Chronic hepatitis B (CHB) is one of the leading causes of liver disease worldwide. HBV infection is still endemic in Tunisia. However, a gradual shift from high to intermediate-to-low endemicity is currently observed mainly due to the implementation of the vaccination program since 1995. According to a recent national survey on viral hepatitis seroprevalence in the years 2014–2015 [1], the hepatitis B surface antigen (HBsAg) carriage rate was 1.8%, confirming the significant decrease in the seroprevalence of HBV infection, which was 6.5 % in the 1990s [2].

During the natural course of hepatitis B e antigen (HBeAg)-negative CHB, fluctuations in both HBV DNA (viral load) and alanine aminotransferase (ALT) levels are often observed, making patient classification very difficult. Although significant variations in HBV DNA levels have been well documented during this phase, little is known about short-term fluctuations in HBV DNA. Thus, serial determinations of these two parameters (HBV DNA and ALT levels) for at least 1 year are mandatory to avoid misclassification of infected patients [3]. Recently, several studies have suggested the potential role of HBsAg quantification (qHBsAg), along with HBV DNA levels, for a reliable and accurate determination of the actual HBV infection phase [4], [5], [6].

This study aimed to describe spontaneous HBV DNA fluctuations and to assess the usefulness of qHBsAg in the diagnosis of HBV infection over a 1-year prospective follow-up period among Tunisian patients with HBeAg-negative chronic HBV infection.