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.
Keywords: Hepatitis B; immunotherapy; interferon; nucleoside/nucleotide inhibitors; therapeutic vaccines.
Chronic hepatitis B virus infection (CHB) is a major cause of liver cirrhosis and liver cancer worldwide. Persons with CHB have a dysfunctional immune response that is not capable of clearing the virus from the liver. Two types of treatment are currently available for individuals with CHB. These treatments can have some impact on reducing the risk of cirrhosis and cancer, but they rarely eliminate the virus, and relapse can occur. There are numerous new treatments, such as new antivirals and immunotherapies, being explored for their ability to restore an effective immune response, although to date, there has been little success in this area. Because of the many ways the hepatitis B virus uses to evade the immune system, it is unlikely that one drug or immunotherapy will be able to reliably silence the infection in significant proportions of patients with CHB. Combination regimens involving direct-acting drugs targeting different stages of the virus life cycle, along with stimulation of antiviral immune response are likely to be needed.