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• Biomarkers for over- & underimmunosuppression are needed for pediatric KTX patients. • TTV plasma loads predict CMViremia & BKViremia one month before onset of viremia. • TTV cut-offs aid to stratify pediatric KTX patients at risk for CMV & BKV infection. : Long-term allograft and patient survival after kidney transplantation (KTX) depends on the balance between over- and under-immunosuppression (IS). High levels of IS predispose to opportunistic infections. Plasma load of Torque Teno Virus (TTV), a non-pathogenic highly prevalent Annellovirus, is associated with its hosts immune status, especially after solid organ transplantation. : To investigate the association of plasma TTV load and opportunistic viral infections after pediatric KTX. : This retrospective study includes all pediatric KTX patients followed at the Medical University of Vienna 2014–2020. PCR for Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), and TTV was performed every 4–8 weeks at routine follow-up visits. : 71 pediatric KTX patients were followed with TTV measurements for a median of 2.7 years. TTV plasma load was associated with CMV DNAemia at the next visit with an OR of 2.37 (95 % CI 1.15–4.87; p = 0.03) after adjustment for time after KTX and recipient age. For a cut-off of 7.68 log10 c/mL TTV a sensitivity of 100 %, a specificity of 61 %, a NPV 100 %, and a PPV of 46 % to detect CMV DNAemia at the next visit was calculated. TTV plasma loads were also associated with BKV DNAuria and BKV DNAemia at the next visit, but not with EBV DNAemia. : This is the first study to analyse associations between TTV plasma loads and opportunistic viral infections in pediatric KTX. We were able to present a TTV cut-off for the prediction of clinically relevant CMV DNAemia that might be useful in clinical care. [ABSTRACT FROM AUTHOR]

• TTV viral load showed a dynamic pattern in renal transplant recipients. • TTV viral load was significantly lower in recipients with graft rejection. • TTV Home Brew PCR and the commercial PCR were highly comparable. • Cut-off values for rejection risk prediction may vary after transplantation. • TTV can be used as a biomarker for renal rejection post-transplantation. Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881–0.9149, p < 0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p < 0.0001). Between (181–270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log 10 copies/mL (by Home-Brew PCR) and 3.10 Log 10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log 10 copies/mL, respectively). Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period. [ABSTRACT FROM AUTHOR]

Background Torque teno viruses (TTV) are small DNA viruses whose replication is closely linked to immune status. A growing number of publications underlined the potential of TTV viral load as an indicator of immunosuppression. Objectives To demonstrate the analytical performance of the first standardized RUO (Research Use Only) assay to detect and quantify human TTV DNA in whole blood and plasma. Study design We established analytical performances for TTV load measurement in various populations. The TTV kinetics were followed in kidney recipients. TTV viral load was analyzed on whole blood samples from 42 kidney recipients follow-up, 53 kidney deceased donors and 31 healthy volunteers. Results The qPCR TTV assay detects the most prevalent human TTV genotypes and does not cross react with other viruses. Limit of detection was 2.2 log 10 copies/mL in whole blood and plasma, linearity and precision were demonstrated over the range 1.61 to 10.61 log 10 copies/mL in whole blood. Prevalence of TTV DNA in blood differed significantly among groups: 45% in healthy volunteers, 74% in donors and 83% in kidney recipients. In kidney recipients, early TTV kinetics were comparable to those previously observed with in-house assays in other transplant settings: viral load increased from an average of 4.3 log 10 to 7.9 log 10 copies/mL within the first 75 days post transplantation. Conclusion This TTV assay showed high analytical sensitivity, specificity, linearity and precision. It is a useful standardized tool to further evaluate TTV load as a biomarker of immune status that could improve individual treatment strategy. [ABSTRACT FROM AUTHOR]

• Plasma TTV levels were lower in kidney transplant recipients (KTR) who developed not only humoral, but also cellular immune responses after two-dose vaccination compared to non-responders. • A cut-off of 106 TTV copies/ml plasma at the time of vaccination reliably predicted seroconversion and cellular response to vaccination in KTR. • Plasma TTV load at the time of vaccination was inversely associated with the probability of seroconversion after vaccination in KTR, but not in dialysis patients. • The association between TTV load and seroconversion was independent of vaccine type. Immunosuppressed individuals such as kidney transplant recipients (KTR) and hemodialysis patients (DP) show impaired immune responses to COVID-19 vaccination. Plasma Torque Teno Virus (TTV) DNA load is used as surrogate for the individual degree of immunosuppression. We now assessed the association of TTV load at time of COVID-19 vaccination with humoral and cellular immune response rates to vaccination in KTR, DP, and healthy medical personnel (MP). A total of 100 KTR, 115 DP and 54 MP were included. All were SARS-CoV-2 seronegative at the time of vaccination with either BNT162b2 or mRNA-1273. Plasma TTV loads were assessed at the time of first vaccination. After two-dose vaccination, seroconversion (de novo detection of SARS-CoV-2 S1-IgA and/or IgG) was determined. In addition, cellular responses as assessed by interferon γ release and neutralizing antibodies were assessed in a subset of participants. ROC analyses were performed to define TTV load cut-offs predicting specific immune responses to vaccination. Plasma TTV loads at the time of first vaccination were negatively associated with seroconversion after two-dose vaccination in KTR (OR 0.87, 95% CI 0.76–0.99). TTV loads were significantly lower in KTR who developed humoral and cellular immune responses to vaccination compared to non-responders (p = 0.0411 and 0.0030, respectively). Of patients with TTV loads above 106 copies/ml, none developed cellular immune responses against SARS-CoV-2, and only 2 of 17 (12%) seroconverted in response to vaccination. Plasma TTV loads at the time of first vaccination in immunosuppressed individuals may be useful to predict individual vaccine-specific immune responses. [ABSTRACT FROM AUTHOR]

Background Torque Teno virus (TTV) plasma DNA load directly correlate with the level of immunosuppresion in different clinical settings. It is uncertain whether this may be the case in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Objectives We characterized the dynamics of TTV DNAemia in patients undergoing T-cell replete allo-SCT. Study design Retrospective single-center observational study including 72 allo-HSCT patients. Plasma TTV DNA loads were quantified before initiating the conditioning regimen and at different time-points after transplant by real-time PCR. White blood cells (WBC) and absolute lymphocyte counts (ALC) were measured by flow cytometry. Results A dramatic drop in plasma TTV DNA load was observed shortly after conditioning. The TTV DNA load increased steadily after engraftment reaching its peak at day +90 after transplant. The increase in TTV DNA load paralleled that of ALC, and was of greater magnitude in patients who developed severe (grades II–IV) acute graft vs. host disease. Conclusion Repopulation of lymphocytes early after allo-HSCT correlates with an increase of plasma TTV DNA load. Prospective studies are nevertheless needed to determine whether the kinetics of TTV DNAemia may allow inference of the degree of overall immunocompetence in these patients. [ABSTRACT FROM AUTHOR]

• BK Polyomavirus (BKPyV) reactivation has become a difficult problem to for kidney transplant community. • Important to identify new prognostic markers. • a promising strategy would be to monitor blood TTV levels. Assessment of the intensity of immunosuppression in transplant recipients to estimate the risk of rejection and infection is not entirely satisfactory at the present time. Determination of Torque teno virus (TTV) viral load appears to be a promising tool in this setting. We evaluated the level of replication and kinetics of TTV during the first three months after kidney transplantation compared to BK virus replication. In a retrospective cohort of 116 renal transplant recipients, TTV viral load gradually increased during the first three months post-transplantation with no significant difference or discriminatory threshold between patients with and without BK virus replication. However, the level of TTV replication appeared to be indirectly related to the risk of BK virus replication, particularly according to the induction treatment used (antithymocyte globulin: ATG or basiliximab). Among patients receiving ATG, those receiving cyclosporine had significantly lower TTV viral loads (p < 0.01) with threefold lower reactivation of BKPyV (13 vs 37%) 3 months post-transplantation. Similarly, among the women in our cohort, TTV viral load was significantly higher in women receiving ATG (6.58 ± 1.57 versus 4.62 ± 2.0 log 10 copies/mL for basiliximab: p < 0.01), also with threefold higher BKPyV reactivation frequencies (40 vs 13,3%). The multiparametric variation of TTV viral load does not appear to be individually appropriate for the early detection or monitoring of possible post-transplant BKPyV virus reactivation in renal transplant recipients. [ABSTRACT FROM AUTHOR]

• A strong correlation between in-house and commercial PCR for quantification of plasma TTV load. • An association between TTV load quantified by commercial PCR and infection/kidney graft rejection. • Performance of a commercial TTV PCR for risk stratification of infection/kidney graft rejection. Torque Teno virus (TTV) is non-pathogenic, highly prevalent and reflects the immune status of its host. TTV plasma load was suggested for risk stratification of graft rejection and infection post kidney-transplantation, for which most studies applied an in-house PCR. Recently, a commercial PCR was CE-certified for clinical use. The present study was designed to assess the performance of TTV load as quantified by the commercial PCR in the prediction of graft rejection and infection. Patients and events were selected from the prospective TTV-POET trial, including 683 consecutive adult recipients of a kidney-graft transplanted at the Medical University Vienna, 2016–2020. TTV was quantified in plasma drawn in Months 4–12 post-transplant by in-house and commercial PCR and associated with consecutive infections and graft rejections until Month 12 post-transplantation. A total of 342 samples from 314 patients with 85 biopsies (rejection, n = 18) and 79 infectious events were assessed. The two PCRs were highly associated (estimate 0.91, 95%CI 0.89–0.93), with a mean difference of 1.38 log 10 copies/mL (95%CI 1.46–1.30). The risk of rejection decreased by 25% with every log 10 increase in TTV load as quantified by commercial PCR (RR 0.75, 95%CI 0.67–0.85), and the risk of infection increased by 6% (RR 1.06, 95%CI 1.00–1.12). These data support the value of TTV quantification by commercial PCR for the risk stratification of graft rejection and infection in the first year post kidney-transplantation. The test performance determined within this study may serve to design clinical trials and subsequently, support application in clinical routine. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Torque teno virus (TTV) is a small virus belongs to Anelloviridea family. TTV is a disease orphan virus but it has often been associated with a variety of pathologies and co-infections. TTV was recently identified as an infectious agent that could potentially be involved in cases of acute enteritis. Objectives To ascertain the presence of TTV in stools from diarrheic and not diarrheic people, and to investigate an association between infection, and patient age and gender. Study design Stool samples from people exhibiting signs of enteritis (954) and from non-diarrheic individuals (76) were collected in the former Chinook Health Region (CHR) in Southwestern Alberta, Canada from May 2008 to April 2009. Viral genetic material was extracted, and detection and quantification of TTV were carried out by real-time PCR. The presence of other viral and bacterial enteric pathogens was also investigated. Results More ( P < 0.001) diarrheic people (38.8%) tested positive for TTV DNA than non-diarrheic individuals (18.4%). Furthermore, viral load was greater ( P < 0.001) in stools from diarrheic (2.0 × 10 7 copies/g) than non-diarrheic (2.0 × 10 3 copies/g) people. TTV DNA was detected most often in diarrheic individuals that were 0–5 (57.3%) and greater than 81 (59.0%) years of age. Combined across age, the prevalence of TTV was higher among men than women ( P = 0.003). Co-infections with other enteric pathogens were observed. Conclusions This study revealed a significant association between TTV prevalence and viral load, and enteritis. Also, TTV prevalence was significantly higher in the very young and elderly suggesting that immunological status is important. [ABSTRACT FROM AUTHOR]

Background Abnormally high levels of T-cell activation can persist in HIV-infected subjects despite effective anti-retroviral therapy (ART) and has been associated with negative health outcomes. The nature of the antigenic drivers or other causes of this residual T-cell activation remain uncertain. Anelloviruses are universally acquired soon after birth, resulting in persistent viremia, and considered part of the commensal human virome. Reduced immunocompetence results in increased anellovirus levels. Objectives To test whether increased levels of anelloviruses or other viruses in plasma are associated with higher levels of persistent T-cell activation during ART. Study design Two amplification methods combined with next generation sequencing were used to detect all viruses and estimate relative anellovirus levels in plasma from 19 adults on effective ART who exhibited a wide range of T-cell activation levels. Results Nucleic acids from HBV and HCV were detected in one patient each while pegivirus A (GBV-C) was found in three patients. Anellovirus DNA was detected in all patients with some individuals carrying up to eight different genotypes. Specific anellovirus genotypes or higher level of co-infections were not detected in subjects with higher levels of T-cell activation. No association was detected between relative plasma anellovirus DNA levels and the percentage of activated CD4 or CD8 T cells. Conclusions Human anelloviruses were detected in all HIV suppressed subjects, exhibited a wide range of viremia levels, and were genetically highly diverse. The level of persistent T-cell activation was not correlated with the level of viremia or genotypes present indicating that anellovirus antigens are unlikely to be a dominant source of antigens driving chronic T-cell activation. [ABSTRACT FROM AUTHOR]

Background Data regarding the influence of the APOBEC3B deletion on infectious diseases remain limited and shown discrepancies. Objectives To characterize the APOBEC3B deletion polymorphism status and its association with prevalence of co-infection with blood-borne pathogens in Indonesian HIV-infected individuals. Materials and methods A total of 597 HIV-positive blood samples were tested for the hepatitis B virus (HBV), hepatitis C virus (HCV), Torque Teno virus (TTV), GB virus-C (GBV-C), and Toxoplasma gondii . Nucleic acid was extracted from plasma samples and used for the molecular detection of HIV RNA, HBV DNA, HCV RNA, TTV DNA, and GBV-C RNA, whereas HBsAg, anti-HCV, IgM and IgG anti- T. gondii were detected through serological testing. The APOBEC3B deletion polymorphism was genotyped by polymerase chain reaction (PCR). Results The deletion genotype was associated with HCV viremia ( p < 0.001) as well as elevated IgG anti-T. gondii (adjusted OR [aOR] = 3.4). The deletion genotype was also associated with decreased levels of HBsAg (aOR = 0.03), and anti-HCV (aOR = 0.1). D/D was frequently found in HIV-infected individuals with CD4 + T cells < 14% (aOR = 5.8). The intact genotype was associated with a reduced likelihood of a CD4 + T cell count < 200 cells/μL (aOR = 0.2) but a higher prevalence of TTV co-infection (aOR = 8.6). Conclusions The APOBEC3B deletion polymorphism was found to be associated with HBV, HCV, TTV, and T. gondii co-infection in Indonesian HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Background Torquetenovirus (TTV) represents a commensal human virus producing life-long viremia in approximately 80% of healthy individuals of all ages. A potential pathogenic role for TTV has been suggested in immunocompromised patients with hepatitis of unknown etiology sustained by strong proinflammatory cytokines. Objectives The aim of this study was to investigate the sera immunological profile linked to TTV infection in bone marrow transplant (BMT) children with liver injury. Study design TTV infection was assessed in sera from 27 BMT patients with altered hepatic parameters and histological features, by the use of quantitative real-time PCR, along with TTV genogroups and coinfection with HEV. The qualitative and quantitative nature of soluble inflammatory factors was evaluated studying a large set of cytokines using the Bioplex platform. As controls, sera from 22 healthy children negative for serological and molecular hepatitis markers including TTV and HEV, and for autoimmune diseases, were selected. Results and conclusions TTV was detected in 81.4% of BMT patients with a viral load ranging from 10 5 to 10 9 copies/mL. All samples were HEV-RNA negative. A pattern of cytokines, IFN-γ, TNF-α, FGF-basic ( p < 0.01) and MCP-3 ( p < 0.001) was found significantly highly expressed in TTV-positive patients compared to TTV-negative and controls. Of note, MCP-3 chemokine showed the highest sera concentration independently of the amount of TTV load and the status of immune system deregulation ( p < 0.001). In this pilot study for the first time, a positive association was found between TTV and increased level of MCP-3 suggesting a indirect role of TTV in liver injury. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of infections in returning international travellers can be challenging because of the broad spectrum of potential infectious etiologies potentially involved. Viral metagenomic next-generation sequencing (mNGS) has the potential to detect any virus present in a patient sample and is increasingly being used for difficult to diagnose cases. The aim of this study was to analyze the performance of mNGS for viral pathogen detection in the clinical setting of international travellers returning with febrile illness. Methods: Thirty-eight serum samples from international travellers returning with febrile illness and presenting at the outpatient clinic of the Leiden University Medical Center in the Netherlands in the time period 2015-2016 were selected retrospectively. Samples were processed for viral metagenomic sequencing using a probe panel capturing all known vertebrate viruses. Bioinformatic analysis was performed using Genome Detective software for metagenomic virus detection. Metagenomic virus findings were compared with viral pathogen detection using conventional methods. Results: In 8 out of the 38 patients (21%), a pathogenic virus was detected by mNGS. All viral pathogens detected by conventional assays were also detected by mNGS: dengue virus (n=4 patients), Epstein-Barr virus (n=2), hepatitis B virus (n=1). In addition, mNGS resulted in additional pathogenic findings in 2 patients (5%): dengue virus (n=1), and hepatitis C virus (n=1). Non-pathogenic viruses detected were: GB virus C (n=1) and torque teno viruses (n=3). High genome coverage and depth using capture probes enabled typing of the dengue viruses detected. Conclusions: Viral metagenomics has the potential to assist the detection of viral pathogens and co-infections in one step in international travellers with a febrile syndrome. Furthermore, viral enrichment by probes resulted in high genome coverage and depth which enabled dengue virus typing. [ABSTRACT FROM AUTHOR]

• HPgV1 prevalence is higher in lung transplant recipients than in general population. • HPgV1 status is not associated with clinical outcome after lung transplantation. • HPgV1 replication remains stable despite post-transplant immunosuppressive therapy. • HPgV1 and TTV show different kinetics in lung transplant recipients. • TTV kinetics are not associated with the patients' HPgV1 status. Human pegivirus 1 (HPgV1) may cause persistent infections in immunocompetent and immunosuppressed individuals. Its clinical relevance, however, has not been determined. Previous studies have described a higher prevalence of HPgV1 infection in organ transplant recipients compared to healthy controls, but its occurrence in lung transplant recipients (LTRs) and its association with immunosuppressive therapy has not been assessed. The aim of this study was to evaluate the prevalence and clinical significance of HPgV1 infection in LTRs, and to compare HPgV1 loads and kinetics to Torque Teno Virus (TTV) kinetics, which reflects the level of immunosuppression. From each of 110 LTRs, five consecutive plasma samples were collected within the first year after transplantation and tested for HPgV1 RNA and TTV DNA loads by quantitative PCR. Data were related to demographic data and clinical parameters followed up for 3 years post transplantation. HPgV1 prevalence in LTRs was 18,2%. HPgV1 detection was significantly associated with younger age, but not with graft rejections or other microbial infections. The viral replication level remained unaffected by immunosuppressive therapy. This was in contrast to TTV loads which increased after initiation of immunosuppressive therapy, independent of the patients' HPgV1 infection status. In contrast to TTV, HPgV1 kinetics do not reflect the level of immunosuppression after lung transplantation, and there is no correlation between the replication of both persistent viruses in the post transplantation follow up. Thus the individual virus host interactions seem to differ substantially and require further investigation. [ABSTRACT FROM AUTHOR]

• TTV loads increase substantially with immunosuppression after kidney transplantation. • With every 10-fold TTV load-increase the risk of organ rejection decreases with 25%. • With every TTV load-increase, the risk of BKV and CMV infection stays the same. • TTV load can be used as a predictive marker of rejection after transplantation. • TTV load values could guide individual immunosuppressive drug dosing. The main challenge of immunosuppressive therapy after solid organ transplantation is to create a new immunological balance that prevents organ rejection and does not promote opportunistic infection. Torque teno virus (TTV), a ubiquitous and non-pathogenic single-stranded DNA virus, has been proposed as a marker of functional immunity in immunocompromised patients. Here we investigate whether TTV loads predict the risk of common viral infection and allograft rejection in kidney transplantation recipients. In a retrospective cohort of 389 kidney transplantation recipients, individual TTV loads in were measured by qPCR in consecutive plasma samples during one year follow-up. The endpoints were allograft rejection, BK polyomavirus (BKPyV) viremia and cytomegalovirus (CMV) viremia. Repeated TTV measurements and rejection and infection survival data were analysed in a joint model. During follow-up, TTV DNA detection in the transplant recipients increased from 85 to 100%. The median viral load increased to 107 genome copies/ml within three months after transplantation. Rejection, BKPyV viremia and CMV viremia occurred in 23%, 27% and 17% of the patients, respectively. With every 10-fold TTV load-increase, the risk of rejection decreased considerably (HR: 0.74, CI 95%: 0.71–0.76), while the risk of BKPyV and CMV viremia remained the same (HR: 1.03, CI 95%: 1.03–1.04 and HR: 1.01, CI 95%: 1.01–1.01). In conclusion, TTV load kinetics predict allograft rejection in kidney transplantation recipients, but not the BKPyV and CMV infection. The potential use of TTV load levels as a guide for optimal immunosuppressive drug dosage to prevent allograft rejection deserves further validation. [Display omitted] [ABSTRACT FROM AUTHOR]

• Low TTV-DNA prevalence in CSF samples of human subject. • TTV-microRNA positivity in CSF was higher than that of TTV-DNA. • TTV-microRNA was present in both TTV-DNA positive and negative CSF samples. • Potential implication of TTV-microRNA in brain inflammatory status. Torque teno virus (TTV) is a widespread anellovirus that establishes persistent infections in humans and represents the most abundant component of the human virome. TTV encodes microRNAs (miRNA) which are found both in viremic and not viremic subjects being potentially ideal tools for the virus to evade the immune system response and to maintain chronic infection in the host. To investigate TTV-DNA loads and TTV-miRNAs expression in cerebrospinal fluids (CSF) from subjects under analysis for the assessment of neurological diseases. Detection of TTV-DNA and TTV-miRNAs (e. g. miRNA t1a, t3b, and tth8) were carried out from CSF samples of 93 subjects with neurological diseases by using universal real-time PCR, real-time RT-PCR, and next-generation sequencing (NGS) analyses. TTV-DNA was detected in 11 of 93 (12 %) CSFs with a mean TTV load of 155 copies/mL. Conversely, 29 CSF samples (31 %) were positive for at least one TTV-miRNA, while 15 (16 %) CSFs contained all the TTV-miRNAs examined. Overall, TTV-miRNA tth8 was detected in 62 % of samples, followed by TTV miRNA t3b (56 %), and t1a (29 %). Interestingly, TTV-miRNAs were found in CSF samples that were negative for the presence of TTV-DNA. Next-generation sequencing analysis carried out from 4 TTV-DNA negative CSF samples detected reads mapped in TTV-miRNA sequences region. These results shed novel light on the relationship between TTV and the central nervous system and make compelling furthered studies for investigating the potential role of TTV-miRNAs in neurological disorders. [ABSTRACT FROM AUTHOR]

Abstract: Here we report the case of a 32-year-old Pakistani male, who developed severe aplastic anaemia after a severe attack of acute hepatitis E virus (HEV) infection. His laboratory test values were not in normal ranges. The liver enzymes were elevated. Serologic and/or molecular-based tests for hepatitis A, B, C, D, G, transfusion transmitted virus (TTV) and B19 were negative, whereas anti-HEV IgM and HEV RNA polymerase chain reaction (PCR) was also detected in the patient sample. The patient received immunosuppressive therapy for 6 months; however, he did not show response to this kind of therapy. The results of our case clearly show the causative role of HEV in the development of aplastic anaemia that might not be ignored. [Copyright &y& Elsevier]