• Edema
• Renal failure
• Variceal bleeding
• Spontaneous bacterial peritonitis
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Hematologic disorders
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 Essential mixed
cryoglobulinemia
 Monoclonal gammopathies
 Lymphoma (non-Hodgkin’s B
cell)
 Anemia, thrombocytopenia,
coagulopathy
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 Porphyria cutanea tarda
 Leukocytoclastic vasculitis
 Lichen planus
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Cardiac
 Myocarditis
 Cardiomyopathy
Cacoub et al. The GERMIVIC 2000;79:47.
Rheumatologic
 Arthritis
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Renal
 Membranoproliferative
Autoimmune disorders
 Autoantibodies
 Autoimmune hepatitis
 Thyroid disease
Dermatologic
glomerulonephritis
 Membranous nephropathy
 Renal failure
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Endocrine
 Diabetes mellitus
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National survey of PCPs revealed 73% of respondents
reported seeing five or fewer patients with HCV per year,
44% reported no experience with HCV treatment, and only
59% actually screened for HCV
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Due to lack of awareness of the current advances in HCV,
only ~50% of patients with HCV are referred for subspecialty
evaluation
Mitchell et al. Hepatology 2010;51:729-33. Shehab et al. Journal of viral hepatitis 2001;8:377-83.
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An estimated 40 to 85% of persons infected with HCV are
unaware of their HCV infection status
One study reported that amongst HCV-infected injection
drug users who were 15 to 30 years old, 72% were unaware of
their HCV infection status
NHANES study conducted from 2001 through 2008 found
that 50.3% of persons infected with HCV were unaware of
their status
In a study involving persons with access to medical care in
four private health care organizations during the years 2006
to 2008, an estimated 43% were unaware of their HCV
infection
Armstrong et al. Ann Intern Med. 2006;144:705-14. Denniston MM et al. Hepatology 2012;55:1652-61.
Denniston MM et al. Ann Intern Med. 2014;160:293-300.
Patients with at least 1 encounter and
no previous HCV testing
865,659
Percent tested for HCV
13%
Percent of patients who were positive
for HCV
5.1%
Percent patients with ≥2 elevated ALT
results tested for HCV
43.9%
Percent patients positive for HCV after
≥2 elevated ALT results
8.2%
2012 Kaiser study including HI, OR, MI, PA sites
Spradling PR et al. CID 2012;55(8):1047-1055.
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Everyone born from 1945-1965 (one-time)
Past or present injection drug use
Sex with an IDU; other high risk sex
Blood transfusion prior to 1992
Persons with hemophilia
Long-term hemodialysis
Born to an HCV-infected mother
Incarceration
Intranasal drug use
Unregulated tattoo
Occupational percutaneous exposure
Surgery prior to universal precautions
Smith et al. Ann Intern Med 2012;157:817-822. Moyer et al. Ann Intern Med epub 25 June 2013.
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Persons in the birth cohort and those who are at
risk because of potential exposure before
universal blood screening and are not otherwise
at increased risk need only be screened once.
Persons with continued risk for HCV infection
(injection drug users) should be screened
periodically.
 The USPSTF found no evidence about how often
screening should occur in persons who continue to be
at risk for new HCV infection.
http://www.uspreventiveservicestaskforce.org/uspstf12/hepc/hepcfinalrs.htm
HCV ANTIBODY TEST
NON-REACTIVE
REACTIVE
HCV RNA TEST
STOP*
STOP
* For persons who might have been
exposed to HCV within the past 6 months,
testing for HCV RNA or follow-up testing
for HCV antibody should be performed.
For persons who are
immunocompromised, testing for HCV
RNA should be performed.
Rapid or lab-conducted assay
DETECTED
CURRENT HCV INFECTION
Adapted from Centers for Disease Control and Prevention (CDC), 2013.
NOT DETECTED
RESOLVED
INFECTION
FALSE + TEST
FURTHER ANTIBODY
TESTING AS INDICATED
Assay
Manufacturer Format
Abbott HCV EIA 2.0
Abbott
EIA (Manual)
Advia Centaur HCV
Siemens
CIA (Automated)
ARCHITECT Anti-HCV
Abbott
CMIA (Automated)
AxSYM Anti-HCV
Abbott
MEIA (Automated)
OraQuick HCV Rapid Antibody
Test
OraSure
Immunochromatographic (Manual)
Ortho HCV Version 3.0 EIA
Ortho
EIA (Manual)
VITROS Anti-HCV
Ortho
CIA (Automated)
Anti-HCV = HCV antibody; EIA = enzyme immunoassay; CIA = chemiluminescent immunoassay; MEIA
= microparticle enzyme immunoassay; CMIA = chemiluminescent microparticle immunoassay
Ghany MG et al. Hepatology. 2009. 49: 1335-74.
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Molecular Testing (HCV quantitative test)
 Nucleic acid testing
 Not intended for diagnosis of acute hepatitis C
 Abbott Real Time HCV
▪ Detection range 12IUml-100 million IU/ml
 Roche COBAS Taq Man HCV
▪ Detection range 43IU/ml-69 million IU/ml
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Genotypic Testing
 Trugene 5NC HCV Genotyping kit (Siemens Healthcare
Diagnostics Division, Tarrytown, NY)
 Versant HCV Genotyping Assay 2.0 (Siemens Healthcare
Diagnostics Division, Tarrytown, NY)
 INNO-LiPa HCV II, (Innogenetics, Ghent, Belgium)
Ghany MG et al. Hepatology. 2009. 49: 1335-74.
1.2%
0.5%
9.6%
11.3%
Genotype 1a
60.3%
16.7%
Genotype 1b
Genotype 2
Genotype 3
Genotype 4
Genotype 5
Genotype 6
Data reported on https://www.labcorp.com
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Abstinence from alcohol and, when appropriate, interventions to
facilitate cessation of alcohol consumption
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Evaluation for other conditions that may accelerate liver fibrosis,
including HBV and HIV infections
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Evaluation for advanced fibrosis is recommended using liver biopsy,
imaging, or non-invasive markers to facilitate an appropriate decision
regarding HCV treatment strategy and to determine the need for
initiating additional screening measures (hepatocellular carcinoma [HCC]
screening, variceal screening)
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Vaccination against hepatitis A and hepatitis B
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Education on how to avoid HCV transmission to others
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Evaluation by a practitioner who is prepared to provide
comprehensive management including consideration of antiviral
therapy
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Avoid sharing toothbrushes, dental and shaving equipment
and cover any bleeding wound.
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Avoid obtaining tattoos and piercings at non-reputable,
unlicensed facilities that do not sterilize equipment.
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Avoid donating blood and discuss serostatus prior to
donation of body organs, other tissue or semen.
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Use barrier protection for MSM with HIV infection and those
with multiple sex partners. Others with HCV infection should
be counseled that risk of sexual transmission is low and may
not warrant barrier protection.
http://www.hcvguidelines.org
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Decontaminate household surfaces and implements
with visible blood from an HCV-infected person with
dilution of 1 part household bleach:9 parts water.
Wear gloves for cleaning.
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For illicit drug users, stop using and enter substance
abuse treatment. If drug use is continued, then avoid
reusing or sharing syringes, needles, water, cotton
and other drug preparation equipment. New sterile
syringes, filters, and disinfected cookers should be
used. Needles and syringes should be disposed of in
safe, puncture-proof containers.
http://www.hcvguidelines.org
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Age 18 years or older
Detectable serum HCV RNA
Liver biopsy with chronic hepatitis and significant
fibrosis (historic criteria, not currently mandated)
Compensated liver disease
Acceptable hematologic and biochemical indices
Willing to be treated and conform to treatment
requirements
No contraindications to treatment
Need to consider additional factors such as: alcohol use, drug use,
chronic kidney disease, prior liver transplant
Baranova et al. BMJ Gastro 2011;11:91.
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Major uncontrolled depression
Solid organ transplant (e.g., kidney, heart or lung)
Autoimmune hepatitis or other autoimmune
condition
Untreated thyroid disease
Pregnant or unwilling to practice effective birth
control
Severe accompanying diseases, such as very high
blood pressure, heart failure, significant coronary
disease, poorly controlled diabetes and chronic
obstructive disease/emphysema
A parent of children younger than 2 years old
Known allergies to the drugs used to treat HCV
Ribavirin
Interferon
1990
Telapravir and boceprivir
Potential
approval of other
DAAs
Proof of concept
for DAAs (PI)
2000
2005
Pegylated
interferons
2010
2011
Supression of
HCV with DAA
combination (PI
+ NI)
2012
2013
2014
FDA approval of
simeprivir and
sofosbuvir with IFN
2015+
IFN-free therapy
Term
Definition
Treatment Naïve
No previous treatment
Rapid Virologic Response
HCV undetectable at 4 weeks of treatment
Early Virologic Response
≥2log10 reduction in HCV RNA level compared to baseline
level or undetectable at week 12
End-of-treatment Response
HCV RNA undetectable at week 12, 24 or 48 of treatment
Sustained Viral response
HCV RNA undetectable 24 weeks after end of treatment
Non-responder
Failure to clear HCV RNA after 24 weeks of treatment
Null Responder
Failure to decrease HCV RNA by at least 2log10 after 24 weeks
of treatment
Partial Responder
≥2log10 decrease in HCV RNA but still detectable at week 24
Breakthrough
Reappearance of HCV RNA while still on therapy
Relapser
Reappearance of HCV RNA after therapy is discontinued
Modified from: Ghany MG ,et al. Hepatology 2009;49:1335-74. *Developed primarily for response-guided therapy.
Sustained viral response (SVR)
 HCV RNA negativity 6 months post-treatment
 Predicts 99% chance of remaining RNA negative
long-term and considered a cure
SVR (%)
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
>90%
~70%
44%
35%
16%
1991
IFN
1998
IFN/RBV
2001
2011
>2013
PegIFN/RBV TEL or BOC + 2nd Gen DAAs
PR
PegIFN-free
regimens
Schaefer EA et al. Gastroenterology. 2012;142:1340-1350. Ghany MG et al. Hepatology. 2009;49:1335-1374.
Ghany MG et al. Hepatology. 2011;54:1433-1444.
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Prevent viral entry
 Polyclonal and monoclonal antibodies
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Prevent translation of viral RNA
 NS3/4 protease inhibitors
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Inhibit HCV-RNA polymerase
 Nucleoside analogue NS5B poly. inhib
 Non-nucleoside analogue NS5B poly
inhib
 Replication complex inhibitor
 Cyclophilin B inhibitors
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Viral assembly/release
 Glucosidase inhibitor
Pereira et al. Nat Rev Gastroenterol Hepatol. 2009;6:403-411. http://trialx.com
Protease Inhibitors
Nucleos(t)ide
polymerase
inhibitors
Non-nucleoside
polymerase
inhibitors
NS5A inhibitors
Potency
High
(varies by HCV
genotype)
Moderate to high
(consistent across
genotypes, subtype)
Variable
(HCV genotypes)
High
(multiple HCV
genotypes)
Barrier to
resistance
Low
(1a<1b)
High
(1a=1b)
Very low
(1a<1b)
Low
(1a<1b)
Potential for
drug interactions
High
Low
Variable
Low to moderate
Toxicity
Rash, anemia,
hyperbilirubinemia
Mitochoncrial, NRTI
Interactions (ART,
RIBA)
Variable
Variable
Dosing
qd to tid
qd to bid
qd to tid
qd
Comments
2nd generation PI’s
(higher barrier to
resistance, pangenotype)
Single active target
site
Allosteric
Many targets
Multiple antiviral
MOA
Schaefer et al. Gastroenterology 2012;142:1340-1350.
NS3/4A protease inhibitor FDA-approved November 2013
In combination with PR in G1 patients, can achieve overall
SVR rate 75-85%
 Contraindications:
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 Monotherapy
 Substances that are moderate or strong inducers or inhibitors of
cytochrome P450 3A (CYP3A)
 Pregnancy or a male whose female partner is pregnant
No dose adjustment needed for in any type of renal
impairment or mild hepatic impairment
 Adverse reactions: rash, photosensitivity, pruritus, nausea,
myalgia, dyspnea
 Use not indicated in HIV/HCV co-infection, hepatocellular
cancer, liver transplant
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Jacobson I et al. J Hepatol. 2013;58(suppl 1):S574. Abstract 1425.
Manns M et al. J Hepatol. 2013;58(suppl 1):S568. Abstract 1413.
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Need to check Q80K polymorphism prior to
treatment
Simeprivir 150mg + weight-based PR
 Treatment-naïve and prior relapsers (including
cirrhotics):
▪ SIM + PR x 12 weeks + additional PR x 12 weeks
▪ Total duration of therapy = 24 weeks
 Partial and null responders (including cirrhotics):
▪ SIM + PR x 12 weeks + additional PR x 36 weeks
▪ Total duration of therapy = 48 weeks
 Stop all treatment if: HCV RNA ≥25 IU/mL at either
week 4, 12, or 24
Outcomes
Simeprivir triple therapy
P/R alone
80%
50%
75%
47%
Without Q80K
84%
43%
With Q80K
58%
52%
85%
53%
On-treatment failure
8%
33%
Viral relapse
11%
23%
Overall SVR12 (G1a and G1b)
G1a
G1b
Outcomes for all patients without SVR12
•
•
Pooled QUEST 1 and QUEST 2
SVR in treatment-naïve only, rates are lower in prior relapsers,
partial responders and null responders
Jacobson I, et al. J Hepatol. 2013;58(suppl 1):S574. Abstract 1425.
Manns M, et al. J Hepatol. 2013;58(suppl 1):S568. Abstract 1413.
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Nucleotide analog NS5B polymerase inhibitor
FDA-approved December 2013
Contraindications:
 Monotherapy
 P-gp inducers (St. John’s Wort, rifampin)
 Pregnancy or a male patient whose female partner is pregnant
No dose can be recommended in severe renal disease or
end-stage liver disease
 Adverse reactions: headache, fatigue, nausea, insomnia,
anemia
 May be used in HIV/HCV co-infection, hepatocellular cancer,
those awaiting liver transplant
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Lawitz et al. J Hepatol. 2013;58(suppl 1):S567. Abstract 1411. Lawitz et al. N Engl J Med. 2013;368:1878-1887.
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FDA-approved for combination with PR
(pegIFN + RBV) for 12 weeks in genotypes 1, 4
Off-label use in genotypes 5, 6
Can achieve overall SVR > 90%
To be used in treatment-naïve patients only
No resistance detected, 1 relapse in patient
who discontinued therapy
Well-tolerated no additive effects of addition
of sofosbuvir to PR
Lawitz E, et al. J Hepatol. 2013;58(suppl 1):S567. Abstract 1411. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.
Patients (%)
Sofosbuvir 400mg qd + PR (12 weeks)
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
90%
96%
92%
98%
96%
89%
82%
Overall
1a
1b
4
(n=327) (n=255) (n=66) (n=28)
*P<0.001 vs historical SVR rate 60%
100%
92%
87%
80%
5,6
HCV
HCV
No
Yes Non-C
C
(n=7) RNA<6 RNA>6 (n=273) (n=54) (n=232) (n=232)
(n=71) (n=256)
Cirrhotic
IL-28B
Lawitz E, et al. J Hepatol. 2013;58(suppl 1):S567. Abstract 1411. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.
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FDA-approved for genotypes 2, 3, 4
Sofosbuvir 400mg + weight-based RBV
 Genotype 2: 12 weeks
 Genotype 3: 24 weeks
 Genotype 4: 24 weeks
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Treatment-naïve and experienced patients
Alternate therapy for interferon-intolerant G1
patients
Gane E et al. J Hepatol. 2013;58(suppl 1);S3. Abstract 5. Lawitz E et al. N Engl J Med. 2013;368:1878-1887. Nelson ER, et al. J Hepatol.
2013;58(suppl 1):S3-S4. Abstract 6. Jacobson IM, et al. N Engl J Med. 2013;368;1867-1877. Jacobson IM, et a. J Hepatol. 2013;58 (suppl 1);S28.
Abstract 61.
FISSION
FUSION
POSITRON
SOF +
RBV
67%
PR
12 WKS
16 WKS
67%
50%
73%
78%
G2
97%
78%
86%
94%
93%
G3
56%
63%
30%
62%
61%
HCV RNA <6
75%
67%
50%
62%
76%
HCV RNA >6
62%
66%
50%
77%
79%
Non-cirrhotic
72%
74%
61%
76%
81%
Cirrhotic
47%
38%
31%
66%
61%
Male
61%
62%
42%
66%
73%
Female
79%
76%
69%
87%
84%
Overall
Gane E et al. J Hepatol. 2013;58(suppl 1);S3. Abstract 5. Lawitz E et al. N Engl J Med. 2013;368:1878-1887. Nelson ER, et al. J Hepatol.
2013;58(suppl 1):S3-S4. Abstract 6. Jacobson IM, et al. N Engl J Med. 2013;368;1867-1877. Jacobson IM, et a. J Hepatol. 2013;58 (suppl 1);S28.
Abstract 61.
Ribavirin Dose Modification Guideline for Coadministration with Sofosbuvir
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Sofosbuvir 400mg daily + weight-based RBV
daily x 12 weeks
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PHOTON-1 Study
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Treatment naïve genotype 1-3
Included compensated cirrhotics
Stable HIV disease
ART was FTC/TDF plus either efavirenz (34%), atazanavir/r
(17%), darunavir/r (18%), raltegravir (16%), rilpivirine (6%)
 SVR 76% (genotype 1, 24 weeks therapy), 88% (genotype 2, 12
weeks), 67% (genotype 3, 12 weeks)
Sulkowski MS et al. Hepatology. 2013;58(suppl 1):313A-314. Abstract 212.
Monitoring does not affect treatment course
99% achieved undetectable HCV RNA at week 4
8% treatment failure due to relapse
No official recommendation to check HCV RNA until
after therapy
 Most providers check RNA level week 4 to
document compliance and at end of treatment
(week 12 or 24)
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Illicit drug use
 No difference in SVR between users and non-users
 Studies with sofosbuvir only included those on opiate replacement
therapy and there was no difference in SVR
 Decision to treat on individual basis
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Alcohol use
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Higher viral loads in alcohol-users (blunts immune response)
Rate and severity of liver damage
Risk for hepatocellular cancer
Cessation leads to SVR rate of non-drinkers
Alcohol treatment program or sober x 6 months
Marijuana use
 Possible hepatic steatosis/fibrosis in daily users
NS3/4A Protease
Inhibitors
PegIFN
RBV
Faldaprevir
(genotype 1)
PegIFN
RBV
• STARTVerso1 Trial:
 Phase 3, treatment-naïve, genotype 1
 Faldaprevir 120mg qd or 240mg qd + PR x 12 weeks + PR
versus Faldaprevir + PR for additional 12 weeks
 Overall SVR12 rates:
79% (Faldaprevir 120mg + PR)
80% (Faldaprevir 240mg + PR)
52% (PR)
Ferenci P et al. J Hepatol. 2013:58(suppl 1):S569-S570. Abstract 1416.
NS3/4A
Protease
Inhibitors
NS5B
Polymerase
Inhibitors
Danoprevir
Mericitabine
Asunaprevir
NS5A
Replication
Complex
Inhibitors
Dacalatasvir
PegIFN
RBV
PegIFN
RBV
PegIFN
RBV
• MATTERHORN Study: Danoprevir + Mericitabine + PR in G1
 Quad treatment  SVR12 86% (partial responders) and 84% (null
responders)
 Virologic breakthrough related to danoprevir resistance
 Regimens were safe and well-tolerated
• Study 011: Daclatasvir + Asunaprevir +/- PR in G1
 SVR12 90% and 97% in quad arms
 No discontinuations
 Adverse effects included headache, diarrhea, fatigue, insomnia
Feld JJ et al. Hepatology. 2012;56(suppl 4):231A-232A. Abstract 81.
NS3/4A
Protease
Inhibitors
NS5B
Polymerase
Inhibitors
Nonnucleoside
Polymerase
Inhibitors
Sofosbuvir
Simeprivir
Ribavirin
Ledipasvir
±RBV
Sofosbuvir
±RBV
Sofosbuvir
Daclatasvir
Asunaprevir
±RBV
Daclatasvir
Faldaprevir
Deleobuvir
ABT-450/r
ABT-333
ABT-450/r
ABT-333
ABT-450/r
ABT-450/r
NS5A
Replication
Complex
Inhibitors
±RBV
ABT-267
RBV
ABT-267
ABT-333
±RBV
ABT-267
RBV
FDA APPROVAL FOR THIS COMBINATION FILED FEB.
10, 2014
 ION-1 Trial: Phase 3, N=865, N Engl J Med 2014; 370:1483-149
 Ledipasvir also an NS5A inhibitor
 Combination tablet of Ledipasvir 90 mg/Sofosbuvir
400 mg once daily + RBV bid
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Combo tablet 12 weeks – SVR 99%
Combo tablet + RBV 12 weeks – SVR 97%
Combo tablet 24 weeks – SVR 98%
Combo tablet + RBV 24 weeks – SVR 99%
3 had virologic failure: 1 suspected non-adherence, 2
relapsed
 No benefit with Ribavirin


ION-2 Trial: Phase 3, patients previously treated
with PR +/- protease inhibitor, N=440, N Engl J Med 2014;
370:1483-1493
Combination tablet of Ledipasvir 90 mg/Sofosbuvir
400 mg once daily + RBV bid
 SVR measured at 12 weeks post-treatment
completion
 Combo tablet 12 weeks – SVR 94%
 Combo tablet + RBV 12 weeks – SVR 96%
 Combo tablet 24 weeks – SVR 99%
 Combo tablet + RBV 24 weeks – SVR 99%
 No drop-outs for side effects
 No significant benefit with RBV

SVR12: No Cirrhosis
93% 96%
100%
93%
79%
80%
Patients (%)
Patients (%)
100%
SVR4: Cirrhosis
60%
40%
20%
100%
100%
100%
93%
Overall
Naives
Nulls
80%
60%
40%
20%
0%
0%
12 weeks

100%
96%
24 weeks
COSMOS study: Open-label, G1, prior PR null responder, non-cirrhotics and cirrhotics


SIM + SOF qd vs SIM + SOF + RBV qd x 12 or 24 weeks
Interim results
Jacobson IM et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-3.
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SAPPHIRE II: Phase 3, placebo-controlled, 12
week regimen, non-cirrhotic, N=394
ABT-450 150mg + ritonavir 100mg +
ombitasvir 25mg + dasabuvir 250mg bid +
RBV 1000-1200mg
Overall SVR12 – 96%
Relapsers SVR12 – 95%
Partial responders SVR12 – 100%
Null responders SVR12- 95%
2.4% relapse rate
Zeuzem S et al. EASL abstract O1. J Hepatology 2014;60(suppl 1):S1.
It is important to recognize patients who should
be screened for hepatitis C infection
 There are many factors that contribute to
treatment decisions
 The decision to treat depends on the patient’s
risk for progression of disease and anticipated
efficacy of the drug combination
 SVR decreases liver-related complications and
all-cause mortality
 Treatment options are rapidly changing

 Traditional prognostic factors becoming obsolete
 Not all patients need to be urgently treated
Results from phase 3 trials for all-oral agents are
excellent, with well tolerated regimens and high
SVR rates
 Interferon-free regimens with high SVR rates are
possible in a variety of populations, including
difficult-to-treat patients
 Ribavirin and IL28B status important for DAA +
PR regimens
 Further study needed in:

 Cirrhosis, HIV coinfection, liver transplant recipients,
genotype 4, patients who fail therapy with newer
DAA’s
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www.hepmag.com
www.AASLD.org/patients
www.cdc.gov/hepatitis/C
www.hepeducation.org
www.hepc.liverfoundation.org
www.hepatitis.va.gov/HEPATITIS