Immunotherapy for hepatitis B in the direct acting antiviral era: Reevaluating the thymosin 1 efficacy trials in the light of a combination therapy approach

Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large numbers of individuals worldwide. Unfortunately, prediction of typical clinical outcome is problematic and there is considerable variability in the frequency, duration and severity of disease progression. The mainstay of HBV treatment is directed towards the suppression of HBV replication by nucleos(t)ide analogs (NUCs). The use of immunomodulators such as -Interferon and thymosin 1 can, in select patients, results in elimination of both HBsAg and HBeAg. Given the observation that viral clearance is most effective in the presence of a strong immune response, this review summarizes data suggesting that the use of a combination of an immune modulator such as T1 with a highly effective NUC may result in a more successful therapeutic approach in patients with chronic hepatitis B (CHB). Results from small studies using combination T1 and NUCs are encouraging, and ongoing clinical trials combining entecavir with T1 are anticipated to provide important data assessing the use of a combination of T1 with a NUC to achieve resolution of CHB.