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Chronic Hepatitis B (CHB) infection has an intermediate prevalence rate in South Asian countries, except for Nepal and Sri Lanka where it has a low rate. HBeAg negative CHB infection has been found to be more pronounced in this part of the world. As described previously, CHB infection has two phases with HBeAg positive and HBeAg negative based on ALT, DNA & biopsy. The latter was previously described to have a benign course. The later guidelines have distinguished HBeAg negative status into two categories with an inactive phase and a reactivation one. In this review article we have highlighted HBeAg Negative status burden in South Asian countries and shown that HBeAg negative CHB infection may not be as benign as previously thought. Furthermore , mutations at precore and basal core promoter region may contribute to disease severity in HBeAg negative CHB infection.