Test for hepatitis B virus infection with radical immunoassay and real-time PCR: Which method is the gold standard?
Authors: Shi-Ying Xuan, Yong-Ning Xin, Yan-Dan Zhong, Ming-Hua Zheng, Hua-Shi Guan
Journal: Journal of Hepatology (2008)

We read with interest the study entitled What can be revealed by extending the sensitivity of HBsAg detection to below the present limit? by Togashi et al. [[1]Togashi H. Hashimoto C. Yokazawa J. Suzuki A. Sugahara K. Saito T. et al.What can be revealed by extending the sensitivity of HBsAg detection to below the present limit?.J Hepatol. 2008; 49: 17-24Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar]. We particularly appreciate their original contribution with regard to HBsAg detection. Our concerns regarding this study are outlined below. The Authors believe that the radical immunoassay method will become a powerful tool for worldwide prevention of vertical and horizontal transmission of occult HBV, including cases with a low virus load. We are afraid we have reservations about this and cannot agree with them. Do the cases with a low virus load (less than 1.0 Log IU/ml) really have horizontal transmissibility except for transfusion? The Authors’ opinion will make the source of infection of hepatitis B expand factitiously and consequently it may cause unnecessary panic in the community. Occult hepatitis B virus infection (HBV) can be defined as the long-lasting persistence of viral genomes in the liver tissue (and in some cases also in the serum) of individuals negative for the HBV surface antigen (HBsAg) [[2]Raimondo G. Pollicino T. Cacciola I. Squadrito G. Occult hepatitis B virus infection.J Hepatol. 2007; 46: 160-170Abstract Full Text Full Text PDF PubMed Scopus (426) Google Scholar]. HBV DNA in liver tissue was not detected in Togashi et al.’s study, and hence, we think the results should be interpreted with caution. To compare the radical immunoassay with that of HBV DNA by real-time PCR, which method can reflect the real infection of HBV? In other words, which method is the gold standard? In this study, high sensitivity and high specificity can be obtained using the radical immunoassay method, and is this method a gold standard for HBsAg? What about its repeatability? The Authors did not mention it. In this study, the Authors considered that the low HBs antigenemia without HBV DNA group is uncertain whether there is actual infection with a low HBV load, and may simply imply a false-positive. How about the method’s negative predictive value and positive predictive value? In this study, among 34 cases with low HBsAg positivity, only nine of 34 cases HBV DNA were positive. If we considered real-time PCR as a gold standard for HBV infection, the method’s positive predictive value was only 26.5% (9/34). That is to say, having a high sensitivity is not necessarily a good thing, a test with 95% sensitivity might accurately identify as being affected only 1% of those who test positive in the general population [[3]Loong T.W. Understanding sensitivity and specificity with the right side of the brain.BMJ. 2003; 327: 716-719Crossref PubMed Scopus (245) Google Scholar]. When the tests are used in clinical practice, we think that they will fail to be helpful.