Hepatitis DEdit
Hepatitis D is a unique and often underappreciated viral hepatitis because it depends on another virus to cause disease. The hepatitis D virus (HDV) is a small, defective RNA virus that cannot replicate on its own. It co-opts the hepatitis B virus (HBV) surface antigen (HBsAg) to assemble infectious particles. For that reason, HDV infections occur only in people who are also infected with HBV, either as a simultaneous coinfection or as a superinfection in someone with chronic HBV. Because of this dependency, efforts to prevent HDV are inseparably tied to efforts to prevent HBV infection in the first place. HDV is found worldwide, but its distribution mirrors HBV prevalence and local public health practices, with higher burdens historically noted in parts of the Mediterranean, the Middle East, parts of Africa, and the Andean regions of South America, among others. Hepatitis B HBsAg
Transmission of HDV occurs through exposure to infectious blood or body fluids, similar to HBV. This includes percutaneous and mucosal routes, putting people who inject drugs, recipients of unscreened blood products, individuals with unsafe medical or tattooing practices, and certain mobile populations at elevated risk. Prevention therefore rests on a combination of HBV vaccination, safer injection practices, and careful screening of blood products. Because HDV requires HBV, vaccination against HBV provides strong, direct protection against HDV as well. Hepatitis B vaccine Intravenous drug use
Epidemiology and transmission
HDV infection is relatively uncommon in the general population in many high-income countries today, but it remains a health concern in regions with ongoing HBV transmission or where HBV vaccination coverage is incomplete. The burden is higher among people who are HBV carriers, particularly those who are not fully engaged with preventive care or who live in settings with limited access to vaccination and healthcare. Accurate estimates depend on testing strategies that look for both anti-HDV antibodies and HDV RNA, especially in individuals with chronic HBV and unexplained liver inflammation. Hepatitis B Hepatitis D virus
Coinfection with HBV and HDV can present as an acute, more severe hepatitis than HBV alone, while superinfection of a person with chronic HBV by HDV can drive rapid progression to cirrhosis and liver failure. The natural history underlines the importance of early detection and prevention, since treatment options are limited and outcomes hinge on liver health and timely intervention. Cirrhosis Liver failure Chronic liver disease
Pathogenesis and clinical course
HDV particles are composed of a single circular RNA genome surrounded by HBV-derived envelope proteins, enabling entry into hepatocytes in a manner that depends on the presence of HBsAg. Once inside, HDV disrupts normal hepatic function, increasing the risk of inflammatory damage and fibrotic progression. Clinically, patients may present with signs and symptoms typical of hepatitis, such as fatigue, jaundice, right upper quadrant pain, and abnormal liver tests, but progression to chronic liver disease is more common with HDV coinfection or superinfection than with HBV alone. RNA virus Liver biopsy
Diagnosis
Diagnosis relies on a combination of serologic and molecular testing. Anti-HDV antibodies indicate exposure to HDV, while HDV RNA testing confirms active infection. In people with chronic HBV who develop worsening liver enzymes, testing for HDV is particularly important because it changes management and prognosis. Laboratories may use a variety of assays, and interpretation should be done in the context of HBV status and clinical presentation. Serology PCR Hepatitis B HBsAg
Prevention
Prevention hinges on preventing HBV infection in the first place. The HBV vaccine is highly effective and also protects against HDV by eliminating the necessary helper virus. Safer medical and social practices to reduce exposure to blood and body fluids, such as sterilization of equipment, safe blood transfusion practices, and harm-reduction measures for people who inject drugs, further reduce HDV transmission. There is no HDV-specific vaccine widely available, and public health strategies thus foreground HBV vaccination and universal infection-control measures. Hepatitis B vaccine Public health Vaccine
Treatment and outcomes
Therapies for HDV have historically been challenging. The mainstay has been pegylated interferon-α, which can lead to virologic response in a subset of patients but is not curative for most, and its use is limited by tolerability and side effects. Newer strategies target different steps in the HDV life cycle, including entry inhibitors and drugs that disrupt viral assembly, and there has been progress with agents such as Bulevirtimab and other antivirals under investigation. Access to these therapies varies by country and health system, and the overall prognosis depends on the degree of liver injury at diagnosis and the success of controlling HBV activity. pegylated interferon Bulevirtimab Chronic liver disease
Public health considerations and controversies
From a policy standpoint, the most cost-effective and impactful approach to HDV is preventing HBV infection through widespread vaccination and ensuring access to preventive care. This aligns with a broader view that emphasizes personal responsibility, market-based health options, and the efficient allocation of resources to interventions with proven population-level benefit. In regions where HDV is prevalent, expanding HBV vaccination coverage and improving screening programs for HBV carriers can reduce HDV incidence without imposing costly, universal screening that may yield diminishing returns.
Controversies in the health-policy space around HDV often revolve around resource allocation, access, and the appropriate balance between public mandates and individual choice. Some observers contend that broad regulatory mandates on vaccination or screening may overstep and crowd out private-sector solutions, while others argue that targeted public health programs are essential for at-risk communities. Critics who frame health policy as identity politics or who emphasize symbolic measures over evidence can misread the science or misallocate scarce resources. From a practical standpoint, policy debates should center on cost-effectiveness, real-world outcomes, and the best ways to reduce severe liver disease caused by HDV and HBV. Proponents of a more market-driven approach argue that affordable vaccines, accessible clinics, and streamlined testing pathways deliver tangible benefits without overreliance on centralized mandates. The science remains clear: preventing HBV infection effectively prevents HDV, and improving access to vaccination and quality care is the core strategy. HBV vaccination Public health policy Vaccine