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Hepatitis C: Simplifying the Cure and the Role of the Nurse Practitioner in Treatment

Texas  Medical  Center  

Saira Khaderi, MD September 26, 2015

CHI Baylor St. Luke’s Medical Center Texas Nurse Practitioners’ 27th Annual

Conference

Educational Objectives

•  Describe the detrimental effects of chronic hepatitis C virus (HCV)

•  Review the diagnosis of HCV and screening guidelines

•  Describe current treatment options

•  Recognize the role of tele-mentoring in treating hepatitis C

Question One

Approximately how many people are affected with chronic hepatitis C in the United States? a.  200,000 b.  1,000,000 c.  3,000,000 d.  7,000,000

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USA – People with Chronic HCV

Num

ber o

f HC

V C

ases

(mill

ions

)

3.2

NHANES Estimate

1.9

HCV Cases Not Included in NHANES*

3.8

5.2

7.1 Conservative estimate Upper limit of estimate

Estimated Total HCV Cases

*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).

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

Question Two

What percentage of patients with chronic hepatitis C are aware of their diagnosis? a.  75% b.  50% c.  25%

HCV–Infected  Persons  in  the  USA  EsBmated  Rates  of  DetecBon,  Referral  to  Care,  

and  Treatment  

Holmberg SD et al. N Engl J Med 2013;368:1859-1861

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Why to Treat

•  Hepatitis C is a hepatotropic virus with numerous effects on health

– Leading cause of cirrhosis

– Leading indication for liver transplantation

– Leading cause of hepatocellular carcinoma

– Many other health effects including non-hepatic death

Annual Prevalence Rates Between 1996 and 2006 Among HCV-Infected Veterans

Progressive Increase in Incidence of HCV-Related Cirrhosis and HCC in US

El-Serag HB. Gastroenterology 2012;142:1264–1273.

Question Three

Hepatitis C is a curable disease. a.  True b.  False

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HCV Can Now Be Cured in Most Patients

•  HCV infection is a curable disease •  What does cure mean?

– Undetectable HCV RNA 12 weeks after completing antiviral therapy

– SVR12 is almost always durable

Ghany MG, et al. Hepatology. 2009;49(4):1335-1374.

Baseline factors significantly associated with all-cause mortality: •  Older age •  GT 3 (2-fold increase

in mortality and HCC)

•  Higher Ishak fibrosis score

•  Diabetes •  Severe alcohol use

SVR patients Non-SVR patients

10-y

ear c

umul

ativ

e oc

curr

ence

rate

(%

)

8.9

26.0

1.9

27.4

5.1

21.8

2.1

29.9

25

20

15

10

5

0

30

All-cause mortality

Liver-related mortality or

liver transplant

HCC Liver failure

530 patients followed for a median of 8.4 years

Van der Meer A, et al. JAMA 2012; 308:2584‒2593.

SVR and All-cause Mortality in CHC Patients with Advanced Fibrosis

Achieving SVR Was Associated With Reduction in the Risk of HCC

Saleem J et al, AASLD 2014; Abstract #44

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Achieving SVR Was Associated With a Reduction in the Risk of Liver Transplantation

Saleem J et al, AASLD 2014; Abstract #44

Question Four

Which of the following is NOT a risk factor for hepatitis C? a.  Intranasal drug use b.  Incarceration c.  Adults born between 1945 and 1965 d.  None of the above

2013  Updated  USPSTF  HCV  Screening  RecommendaBons  

•  Most  important  risk  –  past  or  current  injecBon  drug  use  •  AddiBonal  risk  factors  include:    

– Receiving  a  blood  transfusion  before  1992 – Long-­‐term  hemodialysis – Being  born  to  an  HCV-­‐infected  mother –  IncarceraBon –  Intranasal  drug  use – GeXng  an  unregulated  taYoo,  etc. – Adults  born  between  1945  –  1965  –  “Baby  Boomers”  

*Grade  B  recommendaBon  for  persons  at  high  risk  for  infecBon  and  adults  born  between  1945  and  1965.  Moyer  VA;  on  behalf  of  the  USPSTF.  Ann  Intern  Med.  2013  Jun  11.  [Epub  ahead  of  print].  

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How to Test for HCV

•  Screening – AnB-­‐HCV

•  ConfirmaBon – HCV  viral  load

•  Treatment  decision – Genotype – Prior  treatment – Cirrhosis

Question Five

What is the most common HCV genotype in the United States? a.  1a b.  1b c.  2 d.  3

DistribuBon  of  HCV  Genotypes  in  the  US  

Zein  NN,  et  al.  Ann  Intern  Med.  1996;125:634-­‐639.  

•  Genotypes  1a  and  1b  account  for  79% •  Genotype  2  accounts  for  15%  

1a  58%  1b  

21%  

2  15%  

3  5%  

4  1%  1%  

58%  21%  

15%  

5%  

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Multi-targeted Approach for Treatment: Approved Protease, Polymerase and NS5A Inhibitors

Adapted from McGovern B, Abu Dayyeh B, and Chung RT. Hepatology. 2008; 48:1700-12

Simeprevir (SMV) (protease inhibitor) + sofosbuvir (SOF) (nucleotide polymerase

inhibitor) (COSMOS study)

Multi-targeted Approach for Treatment: Approved Protease, Polymerase and NS5A Inhibitors

Simeprevir

Sofosbuvir

Adapted from McGovern B, Abu Dayyeh B, and Chung RT. Hepatology. 2008; 48:1700-12

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SOF/SMV +/- RBV: SVR12 in Treatment-Naïve and Prior Null Responders (COSMOS)

•  Pooled 12 and 24 week treatment arms

•  Pooled +/- RBV arms

90 94

0

25

50

75

100

20/21 72/80

SVR

12 (%

)

82/87 F0-F2 F3-F4

Lawitz E et al., Lancet, 2014, Vol 384, No. 9956, 1756-1765

86 85 89

84 92 89

85 87 83

90 82

93 87 86

0

25

50

75

100

Overall Cirrhotic Non-cirrhotic Genotype 1a Genotype 1b Naïve Experienced

without RBV with RBV

Adjusted* SVR4 for SOF/SMV±RBV (HCV TARGET)

*Adjusted for 5 characteristics including: cirrhosis status, genotype, treatment naïve/experienced, prior decompensation, and prior triple therapy failure Jensen D, et al. Abstract #45, AASLD 2014

SV

R4

(%)

Ledipasvir (LDV) (NS5A inhibitor) + sofosbuvir (SOF) (nucleotide

polymerase inhibitor)

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Multi-targeted Approach for Treatment: Approved Protease, Polymerase and NS5A Inhibitors

Sofosbuvir

Ledipasvir

Adapted from McGovern B, Abu Dayyeh B, and Chung RT. Hepatology. 2008; 48:1700-12

LDV/SOF + RBV for 12 vs 24 Weeks: SVR12 in GT 1 Treatment-naïve Patients (ION-1)

99 97 98 99

0

20

40

60

80

100

SVR

12 (%

)

179/  180

178/  184

181/  184

179/  181

12 Weeks 24 Weeks

LDV/SOF + RBV

LDV/SOF + RBV

LDV/SOF LDV/SOF

Non-cirrhotic Cirrhotic

94 100 94 100

0

20

40

60

80

100

32/  34

34/  34

31/  33

36/  36

LDV/SOF + RBV

LDV/SOF + RBV

LDV/SOF LDV/SOF

12 Weeks 24 Weeks

SVR

12 (%

)

Afdhal et al. N Eng J Med 2014;370:1889-98

LDV/SOF Lesson Learned:

For Treatment Naïve Patients, Presence/Absence of Cirrhosis Not Relevant For

Treatment Duration

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94. 93.1 95.4

0

20

40

60

80

100

p=0.70 p=0.30

8 Weeks 12 Weeks

LDV/SOF LDV/SOF LDV/SOF + RBV

201/216 202/215 206/216

SV

R12

(%)

p=0.52

LDV/SOF + RBV for 8 vs 12 Weeks: SVR12 in GT 1 Treatment-naïve Non-cirrhotic Patients (ION-3)

Error bars represent 95% confidence intervals. Kowdley KV et al. N Eng J Med 2014; 370:1879-88

GT 1 Treatment Naïve Non-Cirrhotics: Baseline Viral Load Defines Treatment Duration

LDV/SOF  8 Weeks  (N=215)

LDV/SOF  12 Weeks  (N=216)

SVR12 (Overall)

SVR12 (BL viral load <6M IU/mL)

94% (202/215)

97% (119/123)

96% (208/216)

96% (126/131)

Relapse Rates Overall

<6 M IU/mL >6 M IU/mL

5% (11/215)

2% (2/123) 10% (9/92)

1% (3/216)

2% (2/131) 1% (1/85)

LDV/SOF Lesson Learned:

LDV/SOF for 8 weeks can be considered in treatment-naïve patients without cirrhosis who have pre-treatment HCV RNA <6 million IU/mL

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LDV/SOF + RBV for 12 vs 24 Weeks: SVR12 in GT 1 Treatment-experienced Non-cirrhotic Patients (ION-2) (ITT)

95 100 99 99

0

20

40

60

80

100

SVR

12 (%

)

83/87 87/88

12 Weeks 24 Weeks

LDV/SOF + RBV LDV/SOF + RBV LDV/SOF LDV/SOF

Afdhal et al. N Engl J Med 2014;370:1483-93

89/89 85/86

LDV/SOF + RBV for 12 vs 24 Weeks: SVR12 in GT 1 Treatment-experienced Cirrhotic Patients (ION-2) (ITT)

86 82

100 100

0

20

40

60

80

100

SVR

12 (%

)

19/22 22/22

12 Weeks 24 Weeks

LDV/SOF + RBV LDV/SOF + RBV LDV/SOF LDV/SOF

Afdhal et al. N Engl J Med 2014;370:1483-93

18/22 22/22

LDV/SOF Lessons Learned:

Treatment Experienced Patients Without Cirrhosis 12 Week Treatment

Treatment Experienced Patients With Cirrhosis

24 Week Treatment

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LDV/SOF: Points To Consider

•  Renal disease – No dosage adjustment in patients with GFR >30 – No safety/efficacy data for patients with ESRD

•  Severe acid suppression decreases LDV absorption •  P-gp inducers (e.g., rifampin, St. John’s wort,

carbemazepine, phenobarbital) may significantly decrease LDV/SOF plasma concentrations

Paritaprevir/r (protease inhibitor/ritonavir) + ombitasvir (NS5A inhibitor) + dasabuvir

(non-nucleoside polymerase inhibitor) + RBV (PTV/RTV/OMV + DSV + RBV)

Multi-targeted Approach for Treatment: Approved Protease, Polymerase and NS5A Inhibitors

Paritaprevir

Dasabuvir

Ombitasvir

Adapted from McGovern B, Abu Dayyeh B, and Chung RT. Hepatology. 2008; 48:1700-12

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90 90 96 96

0

20

40

60

80

100

All Patients Treatment Naïve

SV

R12

(%)

Placebo Ribavirin

SVR12 in GT 1a Non-cirrhotic Patients Treated with PTV/RTV/OMV + DSV for 12 Weeks (+/- RBV) (SAPPHIRE-I and –II, PEARL-IV)

94 100 95

Relapse Partial Null

Prior PegIFN/RBV Response

p=0.004 p=0.006

182/ 202

569/ 593

182/ 202

403/ 420

47/ 50

36/ 36

83/ 87

Everson G, et al. Abstract #83, AASLD 2014

SVR12 in GT 1a Cirrhotic Patients Treated with PTV/RTV/OMV + DSV + RBV for 12 vs 24 Weeks (TURQUOISE-II)

89 92 93

100

80

95 95 100 100 93

0

20

40

60

80

100

All Patients Treatment Naïve Relapse Partial Responder Null Responder

SV

R12

(%)

12 weeks 24 weeks

p=0.08 p=0.73 p=0.13

126/ 142

115/ 121

61/ 66

53/ 56

14/ 15

13/ 13

11/ 11

10/ 10

40/ 50

39/ 42

Prior PegIFN/RBV Response Everson G, et al. Abstract #83, AASLD 2014

GT 1a patients without cirrhosis benefit from RBV inclusion in 12 week treatment

regimen

GT 1a patients with cirrhosis benefit from a 24 week treatment duration

PTV/RTV/OMV + DSV Lessons Learned

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100 100 100 100 100 98.3 98.9 98.5 98.1 95.6

0.

25.

50.

75.

100.

Overall Treatment naive Relapse Partial response

Null response

SVR12 in GT 1b Non-cirrhotic Patients Treated with PTV/RTV/OMV + DSV for 12 Weeks (+/- RBV)

•  Pooled analysis of Phase 3 trials

SV

R12

(%)

Treatment-experienced *Includes 1 treatment-naive G1b pt who was enrolled in PEARL-IV study

*

301 /301

562 /572

210 /210

357 /361

33 /33

67 /68

26 /26

52 /53

32 /32

86 /90

Colombo M, et al. AASLD 2014, Boston. #1931

+ RBV - RBV

99 100 100 86

100 100 100 100 100 100

0

25

50

75

100

Overall Treatment naive Relapse Partial Null

SV

R12

(%)

Treatment-experienced

67 /68

51 /51

22 /22

18 /18

14 /14

10 /10

6 /7

3 /3

25 /25

20 /20

SVR12 in GT 1b Cirrhotic Patients Treated with PTV/RTV/OMV + DSV + RBV for 12 vs 24 Weeks

•  Pooled analysis of Phase 3 trials •  All treated with RBV

Colombo M, et al. AASLD 2014, Boston. #1931

12 Weeks 24 Weeks

Presence/Absence of Cirrhosis Not Relevant For Treatment Duration

GT 1b patients require only 12 weeks of

treatment (without ribavirin)

PTV/RTV/OMV + DSV Lessons Learned

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PTV/RTV/OMV + DSV: Points to Consider

•  No dosage adjustment for patients with renal impairment1

•  Drug interactions – Gemfibrozil, rifampin, St. John’s wort, lovastatin,

simvastatin, efavirenz – Stop Ethinyl estradiol-containing medications (5ALT) – Rosuvastatin (10 mg/day) and pravastatin (40 mg/day)

•  Omeprazole: Decreased efficacy of omeprazole

1Khatri A et al., AASLD 2014. Abstract 238

Daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide polymerase inhibitor)

(DCV/SOF)

Multi-targeted Approach for Treatment: Approved Protease, Polymerase and NS5A Inhibitors

Sofosbuvir

Adapted from McGovern B, Abu Dayyeh B, and Chung RT. Hepatology. 2008; 48:1700-12

Daclatasvir

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DCV/SOF + RBV for 12 vs 24 Weeks: SVR12 in GT 1 Patients

0

20

40

60

80

100 100

SVR

12 (%

)

40/41 39/41 14/14 21/21 15/15 19/20

98 95 100 100 95

Treatment Naive Prior PI/PEG/RBV Failures

12 Weeks 24 Weeks

DCV/SOF + RBV DCV/SOF + RBV DCV/SOF DCV/SOF

Sulkowski MS et al., N Engl J Med 2014;370: 211-21

DCV/SOF Lessons Learned:

Patients Without Cirrhosis 12 Week Treatment

Treatment Experienced Patients With Cirrhosis 24 Week Treatment with our without ribavirin

Project ECHO

Extension  for  Community  Healthcare  Outcomes  

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Project ECHO

Extension  for  Community  Healthcare  Outcomes  

People  need  access  to  

specialty  care  for  their  

complex  health  condiBons.  

There  aren't  enough  specialists  to  treat  

everyone  who  needs  care,  especially  in  rural  

and  underserved  communiBes.  

ECHO  trains  primary  care  

clinicians  to  provide  specialty  care  services.  This  

means  more  people  can  get  the  care  

they  need.  

PaBents  get  the  right  care,  in  the  right  place,  at  the  right  Bme.  This  

improves  outcomes  and  reduces  costs.  

Arora et al. NEJM, 2011"

Effectiveness"

§  >500 HCV Telehealth Clinics "§  >5,000 patients entered HCV treatment "§  27,000 CMEs/CEUs issued – no cost to providers"

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Baylor St. Luke’s Medical Center Project ECHO Clinics

•  Current Clinics –  Hepatitis C –  Hepatitis B –  Advanced Liver

Disease –  Infectious Diseases –  Cardiology

•  Upcoming Clinics –  VAD/Heart

Transplant Medical Review Board

–  Rheumatology –  Behavioral Health –  Pulmonary –  Nephrology

Project ECHO Team