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Professor of Medicine
Chief, Section of Hepatology
Associate Director, Solid Organ Transplantation
Richard B. Capps Chair of Hepatology
Rush University Medical Center
Nancy Reau, MD, consultant/advisor: AbbVie, Antios, Arbutus, Gilead Sciences, Intercept, Salix; researcher: AbbVie, Gilead Sciences, Intercept.
According to estimates, 4.5% to 13% of hepatitis B surface antigen (HBsAg)–positive carriers are coinfected with hepatitis delta virus (HDV). This would equate to approximately 8.7 to almost 19 million individuals with HDV. However, a meta-analysis of published data from 83 countries suggests that this estimate could be much higher at 48-60 million individuals. Given the relatively high burden of this disease, it is imperative that healthcare professionals and patients alike understand who should be screened for HDV infection.
Guidelines on Whom to Screen for HDV Infection
Historically, guidelines have recommended HDV screening only in high-risk individuals. In the United States, these include injection drug users, commercial sex workers, men who have sex with men, persons with hepatitis C virus and/or HIV, persons with cirrhosis and/or hepatocellular carcinoma, and patients on hemodialysis. In addition, migrants from endemic countries are at a higher risk of HDV infection, so considerations of birthplace or mother’s birthplace must factor into screening decisions. Furthermore, individuals who have not been immunized against hepatitis B virus (HBV) infection are more likely to acquire HDV. Finally, mother-to-child transmission of HDV infection has been documented, but at a much lower rate.
The American Association for the Study of Liver Diseases guidelines, updated in 2018, uphold these risk-based screening recommendations for HDV but also recommend testing individuals with low/undetectable HBV DNA and high alanine aminotransferase.
The European guidelines from 2017 are, however, much more permissive and recommend screening all individuals who are infected with HBV. Similarly, the Asian Pacific Association for the Study of the Liver guidelines from 2016 recommend screening all patients with chronic HBV infection and chronic liver disease for HDV.
Who Is Being Tested for HDV Infection?
Recognizing that the European guidelines are more permissive than US guidelines, a research group from Barcelona conducted a retrospective analysis of individuals from January 2015 to May 2021 to determine how many HBsAg-positive individuals are being tested for HDV infection. The data showed that fewer than 10% of HBsAg-positive individuals were tested for HDV, highlighting that European healthcare professionals are not following the guidelines. Guideline adherence was shown to be better at academic medical centers than in primary care, but still only 27% of anti-HDV screening candidates received testing at academic centers vs 3.2% at primary care centers.
If so many HDV cases are being missed in places where universal screening for HBsAg-positive individuals is recommended, we can only assume that even more are being missed in the United States, where risk-based screening is recommended. Furthermore, much like in Europe, a lot of HBV in the United States is being managed in primary care settings, so the study’s revelation about low testing rates in primary care is disconcerting. Indeed, not all patients can make it to academic centers. Because of the demographics of HBV, individuals often are concentrated in places that are not necessarily adjacent to academic centers.
What can we do? I believe that primary care physicians need to be educated about the importance of HDV screening. Although guidelines vary on who should be tested, accumulating data support universal testing for HBsAg-positive individuals.
Do you screen all of your patients with HBV for HDV? Join the discussion by posting a comment.