Post Conference Update 64 th Annual Meeting of the American Association for the Study of Liver Diseases Sponsored for CME credit by Rush University Medical

Post Conference Update

64th Annual Meeting of the American Association for the Study of Liver Diseases

Sponsored for CME credit by Rush University Medical Center

Supported by an independent educational grant from Gilead Sciences Medical Affairs

Simply Speaking® Hepatitis Post Conference Update: 64th Annual Meeting of the American Association for the Study of Liver Diseases isCopyrighted 2014 by Practice Point Communications, unless otherwise noted. All rights reserved.

2

Content Development & Training FacultyContent Development & Training Faculty

Fred Poordad, MDProfessor of Medicine

University of Texas Health Science Center

San Antonio, Texas● Disclosures

- Grants/Research Support: AbbVie, Achillion, Anadys, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead Sciences, Janssen, Merck & Co., Novartis, Vertex

- Consultant: None

- Speakers’ Bureau: Genentech, Gilead Sciences, Merck & Co., Salix, Vertex

- Stock Shareholder: None

- Other Financial or Material Support: None

3

Learning ObjectivesLearning Objectives(CME/CNE and CPE)(CME/CNE and CPE)

We Are Eliminating Hard Copy Evaluations!

● Upon completion of this activity, the participant intends to incorporate the following objectives into their practice of medicine:

- Screen and test for hepatitis B and C virus (HBV, HCV) infection in my patients according to the recommendations from the American Association for the Study of Liver Diseases (AASLD) and the Centers for Disease Control and Prevention (CDC)

- Appropriately select antiviral HBV and HCV treatment strategies for my patients with HBV and HCV infection

- Manage safety and tolerability problems with antiviral HBV and HCV agents, including side effect, drug-drug interactions, and resistance

- Evaluate new agents being investigated for HBV and HCV therapy with patients in order to optimize information-based decision making about therapy

CME/CNECME/CNE● Upon completion of this activity, the

pharmacist should be able to:

- Review the screening and testing process for hepatitis B and C virus (HBV, HCV) infection in my patients according to the recommendations from the American Association for the Study of Liver Diseases (AASLD) and the Centers for Disease Control and Prevention (CDC)

- Discuss antiviral HBV and HCV treatment strategies in patients with HBV and HCV infection

- Review safety and tolerability problems with antiviral HBV and HCV agents, including side effect, drug-drug interactions, and resistance

- Evaluate new agents being investigated for HBV and HCV therapy with patients

CPECPE

4

Program Overview

● HCV and HBV: epidemiology and public health considerations

● Chronic HCV infection

- New and emerging HCV regimens

• Interferon-free regimens

• DAA + PR

- HCV/HIV coinfection and triple therapy

- Liver transplantation and triple therapy

● Chronic HBV infection

5

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.

Pat

ien

ts (

%)

45%

Global 2010

26%

HBV

Liver Cancer

20%

30%28%

14%

27%

9%

HCV ETOH Other HBV

CirrhosisHCV ETOH Other

Pat

ien

ts (

%)

16%

USA 2010

40%

HBV

Liver Cancer

29%

9%

40%

14%

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).

6

Primary Care Setting: HCV Persons Unidentified by Risk-Based Screening

● Cross-sectional study (2005-2010)

- 4 large primary care health systems

- >18 years of age

- Median follow-up: 5 months

- Multiple imputation used to predict HCV results for patients not tested for HCV

● Newly enrolled patients (n=209,076)

- Tested for HCV: 8.4%

● Predicted HCV prevalence: 2.9%

● Total HCV cases: 6005 (identified + estimated)

- Proportion unidentified: 81%

Yartel AK, et al. Hepatology. 2013;58(suppl 1):219A. Abstract 24.

Patients(n=209,076)

Tested for HCV (%) Number HCV positive

8.41115 (0.53%)

Predictors of HCV positivity (adjusted odds ratio) Born 1945-1965 Male gender Black Hispanic Elevated ALT IDU

4.4*1.4*1.9*1.5*4.8*6.3*

Not tested for HCV (%) Number estimated HCV positive

91.94890 (2.3%)

Results

*P<0.001.

7

Diagnosis Accuracy of Liver Stiffness in Chronic Viral Hepatitis

● Large US cohort (n=907; HCV 93%, HBV 7%)

- Phase 1 (n=188/237 evaluable biopsy/FSCAN)

- Phase 2 (n=560/670 evaluable biopsy/FSCAN)

- FSCAN/biopsy failure: 10.4%/7.9%

● Liver stiffness has high accuracy for staging >F2 fibrosis

● AUC 0.91

- Elastography excellent for exclusion of cirrhosis

● Higher BMI can affect cutoffs

- XL over M probe preferred

Afdhal NH, et al. Hepatology. 2013;58(suppl 1):278A-279A. Abstract 141.

Sensitivity (95% CI)

Specificity (95% CI)

>F2 Phase 1 Phase 2*

81.9 (72.0-89.5)

57.9 (52.7-63.0)

79.0 (70.0-86.4)

74.9 (68.0-80.9)

>F3 Phase 1 Phase 2

88.3 (77.4-95.2)

71.8 (64.2-77.6)

81.9 (73.4-87.6)

80.1 (76.0-84.3)

F4 Phase 1 Phase 2

84.2 (68.7-94.0)

75.9 (64.0-83.6

86.0 (79.4-91.1)

85.1 (82.1-88.6)

Diagnostic Accuracy Versus Biopsy(HCV and HBV)

*P=0.043 versus phase 1.

FSCAN: FibroScan.

8

NHANES (1999-2010):HCV and Diabetes Risk

● NHANES (n=15,128)

- HCV negative (n=14,484)

- Anti-HCV positive (n=277)

- HCV RNA positive (n=188)

- ADA criteria for diabetes, pre-diabetes, and normal glucose

● Summary of findings

- HCV was not associated with diabetes and pre-diabetes

- Elevated liver enzymes were associated with diabetes regardless of HCV status

- HOMA-IR did not differ by HCV status among those with normal glucose

Ruhl CE, et al. Hepatology. 2013;58(suppl 1):1308A-1309A. Abstract 2275.

Pre

vale

nce

(%

)10.5%

Prevalence of Diabetesand Pre-Diabetes

HCV-

Diabetes

P=NS

Anti-HCV+

HCVRNA+

Pre-Diabetes

HCV- Anti-HCV+

HCVRNA+

10.2%12.0%

32.7%

P=NS

36.4%

39.6%

9

Program Overview





• DAA + PR



- Clinical considerations with boceprevir- and telaprevir-based regimens


10

ELECTRON Study: Once-Daily, Fixed-Dose Combination Sofosbuvir/Ledipasvir + RBV

Gane EJ, et al. Hepatology. 2013;58(suppl 1):243A. Abstract 73.

Sofosbuvir 400 mg (nucleotide NS5B polymerase inhibitor); ledipasvir 90 mg (NS5A inhibitor).Weight-based ribavirin dosing (1000-1200 mg).Baseline characteristics: Male: 52% to 100%; age: 5161 years; white: 80% to 100%. Genotype 1a: 60% to 85%; IL28B non-CC: 60% to 85%. HCV RNA: 6.1 to 6.5 log10 IU/mL.

Sofosbuvir/Ledipasvir qd(n=10)

Sofosbuvir/Ledipasvir qd+ RBV (n=9)

Follow-Up

Phase 2bOpen-labelGenotype 1 Follow-Up

Sofosbuvir/Ledipasvir qd + RBV (n=25)

Follow-Up


Follow-Up

Week 0 6 12 24

Treatment-experienced

Cirrhotic (F4)

Treatment-naiveNon-cirrhotic

(F0-F2)

Cirrhotic(F3/F4)

Sofosbuvir/Ledipasvir qd+ GS-9669 (n=26)

Follow-Up

11

ELECTRON Study:SVR12 Rates

Gane EJ, et al. Hepatology. 2013;58(suppl 1):243A. Abstract 73.*Lawitz E, et al. Hepatology. 2013;58(suppl 1):315A-316A. Abstract 215.

Pat

ien

ts (

%)

Sofosbuvir/Ledipasvir

--(n=10)

70%

100%


RBV(n=9)

Treatment-Experienced Treatment-Naive100% 100%


RBV(n=25)

Sofosbuvir/LedipasvirGS-9669

(n=26)

F4 F3/4

Pat

ien

ts (

%)

12 Weeks(n=25)

68%

100%

8 Weeks*(n=21)

100%

6 Weeks(n=25)

Sofosbuvir/Ledipasvir + RBV(No Cirrhosis)

12

LONESTAR Study: Once-Daily, Fixed-Dose Combination Sofosbuvir/Ledipasvir + RBV

Lawitz E, et al. Hepatology. 2013;58(suppl 1):315A-316A. Abstract 215.

Sofosbuvir 400 mg (nucleotide NS5B polymerase inhibitor); ledipasvir 90 mg (NS5A inhibitor).Weight-based ribavirin dosing (1000-1200 mg).No upper limit to age, BMI, or platelet count. Primary endpoint SVR12.PI-experienced: all had prior virologic failure with either boceprevir (55%) or telaprevir (45%) based triple therapy.Baseline characteristics: age (50 years), male (66%), BMI (29.9 kg/m2), IL28B non-CC (85%), genotype 1a (87%), HCV RNA 6.1 log10 IU/mL.

Sofosbuvir/Ledipasvir qd (n=20)

Sofosbuvir/Ledipasvir qd + RBV (n=21)

Phase 2Open-labelGenotype 1 Follow-Up

Sofosbuvir/Ledipasvir qd (n=19)Follow-Up

Week 0 4 8 12 20 24

Follow-Up

Follow-UpSofosbuvir/Ledipasvir qd (n=19)


Follow-Up

Treatment-naïveNon-cirrhotic

PI-experienced50% cirrhotic

13

LONESTAR Study:SVR12 Results


Pat

ien

ts (

%)


--(n=20)

95%100%


RBV(n=21)

Treatment-Naïve(No Cirrhosis)

PI-Experienced(50% Cirrhotic)

95%


--(n=19)

8 Weeks 12 Weeks

Pat

ien

ts

(%)

95%


--(n=19)


RBV(n=21)

12 Weeks

100%

14

LONESTAR Study:Resistance and Safety Results

● SVR12 and baseline RAVs

- NS5A (n=9): 78%

- NS3/4a (n=28): 100%

● S282T and multiple NS5A RAVs detected at relapse in 1 patient (sofosbuvir/ledipasvir 8 weeks)

- SVR12 achieved after retreatment with sofosbuvir/ledipasvir + RBV for 24 weeks

Lawitz E, et al. Hepatology. 2013;58(suppl 1):315A-316A. Abstract 215.Lawitz E, et al. Hepatology. 2013;58(suppl 1):1092A. Abstract 1844.

No RBV(n=58)

With RBV(n=420)

Adverse events leading to discontinuation (%)

0 0

Grade 3/4 (%) Adverse events Laboratory abnormality

07

1414

Adverse events (%) Nausea Anemia URT infection Headache

5075

14191010

Anemia (%) Hemoglobin <10 g/dL Hemoglobin <8.5 g/dL

00

195

Safety(Sofosbuvir/Ledipasvir)

PR: pegIFN + RBV.URT: upper respiratory tract.

15

COSMOS Study: Simeprevir + Sofosbuvir + RBV

Jacobson IM, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-3.

Simeprevir + Sofosbuvir qd (n=14)

Simeprevir + Sofosbuvir qd+ RBV (n=27)

Phase 2aOpen-labelGenotype 1Prior PR null responder

Week 0 12 24


Simeprevir + Sofosbuvir qd + RBV (n=24)


Simeprevir + Sofosbuvir qd+ RBV (n=27)


Simeprevir + Sofosbuvir qd + RBV (n=30)

Sofosbuvir 400 mg (nucleotide NS5B polymerase inhibitor); simeprevir 150 mg (NS3/4A Inhibitor).Weight-based ribavirin dosing (1000-1200 mg).

Non-cirrhoticNon-cirrhotic(F0-F2)(F0-F2)

CirrhoticCirrhotic(F3-F4)(F3-F4)

16

COSMOS Study: Interim Results With Simeprevir + Sofosbuvir + RBV


Pat

ien

ts (

%)

SVR12: No Cirrhosis (F0-F2)(Prior PR Null Responders)

92.9%

24 Weeks(n=24/15)

12 Weeks(n=27/14)

Simeprevir + sofosbuvir No RBV With RBV

96.3% 93.3%

79.2%

Pat

ien

ts (

%)

SVR4: Cirrhosis (F3-F4)*(Naives and Prior PR Null Responders)

100%

Naives(n=7/12)

Overall(n=14/14)

96.3%100%

93.3%

*Interim analysis: SVR4 rates in patients receiving the 12-week regimens.

Nulls(n=7/15)

100%

Simeprevir + sofosbuvir No RBV With RBV

17

COSMOS Study: Interim Safety Results With Simeprevir + Sofosbuvir + RBV


SimeprevirSofosbuvir

RBV(n=54)


--(n=31)

Simeprevir Sofosbuvir

RBV(n=54)


--(n=28)

Discontinuations due to adverse events (%)

3.7 6.5 0 0

Grade 3/4 events (%) Adverse events Hyperbilirubinemia

7.49.4

12.93.2

11.15.6

3.63.6

Common adverse events (%) Fatigue Headache Nausea Insomnia Rash Pruritus Anemia

37201117131720

3223137

1033

2417159

159

11

252121144

110

24 Weeks 12 Weeks

18

VALENCE Trial: Sofosbuvir + RBV in Treatment-Naïve, HCV Genotype 2 or 3

Zeuzem S, et al. Hepatology. 2013;58(suppl 1):733A-734A. Abstract 1085.

Sofosbuvir qd + RBV(n=73/11)

Sofosbuvir qd + RBV (n=250)

Phase 3 (Europe)Open-labelGenotype 1HCV treatment- naïve and experiencedCirrhosis allowed

Week 0 12 24

GenotypeGenotype2 or 32 or 3

Genotype 3Genotype 3(amended(amendedprotocol)protocol)

Sofosbuvir 400 mg (nucleotide NS5B polymerase inhibitor) + weight-based ribavirin dosing (1000-1200 mg).Primary endpoint: SVR12.Baseline demographics and disease characteristics: Male: 55% to 62%. IL28B non-CC: 64% to 74%. HCV RNA (log10 IU/mL): 6.2-6.5. Cirrhosis: 14% to 23%. Prior pegIFN + RBV nonresponder: 24% to 44% Prior pegIFN + RBV relapser: 56% to 68%.

19

VALENCE Trial:SVR12 Rates in HCV Genotype 2 or 3

Zeuzem S, et al. Hepatology. 2013;58(suppl 1):733A-734A. Abstract 1085.

Pat

ien

ts (

%)

93%100%

85%91%

97%

Overall(n=73/250)

94% 92%87%

Genotype 2Genotype 3

Noncirrhotic(n=30/92)

60%

88%

Treatment-Naive

Cirrhotic(n=2/13)

Noncirrhotic(n=33/100)

Cirrhotic(n=8/45)

Treatment-Experienced

No resistance detected in patients with relapse.

20

Sofosbuvir + RBV + PegIFN:SVR12 by Fibrosis Stage

● Retrospective analysis of 4 phase 3 clinical trials

- Sofosbuvir + RBV (12 weeks) in HCV genotype 2/3

• FISSION (treatment-naïve)

• FUSION (treatment-experienced)

• POSITRON (IFN incapable)

- Sofosbuvir + RBV (16 weeks) in HCV genotype 2/3

• FUSION (treatment-experienced)

- Sofosbuvir + pegIFN + RBV (12 weeks) in HCV genotype 1/4/5/6

• NEUTRINO (treatment-naïve)

● Baseline fibrosis stage by FibroTest/FibroSure

- F0-F2 (55%), F3 (17%), F4 (28%)

● SVR12 rates among patients with thrombocytopenia (platelets <125/mm3) were similar to rates in cirrhotic patients across all HCV genotypes

Patel K, et al. Hepatology. 2013;58(suppl 1):738A-739A. Abstract 1093.

21

Sofosbuvir + RBV (12 Weeks): SVR12 by Baseline Fibrosis Stage (FibroTest)


Pat

ien

ts (

%)

100%

88%

Genotype 2 Genotype 3

86%

F1-F2(n=12/39/13)

F4(n=13/25/9)

F3(n=6/13/7)

F0(n=13/32/7)

FISSION (treatment-naïve) POSITRON (IFN incapable)

FUSION (treatment-experienced)

92%97%

100% 100%

92%

86%

100%

92%

67%

Pat

ien

ts (

%) 67%

75%

0%

F1-F2(n=38/37/14)

F4(n=21/26/29)

F3(n=16/12/18)

F0(n=27/24/3)

FISSION (treatment-naïve) POSITRON (IFN incapable)

FUSION (treatment-experienced)

53%

62%

50%

38%

58%

22%

48%

28%

48%

22

Sofosbuvir + RBV + PegIFN: SVR12 by Baseline Fibrosis Stage (FibroTest)


Pat

ien

ts (

%)

100%

Sofosbuvir + RBV (FUSION)(16 weeks, treatment-experienced)

80%

F1-F2(n=14/21)

F4(n=9/27)

F3(n=5/10)

F0(n=4/5)

Genotype 2 Genotype 3

67%

100%

Pat

ien

ts (

%)

96%97%

F1-F2(n=105)

F4(n=86)

F3(n=54)

F0(n=78)

85%79%

Sofosbuvir + PR (NEUTRINO)(12 weeks, treatment-naïve)

Genotypes 1, 4-6

80%

40%

63%

89%

PR: pegIFN + RBV.

23

Sofosbuvir + RBV in US Patients of Egyptian Ancestry (Genotype 4)

Ruane PJ, et al. Hepatology. 2013;58(suppl 1):736A. Abstract 1090.

Phase 2 (open-label)Open-labelGenotype 4

Treatment-experienced

Sofosbuvir 400 mg (nucleotide NS5B polymerase inhibitor).Weight-based ribavirin dosing (1000-1200 mg).Egyptian born with documented maternal and parenteral Egyptian ancestry.Baseline characteristics: Male (68%), cirrhosis (23%), HCV RNA (5.7 to 6.1 log10 IU/mL), IL28B non-CC (83%).

Week 0 12 24





Treatment-naive

24

Sofosbuvir + RBV: SVR Rates in an US Patients of Egyptian Ancestry (Genotype 4)

Ruane PJ, et al. Hepatology. 2013;58(suppl 1):736A. Abstract 1090.

Pat

ien

ts (

%)

Treatment-Naive100%

79%

N/A

12 Weeks(n=14/14)

24 Weeks(n=14)

Pat

ien

ts (

%)

Treatment-Experienced

59%

93%

N/A

12 Weeks(n=17/17)

24 Weeks(n=15)

SVR4SVR12

SVR4SVR12

N/A: data not available.

79%

59%

25

AVIATOR Study: Concordance of SVR4 and SVR12 With SVR24 in HCV Genotype 1

● Pooled analysis (treatment-naïve and prior null responders) of ABT-450/r + ABT-267 + ABT-333 + RBV for 12 or 24 weeks (n=247)

- SVR4 and 12: 96.4% and 95.5%

- SVR24: 93.9%

● Patients achieving SVR4

- No relapses in post-treatment week 12 or 24

● 84% concordance between SVR12 and SVR24

● Results support the use of SVR12 as a primary efficacy endpoint for this IFN-free regimen in HCV genotype 1

Poordad F, et al. Hepatology. 2013;58(suppl 1):735A-736A. Abstract 1089.

SVR4 SVR12

Predictive value (%) Positive Negative

97.5100

98.3100

Sensitivity (%) 100 100

Specificity (%) 60.0 73.3

Cohen’s Kappa 0.74 0.84

Concordance With SVR24

26

PEARL-1 Study: ABT-450/r + ABT-267in HCV Genotype 1b

● Open-label phase 2 study

- HCV genotype 1b treatment-naïve and prior PR null responders

- Non-cirrhotic

● ABT-450/r (150/100 mg qd) + ABT-267 (25 mg qd)

● No discontinuations due to adverse events or laboratory abnormalities

- Grade 3 elevations: ALT (n=1); AST (n=2)

● Most common adverse events

- Headache, nausea, dry skin, fatigue, pruritus, diarrhea

Lawitz E, et al. Hepatology. 2013;58(suppl 1):244A. Abstract 75.

ABT-450 (NS3/4A protease inhibitor); ABT-267 (NS5A replication complex inhibitor).PR: pegIFN + RBV.

Treatment-

Naïve(n=42)

Prior Null PRResponders

(n=40)

Baseline Male (%) White (%) Age (years) HCV RNA (log10 IU/mL) IL28B non-CC (%)

59.566.755.86.4

68.3

37.597.553.46.4

95.0

Efficacy (%) HCV RNA <25 IU/mL Week 4 Week 12 SVR4 SVR12

10097.697.695.2

97.597.592.590.0

Outcomes

27

C-SPIRIT Study: Interim Analysis of MK-5172 + RBV in Treatment-Naïve, HCV Genotype 1

● Open-label, proof of concept study

- Treatment-naïve

- IL28B CC genotype

- Non-cirrhotic

● Randomized arms

- MK-5172 100 mg qd + RBV for 12 or 24 weeks

• 12-week arm extended to 24 weeks if HCV RNA detectable at week 4

● Primary endpoint: SVR12

Gane EJ, et al. Hepatology. 2013;58(suppl 1):748A-749A. Abstract 1110.

MK-5172 (NS3/4A protease inhibitor).

Patients(n=23)

SVR4 (%) Overall Genotype 1a (n=11) 1b (n=12) 12-week arm (n=8) Extended arm (n=4) 24-week arm (n=11)

83

7392887582

Common adverse events (%) Headache Asthenia Insomnia Dyspepsia Anemia Nausea

232312121212

Outcomes

28

C-WORTHY Study: MK-5172/MK-8742 + RBV in Treatment-Naïve, HCV Genotype 1

● Open-label, phase 2b study

- Treatment-naïve, genotype 1

- Non-cirrhotic (F0-F2)

- No HBV or HIV

● Randomized arms (12 weeks)

- MK-5172/MK-8742 (100/20 or 100/50 mg qd) + RBV

• Stratified by genotype 1a and 1b

- MK-5172/MK-8742 (100/50 mg qd) (genotype 1b only)

● Primary outcome: SVR12


MK-5172 (NS3/4A protease inhibitor); MK-8742 (NS5A replication complex inhibitor).Weight-based ribavirin dosing (600-1400 mg).

100/20(n=25)

100/50(n=27)

100/50(n=13)

Genotype (%) 1a 1b

7624

7030

0100

Age (years) 48.7 43.9 43.3

Race (%) White 96 89 69

IL28B non-CC (%) 76 78 85

HCV RNA <800K IU/mL (%)

68 63 54

Baseline CharacteristicsMK-5172 + MK-8742

Dose Arms (mg)

29

C-WORTHY Treatment Results: MK-5172/MK-8742 + RBV in Treatment-Naïve, HCV Genotype 1

● Virologic failure (n=1)

- RAVs at baseline and at relapse

• NS5A: Y93N

• NS3: Y56H, D168A/D

● No discontinuations due to adverse events

- No grade 3/4 laboratory abnormalities


- Fatigue (26%), headache (22%), nausea (18%), diarrhea (12%), dizziness (11%), rash (11%)


MK-5172 (NS3/4A protease inhibitor).MK-8742 (NS5A replication complex inhibitor).Weight-based ribavirin dosing (600-1400 mg).

SVR Rates

Pat

ien

ts (

%)

100/20 mg(n=25)

96%

100/50 mg(n=27)

100%

100/50 mg*(n=13)

With RBV

89%

SVR4 SVR12

*Genotype 1b only.

Without RBV

30

Study 014: Daclatasvir + Asunaprevir + BMS-791325 in HCV Genotype 1

Everson GT, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-1.

Phase 2bOpen-labelGenotype 1Treatment-naïveStratified by: 1a and 1b Cirrhosis

Daclatasvie (NS5A inhibitor; asunaprevir (NS3 inhibitor); BMS-791325 (non-nucleoside NS5B inhibitor).Primary endpoint: SVR12.Baseline characteristics: Age: 54 years; male: 67%. Genotype 1a: 82%. HCV RNA 6.4 log10 IU/mL. Cirrhosis (biopsy confirmed): 9%. IL28B non-CC: 67%.

Week 0 12 24

Daclatasvir 30 mg + Asunaprevir 200 mg +

BMS-791325 75 mg bid (n=80)

Daclatasvir 30 mg + Asunaprevir 200 mg +

BMS-791325 150 mg bid (n=86)

Follow-Up

Follow-Up

31

Study 014:SVR 12 Rates in HCV Genotype 1


Pat

ien

ts (

%)

92% 91%

100%

Overall(n=77/84)

94%89%

96%91%

100%

71%

Daclatasvir + Asunaprevir + BMS-791325 75 mg bidDaclatasvir + Asunaprevir + BMS-791325 150 mg bid

91%94%

1a(n=65/68)

1b(n=12/16)

CC(n=24/28)

Non-CC(n=53/56)

Genotype IL28B

Cirrhosis(n=8/7)

NoCirrhosis(n=69/77)

All patients received daclatasvir 30 mg + asunaprevir 200 mg, both bid.

32

Study 014:Virologic Failures and Safety

● Virologic failures (n=11; 6.6%)

- All were HCV genotype 1a

- Signature RAVs detected at virologic failure

• NS3: V36M, T54S, R155K

• NS5B: M28T, Q30E/H/R

• NS5B: P495L/S

● Well tolerated regimen

- Discontinuations due to adverse events (1.1%)

- Most frequent adverse events: headache (25%), diarrhea (15%), fatigue (11%), nausea (10%)

- Grade 3/4 laboratory abnormalities (<1.2%)


33

SOUND-C3: Faldaprevir + Deleobuvir+ RBV in HCV Genotype 1

● Open-label phase 2 study

- Treatment-naïve

- Stratified by HCV genotype 1a and 1b

- Compensated cirrhosis included

● Faldaprevir 120 mg qd + deleobuvir 600 mg bid + RBV for 16 weeks

- Primary endpoint: SVR12

● Phase 3 studies underway

- 16- and 24-week regimens in HCV genotype 1b

Dufour J, et al. Hepatology. 2013;58(suppl 1):744A. Abstract 1102.

Faldaprevir (NS3/4A inhibitor), deleobuvir (formerly BI 207127) (non-nucleoside NS5B inhibitor).

Patients(n=32)

SVR12 (%) Genotype 1a (n=12) 1b (n=20) Cirrhosis (n=4)

1795

100

Discontinuation due to adverse events (%)

9

Common adverse events (%) Anemia Fatigue Vomiting Nausea

16999

Bilirubin (total) >2.6 x ULN (%) 44

Outcomes

34

Program Overview





• DAA + PR




35

QUEST-1 and -2: Simeprevir + PR inDifficult-to-Cure, HCV Genotype 1 Subgroups

Jacobson IM, et al. Hepatology. 2013;58(suppl 1):756A-757A. Abstract 1122.

Simeprevir (NS3/4A protease inhibitor).HCV RNA >10,000 IU/mL.PR: pegIFN (alpha 2a or 2b) + RBV (weight-based dosing: 1000-1200 mg).Response-guided therapy criteria: HCV RNA <25 IU/mL at week 4 and undetectable at week 12.Primary efficacy endpoint: SVR12.

Simeprevir150 mg qd + PR (n=521)

PR

PR

Week 0 12 24 48 72

PR

Follow-Up

Follow-Up

Response-Guided Therapy

PR(n=264)

PRFollow-Up

Phase 3Double-blindTreatment-naiveSubgroups HCV genotype 1a IL28BB TT Cirrhotic (F4) Baseline Q80K mutation

36

QUEST-1 and -2: SVR12 Rates inDifficult-to-Cure, HCV Genotype 1 Subgroups


Pat

ien

ts (

%)

47%

80%*75%

58%

50%

Overall(n=521/264)

52%

80%85%

95%

78%

53%

42%

Simeprevir + RBVPR

61%

21%

1a(n=254/131)

1a + Q80K(n=84/44)

CC(n=152/79)

CT(n=292/147)

Genotype IL28B

F3(n=82/40)

F4(n=48/32)

METAVIR Score

60%

34%

73%

38%

*P<0.001.

1b(n=267/133)

TT(n=77/38)

PR: pegIFN + RBV.

37

PROMISE Trial: Simeprevir + PR inDifficult-to-Cure, HCV Genotype 1 Subgroups

Forns X, et al. Hepatology. 2013;58(suppl 1):737A-738A. Abstract 1092.

Simeprevir150 mg qd + PR (n=260)

Phase 3Double-blindPrior PR relapsersSubgroups HCV genotype 1a IL28BB TT Cirrhotic (F4) Baseline Q80K mutation

PR

PR

Week 0 12 24 48 72

Simeprevir (NS3/4A) protease inhibitor).PR: peginterferon + RBV.Response-guided therapy criteria: HCV RNA <25 IU/mL at week 4 and undetectable at week 12.Primary endpoint: SVR12.Baseline characteristics: Male (59% to 69%), white (94% to 96%), IL28B non-CC (74% to 76%). HCV RNA (6.5 log10 IU/mL); genotype 1a/1b (41% to 43%/57% to 59%).

PR

Follow-Up

Follow-Up

Response-Guided Therapy

PR(n=133)

PRFollow-Up

38

PROMISE Trial: SVR12 Rates inDifficult-to-Cure, HCV Genotype 1 Subgroups


Pat

ien

ts (

%)

27%

79%

70%

47%

37%

Overall(n=260/133)

30%

53%

86% 88%*

78%*

43%

34%

Simeprevir + RBVPR

65%*

19%

1a(n=111/54)

1a + Q80K(n=30/20)

CC(n=62/34)

CT(n=187/83)

Genotype IL28B

F3(n=44/15)

F4(n=29/19)

METAVIR Score

74%*

26%

73%*

20%

*P<0.001.

1b(n=149/79)

TT(n=31/16)

PR: pegIFN + RBV.

39

PROMISE Trial:Safety

● Simeprevir + PR was generally well tolerated

- Majority of adverse events were grade 1 or 2

- Discontinuations due to adverse events (0.4%)


- Fatigue (31.9%), headache (31.9%), influenza-like illness (29.6%)

- Of interest: rash (<20%) and anemia (15%)

- Incidence of ribavirin dose reduction (20% in both arms)


PR: pegIFN + RBV.

40

STARTVerso3: Faldaprevir + PR in Treatment-Experienced, HCV Genotype 1


Week 0 12 24 48 72

ETS, Follow-UpFaldaprevir 240 mg

qd + PR (n=99)

Faldaprevir 240 mg qd + PR (n=102)

PR (n=49)

Faldaprevir (NS3/4A protease inhibitor).No HBV or HIV coinfection. Fibrosis stage >F3: 53%.ETS: early treatment success (HCV RNA <25 IU/mL at week 4 and undetectable at week 8).Primary efficacy endpoint: SVR12.

Phase 3Double-blindGenotype 1

PR Follow-Up

PRPRPrior PR relapser Follow-Up

Follow-Up

Prior PR partial responders



PR (n=29)

PR Follow-Up

PR

Follow-Up

Follow-Up

Prior PR null responders


Faldaprevir 240 mg qd + PR (n=141) PR Follow-Up

PR Follow-Up

41

STARTVerso3: SVR12 Rates With Faldaprevir + PR in HCV Genotype 1


Pat

ien

ts (

%)

Prior Relapsers

70%*

14%

1a(n=46/46/24)

Overall(n=99/102/14)

1b(n=77/75/16)

Pat

ien

ts (

%)

Prior PartialResponders Null Responders

Pat

ien

ts (

%)

HCV Genotype

1a(n=25/26/14)

Overall(n=57/55/29)

1b(n=32/29/15)

HCV Genotype

1a(n=66/69)

Overall(n=145/141)

1b(n=78/72)

HCV Genotype

*P<0.0001 versus PR (pegIFN + RBV).

61%63%

13%

77%75%

16%

58%*

3%

52%

58%

0%

63%

38%

7%

47%*

33%

26%22%

39%43%

Faldaprevir 240 mg qd + PR 12 weeks 24 weeksPR

Faldaprevir 240 mg qd + PR 12 weeks 24 weeksPR

Faldaprevir 240 mg qd + PR 12 weeks 24 weeks

42

STARTVerso3:Resistance and Safety

● Most common emergent RAVs

- Genotype 1a: R155K

- Genotype 1b: D168

● No significant effect of baseline Q80K and other common NS3 polymorphisms on SVR12 in genotype 1a or 1b patients

● Faldaprevir + PR was well tolerated

- Discontinuations due to adverse events: 5.5%

● Adverse event profile of faldaprevir + PR was similar to the PR arm

● Most common adverse events of at least moderate severity

● Gastrointestinal (18%), anemia (10%)

● Total bilirubin elevations >2.6 x ULN with faldaprevir + PR were benign and transient (49%)


43

LONESTAR-2 Study: Sofosbuvir + PR in Treatment-Experienced, HCV Genotype 2 or 3

● Open-label, phase 2 study

- Failed prior PR therapy

- No HBV or HIV

● Sofosbuvir 400 mg qd + PR for 12 weeks

● Baseline

- Male: 68%; BMI: 31 kg/m2

- IL28B CC: 36%

- HCV RNA: 6.2 log10 IU/mL

- Compensated cirrhosis (55%)

- PR relapse/breakthrough: 85%

● Overall SVR12 rate: 89%

- Similar SVR12 rates in patients with and without cirrhosis

Lawitz E, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-4.

PR: pegIFN + RBV.

SVR12 Rates

Pat

ien

ts (

%)

93%96%

Genotype 3(n=24/12/12)

Genotype 2 (n=23/9/14)

Overall

No cirrhosis

Cirrhosis100%

83% 83% 83%

44

LONESTAR-2 Study:Safety Summary

● Sofosbuvir + PR was generally safe and well tolerated

● Safety profile consistent with PR therapy

● Low rate of discontinuations due to adverse events

Lawitz E, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-4.

PR: pegIFN + RBV.

Patients(n=47)

Discontinuation due to adverse events (%)

2

Grade 3/4 Adverse events Laboratory abnormalities

3260

Hemoglobin (%) <10 g/dL <8.5 g/dL

289

Absolute neutrophil count <750/mm3 (%)

28

Common adverse events (%) Flu-like symptoms Fatigue Neutropenia Nausea

55322317

Safety Summary

45

Program Overview





• DAA + PR




46

PHOTON-1 Study: Sofosbuvir + RBVin HCV/HIV Coinfection

Sulkowski MS, et al. Hepatology. 2013;58(suppl 1):313A-314. Abstract 212.

Phase 3Open-labelTreatment-naïve HCV genotype 1-3Compensated cirrhosis allowedStable HIV disease

Week 0 12 24 36

Sofosbuvir + RBV(n=114)

Sofosbuvir + RBV

(n=68)

Follow-UpGenotype 1

Follow-Up

Sofosbuvir 400 mg (nucleotide NS5B polymerase inhibitor).Weight-based ribavirin dosing (1000-1200 mg).Primary endpoint SVR12.ART was FTC/TDF plus either efavirenz (34%), atazanavir/r (17%), darunavir/r (18%), raltegravir (16%), rilpivirine (6%).Baseline characteristics: Male: 82%. BMI: 27 kg/m2. IL28 non-CC: 30%. Cirrhosis: 7%. CD4: 559-636 cells/µL.

Genotype 2,3

47

PHOTON-1 Study:Treatment Outcomes

● SVR12 rates in genotype 1

- Similar regardless of baseline HCV RNA, IL28b genotype, presence of cirrhosis, age, gender, race

- Lower in genotype 1b versus 1a

● No resistance (deep sequencing) detected in virologic failures

● HIV breakthroughs (n=2)

● Discontinuations due to adverse events: 3%


- Fatigue, insomnia, headache, nausea

- Grade >3 hyperbilirubinemia in patients receiving atazanavir versus no atazanavir (13% versus 1%)

Sulkowski MS, et al. Hepatology. 2013;58(suppl 1):313A-314. Abstract 212.

Pat

ien

ts (

%)

SVR12 Rates

76%

88%

Genotype 1 (n=114)

Genotype 2(n=26)

Genotype 3(n=42)

67%

24 WeeksTherapy*

12 WeeksTherapy*

*Sofosbuvir 400 mg qd + RBV.

48

Program Overview





• DAA + PR




49

REFRESH Study: Telaprevir + PR in HCV Genotype 1 Liver Transplant Recipients

Brown K, et al. Hepatology. 2013;58(suppl 1):209A. Abstract 3.

Phase 2bOpen-labelHCV genotype 1 (1b: 22%) HCV RNA >10K IU/mLOn stable tacrolimus (n=39) or cyclosporine (*n=7)HCV treatment-naïve (22%), relapser (20%), partial (11%) and null responder (33%) before (46%) or after (22%) liver transplantation

Excluded: Retransplantation for recurrent HCV Hemoglobin <11 g/dL

Week 0 4 12 24 36 48 60

Telaprevir +PR (n=46)

Telaprevir (1125 mg tid) + pegIFN (180 µg/week) + RBV (600 mg initial dose).Futility rules (all drugs discontinued): HCV RNA >1000 IU/mL at week 4, 8, or 12. Virologic breakthrough at any time; or HCV RNA <25 IU/mL detected at weeks 24 and 36.Primary endpoint: SVR12.Initial cyclosporine and tacrolimus doses reduced ~4 and ~10 fold, respectively, at baseline. Subsequent doses adjusted based on plasma levels.

Study part A: >12 patients who reach week 4 and undergo safety review before enrolling rest of patients.Study part B: remainder of patients enrolled following acceptable safety review of part A patients.

PRFollow-Up

Interim Analysis: Efficacy (weeks 4 and 12) Safety (week 16)

50

REFRESH Study: Telaprevir + PR in HCV Genotype 1 Liver Transplant Recipients

● Interim results with telaprevir + PR show promising efficacy

● Anemia

- Mild or moderate: 41%

- Severe: 6.5%

- RBV dose reduction: 43%

- Erythropoietin/blood transfusions: 30%/6.5%

● No reports of

- Rejections, autoimmune hepatitis, or deaths

- Severe or potentially life-threatening cases of rash or pruritus

Brown K, et al. Hepatology. 2013;58(suppl 1):209A. Abstract 3.

Patients(n=46)

HCV RNA <25 IU/mL (%) Week 4 Week 12

5360

Serious adverse events (%) 15

Adverse events (%) Fatigue Anemia Headache Nausea Anorectal Diarrhea Rash Pruritus

5948464141373522

Grade 3/4 creatinine increase (%) 4

Renal failure 11

Interim Results

PR: pegIFN + RBV.

51

CRUSH-C: Triple Therapy inHCV-Infected Transplant Recipients

• Multicenter, retrospective, cohort study of consecutive HCV-infected, genotype 1 liver transplant recipients (n=112)

– 6 US transplantation centers

• Protease inhibitor + PR

– Telaprevir: 90%

– Boceprevir: 10%

• Median time from liver transplant to triple therapy: 3.4 years

• Median days of LI and total treatment

– LI <90 arm (n=107): 30 and 282 days

– LI >90 arm (n=18): 182 and 370 days

Patients(n=125)

Male (%) 75

Age (years) 58

Race (%) White 61

Genotype 1a (%) 58

IL28B CC (%) 24

Advanced fibrosis F3-F4 (%) 48

Primary immunosuppressant (%) Cyclosporine/tacrolimus/other 58/29/13

Mycophenolate use (%) 79

Corticosteroid use (%) 26

Baseline Characteristics

LI: lead-in period with only PR therapy.

Stravitz R, et al. Hepatology. 2013;58(suppl 1):429A. Abstract 461.

PR: pegIFN + RBV.

52

CRUSH-C:Virologic Response

● eRVR is highly predictive of SVR12

● Treatment duration <36 weeks negatively affects SVR12 rates

● Adverse events led to treatment

- Discontinuations: 20%

- Interruption: 7%

SVR12

Pat

ien

ts (

%)

Yes(n=56)

Overall(n=90)

No(n=32)

<36(n=5/10)

>36(n=46/11)

AchievedeRVR

Treatment Duration (weeks)

16%

59%

50%

93%†

*P<0.001 versus not achieving an eRVR.†P=0.04 versus <36 weeks (eRVR).‡P=0.003 versus <36 weeks (no eRVR).


86%

eRVRNo eRVR

5%

93%‡

53

CRUSH-C:Safety (All Patients)

• High rates of hospitalizations (27%) and >0.5 mg/dL increase in creatinine (41%)

• Anemia is a significant problem

– PegIFN/RBV dose reduction: 38%/86%

– Erythropoietin/blood transfusions: 84%/56

• Death (7%)

– Mainly due to liver-related causes, usually in patients with advanced disease


54

Sofosbuvir + RBV: Treatment ofRecurrent HCV After Liver Transplantation

● Open-label, pilot study

- Genotype 1(83%), 3 (15%), 4 (3%)

- Prior HCV treatment (88%)

- CPT <7 and MELD <17

- Time liver transplantation: 4.3 years

- METAVIR F3/F4: 23%/40%

● Sofosbuvir 400 mg qd + RBV (starting at 400 mg) for up to 24 weeks

● Primary efficacy endpoint: SVR12

● Safety

- No deaths, graft losses, or rejection

- Discontinuations due adverse events: 5%

- RBV dose escalation manageable

- No interactions with common immunosuppressant agents

Charlton MR, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-2.

Patients

(%)

HCV RNA <25 IU/mL Week 4 (n=40) End of treatment (n=39) SVR4 (n=35)

10010077

Concomitant immunosuppression (%) Tacrolimus Mycophenolate mofetil Prednisone Cyclosporin Azathioprine

703528255

Adverse events (%) Fatigue Headache Arthralgia

282523

Grade 3/4 laboratory abnormalities (%) 25/28

Key Results

55

Pre-Liver Transplant Sofosbuvir + RBV:Prevention of Recurrent HCV

● Open-label, phase 2 study (n=61)

- Listed for liver transplantation due to HCC (compensated cirrhosis)

- Genotype 1/2/3/4: 74%/13/12%/2%

- CPT <7 (95%), median MELD (8)

- Prior HCV treatment: 75%

● Up to 48 weeks of sofosbuvir 400 mg + RBV (1000-1200 mg) pre-transplant

● Primary endpoint: SVR12 post-liver transplant

- Strongest predictor: number of consecutive days with HCV RNA target not detected (odds ratio: 1.041; P<0.001)

Curry MP, et al. Hepatology. 2013;58(suppl 1):314A-315A. Abstract 213.

TND: target not detected.Post-transplant, immunosuppressive regimen: tacrolimus + prednisone + mycophenolate mofetil.

Patients

HCV RNA <LLOQ (%) At transplant (n=44) 12-weeks post-transplant (n=39)

9364

Median time of continuously TND prior to transplant (days) No HCV recurrence (n=28) HCV recurrence (n=10)

95.05.5

Discontinuations due to adverse events (%)

3

Selected adverse events (%) Fatigue Anemia Headache Nausea Rash

3823231615

Key Results

56

Sofosbuvir Compassionate Use Program:Recurrent HCV Following Liver Transplantation

● Patients with severe recurrent HCV infection following liver transplantation

- Fibrosing cholestatic hepatitis allowed

● Sofosbuvir 400 mg qd + RBV + pegIFN for up to 48 weeks

● Recommended time of clinical assessments

- On treatment: weeks 4, 12, 24, 36, and 48

- Follow-up: weeks 4, 12, and 24


Sofosbuvir

RBV(n=32)

PR(n=12)

Male (%) 66 83

Age (years) 56 57

Genotype (%) 1a/1b 2/3/4 Mixed

28/530/13/0

6

42/258/8/8

8

ASL/ALT (IU/L) 124/223 81/112

Bilirubin (mg/dL) 7.9 2.6

MELD score 16 13

Fibrosing cholestatic hepatitis (%)

47 33

Time from liver transplantation (months)

40 31

Baseline Characteristics

PR: pegIFN + RBV.

57

Sofosbuvir Compassionate Use Program:Initial Treatment Evaluations

● Overall, liver function tests significantly improved over time

● Most patients improved clinically or remained stable

- Improved:* 64%

- Stable: 11%

- Declined/deceased: 25%

● Treatment-related serious adverse events (3%)

● Deaths (25%) were mostly a result of disease progression in this very sick population


Pat

ien

ts (

%)

SVR Rates

69%

57%

74%

60%

Overall(n=36/28)

Sofosbuvir + RBV

(n=27/20)

SVR4SVR12

Sofosbuvir + PR

(n=9/8)

56%50%

PR: pegIFN + RBV.*Improved: improvement in decompensation events (ie, significant decrease in hepatitic encephalopathy episodes, improvement or disappearance of ascites, and improvement in liver-related laboratory values.

58

Program Overview





• DAA + PR




59

Korean Cohort: Impact of Entecavir and Lamivudine on Survival in HBV (1999-2011)

● Single-center cohort of chronic HBV (n=9615 treatment-naïve)

- Entecavir 0.5 mg/day or lamivudine 100 mg/day

- >20 years of age; no prior HCC, transplant, HCV, HDV, or HIV; HBV DNA >2000 IU/mL

● Treatment with entecavir was associated with

- Minimal risk of drug resistance 1.5% verus 50.8%; P<0.001)

- Minimal need for rescue therapy (1.8% verus 39.3%; P<0.001)

- Significantly lower risk of death or transplantation (adjusted hazard ratio 0.42; P<0.001)

Lim Y, et al. Hepatology. 2013;58(suppl 1):223A. Abstract 32.

Cu

mu

lati

ve R

ates

(%

)

Years

Death or Transplantation(Propensity-Score-Matched)

Solid lines: cirrhoticsDotted lines: no cirrhosis

0 1 2 3 4 5 6

HR: 0.66P=0.005

Entecavir

Lamivudine

Lamivudine

Entecavir

HR: 1.10P=0.81

60

HCC Risk in Caucasian Chronic HBV Patients Treated With Entecavir or Tenofovir DF

● Multi-country cohort (Greece, Itlay, Turkey, Spain, The Netherlands) (n=1231)

- Chronic HBV with no co-infection, liver transplantation, or HCC

- Initiated either entecavir (43%) or tenofovir DF (55%)

● HCC 5-year incidence

- 4.2% at median of 17 months

- 13.5 new HCC cases/1000 person-years

● Strongest HCC risk factors

- Decompensated liver disease (HR: 2.78; P=0.019), lower platelet count (HR: 0.97; P=0.002), older age (HR: 1.05; P=0.12)

● Asian-based HCC risk scores may not be applicable to Caucasians with chronic HBV

Papatheodoridis GV, et al. Hepatology. 2013;58(suppl 1):302A-303A. Abstract 190.

Cu

mu

lati

ve P

rob

abil

ity

Time Since Initiation of Treatment (Years)

Probability of HCC

Log-Rank P<0.001.

0 1 2 3 4 5

20.9%

DecompensatedCirrhosis 29.7%

No Cirrhosis2.5%

Cirrhosis

61

Study 103 and 102: 7-Year Tenofovir DF Treatment for Patients With Chronic HBV

Marcellin P, et al. Hepatology. 2013;58(suppl 1):649A. Abstract 926.

48 WeeksDouble-Blind

Study 103* HBeAg-Positive Treatment-Naïve

Study 102* HBeAg-Negative

Lamivudine naïve or experienced

Tenofovir DF 300 mg

Adefovir 10 mg

Week 0 48 72 † 96 192 384

Randomization2:1

7 YearsOpen-Label

Tenofovir DF 300 mg

Tenofovir DF 300 mg

LiverBiopsy

CurrentAnalysis

*Pretreatment liver biopsy. Other eligibility criteria: age 18-69 years, compensated liver disease, HBV DNA >106 copies/mL, ALT >2 x ULN and <10 x ULN, Knodell necroinflammatory score >3, seronegative for HIV, HDV, and HCV. †If HBV DNA >400 copies/mL, option to add emtricitabine to tenofovir DF in a fixed-dose tablet.

62

Study 102 and 103: Virologic and Biochemical Suppression at Year 7


HBV DNA<400 copies/mL

(n=348/247)

Pat

ien

ts (

%)

HBeAg- (Study 102)HBeAg+ (Study 103)

1%

12%

77%

65%

HBsAg Loss(n=348/247)

ITT: missing=failure.

ALT Normalization(n=325/241)

60%

47%

63

Study 102 and 103: Virologic and Biochemical Suppression at Year 7

● No resistance to tenofovir DF was detect

● Virologic breakthrough was rare (<1.0%)

- Attributed to documented non-adherence in the majority of cases

● Tenofovir DF was well tolerated

- 75% of patients entering open-label phase remained on study at year 7

- Discontinuations due to adverse events: 2.2%

- Renal events were rare: 1.7%

- No evidence of bone loss over 3 years of follow-up


64

HBV Reactivation FollowingRituximab-Containing Chemotherapy

● Single-center cohort with a variety of hematologic diagnoses (n=62) (2011-2013)

- HBsAg negative, anti-HBc positive

- HBV DNA <10 IU/mL

- No concomitant liver disease or prior HBV treatment

- Reactivation: HBV DNA >10 IU/mL regardless of HBsAg status

- Follow-up: 36.6 months

● High rate of reactivation- Majority occurred within the first 6

months (86.7%)

- Presence of low anti-HBs levels was not protective against HBV reactivation

Seto W, et al. Hepatology. 2013;58(suppl 1):224A. Abstract 34.

Pro

bab

ilit

y o

f H

BV

Rea

ctiv

ati

on

(%

)

Months

Cumulative Rate ofHBV Reactivation

9-Month CumulativeRate: 29.3%

0 12 24 36 48 60 72 84 96

Documents

Post Conference Update 64 th Annual Meeting of the American Association for the Study of Liver Diseases Sponsored for CME credit by Rush University Medical