Double reflex testing improves the efficacy and cost effectiveness of hepatitis delta diagnosis in southern Spain.

This study aims to evaluate the prevalence of undiagnosed hepatitis delta in southern Spain (Andalusia) and assess the effectiveness and cost-efficiency of implementing reflex testing for hepatitis D detection in HBsAg-positive patients. A multicenter ambispective study was conducted in 17 Andalusian hospitals. The retrospective phase (January 2018-June 2022) analyzed diagnostic processes for hepatitis delta in HBsAg-positive patients. The prospective phase (October 2022-March 2023) implemented reflex testing, performing anti-HDV serology on all HBsAg-positive patients without prior testing. HDV RNA testing followed for those who tested anti-HDV-positive. In the retrospective phase, out of 18,583 HBsAg-positive patients, anti-HDV tests were performed on 3,436 (18%), identifying 205 (6%) positive cases. HDV RNA was tested in 158 (77%) anti-HDV-positive patients, with 69 (44%) testing positive. In the prospective phase, out of 2,384 HBsAg-positive patients without prior anti-HDV testing, 2,293 (96%) were tested, identifying 109 (4.7%) positive cases. HDV RNA was analyzed in 97 (89%) anti-HDV-positive patients, with 30 (31%) testing positive. Reflex testing increased anti-HDV detection by 77%, resulting in a fourfold increase in detecting anti-HDV-positive patients and a threefold increase in detecting HDV RNA-positive patients, reducing undiagnosed HDV RNA-positive cases to 4% compared to 45% with clinical practice. Cost analysis indicated a saving of €265,954 with reflex testing. Reflex testing improves HDV detection, reduces costs, and simplifies diagnosis, making it an efficient strategy for managing chronic hepatitis D patients.