In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.

Triplex nucleic acid testing detected potentially infectious HBV, along with HIV and HCV, during the window period before seroconversion. HBV vaccination appeared to be protective, with a breakthrough subclinical infection occurring with non-A2 HBV subgenotypes and causing clinically inconsequential outcomes. (Funded by the American Red Cross and others.).

Hepatitis B virus (HBV) presents a higher residual risk of transmission by transfusion than hepatitis C virus (HCV) or human immunodeficiency virus (HIV). While most infectious blood units are removed by screening for hepatitis B surface antigen (HBsAg), there is clear evidence that transmission by HBsAg-negative components occurs, in part, during the serologically negative window period, but more so during the late stages of infection. Donations negative for HBsAg, but positive for HBV DNA, with or without the presence of HBV antibodies, correspond to 'occult' HBV infection (OBI). The frequency of OBI depends on the relative sensitivity of both HBsAg and HBV DNA assays. It also depends on the prevalence of HBV infection in the population. OBI may follow recovery from infection, displaying antibody to hepatitis B surface antigen (anti-HBs) and persistent low-level viraemia, escape mutants undetected by the HBsAg assays, or healthy carriage with antibodies to hepatitis B e antigen (anti-HBe) and to hepatitis B core antigen (anti-HBc). Over time, in the latter situation, anti-HBe and, later, anti-HBc may become undetectable. The critical question is whether or not OBI is infectious by transfusion. All forms have been shown to be infectious in immunocompromised individuals, such as organ- or bone marrow-transplant recipients. In immunocompetent recipients, there is no evidence that anti-HBs-containing components (even at low titre) are infectious. Anti-HBc only, with HBV DNA, can be associated with infectivity, as can rare cases of HBV DNA without any serological HBV marker. If HBV nucleic acid amplification technology (NAT) is considered, the OBI viral load would usually be < 500 IU/ml, making testing of plasma pools unsuitable unless the sensitivity of NAT significantly increases by genome enrichment or test improvement.

The presence of human erythrovirus DNA in 2,440 blood donations from the United Kingdom and subSaharan Africa (Ghana, Malawi, and South Africa) was screened. Sensitive qualitative and real-time quantitative PCR assays revealed a higher prevalence of persistent infection with the simultaneous presence of immunoglobulin G (IgG) and viral DNA (0.55 to 1.3%) than previously reported. This condition was characterized by a low viral load (median, 558 IU/ml; range, 42 to 135,000 IU/ml), antibody-complexed virus, free specific IgG, and potentially infectious free virus. Human erythrovirus genotype 1 (formerly parvovirus B19) was prevalent in the United Kingdom, Malawi, and South Africa. In contrast, only human erythrovirus genotype 3 (erythrovirus variant V9) was prevalent in Ghana. Genotype 3 had considerable genetic diversity, clustering in two probable subtypes. Genotype 1-based antibody assays failed to detect 38.5% of Ghanaian samples containing antibodies to genotype 3 virus but did not fail to detect cases of persistent infection. This study indicates a potential African origin of genotype 3 human erythrovirus and considerable shortcomings in the tools currently used to diagnose erythrovirus infection. Human erythrovirus (formerly parvovirus B19) is a member of the genus Erythrovirus within the family Parvoviridae (24).Erythrovirus infection occurs frequently in humans. The prevalence of specific immunoglobulin G (IgG) antibodies is 2 to 15% in young children, 30 to 60% in adults, and more than 85% in those 70 years old or older (14). The linear singlestranded DNA genome of this small, nonenveloped virus is about 5 kb long and contains two large open reading frames (ORFs). The first ORF encodes nonstructural protein NS1, and the second one encodes both major VP2 and minor VP1 structural capsid proteins. VP1 consists of a unique sequence of 227 amino acids (VP1u) and is followed by the entire VP2 sequence (554 amino acids). Two additional ORFs encoding small proteins (7.5 and 11 kDa) with unknown functions have also been described (see reference 14 for a review).Following viral infection in immunocompetent individuals, the predominant immune response is a humoral response, which is assumed to confer protective, lifelong immunity. The early IgM response is directed against VP2, while the mature response mostly involves the production of IgG to VP1 (see reference 14 for a review). Several VP2 and VP1u regions containing neutralizing epitopes have been identified (10, 32, 43). However, neutralizing linear epitopes seem to cluster in the N terminus of VP1u and the VP1-VP2 junction regions and to elicit a more efficient response than the epitopes in the VP2 region, which are mainly conformational epitopes (21,26,28,31,36). The inability to develop an efficient neutralizing immune response, as observed mainly in immunosuppressed individuals but also in otherwise healthy individuals, may result in the failure to eliminate the virus, thus leading to persistent infection and the possible occurrence of chronic diseases, suc...

Using phylodynamic and phylogeographic methods, Angelos Hatzakis and colleagues find that the global spread of Hepatitis C virus coincided with widespread use of transfused blood and with the expansion of intravenous drug use.