Precision Medicine in Viral Hepatitis: Current Advances, Challenges and Future Perspectives

Abstract

Viral hepatitis is a major global health problem, being the leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. The World Health Organization (WHO) has reported that hepatitis B and C viruses cause 1.34 million deaths yearly, and despite the availability of effective vaccines and treatments, the infections remain a significant health hazard. The application of conventional “one-size-fits-all” treatment and prevention methods cannot be efficient enough in the context of the identified genetic, immunological, and biochemical variability, which may affect individual response to treatment. The precision medicine paradigm aims to account for this complexity in order to individualize prevention, diagnosis, and treatment. This review discusses the state-of-the-art of precision medicine in the context of viral hepatitis. For instance, in the case of hepatitis B, the discussion revolves around the potential of quantitative HBs antigen, hepatitis B core-related antigen, and HBV RNA as biomarkers of treatment cessation and functional cure, as well as gene-editing and RNA-based therapies targeting the hepatitis B covalently closed circular DNA (cccDNA). Turning to hepatitis C, it is noted that, despite the advent of pangenotypic direct-acting antiviral agents (DAAs), the individualization of treatment still requires consideration of IL28B polymorphisms, NS5A resistance-associated substitutions, and other host and viral biomarkers. The first entry inhibitor for hepatitis D, bulevirtide, has also been highlighted, alongside the importance of pharmacogenetic-guided ribavirin dosing, which is still relevant in certain cases. The role of artificial intelligence in precision oncology was also discussed in the context of liver cancer risk prediction, with a particular focus on hepatocellular carcinoma. Among the key challenges in the field are the high costs of individualized therapies and the insufficient consideration of host responses in low- and middle-income countries (LMICs), as well as the lack of high-quality biomarkers for hepatitis E in LMICs, which hinders the personalized approach to prevention and treatment there. The key future directions for precision medicine in viral hepatitis include multi-omics studies, single-cell technologies, artificial intelligence-assisted precision prevention and treatment, and the implementation of these innovations in public health and population health approaches to viral hepatitis elimination by 2030, as envisioned by the WHO.