Efficacy and cost-effectiveness of universal prophylaxis and pre-emptive treatment of CMV infection following liver transplantation

1. Efficacy and Cost-Effectiveness
of Universal Prophylaxis and
Pre-emptive Treatment of CMV
Infection following Liver
Transplantation.
RWL Leong, DW Smith, AW Mitchell,
DI Heath, AK House, GP Jeffrey
WA Liver Transplantation Service

2. Post Transplant Infection
• Immunosuppression
• Cytomegalovirus
– ubiquitous intacellular virus
– most common opportunistic infection
– morbidity and mortality

3. CMV Infection and Disease
• Infection: 23 – 85%
• Disease: 15 – 40%
– mononucleosis syndrome
– pneumonitis
– colitis
– hepatitis

4. CMV Infection and Disease
• Indirect
– bacterial and fungal infections
– hepatitis C virus recurrence
– acute allograft rejection
– chronic allograft rejection
– hepatic artery thrombosis
– higher transplantation cost

5. Reduce the Impact of CMV
Prophylaxis
prevention
- universal vs high risk
Preemptive regular surveillance
Treatment

6. CMV Prophylaxis
• No consensus on the necessity and efficacy
of CMV prophylaxis
Couchoud. Cochrane Database 2000

7. WA Liver Transplantation Service
• Universal prophylaxis
– oral aciclovir (pre 1999)
– oral ganciclovir (1999 onwards)
• High risk: D+/R-, anti-lymphocyte Ab
– IV ganciclovir
• Preemptive therapy: CMV PCR (whole blood, plasma)
– IV ganciclovir
• Treatment
– IV ganciclovir

8. Aims
• Assess the incidence and outcomes of CMV
infection and disease
• Compare the efficacy of ACV & GCV
• Cost analysis of universal prophylaxis &
preemptive therapy

9. Methods
• Single centre
– retrospective analysis
– open comparative
– OLT 1992 – 2000
– exclude graft survival <30d

10. Results
• 95 OLT, 89 recipients
– excluded 12 OLT
– 53M, 36F, mean age 49 years
– median duration prophylaxis: 4 months
– median follow up: 37 months
– ACV n = 55
– GCV n = 24
– No prophylaxis n = 4

11. Seroprevalence
0
5
10
15
20
25
30
35
40
45
50
Aciclovir Ganciclovir No
Prophylaxis
Total n = 83
D+/R+
D+/R-
D-/R+
D-/R-
Prophylaxis
Patients
CMV
Serology
88% Recipients are CMV +ve
65% Donors are CMV +ve

12. CMV- Free Survival
100
80
60
40
20
0
1.0
.8
.6
.4
.2
D–/ R–
D–/ R+
D+/ R+
D+/ R–
Log-rank
P=0.0023
Time (months)
CMV-Free
Cumulative
Survival

13. 100
80
60
40
20
0
1.0
.9
.8
.7
.6
.5
.4
CMV- Free Survival
Ganciclovir
Aciclovir
No prophylaxis
CMV-Free
Cumulative
Survival
Time (months)
Log-rank
ns

14. CMV Infection
No
prophylaxis
Aciclovir Ganciclovir
Incidence
1/4
(25%)
10/55
(18%)
2/24
(8%)
Absolute Risk
Reduction
- 7% 17%
Relative Risk
Reduction
- 27% 67%
Number need
to treat
- 14.7 6.0

15. CMV Infection
• Preemptive therapy:
– IV GCV
– none developed CMV disease

16. CMV Disease
No
prophylaxis
Aciclovir Ganciclovir
Incidence
1/4
(25%)
4/55
(7%)
1/24
(4%)
Absolute Risk
Reduction
- 18% 21%
Relative Risk
Reduction
- 71% 83%
Number need
to treat
- 5.6 4.8

17. CMV Disease
• CMV disease: 2 mononucleosis, 2 colitis, 1
hepatitis, 1 pneumonitis (OKT3)
• no deaths

18. Adverse Effects
• Adverse effects: GCV, ACV Prophylaxis
– Well tolerated, no serious adverse effects
– 1 thrombocytopenia, 2 nausea, 1 malaise
– No GCV resistance
– No requirement for second-line therapy

19. Cost Analysis
Ganciclovir
Treatment of CMV disease
Preemptive therapy
Total
Cost per patient
Universal Prophylaxis
No Prophylaxis
$840,000
$0
$66,800
$417,000
$89,600
$280,000
$996,400
$697,500
Difference +$2,989
$9,960
$6,970
100 simulated
patients; in AUD

20. Cost Analysis
• Immunosuppression: 1 year
– Cyclosporin: $11,000
– Azathioprine: $3,500

21. Conclusion
• GCV reduces incidence CMV infection and
disease
• Treat 5 patients with GCV to prevent 1
CMV disease
• Additional cost $3,000 per patient