Past, present, and future of long-term treatment for hepatitis B virus

The estimated world prevalence of hepatitis B virus (HBV) infection is 316 million. HBV infection was identified in 1963 and nowadays is a major cause of cirrhosis and hepatocellular carcinoma (HCC) despite universal vaccination programs, and effective antiviral therapy. Long-term administration of nucleos(t)ide analogues (NA) has been the treatment of choice for chronic hepatitis B during the last decades. The NA has shown a good safety profile and high efficacy in controlling viral replication, improving histology, and decreasing the HCC incidence, decompensation, and mortality. However, the low probability of HBV surface antigen seroclearance made necessary an indefinite treatment. The knowledge, in recent years, about the different phases of the viral cycle, and the new insights into the role of the immune system have yielded an increase in new therapeutic approaches. Consequently, several clinical trials evaluating combinations of new drugs with different mechanisms of action are ongoing with promising results. This integrative literature review aims to assess the knowledge and major advances from the past of hepatitis B, the present of NA treatment and withdrawal, and the future perspectives with combined molecules to achieve a functional cure.