Edited byMorris Sherman MD BCh PhD FRCP(C)

Associate Professor of MedicineUniversity of Toronto

Protease Inhibitors in Chronic Hepatitis C:An Update

Chapter 4 – Case Study: Treatment Naive

November 2012

Case Study:

Treatment Naive

Edward Tam MD FRCPCMedical Director

LAIR Centre

Ms. MH

31 year old female

Diagnosed in 2004 with genotype 1a HCV

Previous IVDU

Otherwise healthy

Meds: Milk thistle

No Biopsy

ALT 1-2 x ULN on serial monitoring

Ms. MH

Followed periodically with monitoring of liver biochemistry

FibroScan December 9, 2010: 4.9 kPa What evidence supports the use of Milk Thistle? Is FibroScan a reliable and accurate tool for fibrosis

assessment? Does it represent a viable alternative to liver biopsy?

FibroScan versus Liver Biopsy

Myers RP et al. Can J Gastroenterol. 2010 Nov;24(11):661-70

1.00

0.75

0.50

0.25

0.000.250.00 0.50 0.75 1.00

Sen

sitiv

ity

1-Specificity

AUROC (95% CI)≥ F2: 0.74 (0.68-0.80)≥ F3: 0.89 (0.84-0.94) F4: 0.94 (0.90-0.97)

Ms. MH

FibroScan December 9, 2010: 4.9 kPa (consistent with stage 0 – 1 fibrosis)

Discussions with patient throughout 2011 regarding therapy

Although no medical urgency, very keen to pursue therapy for personal reasons

Ms. MH

January 6, 2012, treatment initiated with pegylated interferon alpha-2b (120mcg) plus ribavirin (500mg BID), as planned lead-in to boceprevir-based treatment.

Week 0

HCV RNA 5.29 logs

ALT 106

Hb 144

Plts 295

Neutrophils 6.0

Ms. MH: Week 4 Results

Week 0 Wk 2 Wk 4

HCV RNA 5.29 logs -- Undetectable

ALT 106 53 33

Hb 144 120 108

Plts 295 236 214

Neutrophils 6.0 2.0 2.0

Given the undetectable HCV RNA at the end of WK4 lead-in (dual therapy), is adding Boceprevir necessary?

Significance of Lead-in Response

Vierling et al. EASL 2011.

SPRINT-2: SVR based on degree of early interferon response(log decline in HCV RNA at week 4 of P/R in all patients (cohort 1 + cohort 2)

30

43

60

72 74

89 90 90

<0.5

0.5-

<1.0

1.0-

<1.5

1.5-

<2.0

2.0-

<3.0

3.0-

<4.0

≥4.0

Unde

tect

able

28 28

7065

8089 89 89

<0.5

0.5-

<1.0

1.0-

<1.5

1.5-

<2.0

2.0-

<3.0

3.0-

<4.0

≥4.0

Unde

tect

able

05

21

33

45

58

7997

0

20

40

60

80

100

<0.5

0.5-

<1.0

1.0-

<1.5

1.5-

<2.0

2.0-

<3.0

3.0-

<4.0

≥4.0

Unde

tect

able

PR48 BOC RGT BOC/PR48

Log10 viral load decrease after weeks of P/R lead-in

% o

f pat

ient

s w

ith S

VR

Results Through Week 12

Wk 4 Wk 6 Wk 8 Wk 10 Wk 12HCV RNA Undetectable -- Undetectable -- Undetectable

ALT 33 27 26 22 28

Hb 108 107 101 91 94

Plts 214 179 177 175 174

Neutrophils 2.0 1.3 1.6 1.2 1.2

Boceprevir added with 5th interferon injection HCV RNA remains undetectable Due to worsening anemia and fatigue, RBV dose

reduced to 600mg total daily dose after wk 10 results

Results Through Week 24

Wk 12 Wk 16 Wk 20 Wk 24HCV RNA Undetectable -- -- Undetectable

ALT 28 32 25 24

Hb 94 105 101 103

Plts 174 171 164 169

Neutrophils 1.2 1.4 1.0 1.0

HCV RNA remained undetectable through week 24, and patient qualifies for shortened duration therapy (to D/C at week 28)

The Canadian Liver Foundation (CLF) was the first organization in the world devoted to providing support for research and education into the causes, diagnoses, prevention and treatment of all liver disease. Through its chapters across the country, the CLF strives to promote liver health, improve public awareness and understanding of liver disease,

raise funds for research and provide support to individuals affected by liver disease.

For more information visit www.liver.ca or call 1-800-563-5483.

This project made possible through the financial support of Merck Canada Inc. The views, information and opinions contained herein are those of the authors and do not necessarily reflect the views and opinions of Merck Canada Inc.

The Canadian Liver Foundation gratefully acknowledges the participating health care professionals for their contributions to this project and for their commitment to the liver health of Canadians.