Course and clinical outcomes of chronic hepatitis delta: a longitudinal analysis of 565 patients from the D-SOLVE and HDV-1000 consortia
Abstract
Background: Chronic hepatitis delta (CHD) causes severe chronic viral hepatitis. Objective: This study examines the predictors and outcomes of CHD course in a large contemporary cohort. Design: CHD patients with ≥3 years follow-up from the multicentre retrospective D-SOLVE and hepatitis D virus (HDV)-1000 database (6 European centres) were enrolled. Longitudinal changes in biochemical and laboratory markers were analysed. Time-to-event analysis was performed and predictors of liver-related events (LREs) were assessed with univariable and multivariable Cox regression analysis. Results: Among a total of 1004 patients, 565 (56%) with ≥3 years follow-up were included. Patients had a mean (SD) age of 45 (12) years, with 55% men and 60% of European origin. At baseline, 77.8% were HDV RNA+, 39.8% had cirrhosis and 45% had previous interferon therapy. During a median (IQR) follow-up of 55 (46-62) months, 48 patients progressed to cirrhosis at 1, 3 and 5-year cumulative incidence of 1.8%, 5.6% and 13.6%, respectively. De-novo LREs occurred in 47 (9%) patients at 1, 3 and 5-year cumulative incidence of 0.8%, 2.4% and 10.8%, respectively. Cox regression analysis showed that anti-hepatitis C virus+ (adjusted hazard ratio (aHR)=1.72, 95% CI 1.22 to 5.88) and elevated gamma-glutamyl transferase (GGT) (aHR=2.77, 95% CI 1.22 to 6.27) at baseline were significantly associated with cirrhosis onset, while older age (aHR=1.03, 95% CI 1.00 to 1.07), elevated GGT (aHR=4.38, 95% CI 1.81 to 10.57), detectable HDV RNA (aHR=10.32, 95% CI 1.34 to 79.53) and cirrhosis diagnosis (aHR=2.23, 95% CI 1.03 to 4.84) correlated with LREs. The risk for LREs increased from HDV RNA ≥1000 IU/mL, while hepatitis B surface antigen (HBsAg) levels did not correlate with disease progression. Conclusions: In a large real-life cohort of CHD patients, older age, GGT elevation, cirrhosis and detectable HDV RNA were the main determinants of liver-related outcomes, with worse prognosis noted from HDV RNA ≥1000 IU/mL.
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BibTeX
@article{kamal2026course,
title = {{Course and clinical outcomes of chronic hepatitis delta: a longitudinal analysis of 565 patients from the D-SOLVE and HDV-1000 consortia}},
author = {Habiba Kamal and Elisabetta Degasperi and Monica Radu and Dana Sambarino and Anika Wranke and Ivana Carey and Miroslava Subic-Levrero and Karin Lindahl and Lisa Sandmann and Petra Dörge and Julia Kahlhöfer and Fabien Zoulim and Kosh Agarwal and Soo Aleman and Florin Alexandru Caruntu and Pietro Lampertico and Heiner Wedemeyer and Thomas F. Baumert and Frank Jühling and Joachim Lupberger and Eloi Verrier},
journal = {Gut},
year = {2026},
month = nov,
doi = {10.1136/gutjnl-2025-336234},
url = {https://univoak.hal.science/hal-05856635v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Course and clinical outcomes of chronic hepatitis delta: a longitudinal analysis of 565 patients from the D-SOLVE and HDV-1000 consortia
AU - Habiba Kamal
AU - Elisabetta Degasperi
AU - Monica Radu
AU - Dana Sambarino
AU - Anika Wranke
AU - Ivana Carey
AU - Miroslava Subic-Levrero
AU - Karin Lindahl
AU - Lisa Sandmann
AU - Petra Dörge
AU - Julia Kahlhöfer
AU - Fabien Zoulim
AU - Kosh Agarwal
AU - Soo Aleman
AU - Florin Alexandru Caruntu
AU - Pietro Lampertico
AU - Heiner Wedemeyer
AU - Thomas F. Baumert
AU - Frank Jühling
AU - Joachim Lupberger
AU - Eloi Verrier
PY - 2026
DA - 2026/11/08
JO - Gut
DO - 10.1136/gutjnl-2025-336234
UR - https://univoak.hal.science/hal-05856635v1
AB - Background: Chronic hepatitis delta (CHD) causes severe chronic viral hepatitis. Objective: This study examines the predictors and outcomes of CHD course in a large contemporary cohort. Design: CHD patients with ≥3 years follow-up from the multicentre retrospective D-SOLVE and hepatitis D virus (HDV)-1000 database (6 European centres) were enrolled. Longitudinal changes in biochemical and laboratory markers were analysed. Time-to-event analysis was performed and predictors of liver-related events (LREs) were assessed with univariable and multivariable Cox regression analysis. Results: Among a total of 1004 patients, 565 (56%) with ≥3 years follow-up were included. Patients had a mean (SD) age of 45 (12) years, with 55% men and 60% of European origin. At baseline, 77.8% were HDV RNA+, 39.8% had cirrhosis and 45% had previous interferon therapy. During a median (IQR) follow-up of 55 (46-62) months, 48 patients progressed to cirrhosis at 1, 3 and 5-year cumulative incidence of 1.8%, 5.6% and 13.6%, respectively. De-novo LREs occurred in 47 (9%) patients at 1, 3 and 5-year cumulative incidence of 0.8%, 2.4% and 10.8%, respectively. Cox regression analysis showed that anti-hepatitis C virus+ (adjusted hazard ratio (aHR)=1.72, 95% CI 1.22 to 5.88) and elevated gamma-glutamyl transferase (GGT) (aHR=2.77, 95% CI 1.22 to 6.27) at baseline were significantly associated with cirrhosis onset, while older age (aHR=1.03, 95% CI 1.00 to 1.07), elevated GGT (aHR=4.38, 95% CI 1.81 to 10.57), detectable HDV RNA (aHR=10.32, 95% CI 1.34 to 79.53) and cirrhosis diagnosis (aHR=2.23, 95% CI 1.03 to 4.84) correlated with LREs. The risk for LREs increased from HDV RNA ≥1000 IU/mL, while hepatitis B surface antigen (HBsAg) levels did not correlate with disease progression. Conclusions: In a large real-life cohort of CHD patients, older age, GGT elevation, cirrhosis and detectable HDV RNA were the main determinants of liver-related outcomes, with worse prognosis noted from HDV RNA ≥1000 IU/mL.
SN - 0017-5749
SN - 1468-3288
ER -