Treatment of HCV in Cirrhotic Patient Mark Thursz.

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

10

20

30

40

50

60

70

80

0

1

2

3

4

5

6

7

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

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

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




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


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


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%


Issues


Impact of intervention with HBV

Potential drawbacks of HBV treatment




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






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

Treatment of HCV in Cirrhotic Patient Mark Thursz.

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