5 Registrar, Neonatology, Apollo Hospitals, Bangladesh
6Assistant Professor of Gynaecology & Obstetrics, National Institute for Cancer Research Hospital (NICRH), Bangladesh
Submission: April 05, 2017; Published: June 07, 2017
*Corresponding author: Dr. Salahuddin Mahmud, Assistant Professor, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh.
How to cite this article: Salahuddin M, Manzoor H, Syed S A, Manjuma R, Farhana T, et al. Burden of HCV in Bangladesh: Warrants the
Screening for Blood Donors. Acad J Ped Neonatol. 2017; 4(5): 555706. DOI: 10.19080/AJPN.2017.04.555706
Globally, the morbidity and mortality attributable to hepatitis C virus (HCV) infection continues to increase. Approximately 7,00,000 persons die each year from HCV related complications, which include cirrhosis, hepatocellular carcinoma (HCC) and liver failure. It is estimated about 180 million people having hepatitis C virus infection but most are unaware of their infection. Highest number of transmission of HCV through unscreened or improperly screened blood transfusion (BT). In every case of BT in Bangladesh, so called proper donor screening done every day. But After reviewing lots of national & international guidelines and papers of blood transfusion, proved that blood donor screening tests and method of testing are not adequate & inappropriate. Lots of multi-transfused thalassemic and hemophiliac patients getting hepatitis C virus undoubtedly. Transfusions should be planned judiciously and side by side, efforts should be made to minimize the risk of transfusion transmissible infections (TTI) through adopting the international guidelines for safe blood transfusion. Awareness and knowledge would be the key to prevent the transfusion of transmissible diseases. Implementations of strict donor selection criteria and use of sensitive laboratory screening tests reduces the incidence of HCV transfusion.
Transfusion of blood components (TBC) continues to be an important therapeutic resource into the 21st century . It is a specialized modality of patient management saves million of lives but many patients requiring transfusion do not have timely access to safe blood . The safety of the transfusion lies not only in the correct selection, preparation and administration of blood products, but also in the ability to correctly interpret when such intervention is appropriate . Providing safe and adequate blood should be an integral part of every country’s national health care policy and infrastructure .
The microbiological safety of blood donations may be affected by donor’s exposure to HIV, hepatitis B, hepatitis C, syphilis and
other transfusion-transmissible infections (TTI). Through unsafe blood transfusion these microbial agents may transmit to the recipient blood and can cause morbidity and mortality . The infectious agents may present in the blood for long periods, sometimes in high titers, stability in blood stored at 4 ̊C or lower, long incubation period before the appearance of clinical signs, asymptomatic phase or only mild symptoms in the blood donor, hence not identifiable during the blood donor selection process .
The primary responsibility of a blood transfusion service (BTS) is to provide a safe, sufficient and timely supply of blood and blood products. In fulfilling this responsibility, the BTS should ensure that the act of blood donation is safe and causes no harm to the donor . However, in developing countries transmission
of infectious agents through blood transfusion are continuing .
This is mostly due to inability of the test to detect the disease or
the diagnostic window during which an acutely infected blood
donor may harbor large amounts of highly infectious viruses
without developing symptoms or detectable antigen and antibody
concentration or laboratory errors .
Hepatitis C virus (HCV) is serious threat for South East Asia
. Bangladesh, a developing country of South-East Asia, has a
population of 160 million . HCV is emerging as one of the major
health problem in Bangladesh . It is encountered sporadically
in this country . It is one of the main causes of chronic liver
disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide
and also in Bangladesh [10,11]. It is imperative to screen and
diagnose HCV infection in high risk population specially blood
donors so that those at risk of progressive liver disease may benefit
from anti-viral therapy and counseling . The introduction of
highly sensitive second-generation & third-generation screening
assays for HCV antibodies (anti-HCV) everywhere, where as
Bangladesh usually practiced rapid strip method which is less
sensitive & specific with lots of chance of viral missing [6,13]. This
review aims to aware all health care practitioners about present
dangerous situation of donor screening and wake up the policy
makers regarding safe blood transfusion.
Hepatitis C virus (HCV) is a hepatotropic RNA virus of the genus
Hepacivirus in the Flaviviridae family . It was discovered in
1989, and since been identified as the major cause of transfusion
associated non-A, non-B hepatitis .
The number of deaths per year due to HCV-related diseases
continues to increase. According to estimates from the Global
Burden of Disease study, the number of deaths due to hepatitis
C was 3,33,000 in 1990, 4,99,000 in 2010 and 7,04,000 in 2013.A
more recent systematic review estimated that 115 million persons
are anti-HCV (antibody to HCV) positive and 80 million have
chronic infection. The increase in number of deaths reflects the
high incidence of hepatitis C . There is lack of representative
population study in Bangladesh regarding prevalence of HCV
infection . In the past, it was 2.4% (WHO, 1999) . In a recent
study from Mahtab et al.  that was 0.88%. HCV poses a huge
burden on the health of Bangladeshis, being a leading cause of all
forms of chronic liver diseases next only to HBV [16,17]. This is
similar to the experience in India [18,19], Pakistan  and Nepal
[21,22]. HCV also ranks to be a leading cause of HCC in Bangladesh
 as well as in the region including India  and Pakistan
. There are also published data from Bangladesh identifying
HCV to be the etiological agent in 24.1% of patients with chronic
liver diseases . In another study in Bangladesh, anti-HCV was
positive in 1.7% in acute viral hepatitis, 5.5% in sub-acute hepatic
failure, 6.8% in post transfusion hepatitis, 24.1% of chronic liver
disease, 9.6% cases hepatocellular carcinoma .
HCV infection can be cured by antiviral treatment; however,
due to the asymptomatic nature of the disease, many infected
persons are unaware of their infection and for those who are
diagnosed, access to treatment remains poor in many settings
Figure 1 .
Acute Hepatitis C Virus (HCV) Infection: Most of the cases of
acute hepatitis C are asymptomatic (85-90%). Symptomatic acute
hepatitis with jaundice is seen in 10-15% cases and asymptomatic
infection in 85-90% cases . Diagnosis of acute HCV infection
is based on detection of antibodies to HCV (Anti-HCV) by enzyme
immunoassay. Presence of anti-HCV indicating history of exposure
to HCV but not indicate the resolved infection or chronicity and
persist throughout the life .
Resolved infection: In 15-45% cases a person clear the HCV
within 6 months of exposure without any chronicity. A negative
test result for hepatitis C virus RNA in the presence of a positive
antibody indicates a resolved infection. The persons who already
resolved infection, anti-HCV may persist life-long but are no longer
infected with HCV (Figure 2) .
Chronic Hepatitis C Virus (HCV) infection: Continued
presence of HCV RNA in the blood six months or more after
acquiring infection is called chronicity. Chronic infection with HCV
is usually clinically silent, and is only very rarely associated with life-threatening disease. Left untreated, chronic HCV infection can
cause chronic liver disease (70-80%), cirrhosis (10-20%) and
hepatocellular carcinoma (HCC) (1-4%) (Figure 3) [12,15].
Many viruses [mostly hepatitis B virus, hepatitis C virus, HIV
and less commonly cytomegalovirus (CMV) and Epstein Barr Virus
(EBV)], bacteria (treponema pallidum) and protozoa (malarial
parasite) can be transmitted by transfusion [3,28]. Like other
developing countries, blood banking in Bangladesh does not get
enough attention for development from authorities. Many blood
recipients remained at risk of TTI transmission as a result of poor
blood donor recruitment and the use of low-quality testing in TTI
HCV is spread predominantly by percutaneous or mucosal
exposure to infected blood . Several studies from different
countries including Bangladesh indicate that, blood transfusion is
the main source for transmission of HCV (Table 1 & 2).
Nowadays in Bangladesh, routine screening of blood donors
for HCV is only anti-HBC (antibody to HCV) . Along this test,
International organizations added some recent tests for prevention
of HCV transmission. With anti-HCV, American red cross ,
Australian red cross, U.S. food & drug administration (FDA)
, United Kingdom (UK) , Singapore health science
authority , recommends Nuclieic acid testing (NAT)  (It
is a molecular technique for screening of HCV which providing
an additional layer of blood safety). Centers for disease control &
prevention (CDC)  recommends the cost effective approach.
If anti-HCV positive then they advice HCV RNA. World Health
Organization (WHO)  recommends HCV antibody immunoassay
or a combination HCV antigen-antibody immunoassay. American
association for the study of liver diseases (AASLD)  and
American family physician (AFP)  recommends like CDC. But
when history of exposure to HCV or having suspected liver disease
or HCV infection should do HCV RNA. European association for the
study of liver (EASL)  is little bit different. With positive anti-
HCV, HCV RNA is recommended. If HCV RNA not possible then HCV
core antigen (HCV Ag) is the answer. I think western world doing
the great job with no chance of missing HCV.
Anti-HCV usually appear in the blood after 6-10 weeks of
infection by enzyme immunoassay. Due to large gap between
infection & anti-body appearance, lots of chance of false positive
& false negative results.
I. Antibodies that the immune system has produced to combat
infections other than hepatitis C (known as “cross-reactive”).
The ELISA winds up picking up on these antibodies’ presence
and incorrectly coming up positive.
II. If individuals suffering from autoimmune disorders like
During the past decade, several assays for the detection of
the core antigen of HCV by ELISA (Enzyme immunoassays) or
CLIA (Chemiluminescent immunoassays) have been developed.
These assays were envisioned as alternatives to NAT to be used
in resource-limited settings, where molecular laboratory services
are either not available or not widely utilized owing to cost issues.
Since these assays are either ELISA or CLIA based, they are user
friendly, require less technical expertise and are less expensive
compared to molecular techniques . HCV core antigen assays
are less sensitive than HCV RNA assays (lower limit of detection
equivalent to approximately 500 to 3000 HCV RNAIU/ml) . But
it is more sensitive than anti-HCV. It appears just after appearing
of HCV RNA (about 7-8 weeks earlier than the anti-HCV) with
small window period and it’s follow the HCV RNA dynamics .
It is the beautiful test which developed world already adopted.
It diagnosed HCV infection in incubation period (after 1 week of
infection), window period and with low viremia (as low as 30
copies/ml). Nucleic acid testing (NAT) is considered the ‘gold
standard’ for detecting active HCV replication. It is extremely useful
in establishing the diagnosis of acute HCV infection, since RNA is
detectable as early as 1 week after exposure via needle-stick or
blood transfusion, and at least 4-6 weeks prior to seroconversion
as demonstrated in a number of transmission settings. The
diagnosis of HCV infection is established with antibody screening
followed by NAT for HCV RNA (Table 3) .
Only rapid tests may be considered in case emergency
screening (when blood is needed urgently) or in remote areas
with low workloads or limited number of tests are performed
daily and limited facilities, when equipment is lacking or where
there may be no electricity e.g. district blood centers and Upazila
health complexes .
In case of rapid strip test, lots of false positive/negative
results may occur. It is most commonly used, only 30 taka/strip,
less sensitive & specific, manual entry of test results and not
recommended by WHO as a universal screening of blood donors
in Bangladesh. When false positive results occur, prospective
blood donors are unnecessarily excluded from blood donation.
On the other hand, when false negatives occur, this poses a great
challenge to the quality and reliability of blood screening and
to patient safety. Errors may also be produced if samples for retesting
are improperly stored and/or transported. On the other
side, quite unlikely to occur when screening is done by EIA,
Chemiluminoassay, or PCR technology .
In Bangladesh, Transfusion Transmissible Infections (TTI)
screening is done mainly by rapid assay. Only at private sector
centers (Square Hospital Limited  & another is Apollo Hospital,
Dhaka ) are screening done by EIA/ CLIA (Chemiluminescent
Assay). The blood donation system in Bangladesh is decentralized;
all centers collect, and process and distribute blood. A beautiful
study was done in 2013, which was organized by WHO, DGHS
(Director General Health Services) & IEDCR (Institute of
Epidemiology, Disease Control and Research) to assess the
donor screening quality of different blood transfusion centers of
Bangladesh. A total of 12 centers from Dhaka city (Apollo hospital,
Square hospital, United hospital, Lab Aid hospital, Armed forces
institutes of pathology, Bangladesh Medical College hospital,
Cancer and rehabilitation hospital, Chest diseases hospital, Kidney
and urology hospital, Institutes of child and maternal health etc)
and 15 centers from outside the Dhaka (Rajshahi medical college
hospital, Khulna medical college hospital, Faridpur medical
college hospital, Comilla medical college hospital & lots of district
hospitals) were included in this study. A total 915 blood samples
were received from testing centers and all samples were accepted
forre‐testing in IEDCR. Out of 27 testing centers, results from 18
centers were correct (66.67%) and those from 9 centers were
incorrect (33.33%) when compared with the results obtained at
IEDCR. Among incorrect results, HBV (53.3%) is the dominant one
followed by HCV (40%) and malaria (6.7%). No results of disparity
observed among HIV and syphilis cases .
Although so called proper donor screening prior to blood
transfusion every time, they were unable to prevent HCV
transmission. Lots of national & international studies proved that,
multi-transfused thalassemic & hemophiliac patients gradually
positive with HCV after few times of blood transfusion. Not only
the strip method but also only antibody (anti-HBC) screening
may missing the HCV anytime. The risk of disease transmission
increases many fold if blood donor selection is inappropriate
and method of testing is inadequate. The hazards of blood
transfusion, specially the risk of transfusion transmissible
infections especially HCV are now the burning issue. The policy
makers, academicians, physicians and hepatologists are equally
unaware of the seriousness, loop holes and magnitudes of ongoing
blood transfusion program of this country. Percentage of anti-HCV
negative (with strip method) healthy donors without knowing
the HCV RNA status warrants the decision makers for rethinking
about silent HCV infection.
Establishment of a nationally coordinated blood transfusion
service, collection of blood only from voluntary donors, testing of
all blood for compatibility and transfusion transmissible infections
(TTIs) with appropriate method of testing and reduction of
unnecessary transfusion will be the key factors for excellent blood
transfusion service (BTS) in future.