The correlation between baseline serum hepatitis B surface antigen level and levels of other baseline markers of viral activity in patients with chronic hepatitis B viral infection at the University Teaching Hospital

Abstract

Title: The correlation between baseline serum hepatitis B surface antigen level and levels of other baseline markers of viral activity in chronic hepatitis B viral infection at the University Teaching Hospital. Background: Hepatitis B viral (HBV) infection rate among healthy blood donors in Zambia is about 8%, with about 100 000 patients requiring treatment. Effective monitoring of these patients requires the use of the technically difficult and expensive serum HBV DNA levels. Quantifying serum Hepatitis B surface antigen (HBsAg) which is produced by the covalently closed circular DNA (cccDNA), may be a more reliable, simple, inexpensive and non-invasive way of monitoring patients with chronic hepatitis b (CHB) infection. There is a correlation between reduction in serum HBsAg and in cccDNA and total intrahepatic HBV DNA among patients on treatment. However, it remains inconclusive whether serum HBsAg correlates with serum HBV DNA, which would make it helpful in predicting serum viral load. Objective: To determine whether baseline serum HBsAg quantification correlates with other baseline serum hepatitis B viral markers Methodology: This was a cross sectional study. Patients with hepatitis B infection were recruited under the STEP-HEP Study from blood donors in Lusaka, Zambia, medical wards and out-patient medical clinics at UTH over a 15 month period. We screened 49 Patients (HBeAg positive: n=14, HBeAg negative: n=35) with chronic HBV (HBsAg positive for at least 24 weeks) for other causes of liver disease and those with alternative causes of hepatitis were excluded. Blood testing was performed for baseline ALT, serum viral load, HBeAg status and serum HBsAg level. Patients with HBV DNA >2000IU/ml and ALT above the upper limit of normal (35U/L) who did not have radiological evidence of cirrhosis were included in the study. Serum HBV DNA and HBsAg were logarithmically transformed for analysis. Categorical variables were compared by the Pearson chi-square test or the Fisher exact test as appropriate. The Pearson and Spearman correlation coefficients were tested for parametric and non-parametric variables respectively. Statistical significance was defined as a P value of less than 0.05 Results: There was a significant inverse correlation between baseline HBsAg and serum HBV DNA (r = -0.38, P= 0.02). The correlation between serum HBsAg and ALT was not significant (p= 0.94). There was no significant difference in HBsAg level between HBeAg positive and HBeAg negative patients (p= 0.06). The correlation between serum viral load and ALT was also not significant (p=0.26). There was significantly higher ALT in HBeAg positive than in HBeAg negative patients (p=0.016). The serum viral load was significantly higher in HBeAg positive than in HBeAg negative patients (p=0.0001) Conclusion: The inverse correlation between baseline serum HBsAg level and serum HBV DNA may reflect the inadequacy of serum HBV DNA to represent the level of intrahepatic HBV DNA which correlates with serum HBsAg. However, there was no significant correlation between baseline serum HBsAg and ALT nor was it significantly affected by HBeAg status. The correlation between baseline serum hepatitis B viral load and ALT was not significant. ALT and serum HBV DNA were significantly higher in HBeAg positive than in HBeAg negative patients. Therefore, baseline serum HBsAg quantification may not be a useful surrogate marker of other serum markers of viral activity in CHB infection, but requires further evaluation