Transfusion-transmitted HCV Research Articles

Investigation of transfusion associated hepatitis C virus infection in Taiwan, 2015–2018

Continuous strengthening of the safety of blood products to reduce the risk of transfusion-transmitted HCV in recipients is an important issue of Taiwanese government concern. Since 2013, highly sensitivity serology and NAT assays were simultaneously used for blood donation screening to shorten the window period of HIV, HBV and HCV infections. 15 cases of suspected transfusion-transmitted HCV infection were analyzed in 2015-2018. No HCV nucleic acid was detected among a total 91 bags of donated blood. Eleven cases among the 15 suspected recipients were positive for HCV nucleic acid, and 9 recipients had genotype results. Of these 9 recipients, five for genotype 1b (5/9, 55.6%), three for genotype 2a (3/9, 33.3%) and one for genotype 2b (1/9, 11.1%). We will continuously monitor the blood safety of recipients. There have been no confirmed cases of acute hepatitis C (AHC) infection due to transfusions of HCV contaminated blood product in 2015-2018 in Taiwan.

PURSUING EPIDEMIOLOGICAL INVESTIGATION OF CASES OF POSSIBLE HBV OR HCV INFECTION OF THE RECIPIENT WITH TRANSFUSIONS OF DONOR BLOOD COMPONENTS

Background. Nosocomial transmission of HBV and HCV is often believed to be associated with transfusion of inapparent infection blood. Nevertheless, recently both promotion of voluntary (fee free) donorship and the evolution of laboratory screening, including the introduction of high-sensitivity tests, have significantly reduced the transfusion-associated complications, including infectious ones. The incidence ratae of primary transfusion-transmitted infections in patients with hematological malignancies remains to be high. A lot of publications are devoted to epidemiological studies on the determination of the source of infection with parenteral viral hepatitis by virtue of molecular analysis of viral strains, which is one of the important tools for obtaining objective data on the presence or absence of epidemiological relationship in the investigation of iatrogenic cases of infection. However, there is still no clear algorithm for pursuing epidemiological investigations of such cases. The aim of this study was to develop the procedure for the epidemiological investigation of probable transfusion-transmitted HBV and HCV infection with the use of Laboratory Information System and Transfusiology Information System software in patients with hematological malignancies. Material and methods. 6 cases of primary HBV and 3 cases of primary HCV were registered in patients with hematological malignancies in the National Medical Research Center for Hematology. All patients had a history of blood transfusions. A two-steps procedure for the epidemiological investigation was developed. 5 epidemiological investigations were held according to this procedure. 35 archival blood samples (7 from patients and 28 from blood donors) were tested for serological and/or molecular markers of HBV and HCV to fulfill this. Results. First step of procedure includes the determination of the date of initial infection (IID). IID is an earliest point of maximal likelihood of the detection of viral markers by laboratory techniques. This value is calculated on the basis of the results of a comprehensive virological examination of the recipient. The second step includes a history of blood transfusions from IID up to date of initial detection of primary infection evaluation. Then the analysis of donor-recipient pairs should be executed for the detection of probable sources of infection. As the result of study 5 epidemiological investigations were held in accordance to the developed procedure and the Laboratory Information System and Transfusiology Information System software. Two of the five investigations cannot be completed because of donors’ rejection to undergo a follow-up examination. In other cases infection transmission through the blood transfusion was excluded. Conclusion. A standard operating procedure of epidemiological investigation of HBV or HCV transmission has been developed and implemented. In order to reveal the latent forms of these infections a protocol of viral screening in patients with hematological malignancies at the admission to hematology ward was also developed and implemented.

Low Yield From Hepatitis C Virus (HCV) Lookback At a Large Cancer Center

While chronic hepatitis due to HCV is a major health problem in the USA, blood transfusions pose a low risk of transmission. The federally mandated lookback process is initiated when a blood donor, previously negative or untested for HCV, now has a positive test. The process serves to identify any possible transmission during the “window period.” While there have been publications on lookback series from single institutions and countries, to date there has not been data presented solely from a cancer center. Moffitt Cancer Center (MCC), a large NCI-designated comprehensive cancer center, has had 291 HCV lookback investigations. Although the average age at time of transfusion was 51, this failed to include a number of patients on whom an electronic medical record was not created. Most of the transfusion recipients had advanced age or were ill from their cancer and had died prior to the investigation, accounting for 234 (80.4%) of the cases. Five of the cases were blood components that had expired and were never transfused. Six cases identified blood components that were never received and were actually transfused at other facilities. One case had no documentation of the recipient of the fresh frozen plasma unit. Eight cases were from patients who were alive but not tested either due to patient decision or inability to get in contact with them. Out of the 37 patients that were subsequently tested, 35 (94.5%) of them tested negative for HCV by either anti-HCV enzyme immunoassays (EIA) or nucleic acid amplification tests (NAT), or both. Only 2 patients (or 0.7% of all cases investigated) tested HCV seropositive (EIA and RIBA confirmed). Both transfusion recipients were elderly women who were asymptomatic for chronic hepatitis and who posed no current or past risk for transmission via their blood or body fluids. In our case series, 80.4% of recipients were deceased at the time of the investigation. The seroprevalence rate in our case series, among the 37 recipients tested for HCV and transfused between 1988 and 2012, was 5.4%. In the USA, HCV prevalence continues to be low with current estimates <1.5%. The CDC has recently expanded the recommendations for HCV testing to any persons born between 1945 and 1965, recipients of blood transfusions before July 1992, and patients with abnormal liver enzymes. Since the initiation of blood donor HCV EIA testing in 1990 and NAT testing in 1999, the risk of transfusion-transmitted HCV infection has plummeted. Given the improved public awareness of HCV, improved blood donor testing, and the low yield of the lookback process to both the recipient and society, discontinuation of the HCV lookback requirement should be considered. This case series also highlights that most transfusion recipients are either older or ill. As with HCV, several recent publications document the infrequency of transmitting human immunodeficiency virus (HIV) through modern transfusions; In England and Wales from October 1995 to December 2008, only 1 HIV positive recipient was identified with the lookback procedure. In conclusion, our large cancer center had almost 300 HCV lookback notifications and most transfusion recipients had advanced cancer and died prior to case investigation. The series found 94.5% of recipients tested had no evidence of HCV transmission. Consideration should be given to focusing HCV detection efforts on the general public and to eliminating the HCV lookback requirement in transfusion recipients. Disclosures: No relevant conflicts of interest to declare.

Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti‐HBc titres or high anti‐HBc titres with high anti‐HBs titres in Japan: a prospective, individual NAT study of transfusion‐transmitted HBV, HCV and HIV infections

The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti-HBs titres. Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451-41,841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non-reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.

Bacterial contamination of blood products

Safety is always at the top priority in transfusion medicine. With improvement of viral testing, although the risk of transfusion-transmitted viral infection is now at its very low level, bacterial sepsis has been reported repeatedly. Not only they can result in serious clinical consequence but can also lead to potential medicolegal problems. Therefore, transfusion experts have looked into the prevalence, pathogenesis, detection and risk minimization of transfusiontransmitted bacterial sepsis over the past years. Below is a short update of the subject.

Estimation of delay in detecting hepatitis C virus antibodies in pools compared to individual testing on seroconversion panels

Testing for anti-hepatitis C virus (HCV) antibodies in pools may reduce blood screening costs, making this approach affordable for developing countries, provided that the dilution of infected blood does not significantly increase the number of undetectable viral particles, especially in seroconverters. This study assessed the delay in detection of HCV antibodies in five HCV seroconversion panels, tested in pools of 6-48 samples, and estimated the risk of transfusion-transmitted HCV caused by pooling. The delay in detection of positive samples was 5-12 days for pools of all sizes, adding 7% to the risk of HCV transmission that occurs when blood donors' samples are tested individually.

Visual Detection of Multiple Viral Amplicons by Dipstick Assay: Its Application in Screening of Blood Donors a Welcome Tool for the Limited Resource Settings

Hepatitis B virus (HBV) is a significant cause of transfusion-transmitted infections. To achieve entirely HBV-safe transfusion still appears to be an unreachable objective, at least in the high-prevalence regions of the developing world. Transfusion-related HBV safety depends on the screening technique adopted by the blood banks and its prevalence in the community, and the more sensitive the screening technique adopted the less the chance of transmitting HBV infection through the transfusion (1). All endeavors towards lowering the risk of transfusion transmitted HBV and/or HCV infection play an important role in prevention of this preventable human suffering. This is particularly significant in the developing countries with limited resources and overstretched health budgets. A recently published report by Dineva et al. is a remarkable achievement in this direction (2). The authors have introduced a simple, sensitive, instrument-independent technique for visual detection of multiple nucleic acid hybridization on the dipstick membrane. The report shows high sensitivity and reproducibility of the test for detection of HBV DNA, HCV RNA, and human immunodeficiency virus RNA among blood donors by minipools. Unfortunately, the genomic screening technology is still expensive and not affordable for the developing regions of the world where these viruses are highly endemic, which not only increases the risk of transfusion-transmitted HBV and/or HCV infection but is perhaps an important mode of spread of this infection. Most of the developing countries are screening the collected units of blood for HBsAg, anti-HBc, anti-HBs, and anti-HCV by enzyme immunoassay. The blood units which are anti-HBc positive or anti-HCV positive are rejected, thus leading to high rejection rates of collected units of blood. At this center, 3.2% of units are rejected because of isolated anti-HBc positivity (4). The rejection of these invaluable collected blood units and exclusion of the munificent volunteer blood donors because of isolated anti-HBc or anti-HCV positivity lead to chronic shortage of blood. The blood units which are isolated as being anti-HBc positive may not necessarily contain HBV DNA when tested by the nucleic acid amplification testing (NAT) technology, or anti-HCV-positive units may not be positive for HCV RNA if tested by PCR. Hence, they can perhaps be utilized if the low-cost genomic screening resources are made available to the developing countries; on the other hand, the anti-HBc- and/or anti-HBs-positive donors might be positive for HBV DNA if tested by the sensitive NAT assay system (3, 5). The visual detection dipstick method for detection of HBV and HCV nucleic acid appears an attractive alternative to the intricate instrument-dependent methods for the countries with limited resources. This simple instrument-independent method is less expensive than the conventional instrument-dependent method and can be adopted by the blood banks of the developing countries where these viruses are highly endemic to possibly ensure the achievement of zero risk of transfusion-transmitted HBV and HCV infection. This will not only ensure the safe blood transfusion at lesser testing cost but will also reduce the preventable human suffering of transfusion-transmitted HBV and HCV infection.

Seroprevalence of hepatitis C virus among blood donors in Rivers State, Nigeria

Anti-HCV pre-transfusion testing among blood donors has not been introduced as a mandatory test in Rivers State, hence the risk of transfusion-transmitted HCV cannot be fully ascertained. One thousand (1000) apparently healthy blood donors were screened using a rapid second - generation test, the HEP C SPOT HCV assay. An overall prevalence of 2.9% was observed in this study. The highest prevalence (8.1%) was found among adults aged between 26 and 33 years and commercial donors.

Karl landsteiner and his major contributions to haematology

Karl landsteiner and his major contributions to haematology

Laboratory assays for diagnosis and management of hepatitis C virus infection.

It was noted in 1974 that 75% of cases of transfusion-associated hepatitis were caused by NANBH, but 15 years passed before advances in molecular biology led to the cloning of the NANBH agent and anti-HCV assays were developed (2). In a little more than a decade, our knowledge of and ability to diagnose and treat HCV infections have increased dramatically. In 1990, mass screening of blood donors was implemented in the United States and was estimated to have prevented 40,000 HCV infections in the first year (2). Improvements in EIAs and the performance of NAT on donations prior to transfusion have further lowered the incidence of transfusion-transmitted HCV (39). Although the incidence of new HCV infections in the United States has declined, the population of individuals infected for ≥20 years who are at risk for serious complications is projected to increase until about 2015 (19). Improvements in therapy have resulted in better virologic response rates, and molecular HCV tests have proved useful in making management decisions. As new therapeutic options evolve and laboratory assays change, the clinical relevance and use of laboratory testing for HCV will require frequent reassessments. Consensus conferences that include experts from a variety of disciplines provide an ideal environment where these issues can be debated (12, 29).

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.

THE DISAPPEARANCE OF TRANSFUSION-TRANSMITTED HEPATITIS C VIRUS INFECTIONS IN THE UNITED STATES

Because of anti-HCV testing, rates of transfusion-transmitted HCV infections have dropped from a high level (approximately 1 per 200 units, even using volunteer, repeat donors) to an extremely low one (approximately 1 per 125,000 units). Moreover, preliminary data indicate that pooled- (and perhaps, eventually, single-) specimen NAT for HCV-RNA or EIA for HCV core antigen may reduce this risk even further. It is anticipated that implementation of one or more of these methods, coupled with one or more pathogen-inactivation steps, may functionally eliminate the risk of transmitting HCV by transfusions.

Testing of individual blood donations for HCV RNA reduces the residual risk of transfusion-transmitted HCV infection.

To allow cost-effective RNA testing with NAT techniques, the national authorities of several countries have planned or already introduced tests of mixed specimens, that is, plasma pools. High-throughput extraction, amplification, and detection of HCV RNA from individual blood donations were optimized and validated. The feasibility of the method and the frequency of anti-HCV-negative, HCV RNA-positive donations were determined in a prospective study of 27,745 allogeneic and 792 autologous individual donations. The 50- and 95-percent detection limits of the method were determined at 44 IU per mL and 162 IU per mL, respectively (World Health Organization HCV reference material). When 201 HCV RNA-positive sera were taken as a reference, the sensitivity was 97.5 percent. The assay specificity was determined at 99.77 percent. During a 20-month period, two seronegative blood donors tested positive in HCV PCR. The viral load of these donations was 6 x 10(6) and 3 x 10(7) copies per mL, respectively. Thus, the yield of HCV RNA testing in this study was 7. 63 per 100,000 screened donations (95% CI, 1.25-22.07). In both PCR-positive donors, seroconversion was found in subsequent blood samples. This study compares the feasibility of single-donation HCV RNA screening, with the detection of a relatively high percentage of window-phase donations, to data reported from groups using HCV RNA testing of plasma pools. The relative yield of NAT of individual donations versus minipools should be directly investigated in the near future.

Hepatitis C lookback programme: a single hospital experience.

As part of the national Hepatitis C (HCV) Lookback Programme, HCV-infected donors donating blood after September 1991 were identified and the fate of their previous donations received at a single hospital were traced; 123 of 160 implicated blood components were traceable and transfused. Only 19 recipients were alive and traceable and were tested for HCV. Nine of the 14 recipients (64%) of HCV-positive donations and 2 of 5 recipients (40%) of HCV-indeterminate donations had evidence of HCV infection. Neither the number of donor exposures nor the type of component was predictive of recipient HCV status. Three recipients have chronic active hepatitis. The Hepatitis C Lookback Programme successfully identifies some but not all cases of transfusion-transmitted HCV. Transfusion records, particularly in the medical case notes, should be substantially improved. Many of the traced recipients are young, so that identification of HCV is of great importance.

P-66 Natural course of transfusion-transmitted HCV infection in childhood

P-66 Natural course of transfusion-transmitted HCV infection in childhood