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. 2025 Feb;45(2):e70003.
doi: 10.1111/liv.70003.

Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection

Lisa Sandmann  1   2   3 , Valerie Ohlendorf  1 , Alena Ehrenbauer  1 , Birgit Bremer  1 , Anke R M Kraft  1   3   4   5 , Markus Cornberg  1   2   3   4   5 , Katja Deterding  1 , Heiner Wedemeyer  1   2   3   4 , Benjamin Maasoumy  1   4
Affiliations

Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection

Lisa Sandmann et al. Liver Int. 2025 Feb.

Abstract

Background and aims: Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection.

Methods: HBcrAg, HBV RNA and quantitative anti-HBc were analysed in samples from HDV-infected patients at three consecutive time points. Results were linked to clinical outcome by univariable and multivariable analyses. Primary endpoint was the composite endpoint of any liver-related event.

Results: Samples from 190 individual patients were analysed with a median clinical follow-up time of 2.69 (IQR 1.13-6.51) years. The majority of patients had cirrhosis (98/190, 52%), and the primary endpoint occurred in 33% (62/190). In univariable analysis, age, cirrhosis, lower quantitative anti-HBc, higher ratio of HBcrAg/anti-HBc and detectable HDV RNA were associated with the primary endpoint. In multivariable analysis, only the presence of liver cirrhosis (HR 7.74, p < 0.001) and age (1.06, p < 0.001) remained independently associated with the primary endpoint. Kinetics of virological parameters during follow-up were similar between the groups. Quantitative anti-HBc was significantly lower in patients with liver cirrhosis (687 (IQR 188-3388) IU/ml vs. 309 (IQR 82-924) IU/ml, p < 0.0004), and lower levels were independently associated with the development of the primary endpoint (HR 1.0, p = 0.014).

Conclusion: In chronic HDV infection, neither baseline values nor kinetics of HBV RNA, HBcrAg and anti-HBc were independently associated with clinical outcome, while stage of liver disease and age were predictors of liver-related events.

Keywords: HBV RNA; HBV/HDV coinfection; HBcrAg; anti‐HBc; outcome.

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Conflict of interest statement

Lisa Sandmann reports lecture honoraria and personal fees from Falk Pharma e.V., Gilead and Roche, and travel support from AbbVie. Markus Cornberg reports personal fees from AbbVie, Falk Foundation, Gilead, Janssen‐Cilag, GSK, MSD, Spring Bank and SOBI. Katja Deterding received lecture and personal fees from Gilead, Falk Pharma e.V., AbbVie, MSD/Merck and Alnylam. Heiner Wedemeyer reports grants/research support from AbbVie, Biotest, BMS, Gilead, Merck/MSD, Novartis, Roche and personal fees from Abbott, AbbVie, Altimmune, Biotest, BMS, BTG, Dicerna, Gilead, Janssen, Merck/MSD, MYR GmbH, Novartis, Roche and Siemens. Benjamin Maasoumy served as a speaker and/or advisory board member for AbbVie, Fujirebio, Gilead, Luvos, MSD, Norgine, Roche and W. L. Gore & Associates and received research support from Altona, EWIMED, Fujirebio and Roche. Anke R.M. Kraft, Birgit Bremer, Alena Ehrenbauer and Valerie Ohlendorf have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Proportion of all (A) or HBeAg‐negative (B) patients with concordant or discordant levels of HBcrAg or HBV RNA at study time points. Undetectable HBcrAg is defined as HBcrAg < 3 U/mL, and undetectable HBV RNA is defined as HBV RNA < 10 IU/ml.
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