4 DISCUSSION
HBV infections remain a major public health problem worldwide and the
main factor for the development of liver cirrhosis. To the best of our
knowledge, this was the first study that combined HBV seroprevalence
with an evaluation of the clinical evolution and insights regarding the
liver disease based on AST/ALT ratio, in a young population rejected for
blood donation in Luanda, the capital city of Angola.
The peak prevalence of HBV infection in Africa has been estimated to be
around 20% while the seroprevalence of HBV in the general population of
Angola has been estimated to be around 26%, higher than the average of
the eight countries in Africa. The HBV seroprevalence observed in this
study (63.4%) (Table 1), indicating to be the main cause of the
rejection of blood donors in Luanda. A previous study carried out by our
research team in 2018 observed an HBV positivity rate of 7.5% among
HIV-positive pregnant women, which was below the infection rate in
Africa, however, in the present study, we observed an HBV positivity
rate of 63.4% among rejected candidates to blood donation, which is
equivalent to 3 times more than the global rate observed in Africa.
Previous studies carried out by Nebenzahl et al (9.3%), Vueba et al
(25.7%), Peliganga et al (22.7%), and Almeida et al (15.1%) have also
reported a high rate of HBV positivity for HBV in Angola using the same
HBsAg biomarker used in the present study. This increase in the
seroprevalence of HBV among rejected blood donors in the capital of
Angola might be explained due the increase of people with high unsafe
sexual activity and a low vaccination coverage rate against HBV among
the young population. The result could also reflect the increase in
socioeconomic inequalities, which is a crucial determinant for the
increase of risk groups in the population. Indeed, the main risk groups
for HBV identified in this study were young people aged 20 - 40 years
(OR: 2.34, p=0.045), females (OR: 1.40, p=0.516), urbanized areas (OR:
1.23, p=0.530), low level of education (OR: 1.54, p=0.458), unemployed
(OR: 1.65, p=0.271), and unmarried (OR: 1.41, p=0.616) (Table 1). These
findings suggest that measures such as awareness-raising and mass
vaccination campaigns to control the spread of HBV in Angola should be
centered on these vulnerable groups, although little statistical power
was observed.
We observed a statistically significant relationship between age and HBV
infection (p<0.001), with those infected (29.2±8.02 years old)
at a lower mean age than the uninfected (33.9±10.0 years old), which
could be attributed to the early onset of sexual activity, ineffective
HBV vaccination programs, as well as, a little awareness about practices
to avoid contracting HBV infection in the young population. Previous
studies have also reported a high rate of HBV infection in the young
population up to 30 years old in different populations from Angola. The
females in our study were 1.4 times more likely to contract HBV (Table
1), which corresponds to the findings of Nebenzahl et al, but differs
from the report of Valente et al, which showed that men have twice the
rate of HBV infection compared to females in Angola. It is worth
mentioning that the high number of individuals with low education,
unemployed and unmarried, might contribute to young people adopting
risky behaviors, including the practice of sex workers, which enhances
the dissemination of HBV as well as other infectious agents that share
the same transmission routes. Therefore, it is crucial to carry out more
studies to understand the sociodemographic and behavioral determinants
that enhance the spread of HBV and other viral infectious diseases in
Angola.
Curiously, no significant difference was observed in the mean values of
AST, ALT, or AST/ALT ratio, among infected and uninfected donors with
HBV (p>0.05), although the infected individuals had a
higher AST/ALT ratio (2.07) than the uninfected (1.90) (Table 1),
suggesting that AST, ALT, and the AST/ALT ratio could not be a suitable
marker to be used as clinical markers of liver disease among individuals
with HBV infection, as previously reported in the previous studies. We
observed that the AST (from 42 to 68) and ALT (from 28 to 49) levels
increased with increasing age among HBV-positive donors.
Based on AST/ALT ratio, about 20% and 80% of those infected with HBV
had a clinical indication of acute or non-alcoholic liver disease and
chronic disease or viral hepatitis, respectively (Table 2). Previous
studies have shown that the AST/ALT ratio is a potential biomarker to
assess health conditions and long-term mortality, especially high values
of the AST/ALT ratio indicating a diagnosis of more severe liver damage
or prediction of future cancer development due to viral hepatitis.
Anderson et al. showed that an AST/ALT ratio of more than one is highly
suggestive of the presence of liver cirrhosis. Based on these
observations from previous studies, our findings showed that around 80%
of rejected candidates due to HBV infection could be at an advanced
stage of liver disease with a high chance of developing liver cirrhosis
in the future, suggesting the need for an urgent review of control
measures, to rejected donors receive a specialized assistant in case
they test positive for viral hepatitis.
It is worth highlighting that some studies have reported that the
AST/ALT ratio seems to have clinical value as an insight into the
diagnosis of cirrhosis but does not define the diagnosis of cirrhosis
and does not effectively predict the degree of fibrosis in patients with
chronic viral hepatitis. The literature disagreement regarding the
clinical utility of the AST/ALT ratio in individuals with HBV infection
is an indication of the need for further studies, especially in terms of
the population with occult HBV infection, such as blood donors. Despite
this, our findings show that the evaluation of enzymes AST and ALT, as
well as the AST/ALT ratio, could be useful in Angola for the timely
identification of candidates with suspected advanced liver damage and
with a high likelihood of developing liver cirrhosis. Furthermore, our
results show that candidates infected with HBV who presented a high odd
of developing liver cirrhosis or clinical progression of liver damage
are donors between 20 - 40 years old (1.97 times), females (1.61 times),
residents in non-urbanized areas (1.69 times), and unemployed candidates
(1.81 times), although no statistical significance was observed
(p>0.05). Sociodemographic, clinical, and behavioral
determinants related to the progression to liver cirrhosis among blood
donors rejected due to viral hepatitis, such as HBV infection, are still
little explored and deserve further investigation. Previous studies have
shown that laboratory algorithms based on HBsAg detection leave a gap
for infected HBsAg negative donors donating blood during the window
period and could potentiate the spread of HBV infection through blood
transfusion. Therefore, due to the high endemicity of HBV in Angola, new
screening strategies including HBV nucleic acid testing (NAT) capable of
detecting HBsAg-negative and anti-HBc-negative blood units donated
during the initial acute HBV infection, should be quickly included in
the testing algorithm for blood donors in Angola. This strategy aims to
strengthen current diagnostic strategies and to prevent or reduce the
transmission of viruses due to blood transfusion, although we recognize
that the Angolan Ministry of Health should consider the need to evaluate
the cost-effectiveness of incorporating the NAT in the algorithms of the
health units responsible for the treatment and blood transfusion.
There are important limitations to be considered when interpreting the
results of this study. Firstly, the small sample size and the regional
limitation of the study among rejected blood donors screened by HBsAg in
Luanda, the capital city of Angola, could have contributed to the low
statistical power of the study as well as not representing a current
epidemiological picture of the HBV infection in the general population.
Secondly, the rate of HBV infection could be underestimated, as other
markers such as NAT, anti-HBc, and anti-HBe, able to define the time of
infection and infectiousness were not screened among HBsAg positive or
negative donors. Finally, the clinical profile of liver damage among
HBV-positive donors was defined only with the biomarkers AST, ALT, and
the AST/ALT ratio, although we recognize the existence of other serum
markers and important clinical procedures that define liver damage or
liver cirrhosis. Furthermore, we know that other conditions including
metabolic disorders, alcohol intake, and physical exercise could affect
AST and ALT values to change capable of inducing a misinterpretation of
liver damage, which reinforces the need for further studies including
behavioral determinants as well as the screening of additional markers
of liver function to help define earlier the stage of liver damage in
blood donors rejected due to HBV infection. Despite the observed
weaknesses, our findings provide an important contribution to a more
comprehensive knowledge of HBV epidemiology and vaccination status in
Angola. However, further studies should be performed to allow a better
characterization of the HBV epidemiology, risk groups, and clinical
profile of the HBV-infected population to reinforce ongoing strategies
to control HBV infection in Angola.
In summary, HBV infection is a burden among young individuals in Luanda,
the capital city of Angola. The high HBV positivity rate could indicate
the failure of viral hepatitis control measures in Angola. HBV
screening, awareness, and control strategies must be urgently reviewed
to prevent the unprecedented spread of HBV infection in the young
population. Angolan health authorities should consider including HBV
nucleic acid testing along with markers of liver function to ensure
early identification of donors with occult HBV infection to improve the
safe blood products and control the spread of chronic HBV infection in
Angola. Further studies must be carried out to better understand the key
determinants associated with HBV infection and progression to chronic
liver disease among the HBV-infected population in Angola.