Who to test and reflex testing for hepatitis D virus infection: evidence and rationale to inform policy recommendations and future directions.

Abstract

Chronic hepatitis D coinfection affects an estimated 12 million people globally, with higher prevalence in low-income and middle-income countries, especially the African and Western Pacific regions. It leads to accelerated progression to liver cirrhosis, hepatocellular carcinoma, and increased mortality. The treatment landscape is evolving with the introduction of bulevirtide, but hepatitis D virus (HDV) testing uptake and case-finding remain low. The 2024 WHO guidelines on the management of chronic hepatitis B provide recommendations for the first time on who to test and how to test for HDV infection. WHO recommends universal anti-HDV testing among all HBsAg-positive individuals, and where this is not feasible, a complementary focused (risk-based) testing approach among higher-risk populations. We present two complementary Reviews-one on who to test and one on how to test for HDV infection. This Review on who to test summarises the evidence base and rationale for the two recommendations regarding the universal and risk-based testing approaches, as well as the recommendation for the laboratory-based reflex HDV testing both for anti-HDV and HDR RNA. Key implementation considerations include the need for countries to incorporate HDV testing into their national policies and guidelines, education and training of health-care providers in counselling and linkage to care, community awareness raising and demand creation, and the establishment of clinical care pathways for HDV infection. Research priorities include the development of HDV rapid diagnostic tests to facilitate decentralisation of HDV testing, the generation of improved epidemiological data across different populations and settings to inform testing approaches, and evaluating the cost-effectiveness and feasibility of both universal and risk-based HDV testing approaches, alongside reflex HDV serology and HDV RNA testing.