Hepatitis Delta Estimates in the United States Revisited

To the Editor—We read with interest the article by Patel and colleagues [1], which reported an unexpected 33% prevalence of anti–hepatitis delta virus antibodies (anti-HDV-Abs) in a large and representative US household population. Estimates of 400 000 individuals with hepatitis delta in the United States could be drawn from the study. These figures are somewhat in line with recent claims of a global burden of up to 60 million people with hepatitis delta [2]. As highlighted by Patel et al [1], high-risk groups were not represented or were underrepresented in their survey of 16 143 US adults. Hepatitis delta is well known to be more frequent in incarcerated persons, homeless persons, injection drug users, human immunodeficiency–positive individuals, etc [3, 4]. Thus, their estimates of hepatitis delta could be an underestimation. This information is in contrast with clinical experience. Given the greater pathogenicity of hepatitis delta virus (HDV), high rates of cirrhosis and hepatocellular carcinoma associated with HDV should have been noticed in the United States. Alerts on the high prevalence of hepatitis delta have not been acknowledged in prior studies conducted either in US asymptomatic populations [5, 6] or at US liver clinics, including those performing liver transplantation [7–9]. It would be very difficult to admit that a huge proportion of hepatitis B surface antigen (HBsAg+) cirrhotic patients or patients with liver transplants in the United States have not been tested for anti-HDV-Abs. Remarkably, hepatitis delta is the only chronic viral hepatitis that can be cured with the transplantation procedure [9]. Our guess is that false-positive results using the DiaSorin antibody test could explain the results obtained by Patel et al [1]. It is unfortunate that the authors did not use another antibody assay as a comparator and/or perform serum HDV-RNA testing to confirm their findings. In a large study conducted in Mongolia, where cirrhosis and liver cancer rates are unusually high [10], nearly 60% of HBsAg+ patients had delta hepatitis. The authors noticed false-positive results (up to 21%) and false-negative results (7%) using the DiaSorin assay, taking as reference HDV-RNA testing and a newly sensitive immune-capture antibody assay [10]. Clearly, solving the uncertainty about hepatitis delta prevalence is a priority, especially at a time when new antivirals against HDV (ie, myrcludex, lonafarnib, REP-2139, peginterferon lambda) are moving to phase III clinical trials [11, 12]. Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.