infected with HBV worldwide [1]. Chronic HBV infection may lead to severe sequelae such as liver fibrosis, cirrhosis and hepatocellular carcinoma [2]. Nearly 1 million people die every year from acute or chronic sequelae of primary infection with HBV. In Egypt, 75%-85% of patients with chronic liver disease have HBV or hepatitis C virus (HCV) infection as a contributing cause [3].

HBV replication itself is not directly cytotoxic to cells, as evidenced by the large numbers of asymptomatic HBV carriers who have minimal liver injury, despite ongoing intrahepatic replication of the virus. The immune responses to HBV antigens are responsible both for viral clearance during acute infection and for disease pathogenesis. In infected humans, viral clearance follows the development of a vigorous immune response associated with acute, self-limited inflammatory liver disease (i.e, acute viral hepatitis) [4].

Clinical outcomes of HBV infection largely depend on the quality and strength of the host’s immune response. Studies have revealed that T cellular immune responses are essential for disease pathogenesis [5], and have identified CD8+ T lymphocytes as the main cellular subset responsible for viral control [6]. Compared with acute self-limiting infection, lack of vigorous and multi specific T cell response in chronic HBV infection has been observed, which leads to the failure of viral clearance and the progression of the disease [7]. The composition of peripheral T cell subpopulations, on the other hand, serves as a valuable index for evaluating T immune status in chronic HBV infection. Impaired balance of peripheral T subpopulations has been reported at various stages of chronic HBV infections, associated with HBV replication levels, and can be partially restored with antiviral therapy [8]. However, results from previous studies are controversial regarding the specific changes arising during chronic HBV infection, and few have gone so far as to investigate the dynamics of particular T cell subpopulations amid antiviral treatment. The abnormal activation of CD8+ T cells in chronic HBV infection can be partially reversed by antiviral therapy. HBV-associated immune activation may be a crucial part of pathogenesis and may provide a promising target for treatment [9].

CD38 is a surface glycoprotein existing on many immune cells. It is ubiquitously expressed on lymphocytes in a unimodal distribution [10,11]. In certain infections, CD8+CD38+ T cells undergo a rapid up-and-down pattern after the infection once the immune control of the acute phase is achieved [12]. However, persistency of immune activation and CD38+ expression throughout the acute and chronic phase is possible, which may reflect the failure of the host’s immune system to fully suppress viral replication. With some infections, a correction of CD38 expression level could also be observed soon after effective treatment, (e.g., HIV, EBV infections) [13,14]. Whether it is the same case with chronic HBV infection deserves more exploration. Quantitating the mean intensity of CD38 expression on CD8 T cells rather than just the proportion of positive cells is preferable and better reflects the continuous distribution of CD38 on CD8 T cells [15].