Occult hepatitis B (HBV) infection (OBI), characterized by low viral loads, accounts for much of the risk of HBV transfusion‐transmitted infection. With anticore antibodies (anti‐HBc) screening introduced in England, the imperative to identify OBI donors has increased. We aimed to develop an ultra‐sensitive PCR system and investigate risk factors for HBV DNA presence in blood donations. Seven extraction methods and three PCR assays were compared. The optimal system was sought to determine HBV DNA presence in anti‐HBc‐positive donations. Predictors of DNA positivity were subsequently investigated. Extraction from 5 mL of plasma increased sample representation and resulted in HBV DNA detection in low viral load samples (~0.5 IU/mL). Screening of 487 763 donations in 2022 identified two OBI donors and 2042 anti‐HBc‐positive donors, 412 of the latter with anti‐HBs < 100 mIU/mL. Testing of 134 anti‐HBc‐positive donations utilizing the 5 mL extraction method identified two further HBV DNA‐positive donations. Higher anti‐HBc titer and anti‐HBs negativity were significant predictors of DNA detectability in anti‐HBc‐positive donations. An ultrasensitive PCR assay identified potentially infectious donations increasing HBV DNA detection in anti‐HBc‐positive donors from 0.5% to 1.9%. Anti‐HBc titers may further complement the risk stratification for DNA positivity in anti‐HBc screening and minimize unnecessary donor deferral.

Background: Hepatitis B core antibody (anti‐HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk.Materials and Methods: A questionnaire on HBV screening and follow‐up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion‐transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed.Results: A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti‐HBc, with 14 also screening all donations for HBV DNA. Anti‐HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low‐endemic countries; however, only 44% of respondents performed additional anti‐HBc testing to exclude false reactivity. 0.68% of anti‐HBc positive, HBsAg‐negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti‐HBc, whereas four respondents did not screen for either. Deferral strategies for anti‐HBc positive donors were highly variable. One transfusion‐transmission from an anti‐HBc negative donor was reported.Discussion: Anti‐HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false‐reactive anti‐HBc results. Whilst confirmation of anti‐HBc results could be improved to reduce donor deferral, transmission risks associated with anti‐HBc negative OBI donors must be considered. In high‐endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.

Blood transfusion is a vital procedure, where transfusion‐transmitted infection of hepatitis B virus (HBV) remains an important issue, especially from blood donors with occult hepatitis B virus infection (OBI). Occult hepatitis B virus infection is a complex entity to detect using surrogate blood biomarkers for intrahepatic viral transcriptional activity, requiring a continually refined battery of tests utilised for screening. This review aims to critically evaluate the latest advances in the current blood biomarkers to guide the identification of OBI donors and discuss novel HBV markers that could be introduced in future diagnostic practice. Challenges in detecting low HBV surface antigen levels, mutants, and complexes necessitate ultrasensitive multivalent dissociation assays, whilst HBV DNA testing requires improved sensitivity but worsens inaccessibility. Anti‐core antibody assays defer almost all potentially infectious donations but have low specificity, and titres of anti‐surface antibodies that prevent infectivity are poorly defined with suboptimal sensitivity. The challenges associated with these traditional blood HBV markers create an urgent need for alternative biomarkers that would help us better understand the OBI. Emerging viral biomarkers, such as pre‐genomic RNA and HBV core‐related antigen, immunological HBV biomarkers of T‐cell reactivity and cytokine levels, and host biomarkers of microRNA and human leucocyte antigen molecules, present potential advances to gauge intrahepatic activity more accurately. Further studies on these markers may uncover an optimal diagnostic algorithm for OBI using quantification of various novel and traditional blood HBV markers. Addressing critical knowledge gaps identified in this review would decrease the residual risk of transfusion‐transmitted HBV infection without compromising the sustainability of blood supplies.

Despite nearly 250 million people worldwide estimated to have chronic HBV infection, health-related quality of life (HRQOL) in HBV-related disease has not been well characterised. Here, we summarise existing data on HBV-related HRQOL and quantify summary utility values by stage of disease. Embase, Global Health, PubMed, and Web of Science were searched for articles investigating HBV HRQOL. Meta-analyses for utility scores were pooled by stage of disease and utility instrument; meta-regression was further adjusted for the effect of current health expenditure as a percentage of gross domestic product (CHE/GDP), as a proxy of the importance of healthcare perceived by different countries. Twenty-two articles from 19 studies, comprising 10,311 patients, were included. Of these studies, 74% were performed in the Western Pacific Region, and 47% used the EuroQoL-5D-3L instrument. HRQOL was found to decrease with advancing stages of HBV-related disease. Meta-regression showed the following predicted mean utility scores for the different stages of chronic HBV infection: non-cirrhotic, 0.842; compensated cirrhosis, 0.820 (p = 0.474 compared with non-cirrhotic); decompensated cirrhosis, 0.722 (p = 0.001); and hepatocellular carcinoma, 0.749 (p = 0.008). The type of tool affected HRQOL and populations with a higher CHE/GDP were associated with higher predicted utility values. Chronic HBV infection impairs the HRQOL of patients, even when there is no evidence of cirrhosis. HRQOL is particularly impaired in the advanced stages of decompensated cirrhosis and hepatocellular carcinoma. These results have important implications for global hepatitis elimination efforts and are useful for economic analyses. However, further research is needed, particularly in high-burden, low-income settings where data are lacking. This study, based on 22 articles and 10,311 patients, provides a comprehensive synthesis of data on the impact of chronic hepatitis B virus (HBV) infection on patients' health-related quality of life (HRQOL) worldwide. These findings, of how HRQOL is affected in people living with HBV, highlight the importance of patient-centred care and holistic approaches to management, even at the early stages of disease. These results are useful for cost-effectiveness analyses and may help inform decision-making in improving public health policy towards the elimination of viral hepatitis. The study also underscores the need for further data from low-to middle-income settings, and on the effects of treatment on HRQOL.

This case-control study aims to compare the efficacy, safety, and postoperative burden of MicroShunt versus trabeculectomy. The first consecutive cohort of MicroShunt procedures (n = 101) was matched to recent historical trabeculectomy procedures (n = 101) at two London hospital trusts. Primary endpoints included changes in intraocular pressure (IOP) and glaucoma medications. Secondary outcome measures included changes in retinal nerve fibre layer (RNFL) thickness, rates of complications, further theatre interventions, and the number of postoperative visits. From the baseline to Month-18, the median [interquartile range] IOP decreased from 22 [17–29] mmHg (on 4 [3–4] medications) to 15 [10–17] mmHg (on 0 [0–2] medications) and from 20 [16–28] mmHg (on 4 [3–4] medications) to 11 [10–13] mmHg (on 0 [0–0] medications) in the MicroShunt and trabeculectomy groups, respectively. IOP from Month-3 was significantly higher in the MicroShunt group (p = 0.006), with an increased number of medications from Month-12 (p = 0.024). There were greater RNFL thicknesses from Month-6 in the MicroShunt group (p = 0.005). The rates of complications were similar (p = 0.060) but with fewer interventions (p = 0.031) and postoperative visits (p = 0.001) in the MicroShunt group. Therefore, MicroShunt has inferior efficacy to trabeculectomy in lowering IOP and medications but provides a better safety profile and postoperative burden and may delay RNFL loss.

The implementation of effective blood donation screening for hepatitis B virus (HBV) anti-core antibodies with highly sensitive molecular HBV DNA detection in low-endemic countries like the United Kingdom has improved blood safety. However, the linkage to care and management for blood donors with occult HBV infection (OBI) is a complex dilemma involving virological, clinical, methodological, and social issues. Limited evidence suggests that OBI may accelerate the progression of liver disease and cancer. The need for a specialist referral for donors identified with OBI carries mixed opinions from blood establishments, hepatologists, and public health. Following extensive multidisciplinary discussions, experts agree upon a need for clear messaging for donors and to consider the oncogenic implications of OBI. Proposals for future studies are identified, and the applicability of the recommendations in low-resource, high-endemic regions is considered, as well as the inclusion of OBI in global hepatitis elimination targets.