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

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 Myers RP et al. Can J Gastroenterol Nov;24(11): Sensitivity 1-Specificity AUROC (95% CI) ≥ F2:0.74 ( ) ≥ F3:0.89 ( ) F4:0.94 ( )

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 RNA5.29 logs ALT106 Hb144 Plts295 Neutrophils6.0

Ms. MH: Week 4 Results Week 0Wk 2Wk 4 HCV RNA5.29 logs--Undetectable ALT Hb Plts Neutrophils 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 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) < < < < < <4.0 ≥4.0 Undetectable < < < < < <4.0 ≥4.0 Undetectable < < < < < <4.0 ≥4.0 Undetectable PR48BOC RGTBOC/PR48 Log 10 viral load decrease after weeks of P/R lead-in % of patients with SVR

Results Through Week 12 Wk 4Wk 6Wk 8Wk 10Wk 12 HCV RNAUndetectable--Undetectable--Undetectable ALT Hb Plts Neutrophils  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

Results Through Week 24 Wk 12Wk 16Wk 20Wk 24 HCV RNAUndetectable-- Undetectable ALT Hb Plts Neutrophils  HCV RNA remained undetectable through week 24, and patient qualifies for shortened duration therapy (to D/C at week 28)

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