Hepatitis B virus (HBV) infection affects 262 million people worldwide, leading to over 820,000 deaths annually. The reason HBV has been a persistent issue for decades is that it is a non-cytopathic, liver-specific virus with the ability for persistent infection, which cannot be completely eliminated by drugs, eventually progressing to cirrhosis and hepatocellular carcinoma (HCC). Although HBV seems to induce little innate immune activation, adaptive immune responses can mediate viral clearance and liver disease. Here, we review the epidemiology, natural history, lifecycle, and modes of transmission of HBV. We also pay particular attention to the adaptive and innate immune responses to HBV and the research progress on therapeutic vaccines, which may provide new insights for targeted HBV treatment.

Chronic hepatitis B (CHB) disease caused by persistent infection with hepatitis B virus (HBV) is a global health problem affecting almost 300 million people worldwide, resulting in up to 1 million deaths each year. The factors contributing to HBV mediated liver disease are yet to be fully resolved, however, multiple studies have suggested that HBV splice variants may be a contributing factor. Recent studies have indicated that novel fusion proteins encoded by splice variants, or the splice-derived RNA itself, may impact replication of wild-type HBV, although the direct mechanisms for these interactions are largely unknown. This review explores the latest knowledge regarding the contribution of splice variants to liver disease and their impact on HBV replication.

Hepatitis C viral infections present a significant global health challenge, carrying substantial economic implications. These infections manifest in various clinical forms, including acute and chronic hepatitis, liver cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC emerge as the primary contributors to mortality in hepatitis virus-induced liver diseases. To alleviate the public health impact of this disease, it is imperative to enhance the diagnosis and treatment rates among hepatitis C virus-infected individuals. The advent of direct-acting antivirals (DAAs), especially pan-genotypic regimens such as a combination of sofosbuvir and velpatasvir, has shown remarkable progress in achieving hepatitis C cure. However, potential obstacles, such as drug adverse effects and resistance-associated substitutions (RASs), warrant attention. Managing chronic hepatitis C (CHC) requires tailored treatment plans, vigilant monitoring, and judicious re-treatment strategies.