November 06, 2020
A report published recently in Emerging Infectious Diseases suggests that pooling plasma donations may increase the risk for transfusion-transmitted hepatitis E virus (HEV), despite the viral level reduction associated with pooling and the putative protective effect of the low concentration of HEV immunoglobulin G (IgG) provided by donors who have resolved their infection.
In the report, investigators discussed the results of investigations undertaken after the December 2012 identification of two solvent/detergent–treated plasma lots that contained HEV RNA in France. The identification resulted in a hemovigilance investigation and the immediate introduction of HEV RNA screening of plasma donors and solvent/detergent–treated plasma lots, which often utilize pooled plasma.
Before the identification, 557 solvent/detergent–treated plasma units of lot A (270) or lot B (287) had been transfused into 143 recipients (61 patients in lot A and 82 patients in lot B), and patients received plasma from one solvent/detergent–treated plasma lot. (All remaining solvent/detergent–treated plasma units from lots that were positive for HEV RNA were destroyed.)
Among the 143 solvent/detergent–treated plasma recipients, 21% were evaluable for viral markers, including the two index patients (30 patients; 13 in lot A and 17 in lot B); 33.6% of patients died prior to the hemovigilance investigation (48 patients; 23 in lot A and 25 in lot B). Results for the remaining 45.4% were not available (65 patients; 25 in lot A and 40 in lot B). Intervals between the solvent/detergent–treated plasma transfusion and recipient assessment ranged from 2-44 months.
In addition to the two index case-patients, one additional recipient was positive for HEV RNA 37 months after transfusion (lot A recipient). Both indexcase patients received similar cumulative HEV viral loads (173,000 IU and 154,000 IU, respectively). However, there was a difference in the number of transfused solvent/detergent–treated plasma units: 2 (from lot A) and 14 (from lot B), respectively. Recipient 3 (lot A) received a higher viral load (433,000 IU).
Among the remaining 27 patients, one recipient was HEV IgG negative and HEV IgM positive (assessed 14 months after transfusion), five were IgG positive and IgM positive (4–16 months after transfusion); seven were IgG positive and IgM negative (2–44 months after transfusion); and 14 were IgG negative and IgM negative (4–31 months after transfusion). Pretransfusion results were available for five recipients at various times before transfusion. Two were HEV IgG positive and IgM negative before and after transfusion. One was IgG negative and IgM negative before transfusion and IgG positive and IgM negative after transfusion. The remaining two were IgG negative and IgM negative before and after transfusion.
HEV RNA viral loads were 433 IU in lot A and 55 IU in lot B. Retrospective studies found that 100% (13/13) of evaluable lot A recipients versus 18% (3/17) of evaluable lot B recipients had been infected by HEV, although the authors noted this was not necessarily at the time of transfusion. Among evaluable recipients, 86% of patients with a transfused HEV RNA load greater than 50,000 IU were HEV-positive, compared to 7% (1/14) of patients with a transfused HEV RNA load less than 50,000 IU. According to the authors, the findings suggest that a large fraction of the seropositive recipients was infected at the time of transfusion and that the infectious risk is proportionate to the transfused viral load.
The authors concluded that the minimal HEV RNA viral load in blood products needed to cause transfusion-transmitted HEV might ultimately be difficult to determine and that risk for transfusion-transmitted hepatitis E might also depend on a combination of additional factors, such as the concentration of HEV antibodies in the blood product, recipient immune competence, immune status, and viral genotypes and subtypes. They believe the optimal strategy for assessment of transfusion-transmitted HEV infection requires testing of molecular and serologic HEV markers at several time points before and after transfusion.