Frequency and load of hepatitis B virus DNA in first-time blood donors with antibodies to hepatitis B core antigen

Abstract

IntroductionThe risk of transfusion-transmitted hepatitis B virus (HBV) infection has been reduced by screening all blood donations for HBV surface antigen (HBsAg) since 1970. It was generally accepted that the disappearance of HBsAg indicates the clearance of HBV. Meanwhile, many reports on positive findings for HBV DNA in the liver and blood of HBsAg-negative individuals positive for antibodies against HBV core antigen (anti-HBc) and/or HBsAg (anti-HBs) have been published. 1-8 Blum et al described, in a patient with HBsAg-negative chronic hepatitis who was positive for anti-HBc, anti-HBs, and antibodies against HBe antigen (anti-HBe), a latent HBV infection in hepatocytes with extrachromosomal presence of a full-length viral genome. 9 Michalak et al demonstrated the long-term persistence of HBV DNA in serum and peripheral blood mononuclear cells of patients up to 70 months after complete clinical, biochemical, and serologic recovery from acute viral hepatitis. 10 Rehermann et al showed that traces of HBV were often detectable in the blood for many years after clinical recovery from acute hepatitis, despite the presence of serum antibodies and HBV-specific cytotoxic T lymphocytes (CTLs). 11 These findings suggest that sterilizing immunity to HBV frequently fails to occur and that traces of virus can maintain the CTL response for decades, apparently creating a negative feedback loop that keeps the virus under control, perhaps for life. This was supported by Pasquetto et al, who showed that cytoplasmic HBV nucleocapsids and their cargo of replicative DNA intermediates survive CTL-induced apoptosis of hepatocytes in vitro, 12 and by other groups that demonstrated ongoing viral replication in the liver tissue of patients and healthy individuals after loss of HBsAg. [13][14][15] Furthermore, reactivation of apparently cured HBV infection has been described under chemotherapy or immunomodulating therapy after renal and bone marrow transplantation, and in some of these cases a reverse seroconversion from anti-HBs to HBsAg has been observed. [16][17][18][19] The residual risk of posttransfusion HBV infection has been calculated by several groups in the United States and Germany on the basis of HBV incidence data and the duration of the early window period until HBsAg becomes detectable to be 1:63 000 and less than 1:100 000 blood donations, respectively. 20,21 It has been shown that blood donations of HBsAg-and anti-HBs-negative but anti-HBc-positive HBV carriers can cause posttransfusion hepatitis B. 22;23 Thus, Mosley et al suggested that anti-HBc screening of blood donations might prevent HBV transmission from HBsAgnegative blood donors and that donors positive for anti-HBs as well should be considered noninfectious for HBV. 24 The feasibility of routine polymerase chain reaction (PCR) screening of blood donations in a blood bank setting has been shown by Roth et al. 25 In Germany, the Paul Ehrlich Institute (PEI, Langen, Germany), the institute that defines German Drug Law and is responsible for specific regulati...

Italian blood donors with anti-HBc and occult hepatitis B virus infection

“…This figure compares with antiHBc prevalence rates among HBsAg-negative blood donors that vary from 0.56% in the United Kingdom, 20 0.84% in United States, 21 1.4% in Germany, 11 15.03% in Greece, 22 16.4% in Saudi Arabia 23 to 76% in Ghana. 20 In our area the current HBsAg-negative/anti-HBc-positive donor population is made up of two groups: one of native Italians and another, on the increase, of foreign donors belonging to immigrant fluxes from EastEuropean and African countries.…”

“…With the development of sensitive assays to detect HBV-DNA it was shown that healthy HBsAg-negative donors who have antibodies to HBV core antigen (antiHBc) may harbor an occult HBV infection and maintain HBV-DNA sequences in their liver and blood, thus representing potential sources of HBV transmission. [6][7][8][9][10][11][12][13][14][15][16][17] AntiHBc screening of blood donations is controversial and variably performed in different countries. Currently it is limited to areas where the seroprevalence of HBV is low (generally <2%), while it is not performed in areas with a high HBV seroprevalence because the impact of the deferral of anti-HBc-positive donors is considered not sustainable.…”

The Role of Hepatitis B Core Antibody Testing in Improving Blood Safety in Resource-Limited Countries Study on Voluntary Blood Donors Fayoum, Egypt

“…A prevalence of 0.07% in the UK and 1.5% in Germany was reported [18,19]. In areas of higher HBV infection prevalence about 20%-70% of subjects are positive for anti-HBc antibody [20].…”

Enhanced hepatitis B virus (HBV) pre-genomic RNA levels and higher transcription efficiency of defective HBV genomes

“…Plasmid-safe DNase digests all linear forms of DNA; HBV cccDNA will remain unaffected by plasmid-safe DNase digestion (Laras et al, 2006). The DNA was column purified and used as a template for the quantification of HBV cccDNA by real-time PCR using primers 59-GTGC-CTTCTCATCTGCCGG-39 (nt 1555-1573) (Laras et al, 2006) and 59-GAACTTTAGGCCCATATTAGTG-39 (nt 2191-2170) and a Taqman probe, 59 FAM-TTCAAGCCTCCAAGCTGTGCCTTGGG-TGGC-TAMRA-39 (nt 1863-1892) (Hennig et al, 2002) by using Premix Ex Taq (Takara). This assay is highly specific for HBV cccDNA and does not amplify linear transfected HBV DNA (WT or dHBV constructs).…”