The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection

Abstract

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk-based screening approach. Our aim was to ascertain if the risk-based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV−) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk-based screening approach due to unreported or negative risk factors (see Table ). A significantly higher number of HDV+ patients had developed significant fibrosis (p = 0.001) and cirrhosis (p < 0.01) by the time of screening than HDV− (n = 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk-based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients.

A changing landscape: Tracking and analysis of the international HDV epidemiology 1999–2020

“…This is in contrast to standard testing protocols that rely on detection of HBV to trigger HDV testing and, only then, a limited number of HBV patients are tested for evidence of an HDV co-infection. In the United States, multiple studies have reported that less than 20% of HBV patients are tested for HDV[ 6 , 34 , 47 – 49 ]. Therefore, national testing guidelines, local reporting requirements and compliance in testing HBV patients for HDV may significantly impact the reported cases of HBV and HDV.…”

Recent prevalence and characteristics of patients with hepatitis delta virus in Hokkaido, Japan

“…In this study, among patients with anti‐HDV antibody positivity, 40% had detectable HDV RNA. However, because most HDV superinfections in patients with HBV infection progress to chronic HDV infection, and HDV RNA levels decline over time, most patients with HBV infection with anti‐HDV antibody serum positivity could be assumed to have current or resolved HDV chronic infection 24 . Notably, no standardized HDV RNA assays exist 21 ; a negative HBV RNA assay could indicate resolved hepatitis D, low viremia, or a false‐negative test result 24 .…”

“…However, because most HDV superinfections in patients with HBV infection progress to chronic HDV infection, and HDV RNA levels decline over time, most patients with HBV infection with anti‐HDV antibody serum positivity could be assumed to have current or resolved HDV chronic infection 24 . Notably, no standardized HDV RNA assays exist 21 ; a negative HBV RNA assay could indicate resolved hepatitis D, low viremia, or a false‐negative test result 24 . Additionally, the changes in the FIB‐4 index were similar between patients with anti‐HDV positivity with or without HDV RNA positivity.…”

“…24 Notably, no standardized HDV RNA assays exist 21 ; a negative HBV RNA assay could indicate resolved hepatitis D, low viremia, or a falsenegative test result. 24 Additionally, the changes in the FIB-4 index were similar between patients with anti-HDV positivity with or without HDV RNA positivity. However, the number of patients was limited; thus, further analysis is required (Figure S2).…”

Hepatitis Delta Virus Reporting Requirements in the United States and Territories: A Systematic Review

“…Currently, the AASLD guidelines recommend HDV testing only in HBV patients with known risk factors for HDV, including those born in regions with high HDV prevalence, men who have sex with men (MSM), intravenous drug use (IVDU), patients with a history of HCV and HIV, multiple sexual partners, or elevated liver enzymes with limited detectable HBV DNA. The AASLD guidelines may lead to limited HDV testing in patients with HBV who do not present with or have unreported risk factors 7 . For those tested, AASLD recommends testing for anti-HDV antibodies and, subsequently, HDV RNA in patients who are HDV antibody positive (Fig 1) 6 .…”