Absence of anti‐HBc reactivity with detectable anti‐HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon ...condition were investigated over time in Chinese blood donors with OBI. Isolated anti‐HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow‐up (range: 2.6–84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti‐HBs as only serological marker. Isolated anti‐HBs OBIs differed from anti‐HBc‐reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti‐HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti‐HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti‐HBs level at index (48% vs 9% with anti‐HBs >100 IU/L) and higher frequency of anti‐HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow‐up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti‐HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti‐HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.
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.
Summary
Blood transfusion safety in sub‐Saharan Africa (SSA) is marred by the high prevalence of infectious agents, chronic blood shortage and lack of resources. However, considerable pressure is ...applied by richer countries and international transfusion bodies to establish voluntary, non‐remunerated blood donors (VNRD) as the only source of blood, excluding the traditional family/replacement donors on the grounds of a higher level of safety. Such a policy increases the cost of a unit of blood by two to fivefold and exacerbates the pre‐existing blood shortage. This review provides compelling evidence that first‐time VNRD are no safer than family/replacement donors and that only repeat donation provides improved blood safety. In order to limit blood shortage and maintain affordability of the blood supply in SSA, both types of donors should be accepted and both should be encouraged to donate regularly.
HBV testing and diagnosis of HBV-related liver disease in low-income and middle-income countries differs substantially from that in developed countries in terms of access to resources and expensive ...technologies requiring highly specialized staff. For identification and classification of HBV infection, genomic amplification methods to detect and quantify HBV DNA are often nonexistent or available only in central laboratories of major cities. When samples from peripheral locations do arrive, delays in receiving results generate loss to follow-up. Testing is often limited to measurement of hepatitis B surface antigen (HBsAg), alanine aminotransferase levels, aspartate aminotransferase to platelet ratio index and hepatitis B e antigen (HBeAg) to determine indications for antiviral therapy (AVT). Utilization of AVT is limited by cost and availability, particularly when patients are not covered by health insurance. The natural history of HBV infection is influenced by genotypes B and C in East Asia, where decades of immune tolerance have led to mostly vertical transmission; in sub-Saharan Africa, where genotypes A1 and E predominate, infection is transmitted horizontally between young children, followed by a nonreplicative phase. In both regions, cirrhosis and hepatocellular carcinoma are common and would be considerably ameliorated by AVT. Implementation of the HBV vaccine since the 1990s in Asia and 2000s in Africa has decreased the incidence of HBV, but vaccine failure and insufficiently effective prevention remain concerning issues.
The origin of hepatitis B virus (HBV) infection in humans and other primates remains largely unresolved. Understanding the origin of HBV is crucial because it provides a framework for studying the ...burden, and subsequently the evolution, of HBV pathogenicity with respect to changes in human population size and life expectancy. To investigate this controversy we examined the relationship between HBV phylogeny and genetic diversity of modern humans, investigated the timescale of global HBV dispersal, and tested the hypothesis of HBV‐human co‐divergence. We find that the global distribution of HBV genotypes and subgenotypes are consistent with the major prehistoric modern human migrations. We calibrate the HBV molecular clock using the divergence times of different indigenous human populations based on archaeological and genetic evidence and show that HBV jumped into humans around 33,600 years ago; 95% higher posterior density (HPD): 22,000‐47,100 years ago (estimated substitution rate: 2.2 × 10−6; 95% HPD: 1.5‐3.0 × 10−6 substitutions/site/year). This coincides with the origin of modern non‐African humans. Crucially, the most pronounced increase in the HBV pandemic correlates with the global population increase over the last 5,000 years. We also show that the non‐human HBV clades in orangutans and gibbons resulted from cross‐species transmission events from humans that occurred no earlier than 6,100 years ago. Conclusion: Our study provides, for the first time, an estimated timescale for the HBV epidemic that closely coincides with dates of human dispersals, supporting the hypothesis that HBV has been co‐expanding and co‐migrating with human populations for the last 40,000 years. (HEPATOLOGY 2013)
Hepatitis B virus (HBV) remains a major risk of transfusion-transmitted infection due to the pre-seroconversion window period (WP), infection with immunovariant viruses, and with occult carriage of ...HBV infection (OBI). Reduction of HBV residual risk depends upon developing more sensitive HBV surface antigen (HBsAg) tests, adopting anti-HBc screening when appropriate, and implementing HBV nucleic acid testing (NAT), either in minipools or more efficiently in individual samples. HBV NAT combines the ability to significantly reduce the window period and to detect occult HBV carriage substantiating decades of clinical observation that HBsAg-negative/anti-HBc-positive blood could transmit HBV. Clinical observations suggest limited transmission rate of occult HBV compared to WP. Low transmission rate might be related to low viral load observed in OBIs or to the presence of mutants associated with occult carriage. OBIs carrying detectable anti-HBs (∼50%) are essentially not infectious by transfusion. However, recent data suggest that the neutralizing capacity of low anti-HBs may be inefficient when overcome by exposure to high viral load. Anti-HBc blood units without detectable anti-HBs appear moderately infectious except in immunocompromised recipients. Immunodeficient elderly and patients receiving immunosuppressive treatments may be susceptible to infection with lower infectious dose even in the presence of anti-HBs. The immune status of blood recipients should be taken into consideration when investigating “post-transfusion” HBV infection. Pre-transfusion testing and post-transfusion long-term follow-up of recipients, and molecular analysis of the virus infecting both donor and recipient are critical to definitively incriminate transfusion in the transmission of HBV.
Summary Background Transfusion-transmitted malaria is a frequent but neglected adverse event in Ghana. We did a randomised controlled clinical trial to assess the efficacy and safety of a whole blood ...pathogen reduction technology at preventing transfusion transmission of Plasmodium spp parasites. Methods For this randomised, double-blind, parallel-group clinical trial, eligible adult patients (aged ≥18 years) with blood group O+, who required up to two whole blood unit transfusions within 3 days of randomisation and were anticipated to remain in hospital for at least 3 consecutive days after initial transfusion, were enrolled from Komfo Anokye Teaching Hospital in Kumasi, Ghana. The main exclusion criteria were symptoms of clinical malaria, antimalaria treatment within 7 days before randomisation, fever, and haemorrhage expected to require transfusion with up to two units of whole blood during the 3 days following study entry. Eligible patients were randomly assigned 1:1 by computer-generated permuted block randomisation (block size four) list to receive transfusion with either pathogen-reduced whole blood (treated) or whole blood prepared and transfused by standard local practice (untreated). Patients, health-care providers, and data collectors were masked to treatment allocation. Patients in both groups received up to two whole blood unit transfusions that were retrospectively tested for parasitaemia. Pre-transfusion and post-transfusion blood samples (taken on days 0, 1, 3, 7, and 28) were tested for presence and amount of parasite genome, and assessed for haematological and biochemical parameters. The primary endpoint was the incidence of transfusion-transmitted malaria in non-parasitaemic recipients exposed to parasitaemic whole blood, defined as two consecutive parasitaemic post-transfusion samples with parasite allelic matching, assessed at 1–7 days after transfusion. Secondary endpoints included haematological parameters and a safety analysis of adverse events in patients. This study is registered with ClinicalTrials.gov , number NCT02118428 , and with the Pan African Clinical Trials Registry, number PACTR201406000777310. Findings Between March 12, 2014, and Nov 7, 2014, 227 patients were enrolled into the study, one of whom was subsequently excluded because she did not meet the inclusion criteria. Of the 226 randomised patients, 113 were allocated to receive treated whole blood and 113 to receive standard untreated whole blood. 223 patients (111 treated and 112 untreated) received study-related transfusions, whereas three patients (two treated and one untreated) did not. 214 patients (107 treated and 107 untreated) completed the protocol as planned and comprised the per-protocol population. Overall, 65 non-parasitaemic patients (28 treated and 37 untreated) were exposed to parasitaemic blood. The incidence of transfusion-transmitted malaria was significantly lower for the pathogen-reduced (treated) patients (1 4% of 28 patients) than the untreated group (8 22% of 37 patients) in this population (p=0·039). Overall, 92 (41%) of 223 patients reported 145 treatment-related emergent adverse events during the conduct of the study, with a similar incidence of adverse events between groups receiving untreated or treated whole blood. No transfusion-related deaths occurred in the trial. Interpretation Treatment of whole blood with the Mirasol pathogen reduction system for whole blood reduced the incidence of transfusion-transmitted malaria. The primary endpoint of the study was achieved in the population of non-parasitaemic patients receiving parasitaemic whole blood. The safety profile and clinical outcomes were similar across the two treatment groups. Funding Terumo BCT Inc.
In this study involving 3.7 million blood donors, nucleic acid testing identified 9 donors with HBV infection who were not identified by routine serologic testing. The single triplex assay also ...identified 2 donors with HIV and 15 with HCV.
The transfusion of blood containing hepatitis B surface antigen (HBsAg) is associated with post-transfusion infection with hepatitis B virus (HBV). Blood that is free of HBsAg but has high-titer antibodies against hepatitis B core antigen (anti-HBc) in the absence of antibodies against hepatitis B surface antigen (anti-HBs) can also transmit HBV infection.
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In 1986, screening for anti-HBc was implemented in the United States to reduce HBV transmission and as a surrogate marker for non-A, non-B hepatitis (i.e., hepatitis C virus HCV).
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However, a small proportion of donors with anti-HBc in the absence of HBsAg have circulating HBV DNA . . .
HBV infectivity data were reviewed and the 50% infectious dose (ID50) was reassessed in different HBsAg positive infection stages enabling modelling of transfusion‐transmitted (TT)‐HBV infection risk ...if HBsAg donor screening was replaced by individual donation nucleic acid amplification technology (ID‐NAT). Quantitative HBsAg and HBV‐DNA assays were performed against international standards to compare the ratio between potential infectious HBV virions and subviral HBsAg particles in Egyptian HBsAg positive blood donors as well as in Japanese chimpanzee samples of known infectivity. HBV‐DNA load below the quantification limit of detection was estimated against a reference standard by replicate NAT testing (n = 25). Infectivity of chimpanzee samples collected during ramp‐up and declining viremic phase were tested in a human liver chimeric mice (HLCM) model and compared with published infectivity data from different HBsAg positive infection stages. Lowest estimates of ID50 in HBsAg positive plasma were 3–6 HBV virions in chimpanzee studies. Infectivity decreased approximately 10–100‐fold in the declining viremic phase using HLCM. In acute‐phase samples, HBV to HBsAg particle ratios varied between 1:102–104 but in HBsAg positive blood donors this particle ratio reached 1:106–1012 when viral load was below 100 HBV‐DNA copies/ml. Modelled TT‐HBV risk of an HBsAg positive/ID‐NAT nonreactive blood transfusion was estimated at 9%–46% for components containing 20–200 ml of plasma assuming an ID50 of 316 (point estimate between 100 and 1000) virions. In the Egyptian setting, discontinuation of HBsAg donor screening and reliance on ID‐NAT alone seems to be unsafe.
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