CONCURRENT HEPATITIS B SURFACE ANTIGEN AND ANTIBODY IN SINGAPORE HBV CARRIERS AND OTHER RELATED STUDY : PREVALENCE AND CLINICAL SIGNIFICANCE

Abstract

Hepatitis B serological markers were investigated in 1132 consecutive Singaporean hepatitis B virus (HBV) carriers. Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were found concurrently in 234 HBV carriers (234/1132 or 21%) Serum anti-HBs levels were more than 10 mIU/ml in 80 of these carriers (80/234 or 34%). There were no statistical significance in HBV e antigen (HBeAg) positive status, as well as HBV deoxyribonucleic acid (HBV-DNA) positive status in concurrent HBsAg/anti-HBs carriers compared to HBV carriers without anti-HBs (p>0.05). Our results suggested that concurrent HBsAg and anti-HBs is a common serologic pattern in Singaporean HBV carriers.

We further analyzed pre-S/S region of HBV in serial samples from 6 asymptomatic HBV carriers (ASC) (group A) and 4 hepatocellular carcinoma (HCC) (group B) patients with specific serologic pattern (HBsAg/anti-HBs), and another 5 asymptomatic HBV carriers without anti-HBs as controls (group C). Pre-S/S regions of HBV-DNA were amplified by polymerase chain reaction (PCR), cloned and sequenced. Two patients (one in group A and another in group B) had point mutations in S gene "a" determinants, resulting in conversion from Ala-157 of wildtype virus to Trp-157 and lle-126 to Asn-126, respectively. Five group A patients, 3 group B patients and one group C patient also had mutants with deletions in the pre-S2 gene. No mutation was detected in "a" determinant in group C patients although they still exhibited many point mutations. Furthermore, group A and B patients had a significantly greater divergence rates of amino acid for pre-S/S genes compared to group C patients (p<0.05). Our results suggested that the HBV mutants observed in pre-S/S gene might have led to changes in immunogenicity of the viral particles, and thus influence the viral behaviour and clinical course. Therefore, some HB Y patients with concurrent HBsAg and anti-HBs might have HBV S mutants.

In addition, to clarify the etiologic association of HBY and hepatitis C virus (HCV) with HCC in Singapore, a total of 63 consecutive patients with HCC and 446 hepatitis virus carriers were studied. The prevalence of HBsAg and anti-HCV in patients with HCC were 80.9% (51/63) and 14.3% (9/63), respectively. The mean ages of HBsAg-positive patients with HCC and hepatitis virus carriers were younger than that of anti-HVC-positive patients (p<0.01). The prevalence of coinfection with HBV and HCV were found in 7.9% (5/63) of HCC patients and in 6.9% (31/446) of hepatitis virus carriers. In hepatitis virus carriers, a significant difference for anti-HCV reactivity and HCV-RNA positivity were observed between HCV infected patients and coinfected patients (p<0.01). These results suggest that, in contrast with some country, HBV plays the major role in the development of HCC, and HCV may have a secondary role for certain elderly cases in Singapore. This study also demonstrates the possible interaction between hepatitis B and C virus life cycles, and suggests that HCV replication may be negatively affected by HBV.