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.