Despite the availability of an effective vaccine, hepatitis B virus(HBV) infection remains a major health problem, with more than 350 million chronically infected people worldwide and over 1 million annual deaths due to cirrhosis and liver cancer. HBV mutations are primarily generated due both to a lack of proofreading capacity by HBV polymerase and to host immune pressure, which is a very important factor for predicting disease progression and therapeutic outcomes. Several types of HBV precore/core(preC/C) mutations have been described to date. The host immune response against T cells drives mutation in the pre C/C region. Specifically, pre C/C mutations in the MHC class Ⅱ restricted region are more common than in other regions and are significantly related to hepatocellular carcinoma. Certain mutations, including preC G1896 A, are also significantly related to HBe Ag-negative chronic infection. This review article mainly focuses on the HBV pre C/C mutations that are related to disease severity and on the HBe Ag serostatus of chronically infected patients. Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem, with more than 350 million chronically infected people worldwide and over 1 million annual deaths due to cirrhosis and liver cancer. to a lack of proofreading capacity by HBV polymerase and to host immune pressure, which is a very important factor for predicting disease progression and therapeutic outcomes. Several types of HBV precore / core (preC / C) Immune response against T cell drives mutation in the pre C / C region. Specifically, pre C / C mutations in the MHC class II restricted regions are more common than in other regions and are related related to hepatocellular carcinoma. Certain mutations, including preC G1896 This review article focuses focuses on the HBV pre C / C mutations that are related to dise ase severity and on the HBe Ag serostatus of chronically infected patients.