Advances in the Pharmacological Management of Chronic Hepatitis B

Background: Hepatitis B, a vaccine-preventable liver infection, remains a global public health problem. Dedicated groups of experts and funding are focusing on achieving a functional cure to eradicate this disease by 2030. Areas of Uncertainty: With more than 40 molecules available or under investigation as new treatments for hepatitis B virus (HBV) infection, none of them is curative so far. Available treatments are effective in suppressing HBV replication and in decreasing the risk of developing cirrhosis, liver failure, hepatocellular carcinoma, and death, but do not eliminate the virus, and the risk of hepatocellular carcinoma remains. Nucleoside/nucleotide analogs are recommended as first-line therapy for patients with chronic hepatitis B infection to inhibit viral replication and lower the HBV DNA values, but long-term therapy is usually needed to maintain suppression. Cessation of the therapy in accordance with clinical guidelines can result in virological and clinical relapse. Data Sources: PubMed, Web of Science, clinicaltrials.gov, and gray literature sources were searched for articles discussing HBV management and new therapies. Results: With current nucleoside/nucleotide analog therapies, fewer than 5% of patients lose hepatitis B surface antigen after 12 months, which underscores the need for new drugs that can achieve a functional cure. New therapies are being developed, including small interfering RNAs. Bepirovirsen, a modified antisense oligonucleotide, shows promising results and a good safety profile, but requires further exploration in larger number of patients to determine whether a functional cure is possible. Conclusions: Eradication of HBV infection with currently available therapies is not yet possible. Experts are developing innovative treatments, such as bepirovirsen, to achieve functional cure for this disease and to reduce morbidity and mortality associated with hepatic cirrhosis and hepatocellular carcinoma.