The Delta Delta

Gaps in Screening and Patient Assessment for Hepatitis D Virus Infection

Rohit Nathani; Randy Leibowitz; Dewan Giri; Carolina Villarroel; Sidra Salman; Mantej Sehmbhi; Bo Hyung Yoon; Amreen Dinani; Ilan Weisberg


J Viral Hepat. 2023;30(3):195-200. 

In This Article

Abstract and Introduction


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.


Hepatitis D virus (HDV) is a small defective RNA virus that can propagate only in individuals infected with the Hepatitis B Virus (HBV). This infection can either be concurrent coinfection with HBV or superinfection in a patient with chronic hepatitis B (CHB).[1] Chronic HDV infection is the most severe form of chronic viral hepatitis and is associated with increased progression to liver cirrhosis, hepatocellular carcinoma (HCC), mortality from liver failure, and the need for liver transplant (LT).[2–4] Despite its discovery almost 45 years ago in 1977 by Rizzetto et al,[5] the global burden of HDV infection remains poorly defined. A recent study estimated the prevalence of HDV seropositivity to be about 4.5% in hepatitis B surface antigen (HBsAg)-positive patients.[6] The actual number of cases may be much higher due to underscreening and underreporting of HDV cases in both high- and low-income countries.

There are varied screening recommendations for HDV among major societies. Asian Pacific Association for the Study of the Liver (APASL) and the European Association for the Study of the Liver (EASL) recommend routine screening of all HBsAg-positive patients for HDV infection.[7,8] In contrast, 2018 American Association for the Study of Liver Diseases (AASLD) guidelines recommend a risk-based screening approach.[9]

The absence of safe and effective treatments for HDV has slowed the development of standardized tests (both HDV antibody and RNA tests). The only therapy currently recommended per the AASLD guidelines is interferon-alpha, which is associated with poor viral response rates, many side effects, and is not Food and Drug Administration (FDA) approved for this indication in the United States (US).[9]

Despite initial success in reducing HDV rates with HBV vaccination programmes, high-income countries are now seeing an uptrend in HDV infections due to increased immigration from HDV-endemic countries (HEC) and rising intravenous drug use (IVDU).[10–12] In addition, HDV was recently awarded "orphan disease" status creating much interest in the development of pharmacological interventions and effective disease awareness and recognition strategies. The virus entry inhibitor bulevirtide has been approved for the treatment of HDV infection in the European Union and is pending approval by the United States FDA, with several other pharmacological targets in phase 2 clinical trials.[13]

Given the significant health burden of this disease and the promise of novel therapeutics on the horizon, this study was conducted to ascertain if the risk-based screening approach leads to appropriate HDV screening, identify targets to improve screening rates, and to study HDV clinical burden.