Protease Inhibitors in Chronic Hepatitis C:
An Update
Chapter 4 – Case Study: Treatment Naive
Edited by
Morris Sherman MD BCh PhD FRCP(C)
Associate Professor of Medicine
University of Toronto
November 2012
Case Study:
Treatment Naive
Edward Tam MD FRCPC
Medical 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
1.00
Sensitivity
0.75
0.50
AUROC (95% CI)
≥ F2: 0.74 (0.68-0.80)
≥ F3: 0.89 (0.84-0.94)
F4: 0.94 (0.90-0.97)
0.25
0.00
0.00
0.25
0.50
0.75
1.00
1-Specificity
Myers RP et al. Can J Gastroenterol. 2010 Nov;24(11):661-70
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
5.29 logs
--
Undetectable
ALT
106
53
33
Hb
144
120
108
Plts
295
236
214
Neutrophils
6.0
2.0
2.0
HCV RNA
Given the undetectable HCV RNA at the end of WK4 lead-in
(dual therapy), is adding Boceprevir necessary?
Significance of Lead-in Response
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)
PR48
BOC RGT
100
% of patients with SVR
89 90 90
89 89 89
97
80
79
80
BOC/PR48
70
72 74
65
60
58
60
45
40
33
43
28 28
30
21
20
0
0
5
Log10 viral load decrease after weeks of P/R lead-in
Vierling et al. EASL 2011.
Results Through Week 12
Wk 4
Wk 6
Wk 8
Wk 10
Wk 12
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
HCV RNA
 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 24
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
 HCV RNA remained undetectable through week 24, and
patient qualifies for shortened duration therapy (to D/C at
week 28)
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.
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.