1. Edited by Morris Sherman MD BCh PhD FRCP(C) Associate Professor of Medicine University of Toronto Protease Inhibitors in Chronic Hepatitis C: An Update Chapter 4 – Case Study: Treatment Naive November 2012

2. Case Study: Treatment Naive Edward Tam MD FRCPC Medical Director LAIR Centre

3. 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

4. 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?

5. 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 0.00 0.250.000.500.751.00 Sensitivity 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)

6. 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

7. 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 RNA5.29 logs ALT106 Hb144 Plts295 Neutrophils6.0

8. Ms. MH: Week 4 Results Week 0Wk 2Wk 4 HCV RNA5.29 logs--Undetectable ALT1065333 Hb144120108 Plts295236214 Neutrophils6.02.0 Given the undetectable HCV RNA at the end of WK4 lead-in (dual therapy), is adding Boceprevir necessary?

9. 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 <0.5 0.5-<1.01.0-<1.51.5-<2.02.0-<3.0 3.0-<4.0 ≥4.0 Undetectable 28 70 65 80 89 <0.5 0.5-<1.01.0-<1.51.5-<2.02.0-<3.03.0-<4.0 ≥4.0 Undetectable 0 5 21 33 45 58 79 97 0 20 40 60 80 100 <0.5 0.5-<1.01.0-<1.51.5-<2.0 2.0-<3.03.0-<4.0 ≥4.0 Undetectable PR48BOC RGTBOC/PR48 Log 10 viral load decrease after weeks of P/R lead-in % of patients with SVR

10. Results Through Week 12 Wk 4Wk 6Wk 8Wk 10Wk 12 HCV RNAUndetectable--Undetectable--Undetectable ALT3327262228 Hb1081071019194 Plts214179177175174 Neutrophils2.01.31.61.2  Boceprevir added with 5 th interferon injection  HCV RNA remains undetectable  Due to worsening anemia and fatigue, RBV dose reduced to 600mg total daily dose after wk 10 results

11. Results Through Week 24 Wk 12Wk 16Wk 20Wk 24 HCV RNAUndetectable-- Undetectable ALT28322524 Hb94105101103 Plts174171164169 Neutrophils1.21.41.0  HCV RNA remained undetectable through week 24, and patient qualifies for shortened duration therapy (to D/C at week 28)

12. 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.www.liver.ca 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.