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