treatment of hcv in cirrhotic patient mark thursz
TRANSCRIPT
Treatment of HCV in Cirrhotic Patient
Mark Thursz
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
Examination
• Generally well• Palmar erythema and spider naevi• 4cm hepatomegaly• No splenomegaly• No ascites• No oedema• No encephalopathy
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
Ultrasound
• Irregular liver margin• Portal vein patent, diameter 17mm• No focal lesion• Spleen – 17.5 cm
Biopsy or not?
Biopsy or not?
Fibroscan 38.5 kPa
OGD
• Small varices• Propranolol 40mg tds
• Not tolerated
• Carvidolol 25 mg od
Summary
• 48 year old woman• HCV cirrhosis (Child-Pugh A)• Portal hypertension• Low platelets and neutrophils
• Treat now?
Treatment
Pegylated interferon a2a 180 ug o.w.
Ribavirin 600 mg b.d
Progress
0 10 20 30 40 50 60 70 800
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Hb Platelets HCV RNA Neutrophils
Case Review
• 49 year old woman• HCV Gt 1 • Relapse Responder• Portal hypertension• Low platelets• Low neutrophils
• Options• Triple therapy• Await transplantation
0 10 20 30 40 50 60 70 800
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20
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70
0
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Hb Platelets HCV RNA Neutrophils
Option 2
Telaprevir
Pegasys
Ribavirin
Sinusitis Transfusion
Follow-up
• USS every 6 Months• ? Biopsy in 5 years
Issues
Prognosis with decompensated cirrhosis – HCV
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
Progression of Disease in HCV
7.7% 6.3%
8.1 – 54.5%
9.9 – 20%
3.7%
Alazawi. APT 2010
4.6%
Survival in Decompensated HCV Cirrhosis
Fattovich Gastro 1997
5 yr Survival - 50%
Issues
Prognosis with decompensated cirrhosis
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
Treatment of HCV Cirrhosis Prevents Decompensation
Bruno Hepatology 2007
Treatment of HCV Cirrhosis Reduces the Risk of HCC
Bruno Hepatology 2007
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%
Treatment of Decompensated HCV Cirrhosis
Everson Hepatology 2005
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
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
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%
Issues
Prognosis with decompensated cirrhosis
Impact of intervention with HCV
Potential drawbacks of HCV treatment
Benefits of treatment before transplant
Everson Hepatology 2005
Reinfection post transplant
Gane NEJM 1996
Outcome of HCV Post-Transplant
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
HCV Therapy Post-Transplant
Vezali Clinical Therapeutics 2010