How can overcome problem of Hepatitis C transmission during window period among blood donors?
Post-transfusion hepatitis
Post-transfusion hepatitis is the most common disease transmitted by blood transfusion and it has a major health impact. Post-transfusion hepatitis can be due to hepatitis C virus, hepatitis B virus, hepatitis A virus, CMV or Epstein–Barr virus. The incidence varies in different parts of the world. In the US there are about 90–111 cases of post-transfusion hepatitis C and 66–153 of post-transfusion hepatitis B annually per million units of laboratory tested blood.122–124
Hepatitis A usually has a short period of viremia and generally does not involve a carrier state. Thus, post-transfusion hepatitis A is rare, although it can occur if an individual donates blood during the short period of viremia before symptoms develop.125,126 Donated blood is not tested for hepatitis A because hepatitis A antibodies are not present at this early stage of infection, there is no practical screening test for the virus itself, and post-transfusion hepatitis A is rare.
Most individuals infected with the hepatitis B virus are asymptomatic but about 10% develop persistent viremia and chronic hepatitis B. Thus, an infectious, but apparently healthy, individual may meet all of the donor medical history criteria and donate a unit of infectious blood. Routine screening of blood donors for hepatitis B surface antigen has reduced the previous high incidence of post-transfusion hepatitis B.
In the late 1980s, the hepatitis C virus was discovered127,128 and this virus accounts for almost all cases of non-A, non-B hepatitis. Testing for antibodies to hepatitis C virus was introduced in the early 1990s and has greatly reduced post-transfusion hepatitis C. Because the screening test for hepatitis C detects antibody to the virus, there is a ‘window’ period during which the individual has viremia and is infectious, but during which the test for antibodies to hepatitis C virus is negative. Blood donation by asymptomatic individuals during this window period accounts for much of the remaining post-transfusion hepatitis. This delay in antibody production had led to the development of tests to screen donated blood by detection of viral DNA or RNA. This method has been referred to as nucleic acid amplification testing (NAT) and will be discussed later.
Viral Hepatitis
S.A. Weinman, R. Taylor, in Pathobiology of Human Disease, 2014
History
Transfusion-associated hepatitis was a major impediment to the use of blood transfusion during the latter half of the twentieth century. There were estimates that by the early 1960s, there was as much as a 30% risk of hepatitis from a single transfusion. After the discovery of the HBsAg and its application to screening the blood supply, there was a widespread expectation that the problem of transfusion-associated hepatitis would be solved. Unfortunately, HBV screening revealed that almost 85% of posttransfusion hepatitis was caused by an agent other than HBV. This agent was referred to as non-A, non-B (NANB) hepatitis, and although its viral nature was clear because filtered serum extracts were able to infect chimpanzees, the virus itself eluded identification by conventional morphological techniques.
The problem was solved by Dr. Michael Houghton and his colleagues at Chiron Corporation who used a large-scale screening technique to find the virus. It was already known that NANB could be transmitted from human to chimpanzee and there were well-studied samples of very high-titer infectious chimp serum. Houghton and his colleagues reasoned that patients who had developed posttransfusion NANB hepatitis should have antibodies that would react with a protein encoded by viral nucleic acid present in the infectious chimp serum. They generated a phage library derived from total nucleic acid (DNA and RNA) present in the chimp serum and expressed these as clones in bacteria. They screened one million clones for immunoreactivity to human posttransfusion hepatitis serum and obtained one hit. This identified an epitope on one of the viral proteins, and from that point, the rest of the virus could be readily identified.
Foreword
Jules L. Dienstag MD, in Handbook of Liver Disease (Third Edition), 2012
Transfusion-associated hepatitis—most of which, in retrospect, was caused by hepatitis C—occurred in 30% of transfusion recipients prior to the 1970s; it declined to 10% in the early 1970s with the switch from commercial to volunteer blood donors, to under 5% when surrogate markers were introduced to screen blood, and to almost never (1 in 2.3 million transfusions) with sensitive nucleic acid amplification to test donor blood. Who could have predicted in the 1970s that hepatitis C was not primarily a transfusion-associated disease or that the annual incidence of acute hepatitis C would fall by almost 90% in the 1990s?
Transfusion-Transmitted Diseases
Susan L. Stramer, Roger Y. Dodd, in Hematology (Seventh Edition), 2018
Non–A-E Hepatitis
Cases of posttransfusion hepatitis only rarely if ever occur but there remains speculation that undiscovered hepatitis agents exist. A small but consistent percentage of community-acquired hepatitis cases test negative for known hepatitis viruses, some cirrhosis is classified as “cryptogenic,” an etiologic agent for hepatitis-associated aplastic anemia eludes description, and the cause of some cases of acute liver failure remains elusive. Several candidate agents have been proposed as non–A-E hepatitis viruses. None of these agents have been shown to be pathogenic and are instead likely commensal and nonpathogenic.
GBV-C (initially called hepatitis G virus) is a flavivirus with no confirmed disease association that is transmitted parenterally, including frequently from transfusion. Of interest, GBV-C infection may delay progression of disease in those co-infected with HIV, which has led to studies of the interactions of these viruses.16
From 1% to 4% of US blood donors are viremic compared with 15% to 20% of injection drug users who have detectable GBV-C RNA. Infection occurs frequently among those infected with HCV and HIV. More people have antibodies against the E2 envelope protein, in the absence of RNA, suggesting viral clearance. GBV-C has not been shown to cause liver disease or other morbidity, and hence there is no consideration of donor screening at this time. GBV-C is now referred to as a human pegivirus. A second human pegivirus has recently been described associated with HCV likely as a result of an acute parenteral co-infection event, but again, has not been associated with hepatitis or any pathology. This virus was identified by next generation sequencing.17 Likely other such commensal agents will continue to be identified by use of sophisticated molecular techniques.
The torque teno virus (TTV) complex is a genetically diverse group of nonenveloped DNA viruses in the family Circoviridae, which was discovered in 1997. They cause viremia, and they are transmitted by transfusion, but they cause no recognized liver disease or other clinical illness.
SEN virus (SENV), another member of the Circoviridae, was described using degenerate polymerase chain reaction (PCR) primers while working with TTV. After an initial report associating SENV variants in two patients with transfusion-associated non–A-E hepatitis, subsequent epidemiologic studies have failed to link SENV with clinical hepatitis.
Viral Hepatitis
Samer S. El-Kamary, ... Shyamasundaran Kottilil, in Hunter's Tropical Medicine and Emerging Infectious Diseases (Tenth Edition), 2020
Prevention and Control
Dramatic reductions in post-transfusion hepatitis C occurred after the institution of screening of blood donors for HCV antibodies and HCV RNA, which were highly effective in developed countries but not as rigorously applied in developing countries. Activities in the communities, for example, cuts from barbers, dental procedures, and injections from traditional healers as well as health care providers, all may transmit HCV and can be influenced by appropriate health education.20
There is no available vaccine to prevent HCV infection, and, due to the extent of viral heterogeneity, a universally effective HCV vaccine will be difficult to develop.10
Viral Hepatitis
G Thomas Strickland, Samer S El-Kamary, in Hunter's Tropical Medicine and Emerging Infectious Disease (Ninth Edition), 2013
Prevention and Control
Dramatic reductions in post-transfusion hepatitis C occurred after the institution of screening of blood donors for HCV antibodies. However, screening of blood products may be variable in some developing countries where the risk of infection is increased because of a high prevalence of chronic HCV infection. Activities in the communities, for example cuts from barbers, dental procedures and injections from traditional healers, as well as healthcare providers, may all transmit HCV and can be influenced by appropriate health education [71]. The relatively high percentage of cases that occur without identifiable exposures, other than HCV infections among family members, complicates preventive efforts [10].
There is no available vaccine to prevent HCV infection, and, owing to the extent of viral heterogeneity, a universally effective HCV vaccine will be difficult to develop, although several are undergoing clinical trials [29]. However, protective immunity to HCV has been demonstrated. Some HCV epitopes produce neutralizing antibodies in experimental animals; primates have been protected from challenge from homologous strains when immunized with recombinant antigens; and individuals at high risk of exposure have HCV-specific cell-mediated immunity (CMI) T-cell responses in the absence of HCV-antibody or RNA. Therapeutic vaccines that assist in clearance of chronic infections or that hinder development of chronic infections could prevent chronic complications of the infection.
TRANSFUSION MEDICINE
Roger Y. Dodd, in Blood Banking and Transfusion Medicine (Second Edition), 2007
HEPATITIS G VIRUS/GBV-C
The vast majority of cases of posttransfusion hepatitis have been shown to be caused by HBV or HCV. Nevertheless, there continue to be some residual cases of hepatitis associated with transfusion. For example, in Alter's continuing studies at the National Institutes of Health, approximately 12% of cases of non-A, non-B hepatitis could not be attributed to either HBV or HCV. These residual cases appear to be mild and self-limited, and some may not even have an infectious etiology. Such cases have, however, led to a continuing search for additional hepatitis viruses. The first of such putative hepatitis viruses was identified by two separate groups in the late 1990s. In one case, scientists at Abbott Laboratories looked for genomic sequences related to those of an existing isolate known as the GB virus (GBV), which had previously been associated with hepatitis in a physician. Three viruses were identified, one of which (termed GBV-C) was found among a number of human sources.48 Working in parallel, but using a different approach, scientists at Gene-Labs isolated viral RNA sequences and characterized a virus they termed hepatitis G virus (HGV).49 It is generally accepted that these two isolates were, in fact, representatives of essentially the same virus group, which is now known as HGV.
HGV, like HCV, appears to be closely related to the Flavivirus group. It is found among a relatively high proportion of the normal population, as exemplified by blood donors. Its presence has been demonstrated both by seroprevalence studies, in which the frequency of antibodies is 3% to 15%, and more interestingly by detection of viral RNA in the plasma of 1% to 3% of normal subjects.50 Perhaps not surprisingly, the virus is readily transmissible by transfusion and is found at high prevalence among individuals who have undergone multiple transfusions. However, it has not proved possible to demonstrate that infection with HGV is associated with hepatitis or even with signs of mild liver disease, such as elevated ALT levels. Indeed, HGV appears to be a virus that is currently in search of a disease. The term hepatitis in its name may be a misnomer, attributable only to the fact that the virus was found in association with hepatitis in the first place. It is also important to recognize that the worldwide distribution of HGV clearly shows that it is not a new virus but rather one that has coexisted with humans for many centuries.
There have, however, been some intriguing observations that clearly suggest that HGV/GBV-C may have an impact on the course of HIV disease. For example, studies have shown lower mortality among co-infected individuals relative to those with HIV only.51,52 The mechanism for this effect is unclear, but it may be due to the effects of infection on the levels of a number of chemokines.53
Infectious Complications
Faranak Jamali MD, Paul M. Ness MD, in Handbook of Pediatric Transfusion Medicine, 2004
Etiologies and Definitions
Although AIDS has received most of the attention, posttransfusion hepatitis (PTH) has been a more common problem and an under-recognized cause of morbidity in transfusion recipients. Transfusion-associated hepatitis (TAH) is almost exclusively caused by viruses. These viruses include hepatitis viruses A through E (HAV, HBV, HCV, HDV, HEV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and possibly newly described hepatitis viruses (such as GBV-C, TTV, and SEN-V). Blood donors with HBV and HCV can have a prolonged asymptomatic carrier state, whereas HAV and HEV are enterically transmitted viruses, which circulate only transiently during the acute phase of infection with no carrier state, and the viremic individual is usually clinically ill and symptomatic. Therefore HAV and HEV are not considered as important etiologies for TAH. Hepatitis D virus is a defective virus, which is found only in the presence of HBV infection; therefore screening donors for HBV simultaneously eliminates the risk of HDV.
Anellovirus
P. Biagini, P. de Micco, in Encyclopedia of Virology (Third Edition), 2008
Clinical Significance
Since their discovery, the question of a possible implication of anelloviruses in a particular disease is still a matter to debate.
Historical presentation of TTV as associated with elevated transaminase levels in post-transfusion hepatitis of unknown etiology suggested that the virus was able to induce non-A–G hepatitis. Therefore, TTV was suspected as a possible cause of some forms of acute and chronic hepatitis and fulminant liver failure, and could be involved in liver diseases. The identification of TTV in the general population seems to refute this interpretation and led to the suggestion that the virus may cause only occasional liver injury, either by the implication of hepatotropic variants or by the presence of host determinants enhancing the pathogenicity of TTV.
The further identification of TTMV and ‘small anellovirus’ DNA in humans has increased the number of hypotheses concerning the impact of anelloviruses in human health. Hence, based on studies involving patient cohorts with well-defined health disorders, it has been suggested that this class of viruses may also be implicated in various diseases such as pancreatic cancer, systemic lupus eythematosus, idiopathic inflammatory myopathies, or chromosomal translocations. The implication of anelloviruses in respiratory diseases has also been proposed following studies involving cohorts of children suffering from asthma or rhinitis. It has also been suggested that the respiratory tract could be a site of primary infection in young children and a site of continual replication of TTV and related viruses.
Other studies suggested a possible link between the viral load and the immune status of the host because of high TTV or TTMV titers in plasma samples from immuno-compromised patients, but this remains hypothetical since the loads of TTV and TTMV can differ extensively among individuals in the general population.
To overcome the limitations of a diagnosis of anellovirus infection based only on highly conserved amplification systems, it has been suggested that it would be useful to compare individuals with specific diseases with a refererence population such as blood donors. Such an approach may lead to the recognition of a possible pathogenic role of these viruses.
Alternatively, anelloviruses may be considered as part of the ‘normal’ human flora.
Hepatitis B and Hepatitis Delta Viruses
Christopher J. Burrell, ... Frederick A. Murphy, in Fenner and White's Medical Virology (Fifth Edition), 2017
Prevention of Transmission
Routine screening of blood donations for HBsAg using sensitive immunoassays has almost eliminated post-transfusion hepatitis B in economically developed regions. Intravenous drug users are frequently the targets of educational campaigns in order to reduce the high risk of transmission accompanying the sharing of contaminated syringe needles. The prevention of sexual transmission is addressed by general education advocating safe sex practices, monogamy, and screening of sexual partners for HBsAg. Partners of known carriers should be vaccinated and encouraged to avoid contact with the carrier’s blood or other secretions, for example, by using condoms, covering skin sores or abrasions, and avoiding the sharing of toothbrushes, razors, eating utensils, etc. Perinatal transmission to newborn infants of carrier mothers can be minimized by inoculation at birth with the combined use of hepatitis B vaccine and hepatitis B immune globulin.
Prevention of infection in healthcare workers and their patients is based upon vaccination and universal precautions in the ward, theater, and laboratory founded on the presumption that any patient may be infectious. Barrier techniques include wearing of gloves, gowns, masks, and eye-shields to prevent exposure to blood in high-risk situations, such as during invasive procedures, avoidance of mouth-pipetting and of eating or smoking while working, meticulous handwashing routines, careful attention to the disposal of blood and body fluids and to the cleaning-up of blood spills with appropriate chemical disinfectants (such as 0.5% sodium hypochlorite [5000 ppm available chlorine]—glutaraldehyde and formalin are no longer used in most countries because of the cancer risk to staff), special precautions in disposal of used needles, the use of disposable equipment wherever possible, and appropriate procedures for the sterilization of reusable equipment. These approaches to aseptic technique and sterilization of equipment should apply equally to dentists, acupuncturists, tattooists, etc.
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https://www.who.int/bloodproducts/brn/ResRiskGL_WHO_TRS_1004_web_Annex_4.pdf?ua=1
It is done by examining blood and making sure that it is free of any pathogenic substances by the blood laboratory.
Article Risk of Window Period Hepatitis-C Infection in High Infectio...
https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934252/&ved=2ahUKEwjkvsXpgsfqAhUBGewKHd-JBU4QFjAKegQIARAB&usg=AOvVaw0OW4D-zcyh5pQg2UClyNCU
Hi Dr.
Article Hepatitis C among blood donors: cascade of care and predicto...
Dear dr.
Article Hepatitis C among blood donors: cascade of care and predicto...
Hi Dr.
https://www.researchgate.net/deref/https%3A%2F%2Fwww.medicalnewstoday.com%2Farticles%2F320375
https://www.researchgate.net/deref/https%3A%2F%2Fwww.medicalnewstoday.com%2Farticles%2F320375
Good morning Dr.
https://www.researchgate.net/deref/https%3A%2F%2Fwww.medicalnewstoday.com%2Farticles%2F320375
With a good control of testing HVC in all blood-donors might be enough
By examining blood in a laboratory, and when it is sure that it is free of pathogenic microbes, it is given to those in need or a diaper in a blood bank.
Using detection of HCV RNA by PCR in blood donors excludes almost completely the risk of HCV transmission. That is the strategy used in France since many years, using a simple strategy of screening pools of blood samples. therefore, the risk of HCV transmission by transfusion is estimated to be close to zero in France.
By performing PCR test that is more sensible than the other screening tests
Dear Dr.
1- Real time PCR to detect viral load
2- Indirect ELISA
A thorough medical history concerning the blood donor and the detection of HCV RNA using real time PCR, along with HCV antibodies could be of great importance