Author reply

Abstract

We are pleased to respond to the comments of R.S. Jayshree and H. Sridhar who have suggested that use of multiple primers/probes from surface(S), core(C), and X gene of hepatitis B virus genome can improve detection of HBV infection in HCC. On principle, we agree with their suggestion, but in the present study the need to use S and X gene primers in addition to that of a core gene was considered not necessary. As indicated in their comments, the present study1 was directed primarily to analyse the p53 gene mutation in HCC in India. But since p53 mutation was found in only 3 of 21 cases analysed (14.28%, CI: −0.7 to 29.3), the study was extended to examine infection of hepatitis B virus which has been strongly implicated in the development of hepatocellular carcinoma. For our study, we used primer sequences from the core(C) region of the HBV genome, the gene organization of which is well conserved irrespective of subtypes.2, This is true because 19 of 21 HCC cases (90.45%) were positive for the core primers. Although several mutations or alterations of the four major genes of HBV genome have been reported, it is unlikely to find a HCC patient infected by HBV without a core or other open reading frames. It is well established that if there is a mutation or deletion of core or precore region, no hepatitis B e antigen (HBeAg) is produced.4, 5 Because the two HBV–PCR negative cases in question are positive for HBeAg, as well as HbsAg, it is quite unlikely that the infected HBV genome was without the core or S gene. It is possible that following initial infection, HBV DNA remained in an unintegrated state in these patients and later got cleared by strong immunologic response of the host or by some yet unknown mechanism(s), but the viral gene products such as hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) remained in the circulation or in the target issue. But there are several HCC cases that also may test negative for these HBV serologic markers (see Table 2 of reference 1). Therefore, for a reliable estimate of HBV infection in HCC, both PCR and serologic ELISA should be used as screening assays. Bhudev C. Das Ph.D.*, Varsha Thakur M.Sc. , Raj C. Guptan M.D. , Shiv K. Sarin M.D. , * Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), Maulana Azad Medical College Campus, New Delhi, India, Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India