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Management of Patients with Chronic Hepatitis C: The Route to Safe and Effective CareSameh W. Boktor, MD, MPHMedical EpidemiologistPennsylvania Department of HealthHarrisburg, Pennsylvania
Disclosures
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.
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.
Learning Objectives
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
Hepatitis C: Burden of Disease in the U.S.
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 HCV Infection May Lead to Chronic Liver Disease or Liver Cancer
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 10-20% patients
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
Davis et al. Gastroenterology 2009;138(2):513-521.Huffman et al. JABFM 2014;27(2):284-291.
Extrahepatic Manifestations of Chronic Hepatitis C
Hematologic disorders Essential mixed
cryoglobulinemia Monoclonal gammopathies Lymphoma (non-Hodgkin’s
B cell) Anemia, thrombocytopenia,
coagulopathy Autoimmune disorders
Autoantibodies Autoimmune hepatitis Thyroid disease
Cardiac Myocarditis Cardiomyopathy
Dermatologic Porphyria cutanea tarda Leukocytoclastic vasculitis Lichen planus
Rheumatologic Arthritis
Renal Membranoproliferative
glomerulonephritis Membranous nephropathy Renal failure
Endocrine Diabetes mellitus
Cacoub et al. The GERMIVIC 2000;79:47.
Gaps in Hepatitis C Screening and Treatment
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
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.
Identifying Patients With Chronic Hepatitis C 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.
Hepatitis C Testing in the U.S.
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.
Who Should be Tested: USPSTF Grade B Recommendations 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.
HCV Screening Interval
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 Testing Algorithm
Rapid or lab-conducted assay
NON-REACTIVE
STOP
REACTIVE
DETECTED
NOT DETECTED
RESOLVEDINFECTION
FALSE + TEST
FURTHER ANTIBODYTESTING AS INDICATED
CURRENT HCV INFECTION
HCV ANTIBODY TEST
HCV RNA TEST
Adapted from Centers for Disease Control and Prevention (CDC), 2013.
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.
FDA-approved Commercially Available HCV Antibody Tests
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.
Confirmatory Testing for HCV Infection
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
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.
HCV Genotype Distribution in the United States
Genotype 1aGenotype 1bGenotype 2Genotype 3Genotype 4Genotype 5Genotype 6
60.3%16.7%
11.3%
9.6%
1.2% 0.5%
Data reported on https://www.labcorp.com
Next Steps in Evaluation of HCV Infected Individuals
Abstinence from alcohol and, when appropriate, interventions to facilitate cessation of alcohol consumption
Evaluation for other conditions that may accelerate liver fibrosis, including HBV and HIV infections
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)
Vaccination against hepatitis A and hepatitis B
Education on how to avoid HCV transmission to others
Evaluation by a practitioner who is prepared to provide comprehensive management including consideration of antiviral therapy
Recommendations for Preventing Transmission Avoid sharing toothbrushes, dental and shaving
equipment and cover any bleeding wound.
Avoid obtaining tattoos and piercings at non-reputable, unlicensed facilities that do not sterilize equipment.
Avoid donating blood and discuss serostatus prior to donation of body organs, other tissue or semen.
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
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.
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.
Recommendations for Preventing Transmission
http://www.hcvguidelines.org
Eligibility Criteria for Chronic HCV Treatment
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
Non-invasive Biomarkers of Fibrosis
Baranova et al. BMJ Gastro 2011;11:91.
Contraindications to Treatment with Peg-IFN
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
Evolution of Hepatitis C Treatment
1990 2000 2005 2015+20142013201220112010
Interferon
Ribavirin
Proof of concept for DAAs (PI)
Pegylated interferons
Supression of HCV with DAA combination (PI + NI)
Telapravir and boceprivir
FDA approval of simeprivir and sofosbuvir with IFN
Potential approval of other DAAs
IFN-free therapy
Categories of Therapy Response
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.
Goal of Treatment
HCV RNA negativity 6 months post-treatment
Predicts 99% chance of remaining RNA negative long-term and considered a cure
Sustained viral response (SVR)
Chronic HCV Therapy (Genotype 1): Advances in Raising Cure Rates
1991
IFN
1998
IFN/R
BV
2001
PegI
FN/R
BV
2011
TEL or
BOC +
PR
>20
13
2nd
Gen D
AAs
PegI
FN-fr
ee re
gim
ens
0%
20%
40%
60%
80%
100%
SV
R (
%)
>90%
~70%
44%35%
16%
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.
Targets for Direct-Acting Antiviral Agents (DAAs)
Prevent viral entry Polyclonal and monoclonal
antibodies Prevent translation of viral RNA
NS3/4 protease inhibitors Inhibit HCV-RNA polymerase
Nucleoside analogue NS5B poly. inhib
Non-nucleoside analogue NS5B poly inhib
Replication complex inhibitor Cyclophilin B inhibitors
Viral assembly/release Glucosidase inhibitor
Pereira et al. Nat Rev Gastroenterol Hepatol. 2009;6:403-411. http://trialx.com
Selected Characteristics for Direct Acting Agents for Chronic Hepatitis C Infection
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, NRTIInteractions (ART, RIBA)
Variable Variable
Dosing qd to tid qd to bid qd to tid qd
Comments 2nd generation PI’s (higher barrier to resistance, pan-genotype)
Single active target site
AllostericMany targets
Multiple antiviral MOA
Schaefer et al. Gastroenterology 2012;142:1340-1350.
Simeprivir
NS3/4A protease inhibitor FDA-approved November 2013 In combination with PR in G1 patients, can achieve
overall SVR rate 75-85% Contraindications:
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
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.
Simeprivir + PR
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
Simeprivir + PR: SVR Rates
• Pooled QUEST 1 and QUEST 2• SVR in treatment-naïve only, rates are lower in prior
relapsers, partial responders and null responders
Outcomes Simeprivir triple therapy
P/R alone
Overall SVR12 (G1a and G1b)
80% 50%
G1a 75% 47%
Without Q80K 84% 43%
With Q80K 58% 52%
G1b 85% 53%
Outcomes for all patients without SVR12
On-treatment failure 8% 33%
Viral relapse 11% 23%
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.
Sofosbuvir
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 Lawitz et al. J Hepatol. 2013;58(suppl 1):S567. Abstract 1411. Lawitz et al. N Engl J Med.
2013;368:1878-1887.
Sofosbuvir + PR
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 PRLawitz E, et al. J Hepatol. 2013;58(suppl 1):S567. Abstract 1411. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.
SVR12 Rates by Subgroups: NEUTRINO Study
0%10%20%30%40%50%60%70%80%90%
100%90% 92%
82%
96%100%
96%89% 92%
80%
98%
87%
Sofosbuvir 400mg qd + PR (12 weeks)
Pati
en
ts (
%)
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.
*P<0.001 vs historical SVR rate 60%
Cirrhotic IL-28B
Sofosbuvir + Ribavirin
FDA-approved for genotypes 2, 3, 4 Sofosbuvir 400mg + weight-based RBV
Genotype 2: 12 weeks Genotype 3: 24 weeks Genotype 4: 24 weeks
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
PR 12 WKS
16 WKS
Overall 67% 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%
SOF + RBV: SVR12 Rates by Subgroup
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.
Dose Adjustment: Ribavirin
Ribavirin Dose Modification Guideline for Coadministration with Sofosbuvir
Sofosbuvir + RBV: HCV/HIV Coinfection
Sofosbuvir 400mg daily + weight-based RBV daily x 12 weeks
PHOTON-1 Study 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.
HCV RNA Monitoring: Sofosbuvir-based Regimens
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)
Effect of Illicit Drugs, Alcohol, and Marijuana on Treatment
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
Alcohol use 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
Emerging Therapies in Chronic HCV Treatment
DAA + PR in Late-Stage Clinical Development
NS3/4A Protease Inhibitors
PegIFN RBV
Faldaprevir(genotype 1)
PegIFN RBV
• STARTVerso1 Trial: Phase 3, treatment-naïve, genotype 1Faldaprevir 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.
Multiple DAA + PR in Late Stage Clinical DevelopmentNS3/4A Protease Inhibitors
NS5B Polymerase Inhibitors
NS5A Replication Complex Inhibitors
PegIFN RBV
Danoprevir Mericitabine PegIFN RBV
Asunaprevir
Dacalatasvir 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
Feld JJ et al. Hepatology. 2012;56(suppl 4):231A-232A. Abstract 81.
• Study 011: Daclatasvir + Asunaprevir +/- PR in G1 SVR12 90% and 97% in quad arms No discontinuations Adverse effects included headache, diarrhea, fatigue, insomnia
IFN-free Regimens in Late Stage Clinical Development
NS3/4A Protease Inhibitors
NS5B Polymerase Inhibitors
Non-nucleoside Polymerase Inhibitors
NS5A ReplicationComplex Inhibitors
Ribavirin
Sofosbuvir Ledipasvir ±RBV
Simeprivir Sofosbuvir ±RBV
Sofosbuvir Daclatasvir ±RBV
Asunaprevir Daclatasvir
Faldaprevir Deleobuvir ±RBV
ABT-450/r ABT-333 ABT-267 ±RBV
ABT-450/r ABT-333 RBV
ABT-450/r ABT-267 RBV
ABT-450/r ABT-333 ABT-267
Sofosbuvir + Ledipasvir: Treatment-Naïve Patients
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 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
Sofosbuvir + Ledipasvir: Treatment-Experienced Patients
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
Sofosbuvir + Simeprivir ± RBV
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
Overall
Naives Nulls0%
20%
40%
60%
80%
100%100% 100% 100%96% 100%
93%
SVR4: Cirrhosis
Pati
en
ts (
%)
Jacobson IM et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-3.
12 weeks 24 weeks0%
20%
40%
60%
80%
100% 93% 93%96%
79%
SVR12: No Cirrhosis
Pati
en
ts (
%)
ABT-450/R/ABT-267 + ABT-333 + RBV: Treatment-experienced G1
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.
Conclusions
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
Conclusions Cont’d
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
Resources for Patients
www.hepmag.com www.AASLD.org/patients www.cdc.gov/hepatitis/C www.hepeducation.org www.hepc.liverfoundation.org www.hepatitis.va.gov/HEPATITIS