0 5 10 15 20 25 30 35 40 45
fr e q u e n c y
15-29 30-44 45-59 60-74
CHARPTER FIVE DISCUSSION
This study was undertaken to determine the pattern and prevalence of selected serological markers in asymptomatic adult subjects with chronic hepatitis B virus infection in the University of Nigeria Teaching Hospital, Enugu.
All the subjects recruited into this study were HBsAg positive. However, males outnumbered females at a ratio of 2.1: 1. Although the population in Enugu State, Nigeria has a slight bias for females121, a study done in UNTH, Enugu has shown that male attendance at hospitals and health facilities is higher than that of females.122 A good number of the subjects were recruited from the Blood Bank. In this environment females rarely donate blood. Furthermore, about 10%
of patients suffering an acute attack of HBV infection do not clear the virus and will become chronic carriers, this clinical course is more common in males than females.88 These may account for the preponderance of males in this study. This male preponderance has been noted in many other studies on hepatitis B virus serology. In a study by Otegbayo et al, in Ibadan in 2003, they noted a male to female ratio of 9.3: 1. 85 In Brazil, a ratio of 2 : 1 has been noted in favour of males.9
The age groups 15-29 and 30-44years accounted for 81.4% of the study group.
This pattern of age distribution follows the normal population with a typical
pyramidal structure in the general population in Nigeria 123. This may also have been influenced by the study design whereby older patients with HBV infection may have manifested evidence of chronic liver disease and would have been excluded from the study. Also, subjects were referred following incidental finding of HBsAg during blood donation, pre-employment medical examination, pre-school admission medical examination and pre-marriage testing all of which involve predominantly young people. In a study in India, the highest prevalence of chronic HBV infection was in the age range 30 – 39 years accounting for 43%
of all cases.48 This is similar to the finding in this study.
One hundred and forty seven (97.4%) were anti HBc IgG positive signifying evidence of chronic or past infection. Four individuals were anti HBc antibody negative. These may be those with titres too low to be detected by the immunoassay used. All were antiHBc IgM antibody negative indicating that there were no cases of acute hepatitis B virus infection included in the study.
Thirteen (8.6%) of the study population were HBeAg positive showing a low prevalence of active viral replication in the study group. This finding compares favourably with those from previous works done in Nigeria. Otegbayo et al found 10.8% positive HBeAg in a similar population.85 However, in a similar study by Ayoola et al, R working on 3,956 blood donors, in Ibadan in 1986, the prevalence of HBeAg and anti HBe were 41.1% and 25.7% respectively. The
reason for the high prevalence of HBeAg in that study is not clear but may reflect changing pattern of the disease over the years. Although Ojo et al in Ile Ife73 found a much higher prevalence of HBeAg (48%) in a group of 31 patients with HBsAg, these were patients with sequelae of chronic HBV infection, such as chronic active hepatitis, liver cirrhosis and primary hepatocellular carcinoma.
Anti HBe antibody was documented in 75.5% of this study population. Other studies done within Africa have also shown lower values for anti HBe antibody ranging from 25% to 59.5%. 68,124 It is accepted that in sub Saharan Africa, most HBV infections are acquired horizontally in childhood and the level of HBsAg is expected to be high.56,67 With advancing age, spontaneous seroconversion takes place leading to a reduction in the frequency of HBeAg and an increase in anti HBe antibody. Most existing studies of serological markers in children with chronic infection did not assay for HBeAg status.50,77,81 It will therefore be necessary to assay for a more complete serological profile in children with chronic HBV infection to establish the veracity or otherwise of this hypothesis in this environment. An increased level of HBeAg in regions of high endemicity maintains a reservoir for chronic HBV infection. The finding in this research of a low prevalence rate of HBeAg may mean that we have a higher rate of pre core mutants of HBeAg than previously thought. It will be necessary then, to assay for other serological markers such as HBV DNA.
Of the risk factors for acquisition of HBV infection studied, 21.2% reported a past medical history of jaundice. Thirty eight percent of the study population had multiple sexual partners, that is, more than 2 sexual partners and 47.7% admitted to patronizing quacks and medicine stores. Identifiable risk factors reported by Otegbayo et al include indiscriminate injections scarification marks and contact with commercial sex workers.85 Otu in Southern Nigeria found that receiving numerous injections (up to 10 injections per year) was the only risk factor associated with HBsAg positivity.84 These studies, in addition to the present study did not find past history of blood transfusion significant for the acquisition of HBV infection. Contrary to the experience in Ibadan by Otegbayo et al85, scarification marks due to tribal and ethnic habits may not be a significant risk factor in Enugu, South Eastern Nigeria.
There was a positive association between HBeAg positivity and abnormal ALT.
This is expected since the presence of HBeAg denotes active viral replication and on going inflamation with hepatocellular damage. Otegbayo et al noted that all the subjects with raised ALT had HBsAg positive in serum.85 They also noted that all 4 subjects who were positive to HBeAg had raised levels of ALT up to and higher than twice the upper limit of normal. Ayoola et al, on the other hand found only 8% of HBeAg positive subjects with elevated ALT levels.75
Hepatitis C virus (HCV) infection is uncommon in Nigeria and co-infection of HBV and HCV is rare 73 . The contribution of HCV in the finding of strong association between HBV infection and elevated ALT is unlikely to be significant.
CHAPTER SIX
CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS
1. It is concluded from this study that the majority of chronic hepatitis B virus infected individuals were males and the age bracket mostly affected was 20 – 49 years which forms the major workforce of any nation.
2. The prevalence of HBeAg positivity is low (8.6%) while that of anti HBe antibody is high (75.5%). These factors signify a low level of active disease.
3. Presence of HBeAg is associated with elevated ALT levels which were noted in all HBeAg positive subjects.
RECOMMENDATIONS
1. It is recommended that further studies be done to determine the presence of HBV DNA especially in HBeAg negative subjects. It is further recommended that genetic studies be carried out to determine the prevalence of precore mutant species in HBeAg negative subjects.
2. To help prevent further transmission of HBV and the development of long term complications, assessment of serological markers to identify the subset of subjects with active viral replication should be instituted in the routine work-up of such patients.
3. Contact tracing of close associates of such subset especially their spouses, children and household contacts is advocated.
4. A liver biopsy, in conjunction with serology and biochemical tests remains essential in the assessment of chronic HBV infection.
5. Public awareness campaigns should be embarked upon to educate the people on the risk factors and modes of acquisition of the virus as well as its long term complications and the benefit of its prevention especially by immunization.
LIMITATIONS OF THE STUDY
1. HBV DNA estimation would have been necessary for a more complete serological assessment of these subjects. This however was not done because of unavailability of tests and logistic reasons.
2. More investigations such as hepatitis C antibody assay were not done.
HCV infection has not been found to cause significant liver disease in this environment, and as such will not contribute significantly to the ALT results in this study.
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