21th VHPB meeting on “Prevention of viral hepatitis in Italy: lessons learnt and the way forward”

Catania, 7-8 november 2002

RESIDUAL RISK OF RESIDUAL RISK OF

TRANSFUSION- TRANSMITTED TRANSFUSION- TRANSMITTED

HBV, HCV AND HIV INFECTIONSHBV, HCV AND HIV INFECTIONS

IN ITALY IN ITALY

A. ZanettiA. ZanettiInstitute of Virology, University of Milan (Italy) Institute of Virology, University of Milan (Italy)

BLOOD TRANSFUSION SAFETY:BLOOD TRANSFUSION SAFETY:

PREVENTION STRATEGIESPREVENTION STRATEGIES

• Selection of periodic, volunteer,

unremunerated donors

• Evaluation of medical and personal history

• Confidential unit exclusion

• Implementation of donors screening

• Viral inactivation

• Proper use of blood, blood components

and derivates

Residual risk of Residual risk of transfusion-transmitted viral infections transfusion-transmitted viral infections

(TTIs) (1)(TTIs) (1) Mostly related to the use of blood Mostly related to the use of blood

donated during the window period, in donated during the window period, in which an acutely infected donor may which an acutely infected donor may harbor infectious viral particles in the harbor infectious viral particles in the absence of symptoms and absence of symptoms and antigens/antibodiesantigens/antibodies

The probability of transmitting blood-The probability of transmitting blood-borne viruses through transfusion of borne viruses through transfusion of screened blood is related to the screened blood is related to the length of the pre-length of the pre-seroconversion window and to the seroconversion window and to the incidence of HBV, HCV, HIV infections incidence of HBV, HCV, HIV infections among donorsamong donors

Residual risk of TTIs (2)

The magnitude of residual risk may The magnitude of residual risk may differ within countries depending on:differ within countries depending on:

sensitivity of screening assayssensitivity of screening assays

levels of HBV, HCV and HIV endemicitylevels of HBV, HCV and HIV endemicity

Residual risk of TTIs (3)

In most industrialized countries, the In most industrialized countries, the rates of TTIs is so low to render rates of TTIs is so low to render impossible the measurement trhough impossible the measurement trhough specific studies.specific studies.

Mathematical models have been Mathematical models have been developed. developed.

Residual risk of Residual risk of transfusion-transmitted HBV, HCV, transfusion-transmitted HBV, HCV,

HIV by screened blood in ItalyHIV by screened blood in Italy

Aim of the study:Aim of the study:

To assess the risk of transmitting HBV, To assess the risk of transmitting HBV, HCV and HIV by transfusion of HCV and HIV by transfusion of screened blood;screened blood;

To estimate the additional reduction To estimate the additional reduction in risk that may be achieved through in risk that may be achieved through the implementation of direct viral the implementation of direct viral detection assays.detection assays.

Study populationStudy population

• SiteSite: Lombardy

• PeriodPeriod: January 1996 - December 2000

• N. records examined from periodic N. records examined from periodic

volunteer, unpaid donorsvolunteer, unpaid donors: 2,411,800

• Mean donors per yearMean donors per year: 223,500

• Donation indexDonation index: 2.1

• LaboratoryLaboratory: 3rd generation EIA

supplemental assays

The residual risk of HBV, HCV and HIV The residual risk of HBV, HCV and HIV

transmission through antibody-transmission through antibody-

screened blood, was calculated by screened blood, was calculated by

multiplying the adjusted incidence of multiplying the adjusted incidence of

seroconverting donors, expressed seroconverting donors, expressed

per 10per 1055 person/years of observation, person/years of observation,

by the mean lenghtby the mean lenght ** of the window of the window

period before seroconversion, period before seroconversion,

expressed as a year fraction.expressed as a year fraction.

Measurement of HBV, HCV, HIV Measurement of HBV, HCV, HIV residual riskresidual risk

** according to Busch.

Reduction of HBV, HCV, HIV Reduction of HBV, HCV, HIV Residual Risk by NAT Residual Risk by NAT

The yeild in reduction of transfusion-transmitted

HBV, HCV and HIV for the use of NAT in

combination with the existing serologic assays,

was calculated by multiplying the incidence rates

of seroconversion x 100,000 person-years by the

estimated reduction in the length of the

window-periods achieved with NAT and

expressed as the reduction in residual risk

per unit.

Estimated residual risk of transmitting HBV, Estimated residual risk of transmitting HBV, HCV, HIV by transfusion of screened HCV, HIV by transfusion of screened

blood in Italy (1996-2000) blood in Italy (1996-2000) Velati et al, Transfusion 2002Velati et al, Transfusion 2002

RResidual risk esidual risk Estimated Estimated donations +vedonations +ve (95% CI) (95% CI) during the window during the window phasephase x 10x 1066 donations donations (95%CI)(95%CI)

HCVHCV 1 : 126.528 7.9

(100.000-175.438) (5.7 – 10.0)

HBVHBV 1 : 90.000 11.0

(66.666-128.205) (7.8 – 14.9)

HIV HIV 1 : 434.782 2.3

(33.333-588.235) (1.7 – 3.0)

Estimated residual risks to the Estimated residual risks to the blood supply in Europe and in the blood supply in Europe and in the

USAUSA

0

2

4

6

8

10

12

14

16

18

11Couroucé (1996); Couroucé (1996); 22Schreiber (1996); Schreiber (1996); 33Allain (1997)Allain (1997)

15.8315.8322

6.926.9233

8.458.4511

13.5

HBV

15.015.033

9.79.722

4.484.4811

7.7

HCV

2.032.0322

1.751.7511

0.580.5833

2.2

LombardyLombardy

HIV

Cases per 10Cases per 1066 donations donations

Declining time to detection of HBV, HCV, HIV Declining time to detection of HBV, HCV, HIV markers during the window phase following infectionmarkers during the window phase following infection

Infection

HCV RNA HCV Ag

EIA 3.0

EIA 2.0

EIA 1.0

0 13 14 70 80 150 (days)

Infection

HIV RNA

p24 Ag

EIA 3.0

0 11 16 22 (days)

HCVHCV

HIVHIV

Infection

HBV DNA

EIA 3.0

0 41 56

HBVHBV

Estimated reduction of the residual risk of Estimated reduction of the residual risk of transfusion-transmitted HBV, HCV and HIV transfusion-transmitted HBV, HCV and HIV

by implementation of NAT by implementation of NAT

Estimated window Reduction Estimated Residual phase (days) % risk x 106 donations (95% CI) EIA NAT

HBVHBV 56 41 27 8.3 (5.7 – 10.9)

HCVHCV 70 12 83 1.3 (0.9 – 1.6)

HIV HIV 22 11 50 1.1 (0.8 – 1.5)

Conclusions (1)Conclusions (1)

• The risk of acquiring HBV, HCV or HIV through transfusion is extremely low. Nevertheless thesafety of blood supply remains a major source of Public concern, requiring a continuous effort to reach zero risk.

• Advances in viral inactivation thecnologies and the introduction of NAT offer the potential to increase the safety of blood supply.

Conclusions (2)Conclusions (2)

• Assays for the detection of HIV p24 Ag and HCV cAg can represent alternative to NAT that are easy to perform, compatible with the current EIAs and possibly less expensive.

• In the case of HIV, NAT is clearly more sensitive than p24 assay.

• In the case of HCV, NAT and HCV cAg show comparable clinical sensitivity

(mean difference 1-2 days, range 0-10 days).

Conclusions (3)Conclusions (3)• The risk of transmitting HBV, HCV and HIV by transfusion of screened blood collected from periodic donors, properly selected through volunteerism and appropriate medical history, iscurrently very low and can be reduced with theintroduction of direct viral detection assays.

• The need for such assays may vary among countries depending on HBV, HCV and HIV endemicity, on healthcare resources and on the foreseen expected benefits and costs. Ethical and legal issues may also play an important role in policy decision making.