Course and clinical outcomes of chronic hepatitis delta: a longitudinal analysis of 565 patients from the D-SOLVE and HDV-1000 consortia

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.