2nd Edition: How to Adjust the Action Steps for Achieving the Global Hepatitis Virus (HBV/HCV/HDV) Elimination Targets?

Dear Colleagues,

Objective: "Adjusted action steps for achieving global hepatitis virus (HBV/HCV/HDV) elimination".

Introduction: The WHO’s goal of hepatitis elimination by 2030 will not be fulfilled because chronic viral liver disease remains a highly significant global health concern. Current anti-HCV antivirals can cure more than 95% of HCV infections but do not provide protection from re-infection, and without HCV vaccines, the elimination of HCV infection is impossible. Life-long suppression of hepatitis B virus (HBV) replication with nucleot(s)ide analogues is far from ideal because it is burdened by cost and adherence problems. Many new drugs that aim to increase the rate of functional HBV cures (serum HBsAg and HDV-DNA clearance) are under clinical investigation, but none are commercially available. Furthermore, there is an unmet need to fully exploit the potential of both old and new drugs with more personalized treatment approaches based on accurate virologic, immunologic, and clinic–pathologic profiling. The clinical efficacy of new anti-HDV drugs to inhibit viral entry into the hepatocyte remains to be fully elucidated. This Special Issue will gather manuscripts from renowned experts in different fields of viral hepatitis, aiming to propose new action steps towards eliminating the global clinical burden of viral hepatitis caused by HBV, HCV, and HDV.

Summary: The World Health Organization (WHO)’s global hepatitis strategy, endorsed by all WHO Member States, aims to reduce new hepatitis B, C, and D (HBV, HCV and HDV) infections by 90% and deaths by 65% between 2016 and 2030. At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally; although this number has presented a consistent decrease from 2016, forecasts suggest that we are not currently on track to achieve global elimination targets by 2030. In 2020, the Center for Disease Control (CDC) released universal screening recommendations for adults including pregnant women [2] due to continued increases in HCV infections in the USA; since the proper identification of perinatally infected children and their referral to curative treatment are critical to eliminating hepatitis C, the CDC recently released new screening recommendations [3]. Direct-acting antiviral medicines (DAAs) can cure more than 95% of individuals with HCV infection, but they do not provide protection from re-infection, and access to diagnosis and treatment is low. There are currently no effective vaccines against hepatitis C, without which we cannot eliminate HCV infection. Similarly, in spite of a worldwide reduction HBV/HDV infections, the significant global burden of liver disease remains [4-5]. Current HBV treatment relies on the life-long suppression of viral replication with nucleot(s)ide analogues (NUC) and NUC discontinuation before HBsAg loss is questionable. Virological and clinical reasons argue against NUC discontinuation in the vast majority of patients with chronic hepatitis B, and there is an unmet need for new biomarkers to profile and stratify NUC-treated patients to identify the following: (a) those with a high probability of HBsAg loss after NUC discontinuation; (b) those who could benefit from a short, combined treatment with new drugs to anticipate the time of NUC treatment discontinuation; and (d) those who have to be maintained in a continuous pharmacological viral suppression. Extensive research is in progress with the goal of achieving a functional cure for HBV infection (negative serum HBsAg), and clinical trials involving many new drugs with either virologic or immunologic targets are ongoing. Currently, however, no new drugs are commercially available. The overall prevalence of HDV infection is underestimated because of the lack of universal screening for HDV infection in HBsAg-positive carriers [5]. A new anti-HDV drug (Myrcludex) has become available; however, its clinical efficacy is yet to be fully demonstrated [6]. Finally, there is an urgent ethical need to define the value of new medicinal products in terms of cost–benefit from the point of view of the patient and national health systems, in order to ensure referral to care and curative treatments for as many patients as possible worldwide. Bearing in mind Michelangelo’s aphorism, “The greatest danger for most of us is not that our aim is too high and we miss it, but that it is too low and we reach it”, and prompted by the wise lesson from Confucius, who said “when it is obvious that the goal cannot be reached, don't adjust the goal, adjust the action steps”, we wish to organize and publish a Special Issue of Viruses devoted to manuscripts written by renowned experts in different virologic fields of viral hepatitis, aiming to propose new action steps towards eliminating the global clinical burden of viral hepatitis caused by HBV, HCV, and HDV.

1. Polaris Observatory HCV Collaborators. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol. 2022 May;7(5):396-415. doi:10.1016/S2468-1253(21)00472-6.
2. Schillie S et al. CDC Recommendations for Hepatitis C Screening Among Adults United States, 2020. MMWR Recomm Rep 2020;69 (No. RR-29):1–17].
3. Panagiotakopoulos L et Al. CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children United States, 2023. MMWR Recomm Rep 2023;72(No. RR-4):1–19]. doi: http://dx.doi.org/10.15585/mmwr.rr7204a1.
4. Cortesi PA et Al. Hepatitis B and C in Europe: an update from the Global Burden of Disease Study 2019; Lancet Public Health 2023 Sept;8(9): e701-e716. doi:10.1016/S2468-2667(23)00149-4.
5. Colombatto P et Al. Management and Treatment of Patients with Chronic Hepatitis B: Towards Personalized Medicine. Viruses. 2022 Mar 28;14(4):701. doi:10.3390/v14040701.
6. Brunetto MR et Al. EASL Clinical Practice Guidelines on Hepatitis Delta Virus J. Hep. 2023(Aug);79(2):433-460. doi:10.1016/j.jhep.2023.05.001.

Prof. Dr. Ferruccio Bonino
Guest Editor

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