Background: There are now seven antivirals approved for use in the management of chronic HBV infection

Background: There are now seven antivirals approved for use in the management of chronic HBV infection in the US. Current professional guidelines recommend the use of antiviral treatment in only a distinct subset of the total HBV chronically infected population, estimated to be more than 350 million worldwide. The subset of chronically HBV-infected individuals for whom the antivirals have been demonstrated to produce desirable outcomes are those with abnormal liver enzymes and a viral load above a defined threshold, presumably identifying those at highest risk for development of cirrhosis and hepatocellular carcinoma. However, some individuals whose clinical features place them outside these guidelines, for whom treatment is not recommended, are also at significant risk for liver disease complications and liver-related death. Methods: In this report, we produce new estimates of the age-specific risks of liver-related death in people outside the current treatment guidelines using published data from multiple populations. Results: Our results indicate that the age-specific 10-year risks of liver-related mortality in these individuals range from 0.3–4% in the West to 0.3–20% in Asia. Conclusions: The magnitude of these risks and the estimated size of the global population that falls outside of current treatment guidelines have led us to consider whether medical interventions are also needed for these individuals, either with currently approved therapeutics or yet-to-be-discovered medications targeting new mechanisms of antiviral effect. Potential targets for development of new medications are discussed.