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Seroprevalence of transfusion transmissible viral markers in sickle cell disease patients and healthy controls in Ile-Ife, SouthWestern Nigeria: A case–control study

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Background: The risk of acquiring transfusion transmissible viral infections is said to be higher in patients requiring regular blood transfusions such as those with sickle cell disease (SCD). Aim: We determined the seroprevalence of blood transfusion viral markers among our patients with SCD. Subjects and Methods: This a case–control analytical study consisting of 82 confirmed SCD patients on routine follow-up at our facility in steady state and 90 age-matched controls. Demographic and transfusion history were recorded while 5 ml of blood was drawn for hematocrit levels, and serum tested for transfusion transmissible viral markers for hepatitis B, (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B core antibody [HBcAb]), hepatitis C virus (HCV) and human immunodeficiency viruses (HIVs) using the rapid test kits. Ethical approval for the study was obtained from the Institutional Review Board and each participant gave informed consent. Data were analyzed using descriptive and inferential statistics. Results: The seroprevalence of HBsAg, HBsAb, and HBeAg in cases was 2 (2.4%), 7 (8.5%), and 0 (0.0%), respectively, whereas it was 7 (8.5%), 11 (13.4%), 6 (7.3%), and 2 (2.4%) for HBeAb, HBcAb, HCV, and HIV antibodies. Compared to the controls, cases had higher prevalence rate of HBeAb (P = 0.005). No significant difference was observed in those with or without low hematocrit (≤18%) or those that received blood transfusion and those that did not (P > 0.05). Conclusion: We conclude that blood transfusion did not significantly increase the seroprevalence of markers of transfusion transmissible viral infection in SCD patients.
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162 © 2015 Journal of Applied Hematology | Published by Wolters Kluwer - Medknow
cells), leading to vascular occlusion and endothelial
dysfunction.[2,3]
Viral hepatitis caused by hepatitis B and C viruses (HBVs,
HCVs) is of major public health concern worldwide
whereas human immunodeficiency virus/acquired
immunodeficiency syndrome (HIV/AIDS) pandemic
poses a major threat to public health and development
with immense socioeconomic burden worldwide.[4,5]
HBVs and HCVs and HIV share common routes of
transmission such as blood transfusion, injury with
INTRODUCTION
Sickle cell disease (SCD) is an autosomal recessive
disorder in which the sickle hemoglobin is present in
association with other abnormal hemoglobins.[1] It
is characterized by recurrent acute events known as
crises and chronic anemia, in which the homozygous
hemoglobin S phenotype (HbSS) state could lead to
significant end organ dysfunction.[1,2] Sickle red cells
assume an abnormal, rigid shape under conditions
of reduced oxygen tension and equally adhere to the
endothelial walls (in addition with platelets and white
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DOI:
10.4103/1658-5127.171985
Seroprevalence of transfusion transmissible
viral markers in sickle cell disease patients and
healthy controls in Ile‑Ife, South‑Western Nigeria:
A case–control study
Rahman A. Bolarinwa1, John C. Aneke1,2, Samuel A. Olowookere3, Lateef Salawu1
Departments of 1Haematology and 3Family Medicine, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538,
Ile‑Ife, 2Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra, Nigeria
Address for correspondence: Dr. John C. Aneke, Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi,
Anambra, Nigeria. E‑mail: anekejc@ymail.com
Background: The risk of acquiring transfusion transmissible viral infecons is said to be higher in paents requiring regular blood transfusions such
as those with sickle cell disease (SCD). Aim: We determined the seroprevalence of blood transfusion viral markers among our paents with SCD.
Subjects and Methods: This a case–control analycal study consisng of 82 conrmed SCD paents on roune follow‑up at our facility in steady state
and 90 age-matched controls. Demographic and transfusion history were recorded while 5 ml of blood was drawn for hematocrit levels, and serum
tested for transfusion transmissible viral markers for hepas B, (hepas B surface angen [HBsAg], hepas B surface anbody [HBsAb], hepas
B e angen [HBeAg], hepas B e anbody [HBeAb], hepas B core anbody [HBcAb]), hepas C virus (HCV) and human immunodeciency
viruses (HIVs) using the rapid test kits. Ethical approval for the study was obtained from the Instuonal Review Board and each parcipant gave
informed consent. Data were analyzed using descripve and inferenal stascs. Results: The seroprevalence of HBsAg, HBsAb, and HBeAg in
cases was 2 (2.4%), 7 (8.5%), and 0 (0.0%), respecvely, whereas it was 7 (8.5%), 11 (13.4%), 6 (7.3%), and 2 (2.4%) for HBeAb, HBcAb, HCV, and
HIV anbodies. Compared to the controls, cases had higher prevalence rate of HBeAb (P = 0.005). No signicant dierence was observed in those
with or without low hematocrit (≤18%) or those that received blood transfusion and those that did not (P > 0.05). Conclusion: We conclude that
blood transfusion did not signicantly increase the seroprevalence of markers of transfusion transmissible viral infecon in SCD paents.
Key words: Blood transfusion viral markers, seroprevalence, sickle cell disease
How to cite this article: Bolarinwa RA, Aneke JC, Olowookere SA,
Salawu L. Seroprevalence of transfusion transmissible viral markers
in sickle cell disease patients and healthy controls in Ile-Ife, South-
Western Nigeria: A case–control study. J Appl Hematol 2015;6:162-7.
This is an open access arcle distributed under the terms of the Creave Commons
Aribuon‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak,
and build upon the work non-commercially, as long as the author is credited and the
new creaons are licensed under the idencal terms.
For reprints contact: reprints@medknow.com
ABSTRACT
Original Article
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Bolarinwa, et al.: Transfusion‑related viruses in sickle cell disease
Journal of Applied Hematology | Vol. 6 • Issue 4 • October‑December 2015 163
contaminated sharps, and sexual contacts.[4,6] Viral
hepatitis and HIV/AIDS are endemic in tropical Africa
including Nigeria.[7‑9]
While SCD patients are prone to recurrent crises,
end organ dysfunction, and chronic anemia, blood
transfusion support may actually be lifesaving in those
with severe anemia.[10] The transfusion requirements
of SCD patients, therefore, place them at high risk
of infections with transfusion transmissible viruses,
particularly in climes where pretransfusion screening
is inadequate.[11] The morbidity of SCD is significantly
increased following infection with these viruses with
worsened clinical severity, coupled with accelerated
development of end‑organ dysfunction such as liver
cirrhosis.[12,13]
In Nigeria, the burden of transfusion transmissible
infections (TTIs) is high among blood donors and
even in the general population. Studies have reported
prevalence rates of 7.9%, 7.3%, and 5.0% for HBV, HCV,
and HIV, respectively, among blood donors and 12.0%,
3.0%, and 3.0% in the general population.[14‑17] It is,
therefore, important that blood given to SCD patients
is routinely screened for these TTIs, especially those
on regular blood transfusion. This is even made more
imperative by the observation that a larger proportion
of the blood donor pool in Nigeria is commercial (paid)
donors.[18] The reason for this may be attributable to
a number of factors, ranging from poor awareness on
voluntary blood donation to poverty and illiteracy,
particularly among the rural populations of the country.
According to the National Blood Transfusion Service,
Nigeria utilizes up to 1.5 million units of blood annually
and current legislation mandates that all potential
blood donors are screened for HCV hepatitis B surface
antigen (HBsAg), HIV, and syphilis, using a combination
of rapid qualitative immunochromatographic test kits,
enzyme‑linked immunosorbent assays, and p24 antigen
assay (for HIV).[19]
The objective of this work, therefore, was to determine
the seroprevalence of blood transfusion transmissible
viral markers in a cohort of patients with SCD who
regularly attend outpatient follow‑up clinic in our
facility.
SUBJECTS AND METHODS
This is a case–control study carried out at the Hematology
Department of our hospital from August 2011 to March
2012. Subjects included 82 confirmed (by cellulose
acetate hemoglobin electrophoresis, in alkaline ph)
SCD patients (67 HbSS and 15 double heterozygous
S + C [HbSC] hemoglobin phenotypes), who regularly
attend hematology out‑patient clinic in our facility,
and 90 age‑matched healthy hemoglobin AA controls.
Subjects were recruited in steady state conditions,
defined as no manifest crises in last 1 month and no
blood transfusion in 3 months preceding recruitment.[20]
Ethical approval was obtained from the Hospital’s
Health and Research Ethics Committee. Each
participant gave written informed consent. Bio‑data of
participants were recorded in a proforma form, whereas
transfusion history was obtained and recorded similarly
as “transfused” or “never transfused.” Following
standard protocols, 5 ml of venous blood was collected,
packed cell volume (PCV) was determined immediately
after sample collection by the microhematocrit method,
whereas the remaining sample was left on the bench to
clot for approximately 20 min. Serum was thereafter
extracted from the clotted sample by centrifugation
at 5000 rpm for 5 min and pipetted into clean plain
tubes for viral screening. Testing for HBV markers
including the B surface antigen and antibody (HBsAg
and hepatitis B surface antibody [HBsAb]), hepatitis B
e antigen (HBeAg) and hepatitis B e antibody (HBeAb),
and hepatitis B core antibody (HBcAb) was carried out
using the LumiQuick® HBV multiple panel rapid test
kits (LumiQuick Diagnostics, CA, USA) whereas HCV
and HIV antibodies were tested using rapid HCV test
kit (Acumen Labs and diagnostic Centre, Bengaluru,
Karnataka, India) and Determine test kit (Alere
Medical Co., Ltd., 357, Chiba, 270‑2214 Japan),
respectively. The instructions of the manufacturers
were followed for the test runs and each test strip had
in‑built procedural control.
Statistical Analysis
Test results were presented as frequencies, percentages,
and means (±standard deviation). Subjects were
further stratified into those with or without severe
anemia (PCV ≤18% and >18%, respectively) and
those transfused and never transfused. The Chi‑square
statistic was used to compare transfusion transmissible
viral screening test results with variables such as age,
sex, hemoglobin type, and blood transfusion history.
Level of statistical significance was set at P < 0.05.
RESULTS
The mean age of cases was 26.01 ± 7.05 years,
whereas that of controls was 24.78 ± 4.83 years. The
mean PCV in cases was 24.20 ± 5.12 L/L, whereas
it was 34.61 ± 8.34 L/L in controls. The cases
included 44 males (53.7%) and 38 females (46.3%);
67 (53.7%) and 15 (18.3%) had HbSS and HbSC
hemoglobin phenotypes, respectively [Table 1].
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Bolarinwa, et al.: Transfusion‑related viruses in sickle cell disease
164 Journal of Applied Hematology | Vol. 6 • Issue 4 • October‑December 2015
Nine (11.0%) of these had PCV ≤18%, whereas
73(89.0%)hadPCV>18%[Table1].Correspondingly,
40 (48.8%) cases did not receive any blood transfusion,
whereas 42 (51.2%) had received one or more blood
transfusions [Table 1].
The prevalence rates of HBsAg, HBsAb, and HBeAg in
cases were 2 (2.4%), 7 (8.5%), and 0 (0.0%), whereas
it were 2 (2.2%), 14 (15.6%), and 0 (0.0%) in controls,
respectively [Table 2]. Correspondingly, the prevalence
rates of HBeAb, hepatitis B core, and HCV antibodies in
cases were 7 (8.5%), 11 (13.4%), and 6 (7.3%), whereas
it were 0 (0.0%), 8 (8.9%), and 4 (4.4%) in controls,
respectively [Table 2]. HIV antibodies had a prevalence
of 2 (2.4%) in cases and 0 (0.0%) in controls [Table 2].
There was a significant difference in the prevalence rate
of HBeAb in cases and controls [P = 0.005, Table 2].
There were no significant differences in the prevalence
rates of other transfusion transmissible viral markers
in cases and controls [P>0.05,Table2].
Among the cases, 40 (48.8%) did not receive any
previous blood transfusion, whereas 42 (51.2%)
had been transfused at least once at the time of
recruitment. There were no significant differences
in the seroprevalence of all markers of transfusion
transmissible viral infections among cases that
received blood transfusion and those that did
not [P>0.05,Table3].
Among cases and healthy controls above 25 years of age,
females tended to have higher positivity for transfusion
transmissible viral markers, these differences were
however not significantly different (P>0.05).
DISCUSSION
The prevalence of viral infections, particularly those
that are transfusion transmissible has been reported
to be higher in patients who have chronic anemia
and require regular blood transfusions. SCD, either in
the homozygous or the double heterozygous state, is
characterized by chronic anemia, end organ dysfunction,
a number of acute events known as crises, and a defect
in immune surveillance.[21] The subnormal immune
surveillance thus could predispose these patients to a
wide range of infectious agents, including viruses.
Ségbéna et al. reported a prevalence of 20.2%, 6.5%, and
5.04% for HBV, HCV, and HIV infections, respectively,
in a cohort of patients with sickle cell anemia (SCA)
in Togo.[22] The study concluded that SCA patients are
particularly prone to infection with a number of these
viruses due to frequent hospitalizations and attendant
blood transfusions. In this study, the prevalence
of HIV (2.4%) was lower, whereas the HCV was
comparable (7.3%) with earlier reports in blood donors
and patients with SCA subjects.[14,22] HBV infection has
a particularly high prevalence in Nigeria and indeed the
whole of sub‑Saharan Africa.[23] It has been attributed
with the highest risk of residual transmission among
the transfusion transmitted diseases.[24] Okocha et al.
reiterated this observation in a study involving 96 SCA
Table 1: The profile of SCD cases and healthy
controls at enrolment into the study
Variables Cases (%) Controls
Sex
Female 44 (53.7) 40 (44.4)
Male 38 (46.3) 50 (55.6)
Genotype
HbAA 90 (100)
HbSS 67 (81.7)
HbSC 15 (18.3)
PCV (%)
≤18 9 (11.0) 0 (0)
>18 73 (89.0) 90 (100)
Never transfused 40 (48.8) 90 (100)
Transfused 42 (51.2) 0 (0)
HbSS=Homozygous hemoglobin S phenotype; HbSC=Double
heterozygous hemoglobin S + C phenotype; PCV=Packed cell volume;
SCD=Sickle cell disease; HbAA=Hemoglobin AA
Table 2: Comparison of seroprevalence of viral
markers in patients and controls
Study population Negative (%) Positive (%) Total (%) P
HBsAg
Case 80 (97.6) 2 (2.4) 82 (47.7) 0.93
Control 88 (97.8) 2 (2.2) 90 (52.3)
HBsAb
Case 75 (91.5) 7 (8.5) 82 (47.7) 0.16
Control 76 (84.4) 14 (15.6) 90 (52.3)
HBeAg
Case 82 (100.0) 0 (0.0) 82 (47.7)
Control 90 (100.0) 0 (0.0) 90 (52.3)
HBeAb
Case 75 (91.4) 7 (8.5) 82 (47.7) 0.005*
Control 90 (100.0) 0 (0.0) 90 (52.3)
HBcAb
Case 71 (86.6) 11 (13.4) 82 (47.7) 0.34
Control 82 (91.1) 8 (8.9) 90 (52.3)
HCV antibody
Case 76 (92.7) 6 (7.3) 82 (47.7) 0.52
Control 86 (95.6) 4 (4.4) 90 (52.3)
HIV antibody
Case 80 (97.6) 2 (2.4) 82 (47.7) 0.23
Control 90 (100.0) 0 (0.0) 90 (52.3)
*Fisher’s exact test. HBsAg=Hepatitis B surface antigen; HBsAb=Hepatitis B
surface antibody; HBeAg=Hepatitis B e antigen; HBeAb=Hepatitis B e
antibody; HBcAb=Hepatitis B core antibody; HCV=Hepatitis C virus;
HIV=Human immunodeficiency virus
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Bolarinwa, et al.: Transfusion‑related viruses in sickle cell disease
Journal of Applied Hematology | Vol. 6 • Issue 4 • October‑December 2015 165
patients in Benin, Nigeria; however, the prevalence of
HBsAg was much higher than we reported 29.2% versus
2.4%, respectively.[25] Interestingly, this study noted
that the overall risk of HBV infection in SCA patients
was not clearly increased by blood transfusion. This
conclusion is in agreement with the findings in this
study, in which the prevalence of viral markers was not
significantly different in cases that had received blood
transfusion and those who did not [Table 3]. The lower
prevalence of HBV among SCD patients in this study
compared to an earlier study in Nigeria by Okocha
et al.[25] (with a comparable study sample size) may
indeed represent regional differences in rates of viral
transmission in the country; while our patients are from
South‑Western region of the country, the study subjects
in the earlier study were recruited from Mid‑Western
Nigeria. Until recently, SCD patients in Nigeria were
not routinely vaccinated against HBV; however, it is
currently available for patients, being a component of
the National Programme on Immunization. The finding
of nonsignificant association between blood transfusion
and seroprevalence of blood transfusion viral markers
in this study is in contrast with a number of reports
which had consistently linked high blood transfusion
rates with increased predisposition to acquiring
transfusion transmissible viral infections.[22,26,27] This
difference may be related to the transfusion rate; all
the patients evaluated in this study had cumulative
red cell transfusions of <10 units, and none was on
hyper‑transfusion regimen suggesting a low transfusion
rate in our cohort.
Following acute hepatitis B infection, the surface
antigen and the core antibody commonly become
detectable in the serum; both may remain in the serum
even after viral clearance.[28] It is therefore for the above
reason that both markers have been used as evidence
of previous exposure to the virus. The prevalence of
the antigen and core antibody in this study was 2.4%
and 13.4%, respectively; these were not significantly
different from the controls [Table 2]. Detection of
antibody to the surface antigen (HBsAb) is generally
assumed to depict immunity to HBV infection. The
prevalence of HBsAb in cases in this study was 8.5%;
this was also not significantly different from the
controls [Table 2].
In this study, the seroprevalence of HBeAb in the cases
was significantly higher than in controls [8.5% vs.
0.0%, P = 0.005, Table 2], while the corresponding
antigen (HBeAg) had 0.0% prevalence in cases and
controls [Table 2]. The presence of the HBeAg in
the serum generally depicts active HBV replication
within hepatocytes, with attendant high risk of
viral transmission, including maternal to child
transmission (MTCT).[29] Correspondingly, the presence
of the HBeAb in the serum (with HBsAg negativity)
has been recognized to coincide with clinical remission
in chronic HBV infection and equally offers some
protection against HBV MTCT.[30]
Previously, the HBeAg was assumed to be a surrogate
marker for the presence of the HBV DNA, and cases
that were negative to the former were thought to
have achieved viral clearance, however this notion
has been challenged following the discovery of
cases of HBeAg‑negative (HBeAb‑positive) chronic
HBV infection, with very active disease.[31] In fact,
Hadziyannis and Vassilopoulos had emphasized that
patients who are positive for HBsAg and HBeAb but
negative for HBeAg required further evaluation (HBV
DNA, and serum transaminases) to differentiate them
from those with (inactive) HBsAg carrier state.[32]
In this study, the high prevalence of HBeAb (8.5%)
in cases when considered with the low prevalence of
HBsAg (2.4%) may well mean that these group of
patients have cleared the virus and are in remission.
Despite this possibility, further evaluation of these
cohorts for HBV viral activity is necessary.
Table 3: Seroprevalence of viral markers in cases
by transfusion history
Transfusion history Negative (%) Positive (%) Total (%) P
HBsAg
Never transfused 39 (97.5) 1 (2.5) 40 (48.8) 0.97
Transfused 41 (97.6) 1 (2.4) 42 (51.2)
HBsAb
Never transfused 36 (90.0) 3 (7.1) 40 (48.8) 0.64
Transfused 39 (92.9) 3 (7.1) 42 (51.2)
HBeAg
Never transfused 40 (100.0) 0 (0.0) 40 (48.8)
Transfused 42 (100.0) 0 (0.0) 42 (51.2)
HBeAb
Never transfused 36 (90.0) 4 (10.0) 40 (48.8) 0.64
Transfused 39 (92.9) 3 (7.1) 42 (51.2)
HBcAb
Never transfused 33 (82.5) 7 (17.5) 40 (48.8) 0.29
Transfused 38 (90.5) 4 (9.5) 42 (51.2)
HCV antibody
Never transfused 38 (95.0) 2 (5.0) 40 (48.8) 0.43
Transfused 38 (90.5) 4 (9.5) 42 (51.2)
HIV antibody
Never transfused 39 (97.5) 1 (2.5) 40 (48.8) 0.97
Transfused 41 (97.6) 1 (2.4) 42 (51.2)
HIV=Human immunodeficiency virus; HCV=Hepatitis C virus;
HBsAb=Hepatitis B surface antibody; HBeAg=Hepatitis B e antigen;
HBeAb=Hepatitis B e antibody; HBcAb=Hepatitis B core antibody;
HBsAg=Hepatitis B surface antigen
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Bolarinwa, et al.: Transfusion‑related viruses in sickle cell disease
166 Journal of Applied Hematology | Vol. 6 • Issue 4 • October‑December 2015
Previous studies noted significant variations in the
seroprevalence of sexually transmitted viral infections,
particularly HBV across age groups and attributed this
difference to an added influence of horizontal mode
of transmission particularly in the 10–20 year age
group, as well as increasing sexual exposure (sexual
transmission) in the 21–30 year age groups.[25,33]
Although more cases and controls aged ≥25 years
tested positive to markers of viral infection than
those <25 years in this study, the differences were not
statistically different (P>0.05).Whilethereasonfor
this discrepancy was not apparent from this study, it is
likely that increased sexual activity around this period
could be responsible.
Sánchez et al. had earlier noted that the seroprevalence
of viral infections was significantly higher in male
compared to female subjects in Lima, Peru.[34] The
authors attributed this to the increased tendency for
high risk sexual behaviors (including the likelihood
for more sexual partners) in male subjects compared
to females, which could predispose them to acquiring
sexually transmitted viral infections. More recently,
however, Okocha et al. and Matee et al. in studies among
SCA subjects and blood donors, respectively, failed to
show any significant difference in the seroprevalence
of transfusion transmissible viral infections across
gender groups.[25,35] Our report agrees with these
recent observations; no significant differences were
observed in the seroprevalence of markers of transfusion
transmissible viral infection in males and females in
both cases and controls.
CONCLUSION
Blood transfusion did not significantly increase the
seroprevalence of markers of transfusion transmissible
viral infection in our SCD patients; this may be related
to the low transfusion rate observed in patients, coupled
with the universal pretransfusion screening protocols
applied in our center. The high levels of HBeAb and
low HBsAg in this cohort could represent inactive HBV
carrier state.
Limitations of the Study
The study is limited by the nonavailability of
biochemical indices of hepatic damage (particularly
transaminases) and HBV viral load which could help
to adequately delineate cases of chronic (active) HBV
infection that will benefit from further evaluation and
treatment. This will need to be further explored and
evaluated in follow‑up studies.
Financial Support and Sponsorship
Nil.
Conicts of Interest
There are no conflicts of interest.
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... Donors within the 18-25 years age group had the highest representation in this study (39.0%) [ Table 1]; this pattern of donor distribution is in agreement with the report of Bolarinwa et al. in Ile-Ife, South West Nigeria, and represents the most active age stratum of the population. [13] The prevalence rate of G6PD deficiency is known to differ widely among different population groups, being dependent on racial/ethnic composition as well as other sociogeographical determinants. Indeed, the prevalence rates ranging from 3.4% in the Americas to 3.9%, 2.9%, 7.5%, 6.0%, and 4.7% in Europe, the Pacific, Sub-Saharan Africa, the Middle East, and Asia, respectively, have been reported. ...
... Similar (predominantly male) demographic patterns have been replicated in earlier studies in parts of Nigeria and Africa. [13,[16][17][18][19][20] The above observation is equally in keeping with the fact that G6PD deficiency is an X-linked disorder and so predominates in male participants. ...
Article
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Background: Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency and methemoglobinemia adversely impact on blood transfusion safety by significantly increasing blood storage lesion. Objective: To determine G6PD enzyme deficiency and methemoglobin levels among blood donors in a tertiary hospital-based blood bank in Nigeria. Subjects and Methods: One hundred blood donors who met the criteria for blood donation were prospectively studied. Two milliliters of venous blood was collected from each participant into potassium-ethylenediaminetetraacetic acid specimen containers and analyzed for G6PD status and methemoglobin levels by spectrophotometry, on the same day of sample collection. Results: Among the donors, 43% had normal G6PD activity (9.32 ± 2.26 U/gHb), 44% had partially enzyme deficiency (4.92 ± 1.33 U/gHb), while 13% had total deficiency (0.47 ± 3.49 U/gHb); these were statistically different (P < 0.001). Methemoglobin concentration was elevated in 25% of study participants (3.05 ± 2.30%), while it was normal in 75% (0.99% ± 0.60%); these differences were statistically different (P < 0.001). Conclusion: A significant proportion of our blood donor set has G6PD enzyme deficiency (partial or total) as well as evidence of oxidation of hemoglobin; these findings have adverse implications on transfusion safety.
... [13,14] Unfortunately, this age distribution has also been associated with the highest carriage rates of TTIs (arising most probably from increased involvement in high-risk sexual behaviors and experimentation), this, therefore, poses a huge challenge to the country's efforts toward attaining blood transfusion safety. [16][17][18] Supply deficits According to the NBTS, Nigeria, with a population of over 150 million people uses about 1.5 million units of blood every year to cater for the health needs of its citizens. [6] This well approximates to far less than a pint of blood per person and further highlights a very poor blood supply chain in the country. ...
... Bolarinwa et al. [18] Zaria (North-central Nigeria) 2013 General population HBV 12.5 Aminu et al. [33] Benin City (Midwestern Nigeria) 2013 ...
Article
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The attainment of blood transfusion safety in Nigeria (and probably the rest of Sub-Saharan Africa) remains an uphill task due to a number of factors, ranging from shortage of blood, poor implementation of blood transfusion guidelines, infrastructural deficits to high prevalence of transfusion-transmissible infections (TTIs), particularly hepatitis and human immune deficiency viruses. We reviewed available data on blood transfusion practices and safety in Nigeria using the PubMed, PubMed Central, Google Scholar, and African Index Medicus search engines, through a combination of word and phrases relevant to the subject. The World Health Organization has been in the forefront of efforts to establish safe, available, and affordable blood transfusion services in most parts of Africa through encouraging adequate blood donor recruitment, donor blood testing, and collection as well developing strategies for the rational use of blood. Even though modest improvement has been recorded, particularly with regards to donor blood screening for common TTIs, considerable efforts are needed in the form of robust public enlightenment campaigns (on blood donation) and continuous system improvement to drive the current transfusion practices in the country toward safety and self-sustenance.
... Seroprevalence of HIV, one of the common and dreaded TTIs among the transfused sickle cell anemia subjects in our study was 7.9% compared to 8.6% in those not transfused. This prevalence is comparable to previous report among blood donors in Jos but higher than the Nigerian national prevalence of 2.9% reported in 2016 and also the prevalence among same subjects reported in Zaria and Ile-Ife, Nigeria [9][10][11][12]. The marker of a probable flawless system is the HIV prevalence of 0% reported among transfused sickle cell disease (SCD) patients at the Howard University in United States of America (USA) [13]. ...
Article
Full-text available
Aims: This study was aimed at determining the seroprevalence of some common transfusion transmissible viral infections in sickle cell anemia patients attending our adult hematology clinic for qualitative management. Methods: A total of 111 sickle cell anemia patients attending the Hematology Outpatient Clinic (HOPC) of the Jos University Teaching Hospital (JUTH) in steady state were enrolled consecutively in this cross-sectional study irrespective of their blood transfusion status. Relevant demographic information and clinical histories were obtained using a structured questionnaire after obtaining informed consent from the subjects. Ethical approval was also obtained from the Institutions Human Research Ethics Committee. Blood sample was collected for complete blood count using a 3-part Sysmex hematology autoanalyzer, confirmatory hemoglobin electrophoresis and viral antigen/antibody screening using ELISA kits. Data was analyzed using Epi Info version 7.2.0.1 and Microsoft Office Excel version 2010. Results: Majority of our subjects were within the age range of 18–30 years, 48 (43.2%) males and 63 (56.8%) females. Seventy-six (68.5%) had blood transfusion while 35 (31.5%) never had blood transfusion in their life. Seroprevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among the transfused sickle cell anemia patients in this study was 7.9% for HIV, 22.4% for HBV, and 15.8% for HCV while those not transfused had seroprevalence of 8.6% for HIV and 11.4% for both HBV and HCV, respectively. No statistically significant difference was observed between those transfused and those who have not had blood transfusion in their life. Conclusion: Seroprevalence of transfusion transmissible viral infections was relatively high and blood transfusion did not significantly influence the rate of these viral infections in our sickle cell anemia patients. Improved blood screening techniques, provision of antiviral medications, and vaccines at affordable cost are advocated.
... Several researchers have reported varying seroprevalence of hepatitis infections among patients with SCA. This ranged from 3.0% to 39.0% for [22][23][24] HBV and 4.5% to 21.0% for HCV. ...
Article
BACKGROUND: Sickle cell anaemia (SCA) is an important public health problem in Nigeria associated with frequent blood transfusion. Patients with this disease are at increased risk of contracting hepatitis B and C virus through blood transfusions. OBJECTIVE: The study aimed at determining the burden of hepatitis B and C virus infections in patients with sickle cell anaemia and the role of blood transfusion in these infections acquisition in Jos. MATERIALS AND METHODS: This was an observational cross-sectional study conducted on patients with SCA attending the Haematology Out-patient Clinic of Jos University Teaching Hospital,between November 2014 and August 2015.Consenting patients with SCA had their blood screened for anti- HBV and HCV antibodies using fourth generation Elisa techniques after completing a questionnaire. RESULTS: One hundred and eleven patients with SCA participated. Antibodies to Hepatitis B virus (HBV) was detected in 21 (18.9%) while that to Hepatitis C virus (HCV) was found in 16 (14.7%). Seventy six (68.5%) of the participants had history of blood transfusion while 35 (31.5%) were never transfused. 22.4% and 15.8% of those transfused were positive for HBV and HCV antibodies respectively. There was no significant difference in the proportion of those positive for anti HBV or HCV with respect to their transfusion status (p=0.24 and 0.81 respectively). CONCLUSION: The proportion of our patients with SCA that were anti HBV and anti-HCV positive was high. Blood transfusion did not significantly influence their positive status. Strategies aimed at controlling these viral infections in these patients and the general population should be enforced after public awareness campaigns and advocacy are instituted.
Article
Blood transfusion is an integral component in the management of children and adults with sickle cell disease (SCD). Concerns about blood safety due to the high risk of bloodborne infections in sub‐Saharan Africa limits the application of this cost‐effective strategy in the management of individuals with SCD. In a single‐centre, retrospective, longitudinal study in southwest Nigeria, we hypothesised that the use of stringent blood donor selection, along with very sensitive enzyme‐linked immunosorbent assay (ELISA) screening methods would reduce transfusion‐transmitted infections (TTIs). Among 45 002 eligible blood donors at the Lagos University Teaching Hospital in Nigeria, over a 5‐year review period (2015–2019), the seroprevalence rate of viral TTIs was 9.83%. The seroprevalence rates for human immunodeficiency, hepatitis B, and hepatitis C viruses were 1.37%, 6.2%, and 2.25% respectively. Among 172 children with SCD, 71% (122/172) on regular blood transfusion and 29% (50/172) who had never been transfused or had less than two transfusions per lifetime, none acquired any TTIs using our enhanced screening approach during the study period. Thus, safe blood transfusion practices can be provided for children with SCD in sub‐Saharan Africa with the use of stringent donor selection protocols and fourth‐generation ELISA kits for TTI screening.
Article
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Background: Blood transfusion is an invaluable therapeutic intervention in sickle cell anemia (SCA) patients’ care. Sickle cell anemia patients usually require frequent blood transfusion and are at increased risk of contracting human immunodeficiency virus (HIV), hepatitis B and C virus infections through these transfusions. Aims: To determine the seroprevalence of HIV, hepatitis B and C virus infections in patients’ with sickle cell anemia and the role of blood transfusion in the transmission of the infections. Methods: This was a prospective, observational cross-sectional study conducted on adult patients with SCA attending the Haematology Outpatient Clinic of University of Uyo Teaching Hospital, Uyo, from January 1, 2019 through December 31, 2019. Relevant clinical history was obtained from consenting subjects. Blood samples were collected for hemoglobin electrophoresis and viral antigen/antibody screening using ELISA kits. Data were analyzed using Statistical Package for Social Sciences (SPSS) windows version 23.0. Results: Eight-six patients with SCA participated in the study. Forty (46.5%) of the subjects were male and 63 (73.3%) of the participants were within the age range of 20–29 years. Seventy-five (87.2%) of the subjects had blood transfusion while 11 (12.8%) never received blood transfusion in their entire life. Seroprevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among the transfused SCA patients in this study was 9.3%, 24.0%, and 18.7% respectively while those not transfused had seroprevalence of 9.1% for HIV and 0% for both HBV and HCV. One (1.2%) of the transfused subjects tested positive for HIV and HCV. There was no statistically significant difference in the seroprevalence of HIV, HBV, and HCV infections in relation to the transfusion status of the subjects (p=0.98, 0.07, and 0.12, respectively). Conclusion: The proportion of our SCA patients who were HIV, HBV, and HCV positive was considerable. Blood transfusion did not significantly influence the seroprevalence rates of these viral infections. Measures aimed at controlling the infections in the patients and the general population should be scaled up.
Article
Introduction: Hepatitis B virus infection attacks the liver and can cause both acute and chronic disease. Sickle cell disease (SCD) patients are at risk of transmission transmissible viral hepatitis due to their constant need for blood transfusion. However, these patients could have been infected with HBV but may not know their status due to asymptomatic nature of the infection. Therefore, this study was designed to determine the burden of HBV markers of infection among SCD patients attending the hematology clinic at a tertiary health facility in Ibadan, Nigeria. Methodology: A cross-sectional study was investigated among 112 consenting SCD patients (M = 45; F = 67) age ranged 15–60 years (mean age = 26.9; mean PCV = 24 ± 4.8) attending a hematology clinic at the University College Hospital, Ibadan. A structured questionnaire was administered to capture demographic and other relevant information. Blood samples from each participant were tested for HBV markers by ELISA technique, while data were analyzed using SPSS version 21 with P < 0.05 considered significant. Results: A total of 5 (4.5%), 0 (0.0%), and 15 (13.4%) were positive for HBsAg, HBeAg, and HBeAb, respectively. Also, 63 (56.3%) of the participants have never been transfused, while 49 (43.8%) had received blood transfusion at a point in time. No significant difference (P = 0.095) found a prevalence of HBV markers among those that had received blood transfusion and those that did not. Highest rates for HBsAg (3.6%) and HBeAb (10.7%) were observed among female than their male (HBsAg (0.9%) and HBeAb (2.8%) counterparts (P = 0.065)). No significant associations (P > 0.05) were found among those with incisions, among those who are sexually active and among the vaccinated individuals for HBV markers. There was a significant difference (P = 0.025) among the married participants for HBeAb with higher HBeAb rate (64.3%). Conclusion: This study reported high rates of HBV markers of infection among SCD patients. It is therefore advocated that donated blood must pass through rigorous screening processes before it is transfused.
Article
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INTRODUCTION: Caesarean section remains the most common major operation performed on women worldwide and the rate is increasing. The World Health Organization (WHO) consider caesarean section rate of 5-15% to be optimum. OBJECTIVE: To determine the rate of caesarean section, major indications, pregnancy out-come and the complications. SUBJECTS AND METHODS:This is a prospective study of all the cases of caesarean sections performed between 1st of January,2012 and 31th of December,2013 at UDUTH,Sokoto-Nigeria. The data were collated and analyzed using statistical soft package ware for social sciences (SPSS) version 20. RESULTS:A total of 4,115 deliveries were recorded during the study period and 435 of them (10.6%) were through caesarean section (CS). Emergency CS accounted for 65.1% of caesarean deliveries. The mean age was 28±6 years. Previous CS was the commonest indication for caesarean section (25.7%). Elective CS had better fetal outcome (t = 7.440,df =388.523,p < 0.001),while spinal anaesthesia was associated with less blood loss (t = 4.569, df=63.223 and p < 0.001) and better fetal outcome (t = 4.237, df = 57.224, p < 0.001).Anaemia (19.8%) was the commonest complications encountered in the post operative period. CONCLUSION: The CS rate from this study is within the WHO recommended rate. Previous CS was the commonest indication,the outcome was better among women that had elective CS under regional anaesthesia.
Article
Background Hepatitis is a viral infection of the liver. It is mainly transmitted between people through contact with infected blood, frequently from mother to baby in-utero. Hepatitis B poses significant risk to the fetus and up to 85% of infants infected by their mothers at birth develop chronic hepatitis B virus (HBV) infection. Hepatitis B immunoglobulin (HBIG) is a purified solution of human immunoglobulin that could be administered to the mother, newborn, or both. HBIG offers protection against HBV infection when administered to pregnant women who test positive for hepatitis B envelope antigen (HBeAg) or hepatitis B surface antigen (HBsAg), or both. When HBIG is administered to pregnant women, the antibodies passively diffuse across the placenta to the child. This materno-fetal diffusion is maximal during the third trimester of pregnancy. Up to 1% to 9% infants born to HBV-carrying mothers still have HBV infection despite the newborn receiving HBIG plus active HBV vaccine in the immediate neonatal period. This suggests that additional intervention such as HBIG administration to the mother during the antenatal period could be beneficial to reduce the transmission rate in utero. Objectives To determine the benefits and harms of hepatitis B immunoglobulin (HBIG) administration to pregnant women during their third trimester of pregnancy for the prevention of mother-to-child transmission of hepatitis B virus infection. Search methods We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), SCOPUS, African Journals OnLine, and INDEX MEDICUS up to June 2016. We searched ClinicalTrials.gov and portal of the WHO International Clinical Trials Registry Platform (ICTRP) in December 2016. Selection criteria We included randomised clinical trials comparing HBIG versus placebo or no intervention in pregnant women with HBV. Data collection and analysis Two authors extracted data independently. We analysed dichotomous outcome data using risk ratio (RR) and continuous outcome data using mean difference (MD) with 95% confidence intervals (CI). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. If there were statistically significant discrepancies in the results, we reported the more conservative point estimate. If the two estimates were equal, we used the estimate with the widest CI as our main result. We assessed bias control using the Cochrane Hepato-Biliary Group suggested bias risk domains and risk of random errors using Trial Sequential Analysis (TSA). We assessed the quality of the evidence using GRADE. Main results All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo. Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Authors' conclusions Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.
Article
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Perinatal exposure is an important mode of hepatitis B virus (HBV) transmission, resulting in chronic disease in ∼90% of infected infants. Immunoprophylaxis recommended for infants born to hepatitis B surface antigen-positive mothers reduces up to 95% of perinatal HBV infections. We sought to identify factors associated with perinatal HBV transmission. We analyzed prospectively collected data from 5 of 64 US-funded Perinatal Hepatitis B Prevention Programs during 2007-2013. We examined effects of maternal demographic and laboratory results, infant gestational age and birth weight, and immunoprophylactic management on perinatal HBV infection. Data from 17 951 mother-infant pairs were analyzed. Among 9252 (51.5%) infants for whom hepatitis B surface antigen testing results were available, 100 (1.1%) acquired perinatal HBV infection. Both hepatitis B (HepB) vaccine and hepatitis B immune globulin were administered within 12 hours of birth for 10 760 (94.9%) of 11 335 infants with information. Perinatal HBV infection was associated with younger maternal age (P = .01), Asian/Pacific Islander race (P < .01), maternal hepatitis B e-antigen positivity (P < .01), maternal antibody to hepatitis B e-antigen negativity (P < .01), maternal viral load ≥2000 IU/mL (P = .04), and infant receipt of <3 HepB vaccine doses (P = .01). Four infants born to 429 mothers with viral load testing were infected; all 4 were born to mothers with viral loads in the ninth or tenth decile. Perinatal HBV infection occurred among 1% of infants, most of whom received recommended immunoprophylaxis. Infants at greatest risk of infection were those born to women who were younger, hepatitis B e-antigen positive, or who had a high viral load or those infants who received <3 HepB vaccine doses. Copyright © 2015 by the American Academy of Pediatrics.
Article
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Background The generation of antibodies (anti-HBe) against hepatitis B virus (HBV) e antigen (HBeAg) often coincides with clinical remission in chronic HBV patients. We aimed to examine the effect of maternal anti-HBe in protection against HBV mother-to-child transmission (MTCT). Methods A total of 140 chronic HBV-infected pregnant women participated in this study. Before delivery, maternal HBV serological markers and HBV viral load were determined and anti-HBe titers were semi-quantified. Neonatal hepatitis B surface antigen (HBsAg) and HBV-DNA status were determined from cord blood. The children were followed to age 1–3 years. Results The HBV-DNA positive rate in cord blood was 75.61% (31/41) in those who were born to mothers with serum HBV-DNA >106 IU/ml, which was significantly higher than in those who were born to mothers with HBV-DNA <106 IU/ml (3/99, 3.03%; p < 0.0001). However, 10 newborns from mothers with serum HBV-DNA >106 IU/ml had no detectable HBV-DNA in cord blood; anti-HBe was positive with a median titer of 10 (interquartile range 10–55). A total of 84 children who received hepatitis B immune globulin (HBIG) within 12 h after birth and who completed three doses of recombinant HBV vaccination were followed to age 1–3 years (up to May 2014). All 56 children who were born to mothers with serum HBV-DNA levels <106 IU/ml were HBsAg-negative. Five of the 22 children born to anti-HBe-negative mothers with serum HBV-DNA >106 IU/ml acquired an HBsAg-positive status. However, none of the six children who were born to anti-HBe-positive/weak-positive mothers with serum HBV-DNA >106 IU/ml acquired an HBsAg-positive status. Conclusions The presence of maternal anti-HBe is protective against HBV MTCT, independent of the maternal serum HBV viral load.
Article
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Background: Governments are increasingly recognizing the need to focus limited HIV resources on specific geographic areas and specific populations to have a greater impact. Nigeria, with the second largest HIV epidemic in the world, is an important example of where more localized programming has the potential to improve the efficiency of the HIV response. Methods: Using Spectrum software we modelled the Nigerian HIV epidemic using two methods: First, we created national HIV estimates using trends in urban and rural areas. Second, we created national HIV estimates using trends from each of the 37 states in Nigeria and aggregated these results. In both instances we used HIV surveillance data from antenatal clinics and household surveys and aggregated the trends to determine the national epidemic. Results: The state models showed divergent trends in the 37 states. Comparing the national results calculated from the two methods resulted in different conclusions. In the aggregated state files, adult HIV incidence in Nigeria was stable between 2005 and 2013 (change of −6%), whereas the urban and rural file suggested incidence was decreasing over the same time (change of −50%). This difference was also reflected in the HIV prevalence trends, although the two methods showed similar trends in AIDS-related mortality. The two models had similar adult HIV prevalence in 2013: 3.0% (2.0–4.5%) in the aggregated state files versus 3.2% (3.0–3.5%) in the urban/rural file. Conclusion: The state-level estimates provide insight into the variations of the HIV epidemic in each state and provide useful information for programme managers. However, the reliability of the results is highly dependent on the amount and quality of data available from each sub-national area.
Article
Objectives: The reported prevalence of HBsAg in the general Ghanaian population is high (more than 10%). However, it is anticipated that following the establishment of the Sickle Cell Clinic, due to the comprehensive care, the prevalence of HBsAg among the sickle cell patients should be lower. Method: This study was aimed at screening for the HBsAg in 330 sickle cell patients, as well as using some hemato- biochemical parameters to characterize the seropositives, relative their age-, sex- and genotype-matched seronegative counterparts. Results: Twelve of the subjects (3.6%) were seropositive; 6 males and 6 females, this was lower than the prevalence rates reported from the general population. The mean levels of the following indices were higher in the seropositives; ALT (28.3 ± 19.6 U/L), AST (52.9 ± 36.1 U/L), ALP (181.4 ± 98.1 U/L), LDH (1010 ± 223.5 U/L), albumin (4.4 ± 0.5g/dL), creatinine (76.0 ± 18.2 µmol/L), urea (4.4 ± 5.8 mmol/L) and platelets (401.3 ± 152.8 × 10⁹/L). However, it was only the difference in the mean creatinine levels that reached statistical significance (P=0.039). The cases of seropositivity to HBsAg were not active HBV infection, as patients did not show any incriminating symptoms, apart from vaso-occlusive pain. Additionally, the hematologic and biochemical profiles of both groups were similar. Conclusion: Compared to the reports from the general Ghanaian population, the prevalence of HBsAg seropositivity has been shown to be lower, and despite the seropositivity, the hepatic and kidney functions had not been compromised.
Article
Hepatitis C virus (HCV) accounts for 90% of post-transfusion hepatitis. In Uganda, there has been limited research of prevalence of HCV among sickle cell anaemia (SS) patients, a group at risk for multiple transfusions. To establish prevalence of HCV infection and determine whether blood transfusion increases risk among SS patients. 244 SS patients aged 1-18 years were recruited by consecutive sampling. Socio-demographic, clinical and transfusion history was collected. Clinical examination done and blood tested for HCV by MEIA. 244 children were recruited. Of these, 159 (65%) had a history of blood transfusion. Among the transfused, five patients were HCV positive. Four of these were over 12 years of age. Among patients with no history of transfusion, one patient aged 14 years was HCV positive. Risk of HCV was higher among the transfused OR 2.7(CI 0.31-24). Patients who received more than two units were more likely to be HCV positive (p=0.03). HCV prevalence of 2.5% was low but higher than that reported by other investigators in Uganda. Blood transfusion was a major contributing factor in occurrence of HCV. Children who get repeated transfusions should be screened for Hepatitis C and screening of blood for HCV prior to transfusion would help reduce occurrence of the disease.
Article
HBeAg-negative CHB has now a worldwide distribution, developing in the course of HBeAg-positive chronic HBV infection during or after the phase of HBeAg loss and its seroconversion to anti-HBe. It is caused by replicating noncytopathic HBV mutants either unable to produce HBeAg (precore mutants) or with down-regulated transcription of the precore/core messenger RNA (BCP mutants). The most frequently encountered and stable HBeAg-negative mutants in the world are those with a novel translational precore stop codon. They are HBV genotype determined and become selected in genotypes B, C, D, and E (non-A genotypes). They prevail in South Europe, the Mediterranean basin, and Asia, whereas they are rather infrequent in the United States. The incidence of HBeAg-negative CHB is increasing in the world. The selection of HBeAg-negative HBV mutants is determined both by viral and host factors, the same being true for their ability to replicate in the presence of anti-HBe immunity. Clinical, virologic, and biochemical features as well as the natural course of HBe-negative CHB have been reviewed, and the efficacy of IFN-α and lamivudine therapy as well as the problem of viral resistance to lamivudine have been critically presented.
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