Editorial: Chronic Hepatitis B Management: Current Status and Future Directions

Ivana Lazarevic^1*Krzysztof Tomasiewicz²

• ¹Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
• ²Department of Infectious Diseases and Hepatology USK-1, Medical University of Lublin, Lublin, Poland

Infection with the hepatitis B virus (HBV) remains a significant global health challenge. By the latest estimates, roughly two billion people worldwide have been exposed to HBV, and 254 million have persistent infection with a predisposition to develop severe complications, including liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC) (1,2). According to the latest EASL guidelines, based on specific virological, immunological and clinical features, persistent HBV infection evolves through two non-successive phases of chronic infection and two phases of chronic hepatitis B (CHB) (3). Understanding chronic HBV infection has evolved over the years, leading to significant advancements in its diagnosis, management, and prevention. Introducing efficient vaccination and universal vaccination programs has played a crucial role in preventing new infections and reducing the global burden of infection. The introduction of effective antiviral therapies has revolutionised the management of CHB, reducing liver inflammation and preventing liver-related complications. Finally, developing new diagnostic techniques and identifying new biomarkers have facilitated clinical decision-making in managing CHB.The persisting challenges in CHB management include the impossibility of sterilising cure by current therapies, antiviral drug resistance, long-term safety concerns of antiviral treatments, and the difficulty of reaching vulnerable populations in vaccination programs. This Research Topic was designed to gather experiences with new diagnostic approaches, innovative pre-clinical and clinical therapeutic strategies, various monitoring techniques and the impact of vaccination programs on disease prevention and control. It encompassed eight original articles, one brief report, two clinical trials, one case report, one systematic review with meta-analysis and one narrative review. This is a provisional file, not the typeset article The primary goal of CHB therapy is to improve long-term outcomes by consistently 35 inhibiting HBV replication. However, current treatments, pegylated interferon α (PEG-IFNα) and 36 nucleos(t)ide analogues (NAs), cannot achieve a sterilising cure because of their inability to eliminate 37 HBV mini-chromosome in hepatocyte nuclei or viral DNA integrated into the host genome. 38 Therefore, the alternative goal is a "functional cure," characterised by persistently undetectable serum 39HBV DNA and hepatitis B surface antigen (HBsAg), potentially with seroconversion to 40 corresponding antibodies (3,4). The remaining problems with current therapies include their 41 potential adverse effects and the selection of biomarkers capable of predicting a functional cure. this specific serological pattern. One possible explanation for this rare phenomenon is HBV genetic 100 variability, responsible for HBV escape mutants that the corresponding antibodies cannot neutralise 101 (11). The other interpretation can be the immune system's inability due to immunosuppression or 102 immaturity (12). 103The most effective way to prevent HBV infection is active immunisation. However, despite 104 high protection rates in vaccinated individuals, the overall ratio of non-responders is 5-10% and 105 varies significantly in special population groups. Several new vaccines are designed to protect highly 106 vulnerable individuals (13