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Treatment of HCV in Cirrhotic Patient
Mark Thursz
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Mrs LG - Presentation
• 48 year old Latvian woman• HCV diagnosed 2007 – symptoms of fatigue• Source of HCV unknown• No alcohol• No current medications• No significant past medical history
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Examination
• Generally well• Palmar erythema and spider naevi• 4cm hepatomegaly• No splenomegaly• No ascites• No oedema• No encephalopathy
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Initial investigations
• Hb – 12.2• WBC – 4.5 (Neutrophil 1.2)• Platelets – 75• AFP – 18.3• INR – 1.4• Albumin – 32• ALT – 73• Bilirubin 18• HCV RNA – 1,230,000 iu/ml• HCV Gt 1
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Ultrasound
• Irregular liver margin• Portal vein patent, diameter 17mm• No focal lesion• Spleen – 17.5 cm
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Biopsy or not?
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Biopsy or not?
Fibroscan 38.5 kPa
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OGD
• Small varices• Propranolol 40mg tds
• Not tolerated
• Carvidolol 25 mg od
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Summary
• 48 year old woman• HCV cirrhosis (Child-Pugh A)• Portal hypertension• Low platelets and neutrophils
• Treat now?
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Treatment
Pegylated interferon a2a 180 ug o.w.
Ribavirin 600 mg b.d
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Progress
0 10 20 30 40 50 60 70 800
10
20
30
40
50
60
70
80
0
1
2
3
4
5
6
7
Hb Platelets HCV RNA Neutrophils
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Case Review
• 49 year old woman• HCV Gt 1 • Relapse Responder• Portal hypertension• Low platelets• Low neutrophils
• Options• Triple therapy• Await transplantation
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0 10 20 30 40 50 60 70 800
10
20
30
40
50
60
70
0
1
2
3
4
5
6
7
Hb Platelets HCV RNA Neutrophils
Option 2
Telaprevir
Pegasys
Ribavirin
Sinusitis Transfusion
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Follow-up
• USS every 6 Months• ? Biopsy in 5 years
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Issues
Prognosis with decompensated cirrhosis – HCV
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
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Progression of Disease in HCV
7.7% 6.3%
8.1 – 54.5%
9.9 – 20%
3.7%
Alazawi. APT 2010
4.6%
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Survival in Decompensated HCV Cirrhosis
Fattovich Gastro 1997
5 yr Survival - 50%
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Issues
Prognosis with decompensated cirrhosis
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
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Treatment of HCV Cirrhosis Prevents Decompensation
Bruno Hepatology 2007
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Treatment of HCV Cirrhosis Reduces the Risk of HCC
Bruno Hepatology 2007
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HCV Decompensated Cirrhosis Trials
Study Design Exclusions No Discontinue SVR
Crippin 2002
RCT CytopaeniasRenal impairment
15 100% 0%
Thomas 2003
Prospective observational
Cytopaenias 20 0 60%
Forns 2003
Prospective observational
CytopaeniasRenal impairmentEncephalopathy
30 20% 30%
Everson Prospective observational
AscitesRenal impairmentNon-responders
124 13% GT1 – 13%GT2/3 – 46%
Iacobellis 2007
Prospective controlled
Rapid deterioration 66 20% GT1/4 – 7%GT3/4 44%
Iacobellis 2009
Prospective observational
Rapid deteriorationRenal impairment
94 19% GT1/4 – 16%GT3/4 57%
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Treatment of Decompensated HCV Cirrhosis
Everson Hepatology 2005
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Virological Outcomes According to Child’s Pugh Grade
A B C
EOTR Gt 1 35% 28% 21%
EOTR Gt non-1 75% 77% 52%
SVR Gt1 13% 16% 7%
SVR Gt non-1 56% 38% 56%
Everson Hepatology 2005
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Issues
Prognosis with decompensated cirrhosis
Impact of intervention with HBV
Potential drawbacks of HBV treatment
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
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Adverse Events in HCV Treatment Groups
Adverse effect / Treatment discontinuation
Non-Cirrhotics Compensated Cirrhotics
Decompensated Cirrhotics
Fatigue 55% 34% 59%
Headache 50% 54% 45%
Impaired concentration
17% 6% 2%
Infection 2% 0% 4%
Anaemia 15% 35% 50%
Neutropaenia 6% 38% 53%
Thrombocytopaenia
17% 24% 50%
Dose reductions 27% 30% 42%
Discontinuation 13% 12% 20%
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Issues
Prognosis with decompensated cirrhosis
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
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Everson Hepatology 2005
Reinfection post transplant
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Gane NEJM 1996
Outcome of HCV Post-Transplant
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Summary
Decompensated viral-cirrhosis has a poor prognosis
In HBV infection decompensation can be reversed with minimal side effects
In HCV infection treatment is challenging but the rewards are worth the effort
Decompensated cirrhotics cannot wait for IFN-free regimens
Eliminating HCV prior to transplantation will improve the prognosis
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HCV Therapy Post-Transplant
Vezali Clinical Therapeutics 2010