Occult Hepatitis B and C among injection drug users (IDUs): An Overlooked Obstacle in Global Health Efforts.

Abstract

Occult hepatitis B (OBI) and C (OCI) infections represent hidden viral states that evade standard serum diagnostics, posing a significant challenge to global hepatitis control, particularly among high-risk groups like injection drug users (IDUs). OBI is characterized by the persistence of replication-competent hepatitis B virus (HBV) DNA within the liver, often as covalently closed circular DNA (cccDNA), or in blood, in individuals who consistently test negative for hepatitis B surface antigen (HBsAg) through conventional assays. This form of HBV infection is marked by low-level replication within hepatocytes, evading immune detection and remaining undetectable by standard HBsAg tests, thus complicating diagnosis and management. OCI, similarly, is characterized by hepatitis C virus (HCV) RNA in liver cells or peripheral blood mononuclear cells (PBMCs) despite undetectable serum levels. OCI can be seropositive, with anti-HCV antibodies indicating past infection, or seronegative, lacking these antibodies and suggesting minimal immune recognition. Due to practices like needle sharing, IDUs face heightened risks of OBI and OCI, which can silently progress to severe liver disease, including cirrhosis and hepatocellular carcinoma (HCC). The frequent co-occurrence of HIV among IDUs further complicates clinical care, emphasizing the need for multi-disease, integrated screening strategies. The development of sensitive diagnostic tools capable of accurately identifying OBI and OCI in high-risk populations is essential to advance the World Health Organization’s (WHO) hepatitis elimination targets for 2030. Enhanced diagnostics and targeted interventions will support early detection, reduce transmission, and contribute to global efforts to eradicate hepatitis in vulnerable populations.