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Background: Commercial multiplex nucleic acid tests (NATs) for HIV‐1/HIV‐2/HCV/HBV are widely used in developed countries to screen blood donations. HEV NAT screening has been implemented in some blood banks but is tested with a different assay. Study Design and Methods: This study describes the clinical sensitivity and specificity of the Procleix® UltrioPlex E (UPxE) assay on the automated Procleix Panther® system for the simultaneous detection of HIV‐1/HIV‐2/HCV/HBV/HEV. To evaluate routine performance, 10,138 donations were tested in parallel with UPxE (in ID‐NAT) and current assays (Procleix Ultrio Elite [UE] assay in ID‐NAT and Procleix HEV assay in pool of 16). To assess clinical sensitivity, archived donations positive for HCV, HIV‐1, HBV, HEV, or occult HBV infection (OBI) were tested (n = 104–186). Results: Five donations were initially reactive (IR) with UPxE; none of them were reactive with current assays. Two of the three samples IR for HIV‐1/HIV‐2/HCV/HBV were confirmed positive for HBV (HBV NAT and/or anti‐HBV core positive) and classified as OBI. The two samples IR for HEV were confirmed positive (Procleix HEV assay in ID‐NAT and in‐house RT‐PCR HEV assay). One sample IR for HIV‐1/HIV‐2/HCV/HBV with UPxE and another with UE were not confirmed. UPxE showed a specificity of 99.99% for HIV‐1/HIV‐2/HCV/HBV and 100% for HEV. Comparable sensitivities were observed for HIV‐1, HCV, HBV, OBI, and HEV samples tested in the UPxE, UE, and Procleix HEV assays. Discussion: UPxE may provide an efficient solution for the simultaneous detection of HIV‐1, HIV‐2, HCV, HBV, and HEV in blood donations in a single test. [ABSTRACT FROM AUTHOR]

Background: There is a need for new serum biomarkers for early detection of hepatocellular carcinoma (HCC). Haptoglobin (Hp) N-glycosylation is altered in HCC, but the diagnostic value of site-specific Hp glycobiomarkers is rarely reported. We aimed to determine the site-specific glycosylation profile of Hp for early-stage HCC diagnosis. Method: Hp glycosylation was analyzed in the plasma of patients with liver diseases (n=57; controls), early-stage HCC (n=50) and late-stage HCC (n=32). Hp phenotype was determined by immunoblotting. Hp was immunoisolated and digested into peptides. N-glycopeptides were identified and quantified using liquid chromatography-mass spectrometry. Cohort samples were compared using Wilcoxon rank-sum (Mann-Whitney U) tests. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and area under curve (AUC). Results: Significantly higher fucosylation, branching and sialylation of Hp glycans, and expression of high-mannose glycans, was observed as disease progressed from cirrhosis to early- and late-stage HCC. Several glycopeptides demonstrated high values for early diagnosis of HCC, with an AUC of 93% (n=1), >80% (n=3), >75% (n=13) and >70% (n=11), compared with alpha-fetoprotein (AFP; AUC of 79%). The diagnostic performance of the identified biomarkers was only slightly affected by Hp phenotype. Conclusion: We identified a panel of Hp glycopeptides that are significantly differentially regulated in early- and late-stage HCC. Some glycobiomarkers exceeded the diagnostic value of AFP (the most commonly used biomarker for HCC diagnosis). Our findings provide evidence that glycobiomarkers can be effective in the diagnosis of early HCC - individually, as a panel of glycopeptides or combined with conventional serological biomarkers. [ABSTRACT FROM AUTHOR]

Background: Transfusion-transmitted hepatitis E virus (HEV) infections have raised many concerns regarding the safety of blood products. To date, enveloped HEV particles have been described in circulating blood, whereas nonenveloped HEV virions have only been found in feces; however, no exhaustive studies have been performed to fully characterize HEV particles in blood.Methods: Using isopycnic ultracentrifugation, we determined the types of HEV particles in plasma of HEV-infected blood donors.Results: Nonenveloped HEV was detected in 8 of 23 plasma samples, whereas enveloped HEV was found in all of them. No association was observed between the presence of nonenveloped HEV and viral load, gender, or age at infection. However, samples with HEV-positive serology and/or increased levels of liver injury markers contained a higher proportion of nonenveloped HEV than samples with HEV-negative serology and normal levels of liver enzymes. These results were further confirmed by analyzing paired donation and follow-up samples of 10 HEV-infected donors who were HEV seronegative at donation but had anti-HEV antibodies and/or increased levels of liver enzymes at follow up.Conclusions: The HEV-contaminated blood products may contain nonenveloped HEV, which may pose an additional risk to blood safety by behaving differently to pathogen inactivation treatments or increasing infectivity. [ABSTRACT FROM AUTHOR]

Human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) screening is not mandatory in Spanish blood banks. In Catalonia, selective screening was introduced in 2008, followed by universal screening in 2011. We present herein a 10-year experience of HTLV testing in blood donors. HTLV-1/2 selective screening was performed using Ortho-Clinical Diagnostics HTLV-I/HTLV-II Ab-Capture ELISA between February 2008 and May 2009, then Abbott Prism HTLV-I/ HTLV-II assay until December 2010. Abbott Architect rHTLV-I/II assay was then used for HTLV-1/2 universal screening in pooled samples. INNO-LIA HTLV I/II Score (Fujirebio) and in-house HTLV-1/2 proviral DNA real-time PCR were used in reactive samples. Follow-up was offered to confirm HTLV-1/2 donors in Vall d'Hebron Hospital. Between 2008 and 2017, 51 blood donors were confirmed HTLV positive (46 HTLV-1, 4 HTLV-2 and 1 HTLV) out of 2,114,891 blood donations (1 in 41,468). Sixty-nine percent were female, median age was 40 years and most were born in Latin America (69%), followed by Europe (25%), Africa (4%) and Asia (2%). Screening of relatives and partners identified 12 additional HTLV-1 cases. Lookback studies did not show any HTLV-1/2 transmission. HTLV infections found in blood donors mirror epidemiological changes in the population of Spain. Consequently, HTLV should be considered a potential risk for recipients and calls for the design of optimal strategies to ensure transfusion safety. [ABSTRACT FROM AUTHOR]

Background: Despite most controlled trials have shown no measurable benefit of COVID‐19 convalescent plasma (CCP) in patients with COVID‐19, some studies suggest that early administration of CCP with high‐titer anti‐SARS‐CoV‐2 can be beneficial in selected patients. We investigated the efficacy of early administration of high‐titer CCP to patients with COVID‐19 who required hospitalization, Study design and methods: Observational, propensity score (PS) matched case–control study of COVID‐19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti‐SARS‐CoV‐2 sample‐to‐cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high‐standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. Results: A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56–79), and 953 (60%) were men. Presenting factors independently associated with higher 30‐day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d‐dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30‐day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91–0.98; p =.001) that extended to the 60th day after COVID‐19 diagnosis (OR: 0.95; 95% CI: 0.92–0.99; p =.01). Conclusion: Our results suggest that CCP can still be helpful in selected patients with COVID‐19 and call for further studies before withdrawing CCP from the COVID‐19 therapeutic armamentarium. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, has an incidence rate equal to mortality. Over 80% of HCC cases occur within a high‐risk population, mainly patients with both cirrhosis and chronic hepatitis B or C. With a 5‐year survival rate ranging from <16% for advanced HCC to >90% for early stage HCC, there is a high medical need for the early detection of HCC. In this study, we systematically evaluated biomarkers mentioned in international guidelines and peer‐reviewed literature for HCC surveillance and diagnosis with the aim of identifying combinations that display high sensitivity and specificity for early stage HCC. Fifty biomarkers were measured in the first sample panel, panel A (n = 110), and subjected to univariate analysis. Of these, 35 biomarkers (38 assays) from panel A and an additional 13 biomarkers from the literature were prioritized for subsequent multivariate evaluation with lasso regression and exhaustive search of two‐ to four‐biomarker combinations (panel B). Panel B included 1,081 samples from patients with HCC (n = 308) or with chronic liver diseases (n = 740). Among all patients, 61.0% had hepatitis B, 32.9% had hepatitis C, and 60.5% had cirrhosis; 40.6% of patients with HCC had early stage cancer. Protein induced by vitamin K absence‐II (PIVKA‐II; also known as des‐gamma‐carboxy prothrombin [DCP]) and alpha‐fetoprotein (AFP) demonstrated the best clinical performance, both individually and in combination, and the addition of a third biomarker (Lens culinaris agglutinin‐reactive fraction of AFP [AFP‐L3], cartilage oligomeric matrix protein [COMP], insulin‐like growth factor‐binding protein 3 [IGFBP3], or matrix metalloproteinase 3 [MMP3]) further increased sensitivity for the detection of both early stage and all‐stage HCC. The addition of age and sex to the three‐biomarker panel resulted in an improved diagnostic performance. Conclusion: The combination of AFP and PIVKA‐II, with either IGFBP3, COMP or MMP3, plus age and sex, demonstrated the best performance for the detection of early‐ and all‐stage HCC. These novel panels performed similar to that of the GALAD score (sex [gender], age, plus serum levels of AFP, AFP‐L3 and DCP [PIVKA‐II]), a promising screening tool developed for HCC detection. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the major cause of acute viral hepatitis in several countries in Europe. HEV is acquired mainly by consumption of contaminated pork but can also be transmitted through blood transfusion. HEV infection is usually self-limited but can become persistent in immunocompromised persons. During the first 30 months of HEV RNA universal screening of blood donations in Catalonia, Spain, we identified 151 HEV RNA-positive donations (1/4,341 blood donations). Most infected donors reported consumption of pates and sausages, and 58% were negative for HEV IgM and IgG. All HEV isolates belonged to genotype 3. All infected donors spontaneously resolved the infection, and no neurologic symptoms and reinfections were observed after 1 year of follow-up. Since the implementation of HEV RNA universal screening, no new cases of transfusion-transmitted HEV infection were reported. Our data indicate HEV screening of blood donations provides safer blood for all recipients, especially for immunosuppressed persons. [ABSTRACT FROM AUTHOR]

Background & aims: HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods: We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results: We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions: Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA's therapies. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. The minimum criterion for diagnosis of acute infection is detection of anti‐HEV antibodies, although there are scant data on IgM duration. Our aim was to assess the persistence of HEV markers after acute self‐limited hepatitis E. HEV serological tests (IgM by Mikrogen and Wantai and HEV‐Ag) and HEV RNA were carried out in two cohorts: (a) patients with prior acute hepatitis E (ALT >10 x ULN plus positive IgM ± HEV RNA) currently self‐limited and (b) 50 blood donors with positive HEV RNA. Among 25 cases of prior acute hepatitis E, after a median follow‐up of 34 months, all presented undetectable HEV RNA. However, anti‐HEV IgM remained detectable in 14 (56%) by Mikrogen, 6 (24%) by Wantai and none for HEV‐Ag. Anti‐HEV IgM tested positive in 80%‐100% within the second year and 17%‐42% over 3 years later, by Wantai and Mikrogen, respectively. Among HEV RNA‐positive donors, 12 (25%) tested positive for either IgM by Mikrogen or Wantai, 9 (18%) for both and 18 (36%) for HEV‐Ag. HEV‐Ag positivity was more likely as HEV RNA was higher (14% if <2.2 log IU/mL; 64% if RNA ≥ 3.7). Overall, HEV‐Ag performed best, with a positive predictive value of 100% and diagnostic accuracy of 57%. Anti‐HEV IgM exhibited unexpectedly long persistence after a self‐limited acute hepatitis E. HEV‐Ag had the best performance and could be especially useful in settings where HEV RNA is not available. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) can be transmitted by transfusion of any type of blood component, but there are few data on the potential risk of transmitting this virus and the associated complications. We provide evidence that HEV can be transmitted by cryosupernatant plasma, and that HEV infection can act as a trigger for thrombotic thrombocytopenic purpura (TTP).Study Design and Methods: A patient with a history of TTP treated with plasmapheresis 2 months previously developed jaundice and a TTP exacerbation with purpura, thrombocytopenia, schistocytes, and undetectable ADAMTS-13 activity. He was diagnosed with acute hepatitis E and treated with ribavirin. TTP remitted with remission of HEV infection.Results: Traceback to determine the source of the infection showed that 1 cryosupernatant plasma among the 99 different blood components used for the patient's last plasmapheresis was positive for HEV RNA, with an estimated viral load of 5000 to 10,000 IU/mL. Phylogenetic analysis proved the transfusion-transmitted route of acute hepatitis E.Conclusion: In a patient with TTP, acute HEV infection transmitted by cryosupernatant plasma may trigger exacerbation of TTP, which can be controlled on remission of HEV infection with ribavirin. [ABSTRACT FROM AUTHOR]

However, between January 2020 and July 2021, the plasma fractionator has reported only three plasma units positive for B19, from three whole blood donors, one male and two females that donated on 18 January, and 17 and 28 February 2020. Parvovirus B19 (B19) is a small non-enveloped DNA virus, discovered in 1975 by Yvonne Cossart in the blood of a healthy blood donor. B19 infections follow a seasonal pattern in plasma donors, most positive plasma units corresponding to donations obtained between March and July [1]. [Extracted from the article]

Background: Human immunodeficiency virus 1 (HIV-1) subtype B is predominant in Spain. However, the recent arrival of immigrant populations has increased the prevalence of non-B subtypes and circulating recombinant forms. The objective of this study was to determine the prevalence of HIV-1 subtypes and transmitted drug-resistance mutations in blood donors from the Catalonian region (northeastern Spain).Study Design and Methods: HIV-1-positive blood donors identified in Catalonia from 2005 to 2014 were included. Demographic variables and risk factors for HIV-1 acquisition were recorded. HIV-1 subtyping was carried out by HIV-1 DNA polymerase region sequencing, and phylogenetic analyses were performed using the neighbor-joining method.Results: During the study period, 2.8 million blood donations were screened, and 214 HIV-1-positive donors were identified, yielding an overall prevalence of 7.7 per 100,000 donations (89% men; mean age, 34 ± 10 years). Most HIV-1-positive donors were native to Spain (81%), and 61% were regular blood donors. When risk factors were known, 62% reportedly were men who had sex with men. HIV-1 subtyping was possible in 176 HIV-1-positive individuals: 143 (81%) had HIV-1 subtype B, and 33 (19%) had non-B subtypes. Most HIV-1 non-B subtypes were circulating recombinant forms (n = 20; 61%). Factors associated with HIV-1 subtype B were male sex (p = 0.007) and men who had sex with men (p < 0.001). The overall prevalence of transmitted drug-resistance mutations was 14%.Conclusion: Non-B subtypes, circulating recombinant forms, and transmitted drug-resistance mutation sequences circulate among HIV-1-positive blood donors in Catalonia. Continuous local epidemiological surveillance is required to implement optimal prevention strategies for controlling transfusion-transmitted HIV and to improve health policies regarding HIV infection. [ABSTRACT FROM AUTHOR]

Aims: To investigate the influence of IL28B polymorphism in occult hepatitis B infection (OBI) and whether IL28B genetic variants are associated with hepatitis B virus (HBV)-specific T-cell responses. Patients and Methods: The rs12979860 IL28B genotype was determined in 34 OBI blood donors, 22 spontaneous HBV resolvers, 36 inactive HBV carriers and 25 seronegative donors. T-cell responses to HBV recombinant proteins were assessed by interferon-γ enzyme-linked immunospot assay. Results: The frequency of the IL28B CC genotype among OBI patients was similar to that of inactive carriers [41 vs. 39%, respectively, p = 0.961; odds ratio (OR) = 1.10; 95% confidence interval (CI) = 0.42-2.86; p = 0.845]. The IL28B CC genotype was found more frequently in spontaneous resolvers, although the differences were not significant (45 vs. 39%, spontaneous resolvers and inactive carriers, respectively; p = 0.828; OR = 1.31; 95% CI = 0.45-3.83; p = 0.622). HBV-specific T-cell responses were detected in OBIs, and significantly stronger T-cell responses towards hepatitis B envelope antigen were observed in those with the IL28B CC genotype. In spontaneous resolvers and inactive carriers, IL28B CC did not correlate with the magnitude of T-cell responses. Conclusions: In OBI donors, IL28B CC correlates with the intensity of HBV-specific T-cell responses. In this study, IL28B CC is not statistically associated with OBI or with HBV clearance, but a larger number of cases is needed before completely ruling out its role in HBV infection. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Hepatitis E virus ( HEV) is an emerging threat to the safety of blood transfusion. The aim of this study was to determine HEV immunoglobulin ( Ig) G and RNA prevalence in Catalan blood donors. Study Design and Methods Nearly 10,000 samples were collected from anonymized, unpaid donors at the Banc de Sang i Teixits ( Barcelona, Spain) from June to December 2013. For the serology study, a subset of 1082 donations was tested in parallel for HEV IgG using Wantai and Mikrogen enzyme-linked immunosorbent assay tests. Samples were tested individually (individual-donation nucleic acid test [ ID- NAT]) for HEV RNA using the Procleix HEV assay (95% limit of detection 7.9 IU/ mL). Procleix repeat-reactive donations were confirmed by an in-house real-time polymerase chain reaction ( PCR) test. Results The prevalences of IgG anti- HEV in Catalan blood donors were 19.96% ( Wantai assay) and 10.72% ( Mikrogen assay). Screening of 9998 samples with the Procleix HEV assay yielded three real-time PCR-confirmed and IgM and IgG anti- HEV-positive donations with viral loads of 250, 564, and 2755 IU/ mL. The donation with highest viral load was genotype 3f. HEV RNA positivity rate was one per 3333 donations (0.03%; 95% confidence interval, 0.01%-0.09%). Conclusion The Procleix HEV ID- NAT screening system has provided evidence of HEV RNA presence in Catalan blood donors. Further data are needed to assess the impact of HEV infection in at-risk patients to design the best strategy to increase blood safety. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus ( HCV) transmission from a chronic patient to a susceptible individual is a good opportunity to study viral and host factors that may influence the natural course of hepatitis C infection towards either spontaneous recovery or chronicity. To compare a documented case of a bottleneck event in the sexual transmission of HCV from a chronically infected patient to a recipient host that cleared infection. Methods Host genetic components such as Class I and II HLA and IL28B polymorphism (rs12979860 SNPs) were identified by direct sequencing and LightMix analysis, respectively. Deep nucleotide sequence analysis of quasispecies complexity was performed using massive pyrosequencing platform (454 GS- FLX), and the CD4 specific immune response was characterized by ELISPOT. Results and Conclusions Sequencing analysis and CD4 response highlighted several NS3-helicase domains in which an interplay between amino acid variability and CD4 immune response might have contributed either to chronicity in the donor patient or to viral clearance in the receptor (newly infected) patient. [ABSTRACT FROM AUTHOR]

The optimal timing to treat recurrent hepatitis-C virus (HCV) after liver transplantation (LT) remains uncertain. We compared the outcome of early (acute phase) and deferred (chronic phase) antiviral treatment for recurrent HCV infection in this population. Consecutive HCV genotype-1 infected LT patients receiving antiviral therapy between 2001-2010 were retrospectively classified according to histology at treatment start into the early or deferred treatment group. Measured endpoints included sustained virological response (SVR) rates and long-term survival. The study cohort comprised 105 patients: 60 (57%) received early treatment (ET) and 45 (43%) deferred treatment (DT). The median interval from LT to antiviral start was 3 (1-9) and 18 months (11-74) in ET and DT respectively. The SVR rate was similar in both treatment groups (23% ET and 36% DT; p = 0.27). After a median follow-up of 5.8 years, all-cause and liver-related mortality were similar in both groups. Variables independently associated with mortality included pre-treatment bilirubin > 2 mg/dL (HR 6.1, 95%CI: 2.8-13.7; p < 0.001), donor age > 60 (HR 3.1, 95%CI: 1.4-6.7; p = 0.01), and failure to achieve SVR (HR 10.3, 95%CI: 1.3-18.3; p = 0.03). In conclusion, early treatment of recurrent HCV is safe, but does not lead to higher SVR rates. In HCV-infected LT recipients, elevated bilirubin, older donor age, and failure to achieve SVR are independently associated with increased mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood donors are routinely screened for hepatitis C virus (HCV) infection. Some show weak anti-HCV responses, often restricted to a single antigen on confirmatory immunoblot (recombinant immunoblot assay [RIBA]) testing. The aim of this study was to investigate the extent to which such RIBA-indeterminate donors had previously been exposed to HCV. STUDY DESIGN AND METHODS: T-cell responses to HCV recombinant proteins (core, NS3, and NS3 helicase) were analyzed using an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay and quantification of cytokines in culture supernatants in 27 RIBA-indeterminate donors, 60 RIBA-confirmed donors (48 with and 12 without HCV RNA), and 30 RIBA-negative donors. RESULTS: HCV-specific T-cell responses were identified in 13 (48%) RIBA-indeterminate donors, 33 (55%) RIBA-confirmed donors, and 4 (13%) RIBA-negative controls (p = 0.008 and p < 0.001, respectively). The magnitude of the T-cell response among indeterminate donors was similar to that of RIBA-confirmed donors for all HCV antigens and the specificity of the ELISpot results was confirmed by antigen-specific cytokine production (interleukin-2 and IFN-γ) in short-term culture supernatants. CONCLUSIONS: These findings confirm that approximately half of RIBA-indeterminate donors have resolved a previous HCV infection and suggest that ELISpot might be a useful tool to clarify the status of such donors and help in their counseling and management. [ABSTRACT FROM AUTHOR]