global ai- hcv talk

7/31/2019 Global AI- HCV Talk

1/78

Hepatitis CEpidemiology, Diagnosis,

& Current treatment options

Amir Butt, MDAssistant Professor

Medical Director Pancreatico-biliary ServiceDivision of Gastroenterology, Hepatology, & Nutrition

Brody School of Medicine

East Carolina University


2/78

Disclosures


3/78

Objectives

Hepatitis C: Prevalence, transmission &symptoms

Making the diagnosis

Current treatment options


4/78

Help

While suturing a HCV infected patient at 8pm on aSaturday evening, a surgical resident receives a needlestick injury. He shows up to occupational health onMonday morning and after lab work, he is told to be HCV

Ab positive. That afternoon he is in your clinic.

Which of the following is the most appropriate response?

A. Almost all surgeons get HCV Ab sometime in their life

B. You have contracted HCV from the needle stick

C. HCV infection not entirely curable

D. You should have stuck to Internal Medicine

E. You have Hepatitis C from a prior exposure


5/78

Epidemiology


6/78

NANB - Hepatitis


7/78


8/78

Hepatitis C virus: The major causative agentof viral non-A, non-B hepatitis

A blind recombinant immunoscreening approach,of general

application to studies of infectious diseases, was used to cloneand identify the genome of the previously uncharacterizednon-A, non-B hepatitis (NANB) virus. This agent is a positive-strandedRNA virus that appears to be distantly related to theflaviviridae family. Data obtained usingthis assay indicate thatthis agent, termed the hepatitis Cvirus (HCV), is the majorcause of post-transfusion, community-acquiredand

cryptogenic, NANB.

QL Choo, et al. Chiron Corporation, Emeryville California, USA - 1990


9/78

Hepatitis C Virus

Single stranded, positive sense, RNA Flaviviridae family

Spherical, enveloped

Great genetic diversity Six genotypes: 1 through 6

Multiple subtypes: a, b, c, etc

Viral sequences can be used to track acommon source of infection

~ 50 nm


10/78


11/78

HCV: Magnitude of the Problem

Nearly 4 million persons in United States infected Approximately 35,000 new cases yearly 85% of new cases become chronic

Leading cause of Chronic liver disease Cirrhosis Liver cancer Liver transplantation

Centers for Disease Control and Prevention. Hepatitis C fact sheet. February 1, 2006.


12/78

Advanced Liver Disease in ChronicHCV-Infected US Population, 2009-2028

The total number of patients with advanced liver disease in 20 yrs isprojected to be > 4-fold greater than it is today

The Milliman Report. Consequences of Hepatitis C Virus (HCV): May 2009.

Assuming No Changes in SOC

0

50,000

100,000

150,000

200,000

250,000

Individuals

2009 2012 2015 2018 2021 2024 2027Year

Hepatocellularcarcinoma

Decompensatedcirrhosis

Liver transplant


13/78

Annual US Medical Costs for ChronicHCV Infection From 2009-2028

Total medical costs for patients with HCV infection are expected to more thandouble, from $30 billion to more than $85 billion USD over the next 20 yrs

The Milliman Report. Consequences of Hepatitis C Virus (HCV): May 2009.

0

60

100

USD$,

Billions 80

40

20

2009 2012 2015 2018 2021 2024 2027

MedicareUninsuredVAMedicaidCommercial

Assuming No Changes in SOC

Year


14/78

Hepatitis C: A Worldwide Epidemic

Estimated ~ 170 million (3.1%) globally (2003)

1, 2, 31

1, 3

1,3

1

Worldwide: 6

3

4

44

4,5

Asia: 63

Europe8.9 million

(1.03%)

The Americas13.1 million

(1.7%)

Africa31.9 million

(5.3%)

Southeast Asia32.3 million

(2.15%)

Western Pacific62.2 million

(3.9%)

EasternMediterranean21.3 million

(4.6%)

Common Genotype

World Health Organization. Hepatitis C: global prevalence: update. 2003. Farci P, et al. Semin LiverDis. 2000;20:103-126. Wasley A, et al. Semin Liver Dis. 2000;20:1-16.


15/78

HCV: Genotypes in the USA

All others

1%

Type 3

10%

Type 2

17%

Type 1

72%

McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.


16/78

Determination of HCV GenotypeINNOLiPA Assay

HCV genotype

Best pretreatment predictor ofresponse

Determines duration of

therapy

All patients should havegenotype determined priorto initiating therapy

PCR1a

1b

3a3b

4

2b

2a

5


17/78

Large Population Underscreened andHCV Patients Under diagnosed

Current screening practices fail to identify a largeproportion of patients with chronic HCV infection[1]

As few as 25% of patients are diagnosed

Survey of 4000 primary care physicians[2]

Only 59% of 1412 respondents asked all patients aboutHCV risk factors

AASLD recommends that as part of acomprehensive health evaluation, all personsshould be screened for behaviors that place themat high risk for HCV infection[3]

1. Kim WR. Hepatology. 2002;36:S30-S34.2. Shehab TM, et al. J Viral Hepat. 2001;8:377-383.3. Ghany MG, et al. Hepatology. 2009;49:1335-1374.


18/78

HCV Infection: High-Risk Populations inWhich Screening Is Indicated

Injection drug use

Nasal inhalation ofcocaine

Chronic renal failure ondialysis

Incarceration

Multiple sexual partners,MSM, HIV positive

Transplantation ortransfusion of bloodproducts before 1992

Occupational exposure toblood products

Body piercing andpossibly tattoo

Children born to HCV-positive women

Centers for Disease Control and Prevention. April 10, 2007. Verucchi G, et al. Infection.2004;32:33-46.


19/78

High Prevalence of HCV Among IDUs

89

80

67

64

74

0 20 40 60 80 100

HCV (%)

Bulgaria

New Zealand

Russia

Amsterdam

Baltimore

63New York

Thomas DL, et al. Medicine (Baltimore). 1995;74:212-220. Des Jarlais DC, et al. AIDS. 2005;19(suppl 3):S20-S25.

Vassilev ZP, et al. Int J STD AIDS. 2006;17:621-626. Kemp R, et al. N Z Med J. 1998;111:50-53.


20/78

Reasons for High HCV Risk Among Injection

Drug Users Contaminated needles

Contaminated works Syringes, cookers, cottons, rinse water

Old (infected) mentor transmits to young initiate

Villano SA, et al. J Clin Microbiol. 1997;35:3274-3277. Garfein RS, et al.J Acquir Immune Defic Syndr Hum Retrovirol. 1998;18(suppl 1):S11-S19. Thorpe LE, et al.Am J Epidemiol. 2002;155:645-653. Hagan H, et al. Public Health Rep. 2006;121:710-719.


21/78

Modes of HCV Transmission

HCV can probably survive on environmental surfaces atroom temperature for 16-72 hours

Do not exchange blood Razors, toothbrushes, nail clippers

Sexual transmission rate is low Condoms recommended for multiple sexual partners

Not transmitted by casual contact (eg, hugging)


22/78

HCV Prevalence

Sex

0

1.0

2.0

3.0

4.0

All W B H M FRace

A

nti-HCVPosit

ive(%)

Alter MJ, et al. N Eng J Med. 1999;341:556-562.

1.8%


23/78

Prevalence in 2006

0

1

2

3

4

5

6

78

9

10

6-19 20-29 30-39 40-49 50-59 60-69 70+

Age group

PercentAnti-HCV

Po

sitive

NH White NH Black Mex Amer

Armstrong GL, Ann Intern Med 2006;144:705-714


24/78

Prevalence rates of HCV - 2008


25/78

Diagnosis


26/78

Making the diagnosis

Natural History - Acute Infection

Symptoms

Are uncommon (body aches, flu-like symptoms, etc)

On average, appear 6 to 7 weeks after infection.

Testing

6 to 8 weeks: Average time antibodies can be detected.

1 to 3 weeks: Average time virus can be detected.

4 to 12 weeks: Often elevation in ALT


27/78

Serologic Pattern of Acute HCV Infectionwith Recovery

Symptoms +/-

Time after Exposure

Titer

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4YearsMonths

HCV RNA


28/78

Chronic HCV Symptoms

Asymptomatic

Symptomatic

Cirrhosis

0

20

40

60

80

100

Fatigue

Perce

ntageofPatients37%

7%

56%

Unpublished data from MCV Hepatitis Program, 1995.


29/78

Serologic Pattern of Acute HCV Infectionwith Progression to Chronic Infection

Symptoms +/-

Time after Exposure

Titer

Normal

0 1 2 3 4 5 6 1 2 3 4YearsMonths

HCV RNA

anti-HCV


30/78

0

50

100

150

200

0 6 12 18 24

Month

ALT(IU/l)

Resolution

Chronic

HCV RNA+/- + -

HCV Response: Acute vs Chronic


31/78

Hepatitis C Virus Diagnostic Testing

Diagnostic Test Type

Specifications Serologic VirologicMode of detection Antibodies Virus

Sensitivity > 95% > 98%

Specificity Variable > 98%

Detection postexposure 2-6 months 2-6 weeks

Use Screening Confirmation


32/78

Hepatitis C VirusHost Production of HCV Antibodies

HCV infects cell

HCV proteins expressedon surface ofhepatocytes

Antibodies to HCVproteins produced byhost

HCV antibodies doNOTconfer immunity YYY


33/78

Natural History

Stable75% to 95%

HCC orDecompensation

1% to 3%/yr

Stable97% to 99%/yr

Resolved15%

Acute HCV

Cirrhosis5% to 25%

Chronic HCV85%

Thomas DL, et al. Clin Liver Dis. 2005;9:383-398 Strader DB, et al. Eur J Gastroenterol Hepatol. 1996;8:324-328.Seeff LB, et al. Hepatology. 2002;36(suppl):S1-S2. Seeff LB, et al. Hepatology. 2002;36(suppl):S35-S46. Liang TJ, et

al. Ann Intern Med. 2000;132:296-305. Fattovich G, et al. Gastroenterology. 1997;112:463-472.


34/78

Are laboratory data helpful?


35/78

Serum HCV RNA Level

Stability Over Time

Patient

Limit of detection

0

2

4

6

8

Baseline 1 2 3 4

Time (Years)

LogHCVR

NA

(IU/mL)

1

23

4

5

Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.


36/78

HCV RNA effect on Liver Histology & Fibrosis

Genotype

NoFibrosis

PortalFibrosis

BridgingFibrosis

Cirrhosis

Serum HCV RNA does not correlate with level of fibrosis

0

2

4

6

8

L

ogHCVRNA

(copies/mL)

1

2

3

4



37/78

HCV RNA effect on Liver Histology &Inflammation

Genotype

Serum HCV RNA does not correlate with level ofinflammation

0

2

4

6

8

0 2 4 6 8 10 12

Inflammation Score

LogHCVRNA

(copies/mL)

1

2

3

4



38/78

Chronic HCV Infection

Normal vs Elevated Serum ALT

Normal ALT Elevated ALT

Portal

26%

No

fibrosis

23%

Mild39%

Cirrhosis

6%

Bridging

6%Portal

20%

No

fibrosis

16% Mild

33%

Cirrhosis

18%

Bridging

13%

Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.


39/78

HCV Infection - Liver Biopsy

Only test that can accurately assess Severity of inflammation

Degree of fibrosis

Determines the following Risk for developing cirrhosis in future

Need for therapy

Need for ongoing therapy when initial treatment has failed


40/78

Is Liver Biopsy Necessary?

NO

Patient wants treatment evenif no fibrosis

Patient does not wanttreatment or treatmentcontraindicated even ifadvanced fibrosis

Labs and radiographic studiesdo not suggest cirrhosis

Patient achieves SVR

YES

Patient would only accepttreatment if advanced fibrosis

Labs or radiographic studiessuggest cirrhosis may bepresent

Patient fails to achieve SVRand no recent biopsyavailable


41/78

Chronic HCV: Progression to Cirrhosis

0

20

40

60

80

100

0 5 10 15 20

Time (Years)

Bridging

Portal

None

Approxim

atePercenta

geof

PatientsWithCirrho

sis

Yano M, et al. Hepatology. 1996;23:1334-1340.

Proportion of Patients Developing CirrhosisAccording to Initial Level of Fibrosis


42/78

I hope I dont have

Hepatitis C


43/78

HCV and Alcohol

Excessive alcohol intake characterized as > 40 g/day for women and > 60 g/day for men.

0

20

40

60

80

100

10 20 30 40

Years Following Exposure

Cirrhosis

(%)

HCV

HCV + alcohol

Wiley TE, et al. Hepatology. 1998:28:805-809.


44/78

< 10 11-20 21-30 31-40 > 40

Duration of Infection (Years)

FibrosisSc

ore

4.0

3.0

2.0

1.0

0

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

HCV Fibrosis Progression: Effect of Age

Age at time

of infection> 40 years< 40 years


45/78

Viral Kinetics


46/78

Response Definition

RVR HCV RNA negative (< 50 IU/mL) at Wk 4

EVR

Complete

EVR

HCV RNA positive at Wk 4 but negative at Wk 12

PartialEVR

HCV RNA positive at WK 4 and 12 but 2 log10 IU/mLdrop from baseline at Wk 12

Non-EVR < 2 log10 IU/mL drop from baseline at Wk 12

Definitions of On-Treatment Response


47/78

SVR Holy Grail

SVR Sustained virologic response Undetectable viral load measured at 24 weeks after

completing therapy

Patients achieving SVR are considered Cured


48/78

RVR

Achieving RVR is highly predictive of SVR[1] Independent of genotype and treatment regimen

RVR achieved by 15% to 20% with genotype 1; 66% withgenotypes 2/3[1,2]

1. Ferenci P, et al. J Hepatol. 2005;43:425-433.2. Shiffman ML, et al. N Engl J Med. 2007;357:124-134.


49/78

SVR in Patients Who Achieved an RVR

90 282 257 9

GT 1 GT 2 GT 3 GT 4

100

868688

Patients With an RVR

RVR: HCV RNA negative (< 50 IU/mL) at Wk 4

Fried MW, et al. EASL 2008.

0

20

40

60

80

100

SVR(%)

n =


50/78

EVR as Predictor of SVR in Genotype 1Patients

Failure to achieve EVR strongly correlates withnonresponse[1,2] 97% to 100% who do notachieve EVR also fail to achieve SVR

Patients without EVR can discontinue therapy

Achieving EVR is less accurate in predicting SVR[3] 65% to 72% of patients withEVR go on to achieve SVR

cEVR is a better predictor of SVR than pEVR[3] 83% vs 21%, respectively, achieved SVR[2]

1. Fried MW, et al. N Engl J Med. 2002;347:975-982. 2. Davis GL, et al. Hepatology. 2003;38:645-652.3. Ghany MG, et al. Hepatology. 2009;49:1335-1374.


51/78

Viral Kinetics and Outcome Importance of RapidVirologic Response

Wk 4Wk 12Wk 24

Neg

Neg

Neg

> 2 log

Neg

Neg

< 2 log

Neg

Neg

> 2 log

> 2 log

Neg

< 2 log

> 2 log

Neg

Any

Pos

Pos

VirologicResponse(%)

91

72

60

4843

20

20

40

60

80

100

EOT response

SVR

9194

9086

90

13

PegIFN alfa-2a+ RBV (N = 453)

HCV RNA Status

Ferenci P, et al, Predicting sustained virological responses in chronic hepatitis C patients treatedwith peginterferon alfa-2a (40 KD)/ribavirin, 425-433, 2005.


52/78

Factors Associated With Increased SVRRates

Useful for advising patients on their likelihood of an SVR

Absence of favorable factors should not be used to deny therapy

1. Manns MP, et al. Lancet. 2001;358:958-965. 2. Fried MW, et al. N Engl J Med. 2002;347:975-982.3. Hadziyannis SJ, et al. Ann Intern Med. 2004;140:346-355. 4. Nguyen MH, et al. Am J Gastroenterol.

2008;103:1131-1135.

Less Consistently Reported[1,2,4]

Dose of pegIFN (1.5 vs 0.5 g/kg/wk) Lower body weight ( 75 kg)

Dose of RBV (> 10.6 mg/kg) Absence of insulin resistance

Female sex Elevated ALT levels (3 x ULN)Younger age (younger than 40 yrs) Absence of bridging fibrosis or cirrhosis

Nonblack race

Major Predictors[1-3]

Viral genotype (nongenotype 1) Pretreatment HCV RNA( 600,000 IU/mL)


53/78

Current Treatment


54/78

Recommended Regimens for Initial HCVTreatment

Optimal duration of treatment should be based on the viral genotype

Ghany MG, et al. Hepatology. 2009;49:1335-1374.

Genotype 1 PegIFN alfa-2a PegIFN alfa-2b

PegIFN dose (weekly) 180 g 1.5 g/kg

RBV dose (daily) 1000 mg if 75 kg1200 mg if > 75 kg

800 mg if 65 kg1000 mg if > 65 to 85 kg1200 mg if > 85 to 105 kg

1400 mg if >105 kg

Planned duration 48 wks 48 wks

Genotype 2/3 PegIFN alfa-2a PegIFN alfa-2b

PegIFN dose (weekly) 180 g 1.5 g/kg

RBV dose (daily) 800 mg 800 mg

Planned duration 24 wks 24 wks


55/78


56/78

The Future is now

Before 2011

PegIFN/RBV constituted standard of care for patientsinfected with all major HCV genotypes until 2011

Genotypes 1 and 4: 48 wks of therapy

Genotypes 2 and 3: 24 wks of therapy

2011

Patients with genotype 1 HCV have new options with theFDA approval of 2 protease inhibitors: telaprevir and

boceprevir Each agent used in combination with pegIFN/RBV

Patients with genotype 2, 3, or 4 HCV continue to receivepegIFN/RBV


57/78

Treatment of Chronic HCV:

Peginterferon and Ribavirin this was then

0

20

40

60

80

100

1 2-3

Genotype

SustainedVir

ologic

Response(%)

PegIFN-2a/RBV

PegIFN-2b/RBV

Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.


58/78

GT1 SVR Whites vs Blacks this was then

SVR

(%)

0

20

40

60

80

100

PegIFN alfa-2b 1.5 g/kg/wk+ RBV 800-1000 mg/day[1]

Non-Hispanic whites

Blacks

n =

52

19

P< .001

100100

52

28

P< .0001

SVR

(%)

0

20

40

60

80

100

196205

PegIFN alfa-2a 180 g/wk +RBV 1000-1200 mg/day[2]

n =

1. Muir AJ, et al. N Engl J Med. 2004;350:2265-2271.2. Conjeevaram H, et al. Gastroenterology. 2006;131:470-477.


59/78

Boceprevir and Telaprevir

Boceprevir, a potent inhibitor of HCV NS3 protease

Telaprevir, a potent inhibitor of HCV NS3/4A protease

Both agents are to be used in combination with current standard-of-care

(peginterferon alfa-2/ ribavirin)


60/78

Trials reported at AASLD 2010

Boceprevir

SPRINT-III: naive GT1 patients

RESPOND-2: nonresponder GT1 patients

Telaprevir ADVANCE: naive GT1 patients

Ph III SPRINT 2 B i


61/78

Phase III SPRINT-2: Boceprevir +PegIFN/RBV in GT1 Tx-Naive Patients

Treatment-naivepatients withgenotype 1

HCV(2 cohorts:

N = 938nonblack and159 black)

PR*

(n = 316,

52)

PR*

(n = 311 nonblack, 52 black)

Wk 72Wk 48

Follow-up

Follow-up

Wk 28

Follow-up

Wk 4

BOC + PR*

(n = 316 nonblack,

52 black)

BOC + PR*

(n = 311 nonblack, 55 black)

PR*

(n = 311,55)

PR*

*BOC 800 mg q8h; pegIFN alfa-2b 1.5 g/kg/wk; weight-based RBV 600-1400 mg/day.Undetectable HCV RNA at Wk 4 of BOC treatment (ie, at Wk 8) and at all subsequent assays.

Poordad F, et al. AASLD 2010.

Follow-upRVR

NoRV

R

Randomized, placebo-controlled trial

SPRINT 2 R R t A di


62/78

SPRINT-2: Response Rates Accordingto Race

0

20

40

60

80

100

Patients(%)

SVR Relapse

4-wk PR + 44 weeks BOC + PR4-wk PR + response-guided BOC + PR 48-wk PR

67 68

40

8

23

9

0

20

40

60

80

100

Patients(%)

SVR Relapse

42

53

2317 1412

Nonblack Patients Black Patients

P< .0001P= .044

P= .004

Poordad F, et al. AASLD 2010.

n =211 213 125 21 18 37 22 29 12 3 6 2

Ph III ADVANCE T l i


63/78

Phase III ADVANCE: Telaprevir +PegIFN/RBV in GT1 Tx-Naive Patients

Treatment-naivepatients with

genotype1HCV

(N = 1088)

Wk 12

TVR + PR*

(n = 364)

TVR + PR*

(n = 363)

PR*

(n = 361)

eRVR: PR*

Wk 72Wk 48Wk 8

Follow-up

Follow-up

Follow-up

*TVR 750 mg q8h; pegIFN alfa-2a 180 g/wk; weight-based RBV 1000-1200 mg/day.eRVR: extended rapid virologic response = undetectable HCV RNA at Wks 4 and 12.

Jacobson IM, et al. AASLD 2010.

Wk 24

PR*

eRVR: PR*

PR*

Follow-up

Follow-up

Randomized, placebo-controlled trial

ADVANCE O ll SVR d R l


64/78

ADVANCE: Overall SVR and RelapseRates

0

20

40

60

80

100

Patients(%)

69

SVR

75

44

P< .0001 for both treatmentarms vs control

12-wk TVR + PR + 12/36-wk PR (n = 363)

48-wk PR (n = 361)

8-wk TVR + PR + 16/40-wk PR (n = 364)

n = 250 271 158

Relapse

9 9

28

n = 28 27 64

Jacobson IM, et al. AASLD 2010.

ADVANCE: SVR with Telaprevir


65/78

ADVANCE: SVR with Telapreviraccording to Race & Ethnicity

SVR(%)

Race/Ethnicity

Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.

Phase III: genotype 1, treatment naive

75

62

74 75

70

58

66 69

46

25

3944

0

20

40

60

80

100

White Black Latino Non-Latino

325n = 315 318 26 40 28 35 44 38 328 320 323

T12PR

T8PR

PR48

Phase III RESPOND 2: Boceprevir in


66/78

Phase III RESPOND-2: Boceprevir inGT1 Prior Nonresponders to PegIFN/RBV

PR*(n = 80)

PR*(n = 161)

BOC + PR*

BOC + PR*PR*

(n = 162)

BOC+ PR*If detectable

at Wk 8 PR*

Bacon BR, et al. AASLD 2010. Abstract 216.

Treatment-experiencedpatients with

GT1 HCV

(N = 403)

Wk 48Wk 8 Wk 36

Follow-up

Follow-up

Follow-up

Follow-up

*BOC 800 mg TID; pegIFN alfa-2b 1.5 g/kg/wk; weight-based RBV 600-1400 mg/day.Follow-up for 24 wks after completion of therapy.

RESPOND 2: SVR Rates According to


67/78

RESPOND-2: SVR Rates According toTreatment Arm and Prior Response

0

20

40

60

80

100

Overall

SVR(%)

4-wk PR + 44-wkBOC + PR (n = 161)

59*

PreviousNonresponders

PreviousRelapsers

48-wk PR (n = 80)

4-wk PR + response-guidedBOC + PR (n = 162)

66

21

40

52

7

75

29

69

P


68/78

PegIFN adverse effects

AE Occurring in > 20% of Pts, % PegIFN alfa-2a/RBV (n = 1035) PegIFN alfa-2b/RBV (n = 1019)

Fatigue/insomnia 64/41 67/38

Headache 41 50

Nausea 34 40

Anemia 34 35

Rash 34 29

Neutropenia 31 26

Irritability/depression 25/20 25/25

Chills 23 39

Injection-site reactions 23 34

Myalgia/arthralgia 22/22 27/21

Dyspnea 22 21

Pyrexia 21 35

Anorexia 21 29

Alopecia 17 23


69/78

RBV adverse effects

Adverse events occurring more frequently whenRBV added to pegIFN vs pegIFN alone

Hemolytic anemia

Headache

Cough/SOB

Gastrointestinal upset

Rash

Insomnia Teratogenicity

Adverse Events Reported More Frequently


70/78

Adverse Events Reported More FrequentlyWith TVR and BOC vs PegIFN/RBV

Adverse Event, % TVR-Containing Arms(n = 727)

PegIFN/RBV Arm(n = 361)

Pruritus 45-50 36

Nausea 40-43 31

Rash 35-37 24

Anemia 37-39 19

Diarrhea 28-32 22

Adverse Event, % BOC-Containing Arms(n = 734)

PegIFN/RBV Arm(n = 363)

Anemia 49 29

Dysgeusia 37-43 18

Telaprevir[1]

Boceprevir[2]

1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB4.


71/78

Everyone is special !!!

Probabilit

yof

Achievinga

nSVR

100

80

60

40

20

0

89

74

5236

1914

7

Cirrhosis No No No No No No No Yes

ALT quotient 7 2 2 2 2 2 1 1

Age in years 20 20 43 43 43 60 60 60

BMI 20 20 26 26 26 30 30 30

HCV RNA, IU/mL x 103 40 40 40 1200 9000 9000 9000 9000

97


72/78

HCV and Renal Disease

Description GFR,mL/min*1.73 m2

Recommended Treatment

Kidney damage withnormal or increased GFR

90 Routine combination therapy

Kidney damage with mildlydecreased GFR 60-90

Moderately decreased GFR 30-59 PegIFN alfa-2b 1 g/kg/wk or pegIFNalfa-2a 135 g/wk + RBV 200-800 mg/day(starting with lowest dose and increasing

if adverse effects manageable)

Severely decreased GFR 15-29

Kidney failure < 15

Dialysis Standard IFN 3 mU 3x/wk or pegIFNalfa-2b 1 g/kg/wk or pegIFN alfa-2a

135 g/wk markedly reduceddaily RBV dose*



73/78

HCV and Renal Disease

HCV treatment not recommended for patients who haveundergone kidney transplantation, unless fibrosingcholestatic hepatitis develops


R l Di IFN i IFN


74/78

Renal Disease: pegIFN not superior to IFN

78 hemodialysis patients treated with pegIFN alfa-2a 135g/wk[1]

SVR obtained in 14% of patients

Adverse events reported in 83% of patients (flu-like syndrome,mild to moderate thrombocytopenia, leukopenia, and anemia)

32% of patients noncompliant

Randomized trial of 16 patients receiving pegIFN alfa-2b1.0 or 0.5 g/kg/wk discontinued due to adverse eventsand modifications[2]

56% of patients in 1 g/kg/wk group and 28% in 0.5 g/kg/wkexperienced serious adverse events requiring therapydiscontinuation

1. Covic A, et al. J Nephrol 2006;19:794-801.2. Russo MW, et al. Nephrol Dial Transplant. 2006;21:437-443.


75/78

IFN Monotherapy in Dialysis Patients

100

80

60

40

20

0

SVR(%)

2027

21 20 19

56 58

68

33

Russo MW, et al. Am J Gastroenterol. 2003;98:1610-1615.


76/78

Current Contraindications to Treatment

CharacteristicsMajor uncontrolled depressive illness

Most solid organ transplantation (renal, heart, or lung)

Autoimmune hepatitis or other autoimmune condition known to beexacerbated by peginterferon and ribavirin

Untreated thyroid disease

Pregnant or unwilling to comply with adequate contraception

Severe concurrent medical disease such as Severe hypertension, heart failure, significant coronary heart disease,

poorly controlled diabetes, chronic obstructive pulmonary disease

Younger than 2 yrs of age

Known hypersensitivity to drugs used to treat HCV



77/78

Summary

Chronic HCV infection leads to cirrhosis and liverfailure in a large number of persons

Health care providers must recognize that chronic

HCV is common in IDU and high risk behaviors

Effective treatment of chronic HCV can preventfibrosis progression and reduce complications

New treatment modalities in genotype 1 patientsshow improved SVR


78/78

Thank youEmail: [email protected]

global ai- hcv talk

Documents