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  The Liver Meeting
Digital Experience
November 13 - 16 - 2021
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Over 90% of Clinicians Ignore EACS Hep D Screening Advice
  AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
Although European Association for the Study of Liver Disease (EASL) guidelines recommend anti-HDV antibody testing for everyone positive for hepatitis B surface antigen (HBsAg), clinicians in Barcelona followed that advice in only 9.4% of HBsAg-positive people [1]. Anti-HDV guideline adherence proved better at an academic medical center than in primary care practice, but still only 27% of anti-HDV screening candidates got tested at the academic center after EASL guidelines came out.
Researchers from Barcelona's Hospital Universitari Vall D'Hebron reminded AASLD colleagues that hepatitis D ranks as the harshest form of viral hepatitis, marked by swifter development of cirrhosis and hepatic decompensation than HBV infection. Recent estimates of HDV infection prevalence in people positive for HBsAg (which indicates current HBV infection) range from 4.5% [2] to 14.6% [3], representing 12 million to 43 million people worldwide. Limited access to assays for anti-HDV antibodies and HDV RNA explains some but not all of low HDV testing rates.
One protocol for HDV screening calls for anti-HDV antibody testing in everyone positive for HBsAg. A positive anti-HDV antibody result should lead to HDV RNA testing to determine who has active HDV infection. But this straightforward matrix has not fostered much HDV screening, research suggests. One survey of people with HBV infection in US tertiary care centers in 1994-2014 found only 13% screened for HDV [4]. Other US estimates of HDV screening in HBV-positive US veterans and tertiary care patients with HBV or HIV found screening rates of 8.5% (in 1999-2013) [5] and 5% (in 1994-2014) [4].
The Barcelona researchers set out to assess adherence to EASL HDV screening guidelines in serum samples sent to a lab that analyzes samples for 400,000 people in Barcelona. This retrospective look at all anti-HDV antibody orders for HBsAg-positive samples covered records from January 2015 to May 2021. The researchers counted only the first HBsAg sample per person. A central lab analyzed samples from 1 academic hospital and 65 primary care practices in the area. The Vall D'Hebron investigators split results into the period before the EASL HDV screening guidelines (2015-2017) and the period with the guidelines in place (2018-2021).
Of the 4386 HBsAg-positive samples considered throughout the study period, 360 (8.2%) got tested for anti-HDV antibody. Thirty-seven of those 360 screen samples (10.3%) came out anti-HDV positive. Among the 4386 initial HBsAg-positive samples, 1457 (33%) came from the academic hospital and 2929 (67%) from primary care practices. Of the 360 samples assayed for anti-HDV antibody, 282 (78%) came from the academic hospital and 78 (22%) from the 65 primary care clinics.
Thus the academic hospital accounted for 33% of HBsAg-positive samples (1457 of 4386 samples); 19% of those 1457 samples (282 of 1457) got tested for anti-HDV antibodies; and 2.4% of the 1457 samples (35 of 1457) came out anti-HDV positive. In contrast, the primary care practices accounted for 67% of HBsAg-positive samples (2929 of 4386); 2.6% of those 2929 samples (78 of 2929) got an anti-HDV antibody test (P < 0.001 vs 19% at the academic center); and 0.06% (2 of the 2929 HBsAg-positive samples) came back positive for anti-HDV (P = 0.007 vs 2.4% at the academic center).
Promulgation of EASL HDV screening guidelines in 2017 had an apparent modest impact on overall anti-HDV testing rates. In 2015-2017 the anti-HDV testing rate in HBsAg-positive samples stood at 7.5% (203 of 2713). In 2018-2021, that testing rate edged up significantly to 9.4% (157 of 1678) (P = 0.015). But the anti-HDV-positive rate did not budge from before EASL released its guidelines: 0.9% (24 of 2713 samples) in 2015-2017 and 0.8% (13 of 1673 samples) in 2018-2021 (P = 0.178).
Release of the EASL guidelines did significantly improve the anti-HDV testing rate at the academic hospital, from 16.2% before guidelines to 27% with guidelines (P < 0.001). But the improvement in anti-HBV testing rate did not reach statistical significance in the 65 primary care practices, from 2.2% to 3.2% (P = 0.067).
The 37 people who tested positive for anti-HDV antibody were mostly (62%) men averaging 43 years in age. Most, 57%, were born outside of Spain (mainly Romania, Mongolia, and central Africa), 67% had high alanine aminotransferase (ALT), 30% had cirrhosis, 84% were HBeAg-negative, 89% had undetectable HBV DNA, and 80% had detectable HDV RNA. Of the 25 people with detectable HDV RNA, age averaged 43 years, 52% were men, 48% were born outside Spain, 80% had elevated ALT, 36% had cirrhosis, 76% were HBeAg-negative, and 84% were HBV DNA undetectable.
The Vall D'Hebron researchers concluded that EASL anti-HDV antibody screening guidelines marginally improved anti-HDV detection in an academic hospital but not in primary care. To improve screening, they recommended evaluating more clinician education and new strategies for anti-HDV testing, such as reflex testing [6] in all HBsAg-positive people.
1. Palom A, et al. Low adherence to guidelines recommendation for testing hepatitis D in HBsAg positive patients leads to a high rate of undiagnosis. AASLD, The Liver Meeting, November 12-15, 2021. Abstract 224.
2. Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis. J Hepatol. 2020;73:523-532. doi: 10.1016/j.jhep.2020.04.008.
3. Chen HY, Shen DT, Ji DZ, et al. Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis. Gut. 2019;68:512-521. doi: 10.1136/gutjnl-2018-316601.
4. Safaie P, Razeghi S, Rouster SD, Privitera I, Sherman KE. Hepatitis D diagnostics: Utilization and testing in the United States. Virus Res. 2018;250:114-117. doi: 10.1016/j.virusres.2018.03.013.
5. Kushner T, Serper M, Kaplan DE. Delta hepatitis within the Veterans Affairs medical system in the United States: Prevalence, risk factors, and outcomes. J Hepatol. 2015;63:586-592. doi: 10.1016/j.jhep.2015.04.025.
6. UW Medicine. Hepatitis B surface antigen (HBsAg) with reflex to PCR for REACTIVE. https://testguide.labmed.uw.edu/public/view/HBSAG