moore hep cipsos healthcare. prevalence diagnosed treated 4.1 m 1.6 m 89 38% diagnosed 5.5% treated...

2/26/2015

1

Hepatitis C – Are We Winning the War?

Ann Moore, FNP

HCV Infection Worldwide 170 million persons with HCV

3-4 million newly infected each year

•World Health Organization 2008. Available at: http://www.who.int/ith/es/index.html. Accessed October 8, 2010.

> 10%2.5% to 10%1% to 2.5%

Prevalence of infection

NA

*

* *

2/26/2015

2

HCV Prevalence in High-Risk US Populations

•Weinbaum C, et al. MMWR Recomm Rep. 2003;52(RR-1):1-36. Edlin BR. Hepatology. 2002;36(5 suppl 1):210-219. National Survey on Drug Use & Health (NSDUH). NSDUH Report. 2003. Khalili MA, et al. Clin Inf Dis. 2000;31:154-161. LaBreque DR, et al. In: Hepatitic C Choices. 2002. Alter MJ, et al. N Engl J Med. 1999;341(8):556-562. Nyamathi AM, et al. J Gen Intern Med. 2002;17(2):134-143. Bräu N, et al. Am J Gastroenterol. 2002;97(8):2071-2078. Jonas MM. Hepatology. 2002;36(5 suppl 1):S173-S178.

•Homeless•~175,000 (22%)

•Alcoholics•~250,000 (11%-36%)

•IDUs•~300,000 (80%-90%)

•Incarcerated•~310,000 (15%)

•HIV Infected•~300,000 (30%)

•Veterans•~280,000 (8%)

5

Over 5.2 Million People Living With Chronic HCV in the US

0

1

2

3

4

5

6

7

8

Nu

mb

er

of

HC

V C

as

es

(m

illi

on

s)

3.2

NHANESEstimate

*Homeless (n=142,761-337,6100); incarcerated (n=372,754-664,826); veterans (n=1,237,461-2,452,006); active military (n=6805);healthcare workers (n=64,809-259,234); nursing home residents (n=63,609); chronic hemodialysis (n=20,578); hemophiliacs (n=12,971-17,000).

1.9

HCV Cases Not Included in NHANES*

Chak E, et al. Liver Int. 2011; 31:1090-1101.

3.8

5.2

7.1Conservative estimateUpper limit of estimate

EstimatedTotal HCV Cases

6

Global Burden of Disease Study 2010:Causes of Death From Chronic Liver Disease

Cowie BC, et al. Hepatology. 2013;58(suppl 1):218A-219A. Abstract 23.

0

10

20

30

40

50

Pat

ien

ts (

%)

45%

Global 2010

26%

HBV

Liver Cancer

20%

30%28%

14%

27%

9%

HCV ETOH Other HBV

CirrhosisHCV ETOH Other

0

10

20

30

40

50

Pat

ien

ts (

%)

16%

USA 2010

40%

HBV

Liver Cancer

29%

8%

40%

13%

39%

14%

HCV ETOH Other HBV

CirrhosisHCV ETOH Other

Increase in liver-cancer deaths (past 20 years):Globally (from 1.25 to 1.75 million/year); USA (45,000 to 70,000/year).

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3

77

Clinical Considerations on the Progression of HCV Infection

• Of every 100 persons infected with HCV, approximately

– 75% to 85% will develop chronic infection

– 60% to 70% will develop chronic liver disease

– 5% to 20% will develop cirrhosis in 20 to 30 years

– 1% to 5% will die from the consequences of chronic infection (liver cancer or cirrhosis)

http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section2.

8

Extrahepatic Manifestations of Chronic HCV Infection

• Arthralgia

• Arthritis

• Bechet’s disease

• Canities

• Cerebral vasculitis

• Cryoglobulinemia

• Diabetes

• Fatigue

• Fibromyalgia

• Hypertrophic cardiomyopathy

• Immune thrombocytopenic purpura

• Insulin resistance

• Lichen planus

• Lung abnormalities

• Membranoproliferative glomerulonephritis

• Membrane nephropathy

• Mooren corneal ulceration

• Multiple myeloma

• Neutropenia

• Non-Hodgkin’s lymphoma

• Paresthesia

• Porphyria cutanea tarda

• Pruritus

• Raynaud’s syndrome

• Sialadenitis

• Sjogren’s syndrome

• Spider nevi

• Systemic lupus erythematosis

• Thrombocytopenia

• Thyroid disease

• Vasculitis

• Vitiligo

• Waldenstrom macroglobulinemia

Chronic HCV in the US:Underdiagnosed and Untreated

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Nu

mb

er (

in ‘

000s

)

Estimated treatment rate is based on Q2 and Q4 2011 chart audits.

Hepatitis C Monitor. Ipsos Healthcare.

Prevalence Diagnosed Treated

4.1 M

1.6 M

89

38%Diagnosed

5.5%Treated

Unaware of Infection

2/26/2015

4

1010

HCV and HIV Mortality in the US (1999-2007)

• US multiple-cause mortality data (NCHS, 50 states plus DC)

– Death certificate data

– Approximately 21.8 million decedents

• Change in age-adjusted mortality rates (per 100,000 person-years)

– HCV: increased 0.18 (P=0.002)

– HIV: decreased 0.21 (P=0.001)

• New policy initiatives are needed to detect and link HCV patients to care and treatment

Ly KN, et al. Ann Intern Med. 2012;156:271-278.

NCHS: National Center for Health Statistics.*A record listing >1 type of infection was counted

for each type of infection.

Annual Age-Adjusted Mortality Rates*

0

1

2

3

4

5

6

7

Dea

th R

ate

(per

100

,000

Per

son

s)

99 00 01 02 03 04 05 06 07Year

HIV

HCV

1111

HCV Screening and Testing Recommendations(CDC and AASLD/IDSA)

• HCV testing is recommended at least once for persons born between 1945 and 1965

• Other persons should be screened for risk factors for HCV infection

• 1-time testing should be performed for all persons with behaviors, exposures, and conditions associated with an increased risk of HCV infection

• Annual HCV testing is recommended

– Persons who inject drugs

– HIV-positive MSMs who have unprotected sex

• Periodic testing should be offered to other persons with ongoing risk factors for exposure to HCV

Centers for Disease Control and Prevention. MMWR. 2012;61(RR-4):1-33.AASLD and IDSA. http://www.hcvguidelines.org/full-report-view. Version December 19, 2014.

1212

HCV Screening: Behaviors, Exposures, and Conditions Associated With Increased Risk of HCV Infection

• Adults born between 1945 and 1965

• Risk behaviors

– Past or current injection drug use

– Intranasal illicit drug use

• Risk exposures

– Chronic hemodialysis

– Getting tattoo in an unregulated setting

– Persons with recognized exposures (needle-sticks, mucosal exposures)

– Birth to an infected mother

– Recipients of transfusions or organ transplants

– Recipients of clotting factors (prior 1987)

– Ever incarcerated

http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm.Centers for Disease Control and Prevention. MMWR. 2012;61(RR-4):1-33.AASLD and IDSA. http://www.hcvguidelines.org/full-report-view. Version December 19, 2014.

• Other medical conditions

– HIV infection

– Unexplained chronic liver disease and chronic hepatitis including persistently abnormal ALT

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5

13

Prevalence of Antibody to HCV:NHANES (1999-2002)

0

10

20

30

40

50

60

GeneralPopulation

IDU BloodTransfusion

(<1992)

HIV Dialysis

Pre

va

len

ce

(%)

1.6%(1.3-1.9)

57.5%(44.1-69.9)

5.8%(3.7-9.0)

13.8%(5.3-31.3)

7.8%

0

10

20

30

40

50

60

Pre

va

len

ce

(%)

Number of Sex PartnersGeneral Risk Factors

0.5%(0.2-1.4)

1.1%(0.5-2.1)

2.6%(1.5-4.6)

7.5%(5.3-10.6)

12.0%(8.5-16.7)

1 2 3 4 5

Number of Sex Partners

Armstrong GL, et al. Ann Intern Med. 2006;144:705-714.Finelli L, et al. Semin Dial. 2005;18:52-61.

14

Recommended Laboratory Tests forChronic HCV Infection

AASLD and IDSA. http://www.hcvguidelines.org/full-report-view. Version December 19, 2014.

Test Application

Hepatitis C antibody byenzyme immunoassay (EIA)

Screening for past or present HCV infectionSensitive and inexpensive

PCR for HCV RNA Confirmation of positive EIAMedical evaluation and management

15

Markers for Acute HCV Infection

0 4 8 12 16 20 36 48 96 144 192

Weeks After Infection

Chevaliez S, et al. Liver Int. 2009;29:9-16.Pawlotsky JM, et al. Hepatology. 2002;36:S65-S73.

Tit

er

HCV RNASymptoms +/- Total Ant-HCV

Antibodies

ALT

ULN

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6

16

Markers for Chronic HCV Infection

0 4 8 12 16 20 36 48 96 144 192

Weeks After Infection

Tit

er

HCV RNASymptoms +/- Total Ant-HCV

Antibodies

ALT

ULN

Chevaliez S, et al. Liver Int. 2009;29:9-16.

1717

ELISA Screening Tests for HCV

• Serologic assays to detect circulating HCV antibodies

• Sensitivity (97% to 100%)

• Positive predictive value

– 95% with risk factors and elevated ALT

– 50% without risk factors and normal ALT

• False positives

– More likely in patients with low risk of HCV infection

• False negatives

– More likely in severely immunocompromised patients, transplant recipients, patients with chronic renal failure on dialysis, HIV-positive patients


1818

When to Test for HCV RNA(AASLD Recommendation)

• Positive anti-HCV antibody test

• Considering antiviral treatment

– Use sensitive quantitative assay

• Unexplained liver disease and negative anti-HCV antibody test and who are

– Immunocompromised

– Suspected of having acute HCV infection


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7

19

HCV Assays:What the Results Mean


Anti-HCV

HCV RNA Interpretation

+ + Acute or chronic HCV depending on the clinical context

+ False positive HCV antibodyResolved infectionLow-level intermittent viremia

+ Early acute HCV infectionChronic HCV in setting of immunosuppressed stateFalse positive HCV RNA test

Absence of HCV infection

2020

Counseling HCV-Infected Patients:Avoiding Transmitting HCV to Others

• Items to avoid

– Sharing toothbrushes and dental or shaving equipment

– Using illicit drugs

• Those who continue to inject drugs, avoid reusing or sharing syringes, needles, water, cotton or other paraphernalia. Clean the injection site with a new alcohol swab and dispose of syringes and needles after one use in a safe, puncture-proof container

• Bandage bleeding wounds to prevent contact with others

• Do not donate blood, body organs, other tissue or semen

• Safe, sexual practices

– Encourage barrier protection for HIV-positive MSMs and those with multiple sexual partners or STIs

• For others with HCV infection, the risk of sexual transmission of HCV is low


2121

Counseling HCV-Infected Patients:Minimizing Disease Progression

• Avoid alcohol

– HCV-related fibrosis progression is increased with alcohol consumption >50 g/day

– Lower levels of alcohol consumption is associated with increases in HCV RNA levels

• Administer HAV and HBV vaccines as needed

• Consider treatment for chronic HCV infection


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8

2222

Vitamin D and Coffee:Role in Chronic HCV Infection

• Vitamin D levels (HCV genotype 1 [n=197] versus age- and sex-matched healthy controls [n=49])

– 25(OH) D levels significantly lower in HCV versus controls (25 versus 43 µg/L; P<0.001)

– Low levels significantly associated with female sex, increased liver inflammation, increased liver fibrosis, and decreased SVR (n=167)

• Coffee consumption >3 cups/day (HALT-C trial, serial liver biopsies every 2 years)

– Lower rates of disease progression (relative risk 0.47 [P=0.0003])

– Lower insulin and HOMA-2 score

– Independent predictor of improved virologic response to PR (adjusted* odds ratio 1.80 [P=0.034])

Petta S, et al. Hepatology. 2010;51:1158-1167.Freedman ND, et al. Hepatology. 2009;50:1360-1369.Freedman ND, et al. Gastroenterology. 2011;140:1961-1969.

*Adjusted for age, race/ethnicity, sex, alcohol, cirrhosis, AST/ALT ratio, IL28B polymorphism rs12979860, and dose reduction in peginterferon. PR: pegIFN + RBV.

2323

Tobacco and HCC Risk

• The relationship between cigarette smoking and HCC has been examined in >60 studies (both areas of high and low incidence of HCC)

– Both positive associations and no associations have been reported

• Studies with positive associations

– Effects limited to subgroups defined by HCV or HBV status

– Meta-analysis of 16 publications

• HBV and cigarette smoking: more than additive interaction

• HCV and cigarette smoking: more than multiplicative interaction

El-Serag HB. Gastroenterology. 2012;142:1264-1273.Chuang SC, et al. Cancer Epidemiol Biomarkers Prev. 2010;19:1261-1268.

24

HCV Linkage-to-Care: Missed Opportunities in a Large Primary Care Setting (2005-2010)

Brown KA, et al. Hepatology. 2013;58(suppl 1):1291A. Abstract 2240.

Patients with a positive anti-HCV antibody test and visit to primary care from 2005-2010 (n=566).Of these patients, 458 underwent HCV RNA testing.

0

40

80

120

160

200

240

280

320

Nu

mb

er o

f P

atie

nts

HCV RNAPositive

308

117

8

38% ReceivedCare From Specialist

Seen bySpecialist

21

6.8%Treated

Treated AchievedSVR

2.6%Achieved SVR

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9

2525

Stepwise Barriers to Hepatitis C Treatment

HCV Infection Diagnosis

Referral toSpecialist

TreatmentInitiation

McGowan CE, et al. Liver Int. 2012;32(suppl 1):151-156.

BarriersAsymptomatic disease

Poor awareness/educationLack of medical coverageMD failure to screen/test

BarriersNon-adherence

MD failure to identifyneed for referral

Logistical concernsLimited specialists

availability

BarriersPatient fears/misunderstandings

StigmatizationSubstance abuse

Psychiatric comorbidityFinancial concern

Transportation/logistical concernCommunication difficulties

2626

Achieving a Sustained Virologic Response is Associated With Improved Outcomes

• Sustained viral response

– Durable

• 99% stay HCV negative for >10 years

– Leads to improved histology

– Leads to clinical benefits

– Decreased decompensation

– Prevents de novo esophageal varices

– Decreased hepatocellular carcinoma

– Decreased mortality

Bruno S, et al. Hepatology. 2010;51:2069-2076.Veldt BJ, et al. Ann Intern Med. 2007;147:677-684.Maylin S, et al. Gastroenterology. 2008;135:821-829.

27

SVR is Significantly Associated With Reduction inAll-Cause Mortality

Backus LI, et al. Clin Gastroenterol Hepatol. 2011;9:509-516.

Retrospective analysis of veterans who received pegIFN + RBV at any VA medical facility (2001-2008).

Cu

mu

lati

ve M

ort

alit

y (%

)

0 1 2 3 4 5 6

Genotype 1(n=12,166)

Years

0

0.05

0.1

0.15

0.2

0.25

0.3

Cu

mu

lati

ve M

ort

alit

y (%

)

0 1 2 3 4 5 6

Genotype 2(n=2904)

Years

0

0.05

0.1

0.15

0.2

0.25

0.3

Cu

mu

lati

ve M

ort

alit

y (%

)

0 1 2 3 4 5 6

Genotype 3(n=1794)

Years

0

0.05

0.1

0.15

0.2

0.25

0.3

SVR

Non-SVR

P<0.0001

SVR rate: 35%

SVR

Non-SVR

P<0.0001

SVR rate: 72%

SVR

Non-SVR

P<0.0001

SVR rate: 62%

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10

2828

Advanced Liver Disease:Basic Principles

• Hepatic fibrosis

– Not reliably diagnosed by ultrasound or other imaging modalities

• Liver fibrosis rates

– Not predictable or linear

• Progression from compensated cirrhosis to decompensated liver disease

– Occurs in 5% of patients per year

• Hepatocellular carcinoma

– Develops in 1% to 2% of patients with hepatitis-related cirrhosis each year

• Liver Biopsy no longer routinely recommended for Hepatitis C therapy decisions

Sherman KE. Top HIV Med. 2011;19:121-125.

29

Progression of Fibrosis inViral Hepatitis on Biopsy (Metavir)

No Fibrosis Stage 1

Fibrous expansion of some portal areas

Stage 2

Fibrous expansion of most portal areas with occasional

portal to portal bridging

Stage 3 Stage 4

CirrhoticLiver

Fibrous expansion of portal areaswith marked bridging (portal-to-portal

and portal-to-central)

Cirrhosis

Faria SC, et al. Radiographics. 2009;29:1615-1635. Adapted from Everson GT.

Cirrhosis (F4)Normal (F0)

NodulesIrregularsurface

Nodules surrounded by fibrous tissue

Payers and Guidelines are currently restricting access to F3 and F4 patients

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11

Fibroscan 502 Touch

Transient Elastography (Fibroscan®)

• Non invasive liver stiffness measurement

• Received 510(k) clearance from FDA on April 5, 2013

• Manufactured by Echosens (Paris)

• Distributed in the United States by Sandhill Scientific, Inc.

Courtesy of Echosens. Available at http://www.echosens.com/. Accessed January 2014.


• Works by measuring deformation of tissue

caused by mechanical compression

• Non-invasive

• High concordance with biopsy

• Fibroscan® eliminates the need for biopsy

in some patients

Afdhal NH. Gastroenterol Hepatol (N Y) 2012;8:605-607.


• Technical limitations of transient elastography

– Testing cannot be performed in all patients

– Either the test cannot be performed or the results are unreliable in patients who:

• Have ascites

• Are morbidly obese

• Have large amounts of chest wall fat

Afdhal NH. Gastroenterol Hepatol (N Y) 2012;8:605-607.

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12

34

FibroScan “Elastography”

Ziol M, et al. Hepatology. 2005;41:48-54.

The probe induces an elastic wave through the liver

The velocity of the wave is evaluated in a region located from2.5 to 6.5 cm below the skin surface

Diagnostic accuracy:

• Significant fibrosis: 0.79• Advanced fibrosis: 0.91• Cirrhosis: 0.97

8.8 9.6 14.6

FibroScan (kPa)

Liver Fibrosis(METAVIR)

F0-F1 F2 F3 F4

35 Confidential

SuperSonic AixplorerUltrasound

36 Confidential

MultiWave™ Technology

Two waves to better characterize tissue :

One Ultrasound Wave :Impeccable image quality in B-mode

One Shear Wave :Measures and displays, in real time, local tissue elasticity in kilopascals

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13

37 Confidential

Abdomen - Liver

38 Confidential

Liver Fibrosis F2

39 Confidential

Liver Fibrosis F4

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14

40

Chronic HCV Infection:Natural History

Poynard T, et al. Lancet. 1997;349:825-832.

Stable

Liver Decompensation (5%/year)HCC (2%-8%/year)

Resolved

Exposure(Acute phase)

CirrhosisChronic5%-25%

Over 20-30 Years

15%-45% 55%-85%

75%-95%

4141

Risk Factors forProgressive Fibrosis and Cirrhosis

• Persistently elevated ALT levels

• Longer duration of infection

• Alcohol excess (>50 g/day)

• Age >40 years at time of infection

• HIV or HBV coinfection

• High BMI

• Male gender

Poynard T, et al. Lancet. 1997;349:825-832.Kim WR, et al. Gastroenterology. 2004;127:749-755.

4242

Health Maintenance of the Cirrhotic Patient

• Vaccinations

• Bone disease screening, surveillance, and management

• HCC screening and surveillance

• Varices screening and surveillance

• Nutritional support

– Vitamin assessment for vitamin A and D deficiency

– Mineral assessment: zinc and magnesium (Mg++)

• Review medication list

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43

Estimated 3-Month Survival as a Function of MELD

Wiesner R, et al. Gastroenterology. 2003;124:91-96.

0

20

40

60

80

100

3-M

on

th S

urv

ival

(%

)

0 10 20 30 40 50

MELD Score

MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4

4444

When to Refer to Hepatologist

• Any hepatic decompensation

– Ascites

– Jaundice

– Encephalopathy

– Variceal bleeding

• MELD >10

• Hepatocellular carcinoma

45

Chronic HCV Therapy:Advances in Raising Cure Rates

0

20

40

60

80

100

SV

R (

%)

16%

44%

~70%

35%1991

1998

2001

2011

IFN

IFN/RBV

PegIFN/RBV

Telaprevir orBoceprevir +PegIFN/RBV

>90%

>20132nd Generation DAAs

PegIFN-Free Regimens

Schaefer EA, et al. Gastroenterology. 2012;142:1340-1350.AASLD and IDSA. http://www.hcvguidelines.org/full-report-view. Version December 19, 2014.

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4646

DAAs in Late-Stage Clinical Development for Chronic HCV Infection

NS3/4AProteaseInhibitors

NucleotideNS5B

Polymerase Inhibitors

Non-Nucleoside NS5B

Polymerase Inhibitors

NS5AReplication

Complex Inhibitors

Cyclophilin Inhibitors

Approved SimeprevirBoceprevirTelaprevir

Paritaprevir/r

Sofosbuvir Dasabuvir LedipasvirOmbitasvir

Phase 3 Asunaprevir*Grazoprevir

Beclabuvir Daclatasvir*†

ElbasvirGS-5816

Phase 2 GS-9256GS-9451ABT-493

SovaprevirGS-9857

ACH-3422MK-3682

ABT-072GS-9669

TMC647055

ABT-530ACH-3102MK-8408

GSK2336805PPI-668

SCY-635

*Approved in Japan.†Approved in Europe.Not all inclusive.

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17

The “Ideal” HCV Antiviral

High Antiviral Activity

Activity against all genotypes

High barrier to resistance

Simple application (few pills, QD dosing)

Highly favorable safety profile

No Drug-Drug interactions

Short and finite duration of therapy

Efficacious in all patient populations

Cure (very high SVR rates)

High value

Sofosbuvir

HCV-specific nucleotide polymerase inhibitor (chain terminator)

Antiviral activity and clinical efficacy in HCV GT 1‒6

High barrier to resistance

Once-daily, oral, 400-mg tablet

Approved for use in combination with other agents for the treatment of chronic HCV

Safety established in >3000 patients including patients with compensated cirrhosis

50

OO N

NH

O

O

P

O

HN

O

O

OH3C

H3C

CH3

HO F

CH3

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18

Viekira Pak

5454

Genotype 1a Genotype 1b

No Cirrhosis

With Cirrhosis

No Cirrhosis

With Cirrhosis

Ledipasvir/sofosbuvir (90/400 mg qd) 12* 12 12* 12

Sofosbuvir 400 mg + simeprevir 150 mg qd+ RBV†

12 24 12 24

Ombitasvir/paritaprevir/r (25/150/100 mg qd) + dasabuvir 250 mg bid + RBV

12(with RBV)

24‡

(with RBV)12

(no RBV)12

(with RBV)

AASLD and IDSA: Recommended HCV Regimens forTreatment-Naïve Patients (Genotype 1)


Duration of Therapy (weeks)

Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).*8 weeks can be considered in treatment-naïve patients without cirrhosis who have pre-therapy HCV RNA <6 million IU/mL. Shortening

treatment to less than 12 weeks should be done with caution and performed at the discretion of the practitioner.†Role of RBV is unclear, awaiting results from larger phase 3 studies for clarification‡12 weeks may be considered for some patients based on prior treatment history.

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19

5555

AASLD and IDSA: Recommended HCV Regimens forTreatment-Naïve Patients (Genotype 2, 3, 4, 5, 6)


Sofosbuvir 400 mg qd. Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).PR: pegIFN + RBV.

Sofosbuvir + RBV for 12 weeks (16 weeks is recommended for cirrhotics)Genotype 2

Sofosbuvir + RBV for 24 weeksGenotype 3

Ledipasvir/sofosbuvir (90/400 mg qd) for 12 weeksSofosbuvir + RBV for 24 weeksOmbitasvir/paritaprevir/r (25/150/100 mg qd) + dasabuvir 250 mg bid + RBV

for 12 weeks

Genotype 4

Sofosbuvir + PR for 12 weeksGenotype 5

Ledipasvir/sofosbuvir (90/400 mg qd) for 12 weeksGenotype 6

5656

AASLD and IDSA: Alternative HCV Regimens for Treatment-Naïve Patients



NoneGenotype 1

NoneGenotype 2

Sofosbuvir + PR for 12 weeks (IFN eligible)Genotype 3

Sofosbuvir + PR for 12 weeks (IFN eligible)Sofosbuvir (400 mg qd) + simeprevir (150 mg qd) + RBV

Genotype 4

PR for 48 weeks (IFN eligible)Genotype 5


57

AASLD and IDSA: HCV Regimens Not Recommended for Treatment-Naïve Patients


Sofosbuvir + RBV for 24 weeksPR + sofosbuvir, simeprevir, telaprevir or boceprevir for 12 to 48 weeksPR + direct-acting antiviral agent

Genotype 1

PR for 24 weeksMonotherapy with pegIFN, RBV, or a direct-acting antiviral agentTelaprevir-, boceprevir-, or ledipasvir-containing regimens

Genotype 2

PR for 24 to 48 weeksMonotherapy with pegIFN, RBV, or a direct-acting antiviral agentTelaprevir-, boceprevir-, or simeprevir-containing regimens

Genotype 3

PR + simeprevir for 24 to 48 weeksMonotherapy with pegIFN, RBV, or a direct-acting antiviral agentTelaprevir- or boceprevir-based regimens

Genotype 4

Monotherapy with pegIFN, RBV, or a direct-acting antiviral agentTelaprevir- or boceprevir-based regimens

Genotype 5 or 6

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20

5858

Genotype 1a Genotype 1b

No Cirrhosis

With Cirrhosis

No Cirrhosis

With Cirrhosis

Ledipasvir/sofosbuvir (90/400 mg qd) + RBV 12(no RBV)

12(with RBV)

24(no RBV)

12(no RBV)

12(with RBV)

24(no RBV)

Sofosbuvir 400 mg + simeprevir 150 mg qd+ RBV*

12 24 12 24

Ombitasvir/paritaprevir/r (25/150/100 mg qd) + dasabuvir 250 mg bid + RBV

12(with RBV)

24(with RBV)

12(no RBV)

12(with RBV)

AASLD and IDSA: Recommended HCV Regimens forPrior PegIFN + RBV Failure (Genotype 1)


Duration of Therapy (weeks)

Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).*Role of RBV is unclear, awaiting results from larger phase 3 studies for clarification.

5959

AASLD and IDSA: Recommended HCV Regimens forPrior PegIFN + RBV Failure (Genotype 2, 3, 4, 5, 6)



Sofosbuvir + RBV for 12 to 16 weeksGenotype 2

Sofosbuvir + RBV for 24 weeksGenotype 3

Ledipasvir/sofosbuvir (90/400 mg qd) for 12 weeksSofosbuvir + RBV for 24 weeksSofosbuvir + PR for 12 weeks (IFN eligible)Ombitasvir/paritaprevir/r (25/150/100 mg qd) + dasabuvir 250 mg bid

+ RBV for 12 weeks

Genotype 4

Sofosbuvir + PR for 12 weeksGenotype 5

Ledipasvir/sofosbuvir (90/400 mg qd) for 12 weeksGenotype 6

6060

AASLD and IDSA: Alternative HCV Regimens for Prior PegIFN + RBV Failure



NoneGenotype 1



NoneGenotype 4

PR for 48 weeks (IFN eligible)Genotype 5


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AASLD and IDSA: HCV Regimens Not Recommended for Prior PegIFN + RBV Failure


Monotherapy with either pegIFN, RBV, or direct-acting antiviral agentPR + sofosbuvir, simeprevir, telaprevir, or boceprevirAny IFN-free regimen containing an HCV protease inhibitor (simeprevir, paritaprevir)

Genotype 1

PR + telaprevir or boceprevirLedipasvir/sofosbuvirMonotherapy with pegIFN, RBV, or a direct-acting antiviral agent

Genotype 2

PR for 24 to 48 weeksMonotherapy with pegIFN, RBV, or a direct-acting antiviral agentTelaprevir-, boceprevir-, or simeprevir-containing regimens

Genotype 3

PR + telaprevir or boceprevirMonotherapy with pegIFN, RBV, or a direct-acting antiviral agent

Genotype 4

Monotherapy with pegIFN, RBV, or a direct-acting antiviral agentTelaprevir- or boceprevir-based regimens

Genotypes 5 or 6

6262

AASLD and IDSA: Recommended HCV Regimens forPrior Sofosbuvir- or HCV PI-Based Regimen Failure


Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).*Regardless of HCV genotype 1 subtype.

Without advanced fibrosis

Advanced fibrosis

Defer antiviral therapy (patients without an urgent need of therapy)

Ledipasvir/sofosbuvir (90/400 mg qd) + RBV for 24 weeks

Sofosbuvir-BasedRegimen Failure

Without cirrhosis

With cirrhosis

Ledipasvir/sofosbuvir (90/400 mg qd) for 12 weeks

Ledipasvir/sofosbuvir (90/400 mg qd) for 24 weeksLedipasvir/sofosbuvir (90/400 mg qd) + RBV for 12 weeks

HCV PI-BasedRegimen Failure*

• Emerging data suggest that approximately 10% to 15% of patients with HCV genotype 1 infection treated for 12 weeks with the combination of simeprevir plus sofosbuvir will experience treatment failure, typically owing to viral relapse after discontinuing therapy

- Very limited clinical experience and trial data on the retreatment of these patients- For patients with minimal liver disease, consider deferring retreatment pending availability of data- For patients who require urgent retreatment, based on emerging data and the expected pattern of HCV drug resistance, consider

ledipasvir/sofosbuvir + RBV for 24 weeks

6363

Summary

• Active HCV infections with a detectable viral load are at increased risk of death due to hepatic and extrahepatic diseases

• Chronic HCV patients with active infection may benefit from antiviral treatment, once diagnosed, to reduce overall mortality

• HCV-related mortality among baby boomers prompted US health officials and the CDC to expand HCV testing to this entire age group

– Stress the importance of testing and including an HCV RNA test for anti-HCV seropositives in clinical practice

– HCV mortality may be reduced by increased treatment as a result of expanding screening to identify patients unaware of their infection

Lee M-H, et al. J Infect Dis. 2012;206:469-477.Nelson KE. J Infect Dis. 2012;206:461-463.Centers for Disease Control and Prevention. MMWR. 2012;61(RR-4):1-33.AASLD and IDSA. http://www.hcvguidelines.org/full-report-view. Version December 19, 2014.

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Summary

• Active HCV infections with a detectable viral load are at increased risk of death due to hepatic and extrahepatic diseases

• Chronic HCV patients with active infection may benefit from antiviral treatment, once diagnosed, to reduce overall mortality

• Approval of newer, direct-acting, oral agents have high HCV cure rates, fewer adverse events, and negligible resistance compared with the first generation HCV PI

– IFN-free regimens are options for many patients

– PR-based regimens are no longer recommended for treatment-naïve genotypes 1, 2, 3, 4, and 6s

– Further research is needed on regimens based on newer, direct-acting, oral agents, especially for patients who failed previous HCV PI-based therapy

PR: pegIFN + RBV.

6565

•WE CAN WIN THE WAR!

–THANK YOU

HCV: SCREEN, TREAT, CURE!

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