Page 2034 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 120 Transfusion-Transmitted Diseases 1805

At most 20% to 30% of newly infected persons develop recogniz- with an average incubation period of 28 days (range, 15 to 50 days)
able symptoms during acute HCV infection. Some 20% of infected with signs or symptoms persisting for less than 2 months. The inci-
individuals clear their infection over a relatively short initial period, dence of HAV infection in the United States fell by 76% between
remaining antibody positive but RNA negative. Chronic infection 1997 and 2003 after the recommendation for targeted immunization
develops in 75% to 85% of persons infected after 45 years of age and of members in high-risk communities. Populations at risk include
in 50% to 60% of those infected as children or young adults. Chronic those in areas where extended community outbreaks occur and
HCV infection progresses to cirrhosis in 15% to 30% over 30 years children living in states that have high and intermediate rates of
of observation. Hepatocellular carcinoma occurs in 1% to 4% per disease, staff and residents of closed communities, close personal
year in those with cirrhosis. HCV is among the most prevalent causes contacts of cases, the staff and parents of children in day-care centers,
of chronic hepatitis, cirrhosis, and primary liver cancer in the devel- and those with common-source exposure to infected food or water.
oped world and is the most common indication for liver transplanta- For many sporadic cases there is no recognized source. HAV is self-
tion in the United States, resulting in around 2400 procedures limited with no chronic carrier state, but approximately 10% to 15%
annually. of infected individuals develop a more prolonged or relapsing illness.
A single positive anti-HCV result cannot distinguish between It is the most frequent cause of hepatitis among children under 11
acute and chronic HCV infection or between current or cleared years of age.
infection. In 2012 laboratory criteria for the confirmation of anti- Transfusion-related transmission, although rare, is caused by a
HCV reactivity were modified to add one specific assay including blood donation from a recently infected, asymptomatic, viremic
RNA detection, using a supplemental anti-HCV assay (as available) individual. The peak viremia occurs 2 weeks before onset of jaundice
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or a single value above a specific threshold on the screening test. or elevation of hepatocellular enzymes and persists for a median
The risk for posttransfusion HCV infection declined progressively period of 42 days (range, up to 59 days). The virus is quite resistant
with the introduction of surrogate markers for non-A, non-B hepatitis to many inactivation procedures, including the pathogen-reduction
in the 1980s (alanine aminotransferase [ALT] and anti-HBc) and of procedures being developed for cellular blood components (e.g.,
serologic testing for HCV antibodies in May 1990, followed sequen- licensed psoralens or investigational riboflavin, both with ultraviolet
tially by improved serologic testing and NAT. The seronegative- [UV] irradiation) and fresh-frozen plasma (solvent/detergent and
window period for the first-generation HCV antibody test extended methylene blue). Transmission by clotting-factor concentrates treated
to 6 months from infection, but was reduced to 82 and 70 days with with the solvent/detergent pathogen-reduction process occurred in
second- and third-generation assays, respectively. NAT further the 1990s, but not thereafter. Plasma for further manufacture is
reduced the window period to approximately 7 days. The risk per routinely screened for HAV RNA by pooled NAT.
unit declined from an estimated 1 per 276,000 units to 1 per An indefinite deferral for a clinical history of viral hepatitis after
1,935,000 units. 11 age 11 years has been required in the United States (regardless of the
Like HBV, in the United States, testing for HCV RNA has used specific viral agent). Because most viral hepatitis in the United States
NAT in small minipools combining aliquots from 16 to 24 donations before 11 years is HAV, with its relatively brief and self-limited
(currently 6 to 16). Loss of test sensitivity because of sample pooling viremia, individuals with a history of hepatitis before the age of 11
was tolerable given the rapid increase or burst of HCV viremia before are allowed to donate on the assumption they had HAV. As pointed
antibody seroconversion (estimated doubling time of 10.8 hours in out previously, the FDA has now issued new rules for donor suit-
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that period during the 40–50-day window period) and the high titer ability that do not require questioning for a history of viral hepatitis.
of viremia that remains preceding antibody seroconversion. However, A 120-day deferral is recommended after exposure to HAV during
the rest of the world (except the United States, Canada, the United community outbreaks to prevent transfusion transmission. Screening
Kingdom and most of Germany) has implemented NAT for screen- for HAV is not done for donation of blood for transfusion.
ing individual donation samples intended for transfusion. The HCV
RNA yield by NAT in seronegative donations using data from the
American Red Cross is 1 per 225,000 donations. Hepatitis E
As an alternative to NAT assays, enzyme immunoassays (EIAs)
have been developed that detect HCV HBcAg in serum or plasma, The hepatitis E virus (HEV) is a small, nonenveloped single-stranded
either as an individual analyte in parallel with antibody assays or as RNA virus in the Hepeviridae family. HEV was first recognized in
HCV antigen-antibody combination assays. These tests reduce the the 1980s in Afghanistan among soldiers with unexplained hepatitis.
preseroconversion-window period and were adopted in some devel- There is a single serotype but at least four genotypes with differing
oping countries. They are less sensitive than HCV NAT and are not geographic distributions and epidemiologic patterns. Genotypes 1
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approved for blood donor screening in the United States. Since the and 2 are generally associated with large, water-borne (fecal-orally
implementation of NAT, reports of transfusion-transmitted HCV are transmitted) outbreaks in less developed tropical countries. Illness is
virtually nonexistent. usually self-limited but can be lethal in pregnant women, their
The high seroprevalence of HCV at the onset of serology screen- fetuses, and patients with chronic liver disease. Genotypes 3 and 4
ing in the early 1990s, the prolonged interval between infection and appear to be animal viruses that result in zoonotic infection of
clinical manifestations, and the relatively high rate of HCV clinical humans, most often through consumption of inadequately cooked
sequelae prompted blood collection facilities and hospitals to conduct pork products. Genotype 3 seems to be widely distributed and is
“look-back” notification of previous recipients of blood given by present in developed countries, whereas genotype 4 seems to be more
donors found on subsequent donations to be HCV infected. Look- comment in certain Asian countries. Transfusion-related transmis-
back was subsequently made mandatory in companion rules from sion, mostly of serotype 3, has been well-documented in Japan,
FDA and the Centers for Medicare and Medicaid Services. In general, France, England, the Netherlands, and Spain. 13
HCV look-back programs found half or fewer of targeted transfused Recent studies suggest a wide range of seroprevalence rates, but
individuals alive, but were able to find both seropositive and RNA- some of the variability may be attributable to the differences in
positive recipients who were unaware of their status. performance characteristics of the tests used and some to dietary
habits. Most studies indicate a cohort effect, with prevalence rates
Enterically Transmitted Hepatitides increasing with age. Transfusion infectivity is logically associated with
the presence of detectable viral RNA in the plasma and the frequency
of this finding varies between 1 in 1000 to 1 in 10,000 donations.
Hepatitis A In a large study in England, 225,000 donations were tested and
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79, or 1 in 2848, were found to be positive when tested for HEV
The hepatitis A virus (HAV), a nonenveloped picornavirus, genus RNA. For 43 of these, recipient tracing was possible and 18 (42%)
Hepatovirus, is transmitted predominantly by the fecal-oral route, showed evidence of transfusion-transmitted infection. In contrast, in