A role for immune modulation in achieving functional cure for chronic hepatitis B among current changes in the landscape of new treatments.

Introduction: Chronic hepatitis B (CHB) is rarely cured using available treatments. Barriers to cure are: 1) persistence of reservoirs of hepatitis B virus (HBV) replication and antigen production (HBV DNA); 2) high burden of viral antigens that promote T cell exhaustion with T cell dysfunction; 3) CHB-induced impairment of immune responses.

Areas covered: We discuss options for new therapies that could address one or more of the barriers to functional cure, with particular emphasis on the potential role of immunotherapy.

Expert opinion/commentary: Ideally, a sterilizing cure for CHB would translate into finite therapies that result in loss of HBV surface antigen and eradication of HBV DNA. Restoration of a functional adaptive immune response, a key facet of successful CHB treatment, remains elusive. Numerous strategies targeting the high viral DNA and antigen burden and aiming to restore the host immune responses will enter clinical development in coming years. Most patients are likely to require combinations of several drugs, personalized according to virologic and disease characteristics, patient preference, accessibility, and affordability. The management of CHB is a global health priority. Expedited drug development requires collaborations between regulatory agencies, scientists, clinicians, and within the industry to facilitate testing of the best drug combinations.