Rethinking the Inactive Carrier State: Management of Patients with Low-Replicative HBeAg-Negative Chronic Hepatitis B and Normal Liver Enzymes

HBV is the leading cause of chronic liver disease worldwide. Many infected individuals are said to exist in the inactive carrier state, characterized by persistence of hepatitis B surface antigen (HBsAg) and absence of hepatitis B e antigen (HBeAg), HBV DNA below 2000°IU/mL, normal serum alanine aminotransferase (ALT) levels (defined as °30°IU/mL for men and °19°IU/mL for women), and minimal histological disease activity. Since ALT levels fluctuate widely during the course of chronic HBV infection and the inactive carrier state is serologically indistinguishable from HBeAg-negative chronic hepatitis, serial assessment of the liver function panel and HBV DNA levels are essential to ensure correct longitudinal patient classification. The inactive carrier state encompasses a heterogeneous population of patients, including those who are truly inactive and those with low-level viral replication. Given the small but significant risk of progressive liver disease, cirrhosis and hepatocellular carcinoma in individuals with persistent low-level viraemia, the term 'inactive carrier state' should be reconsidered for these latter individuals and replaced with 'low-replicative HBeAg-negative chronic hepatitis B'.