Transfusions of red blood cells from an occult hepatitis B virus carrier without apparent signs of transfusion‐transmitted hepatitis B infection

Dear Sir To minimize the risk of transfusion-transmitted hepatitis B virus (HBV) infections, the Japanese Red Cross (JRC) Blood Centers have adopted a multistep screening system to identify donors at risk of HBV infection. First, donors are examined for the hepatitis B surface antigen (HBsAg) by performing reverse passive haemagglutination tests with a sensitivity of 3 ng mL. HBsAg-negative donations are screened for antibodies against HBsAg and the hepatitis B core antigen (anti-HBs and anti-HBc, respectively) by particle haemagglutination and haemagglutination inhibition (HI) tests, respectively. Donations with a high anti-HBs titre ( 2 dilution equivalent to 200 mIU mL) or a low or zero anti-HBc titre ( 2 dilution) are defined as ‘seronegative’. The cut off value for anti-HBc tests is relatively high compared to that of enzyme-linked immunoassays (EIAs) because HBV DNA was not detected by an in-house polymerase chain reaction (PCR) in donors who tested negative forHBsAg and positive for anti-HBc at anHI titre less than 2 (Iizuka et al., 1992). Since the introduction of nucleic acid amplification test (NAT) technology, all seronegative donations are pooled (initially, at a pool size of 500 and a current pool size of 20, i.e. 20-NAT) and subjected to NAT (AmpliNAT, Roche, IN, USA). If the 20-NAT tests positive, the pooled donations are further subjected to individual NAT (ID-NAT) to identify the blood donation that contains the viral genome. The 95% confidence interval of the detection range for HBV in ID-NAT is 22–60 copies of HBV per millilitre (Meng et al., 2001). Donors who did not fall within the algorithmwould be either categorized in the window period of 20 NAT or assigned an occult HBV status with a low viral load (reviewed by Raimondo et al., 2007). In November 2006, the Osaka Red Cross Blood Center, Japan, identified a repeat donor, namely, a 69year-old female, whose donation was found to be positive for HBV DNA when tested by the latest 20NAT. According to the guidelines for the safety of transfusion in the JRC Blood Centers, the serological status of the donation was re-evaluated. The donated blood was found to be negative for HBsAg, anti-HBs and anti-HBc by routine testing methods and positive for only anti-HBc when tested using EIA (AxSYM; Abbott Laboratories, Abbott Park, IL, USA), indicating that the donor was an occult HBV carrier with a low anti-HBc titre. We retrieved frozen aliquots of previous donations by this donor and found that sera donated on and after 1October 1999 tested positive for HBV DNA when tested by ID-NAT. The amount of HBVDNA in these donations was less than 100 copies per millilitre, except for two donations (Table 1). From the 13 donations made by this donor in the abovementioned period, 11 components were transfused into recipients (recipient number 1–11 in Table 1). We collected the HBV test records of some of the recipients from the medical institutions where each recipient had been hospitalized. Recipients 3, 6, 7 and 9 had succumbed to their primary disease, and no records were available for recipients 10 and 11. Of the remaining five cases, the HBV test was performed at both the preand post-transfusion stages in recipients 1, 4 and 5, but recipients 2 and 8 were tested only at the post-transfusion stage. Recipient 1 was a 70-year-old female who had tested negative for HBsAg and antiHBc by EIA 2 days prior to transfusion. She was transfused with packed red blood cells (RBCs) and tested negative for HBsAg, anti-HBs and anti-HBc by EIA and negative for HBV DNA by PCR 7 months after the transfusion. These data suggest that the latest RBC component from this occult HBV donor did not cause transfusion-transmitted HBV infection. In recipients 2 and 8, the post-transfusion EIA test results for HBsAg were reported negative. Recipient 4 tested negative for HBsAg by EIA at 11 days before Correspondence: Rika A. Furuta, Osaka Red Cross Blood Center, 2-4-43 Morinomiya, Joto-ku, Osaka 536-8505, Japan. Tel.: 181 6 6962 7066; fax: 181 6 6962 7029; e-mail: furuta@osaka.bc.jrc.or.jp