Since viral replication is key to the progression of Hepatitis B, causing liver inflammation, leading to elevated transaminases, histologic deterioration, necrosis and fibrosis, and driving the eventual progression of the disease to liver failure, hepatocellular carcinoma, liver transplantation and even death. So is it acceptable to have a detectable low level of HBVDNA in clinical research and practice?A COX multiple regression analysis of the risk of HCC using continuous HBV viral load and ALT level as correlating variables showed that the higher the time-related HBVDNA level, the higher the risk ratio of HCC, and there was a significant trend as the HBVDNA level increased. Another study showed that changes in serum HBVDNA were strong predictors of HCC risk. The relative risk ratio for developing HCC was highest in those patients who sustained very high (>10^7copies/ml) levels of serum HBVDNA, at about 9.4.Patients whose HBVDNA levels dropped from moderate levels (<10^5copies/ml) to <300copies/ml and remained at that level were very unlikely to develop HCC. This shows that as long as the virus is present, there is a risk of HCC. How can we minimize the risk? We need to maximize the suppression of HBVDNA and keep it below the lowest limit of detection.