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HDV Reflex Testing Increased 5-Fold
the Absolute Numbers of Hepatitis D Cases
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Download the PDF here
Download the PDF here
2 publications in April 2023
Hepatitis D double reflex testing of all hepatitis B carriers in low HBV and high HBV/high HDV prevalence countries.....led to 5-fold increase in the number of HBV cases diagnosed with hepatitis D
Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D
In summary, HDV testing rates in daily clinical practice are low despite EASL guidelines recommending universal screening. HDV infection is associated with significant liver-related mortality; hence, the importance of establishing anti-HDV reflex testing algorithms for an early HDV diagnosis.
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.
A study performed in a London centre with clinic-led anti-HDV testing reviewed the clinical and laboratory data of 168 HBsAg-positive patients and reported a 40% (67/168) prevalence of anti-HDV-positive status.12These reports, along with our findings, highlight the need for health policy initiatives aimed at improving HDV screening, especially relevant since the arrival of new HDV drugs.
There was a considerable difference in the diagnostic yield in our setting following implementation of HDV reflex testing, which led to a 5-fold increase in the number of HBV cases diagnosed with hepatitis D. The increase was similar in both the academic hospital and primary care centres. Reflex testing has been evaluated in other viral infections such as hepatitis C, particularly for viraemia detection. With this approach, additional blood drawn for HCV-RNA testing and an appointment for the results can be avoided in anti-HCV-positive cases.13 A study in the emergency department of an academic hospital showed that reflex testing enables detection of active HCV infection in a single sample.14 The authors reported a 0.7% prevalence of active HCV infection, a value almost 3-fold higher than that seen in the general population. Anti-HDV reflex testing has been evaluated in a single centre in London, but the results obtained were not compared with prior routine testing.12
The overall prevalence of anti-HDV was 8.1% (56/691). This value was similar to the 9.6% (11/114) prevalence observed before the start of reflex testing (2018-2020). However, the absolute number of patients diagnosed with HDV increased from 11 cases in the 3 years before reflex testing to 56 cases in 2021 (Fig. 1).
The profile of our anti-HDV-positive patients is in line with the findings from other European cohorts.[15], [16], [17] A considerable number were migrants from countries where HDV infection is endemic (20%) or patients with blood-borne risk factors (20%). Risk factors were unknown in the remaining 60%, which further supports the rationality of systematic anti-HDV reflex testing in all HBsAg-positive patients, rather than testing according to risk factors. In addition, those with detectable HDV-RNA showed higher ALT levels and more often had cirrhosis,18 and viraemic patients had lower HBV-DNA levels, supporting the theory of HDV suppression over HBV.19
HDV is a hepatotropic single-stranded RNA virus that requires the presence of HBV to propagate. HDV causes one of the most severe forms of chronic viral hepatitis, being associated with a 2- to 3-fold higher risk of developing liver cirrhosis and hepatocellular carcinoma than infection by HBV alone.1,2 Implementation of vaccination programs against HBV in the nineties undoubtedly had an impact on HDV prevalence in young populations.3 In high-income countries, the current burden of HDV mainly encompasses ageing patients with advanced liver fibrosis and young immigrants from endemic areas.4 Still, HDV infection is believed to be underestimated owing to a lack of, or suboptimal, screening programs in HBsAg-positive individuals.5
Anti-HDV testing in all HBsAg-positive patients is recommended in the 2017 EASL guidelines on the management of HBV infection,6 as well as the 2016 Asian-Pacific guidelines on the management of chronic hepatitis B (APASL, Asian-Pacific Association for the Study of the Liver).7 However, the 2018 American Association for the Study of Liver Diseases (AASLD) guidelines recommend anti-HDV testing only in HBsAg-positive individuals who are at risk, such as people who inject drugs, men who have sex with men, individuals at risk of acquiring sexually transmitted diseases, and immigrants from areas where HDV is highly endemic.8 Although anti-HDV testing in all HBsAg-positive individuals is suggested in the European and Asian-Pacific guidelines, it is believed that many cases remain untested.
The aims of the present study were to determine the anti-HDV testing rates in all HBsAg-positive samples in a large population over a 3-year period, to assess the impact of anti-HDV reflex testing to diagnose HDV in HBsAg-positive cases, and to describe the epidemiology and clinical characteristics of anti-HDV-positive individuals in our setting.
Epidemiological and clinical characteristics of anti-HDV-positive individuals in our setting
HDV-RNA was determined in 54 of the 67 anti-HDV-positive patients, and 35 (65%) of them had detectable HDV-RNA. Among the total of anti-HDV-positive patients, most were young Caucasian males, 48% had normal alanine aminotransferase (ALT) levels, 60% advanced fibrosis, and 34% liver cirrhosis. Nine patients were co-infected with HCV, and 1 had detectable HCV-RNA. Four patients were co-infected with HIV; all were receiving antiretroviral therapy. The main epidemiological, clinical, serological, and virological characteristics of anti-HDV-positive individuals are shown in Table 1. Those with detectable HDV-RNA had significantly lower platelet levels, higher ALT, aspartate aminotransferase, and gamma glutamyl transferase levels, and more often advanced fibrosis and liver cirrhosis than those with undetectable HDV-RNA. In addition, patients with detectable HDV-RNA showed statistically lower HBsAg levels and had undetectable HBV-DNA more often. In addition, a considerable pool of patients (39%) had detectable but unquantifiable HBV-DNA (<20 IU/ml).
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Pdf attached
Implementation of anti-HDV reflex testing among HBsAg-positive individuals increases testing for hepatitis D
Highlights
• HDV testing rates in daily clinical practice are low despite EASL guidelines recommending universal screening.
• Implementation of HDV reflex testing led to a 5-fold increase in the number of HBV cases diagnosed with hepatitis D.
• Risk factors were unknown in 60% of anti-HDV positive cases, supporting systematic anti-HDV reflex testing in all HBsAg-positive patients.
• It would be of great value to assess the cost-effectiveness of anti-HDV reflex testing.
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.
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