edited by morris sherman md bch phd frcp(c) associate professor of medicine
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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 5 – Case Study: Cirrhosis. November 2012. Case Study: Cirrhosis. Nir Hilzenrat, MD - PowerPoint PPT PresentationTRANSCRIPT
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Edited byMorris Sherman MD BCh PhD FRCP(C)
Associate Professor of MedicineUniversity of Toronto
Protease Inhibitors in Chronic Hepatitis C:An Update
Chapter 5 – Case Study: Cirrhosis
November 2012
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Case Study:
Cirrhosis
Nir Hilzenrat, MDGastrointestinal Division, Department of Medicine,
SMBD- Jewish General Hospital,Associate Professor of Medicine,
McGill University, Montreal, Quebec
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Case History
58 year old woman, acquired hepatitis C from blood transfusion 30 years prior
Symptoms – mild fatigue and depression ALT 2xULN Synthetic function normal Viral load 3x105 IU/mL Liver biopsy (2002)
F 3/4, activity 2/4
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Case History
Previous treatment in 2000 with pegylated interferon and ribavirin
< 1 log drop at week 12 Treatment discontinued
Treatment-related side effects Severe fatigue Fall in Hb level (148 g/L to 108 g/L).
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Comments
Previous treatment failures classified into Null responder
Viral load does not fall by 2 logs at week 12 Partial responder
Viral load falls by > 2 logs, but never negative Relapser
Viral load negative on therapy but positive after therapy
Telaprevir (REALIZE study ) response in null responders was 29% (21/72)
Boceprevir (PROVIDE study) response in null responders was 40% (19/47)
Zeuzem, S. et al. N Engl J Med 2011; 364: 2417-28Bronowicki, JP., International Liver Congress 2012, Abstract 204, EASL 2012
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Comments
Probability of response with F3 or F4 and prior treatment failure (48 weeks of therapy)
Telaprevir Boceprevir
% n % n
Relapser 87 48/55 83 15/18
Partial responder 34 11/32 46 6/13
Null responder 14 7/50 - -
Bruno,S., Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus Genotype-1 With Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies, Oral Presentation, EASL 2011
Vertex Pharmaceutical (Canada) Incorporated. Product Monograph: Incivek (Telaprevir tablets). http://pi.vrtx.com/files/canadapm_telaprevir_en.pdf (Accessed February 1, 2012)
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Case Continued
Patient made aware of low probability of cure (15-40%) However, she was willing to start treatment It was accepted that we will assess the continuity of the
treatment based on the response rate, i.e., HCV-RNA level, and the severity of adverse effect during the treatment
Fibroscan prior suggested cirrhosis ALT x 4 ULN Liver synthetic function normal Viral load 2.8x106 IU/ml
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Case Continued
Treatment was started with Peg INF/RIBA and boceprevir
At week 4 viral load decline was 0.8 logs
Question How important is the magnitude of the decline in viral
load following the lead-in phase (TW4) of the PR & BOC treatment?
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Importance of 4-Week HCV RNA in Boceprevir Triple Therapy
In RESPOND-2 likelihood of SVR for relapsers and partial-responders was associated with response to interferon in the lead-in phase
SVR in all patients SVR in F3/F4
< 1 log drop at wk 4 33% 14-25%
> 1 log drop at wk 4 73% 55-87%
Bruno,S., Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus Genotype-1 With Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies, Oral Presentation, EASL 2011
Bacon BR et al. N Engl J Med 2011;364:1207-17
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Comments
In the PROVIDE study, the SVR for null responders was 40%
Week 4 HCV RNA < 1 log decline from baseline SVR 36%
Week 4 HCV RNA >1 log decline from baseline SVR 55%
Bronowicki, JP., Sustained Virologic Response (SVR) in Prior PegInterferon/Ribavirin (PR) Treatment Failures After Retreatment with Boceprevir (BOC) + PR: PROVIDE Study Interim Results, International Liver Congress 2012, Abstract 204, EASL 2012
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Case Continued
The result was discussed with the patient.
She was made aware that the likelihood of achieving SVR is poor.
However, the patient asked to reassess the probability of her success rate after 4W of PR & BOC treatment, i.e., 8W of the whole treatment.
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Question
The HCV RNA at week 8 was undetectable
What is the likelihood of achieving SVR?
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Question
How long should she be treated for?
At week 12 and 24 the HCV RNA remained undetectable
Usual side effects, anemia, fatigue and depression
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Question
What are the recommended approaches for this patient (i.e. cirrhotic null responder to previous PR treatment) according to the American Association of the Study of Liver Diseases (AASLD) and Canadian Association of the Study of Liver Diseases (CASL) updated guidelines?
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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.