Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D

Adriana Palom; Ariadna Rando-Segura; Judit Vico; Beatriz Pacín; Elena Vargas; Ana Barreira-Díaz; Francisco Rodríguez-Frías; Mar Riveiro-Barciela; Rafael Esteban; Maria Buti

doi:10.1016/j.jhepr.2022.100547

Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D

JHEP Rep. 2022 Jul 21;4(10):100547. doi: 10.1016/j.jhepr.2022.100547. eCollection 2022 Oct.

Authors

Adriana Palom^{1

2}, Ariadna Rando-Segura³, Judit Vico¹, Beatriz Pacín^{3

4}, Elena Vargas^{1

2}, Ana Barreira-Díaz^{1

2

5}, Francisco Rodríguez-Frías^{3

4

5}, Mar Riveiro-Barciela^{1

2

5}, Rafael Esteban^{1

2

5}, Maria Buti^{1

2

5}

Affiliations

¹ Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
² Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
³ Microbiology Department, Clinical Laboratories, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁴ Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁵ Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.

Abstract

Background & aims: Although EASL guidelines recommend anti-HDV testing in all HBsAg-positive individuals, HDV infection remains an underdiagnosed condition. We describe the impact of an HDV screening program by reflex anti-HDV testing in all HBsAg-positive samples and compare the results before and after its implementation.

Methods: In total, 2,236 HBsAg-positive determinations were included from January 2018 to December 2021. Only the first sample from each participant was evaluated: 1,492 samples before reflex anti-HDV testing (2018-2020) and 744 samples after (2021). Demographic and clinical characteristics of anti-HDV-positive patients were collected.

Results: Before reflex testing, anti-HDV had been tested in 7.6% (114/1492) of HBsAg-positive individuals: 23% (91/390) attended in an academic hospital and only 2% (23/1,102) in primary care centres. After reflex testing was established, 93% (691/744) of HBsAg-positive cases were evaluated for anti-HDV: 91% (533/586) in the academic hospital and 100% (158/158) in primary care. The anti-HDV-positive prevalence was similar before and after reflex testing: 9.6% (11/114) and 8.1% (56/691), respectively. However, the absolute number of anti-HDV-positive patients increased. Most anti-HDV-positive patients were young, HBeAg-negative, Caucasian males. HDV-RNA was detectable in 35 (65%) of 54 tested, HBV-DNA was undetectable in 64%, and alanine aminotransferase levels were normal in 48%.

Conclusions: Anti-HDV reflex testing quintupled the absolute number of diagnoses of chronic hepatitis D infection. Before the reflex test, a large percentage of HBsAg-positive individuals had not undergone any anti-HDV determination. Implementation of reflex testing increases the diagnosis of patients with chronic hepatitis D.

Lay summary: Chronic hepatitis delta (CHD) is a viral disease caused by HDV, which requires the presence of HBV to propagate. HDV infection can cause rapid progression to cirrhosis, among other severe complications. The prevalence of CHD worldwide is controversial, and the infection often goes unrecognised, mainly because of unawareness among physicians. Use of reflex testing in other viral hepatitis has proven to increase detection and linking-to-care of infected patients. Implementation of anti-HDV testing in all HBsAg-positive patients has led to a 5-fold increase in the number of HDV diagnoses in an academic hospital and primary care centres.

Keywords: AASLD, American Association for the Study of Liver Diseases; ALT, alanine aminotransferase; APASL, Asian-Pacific Association for the Study of the Liver; APRI, AST to platelet ratio index; AST, aspartate aminotransferase; Anti-HDV reflex testing; Anti-HDV screening; Chronic hepatitis D; FIB-4, fibrosis-4; GGT, gamma glutamyl transferase; HDV diagnosis; PWID, people who inject drugs.