Severe Liver-Related Outcomes in Patients With Hepatitis Delta: Results From a Multi-Ethnic Multicenter Long-Term Follow-Up Study

Abstract

Hepatitis B virus (HBV)–hepatitis delta virus (HDV) coinfection is the most severe form of chronic viral hepatitis, but the factors that determine disease progression and severity are incompletely characterised. This long-term follow-up study aims to identify risk factors for severe liver-related outcomes. In this multicentre national cohort study, data from admission until the last visit between 2001 and 2023 was retrospectively collected from 162 HBV-HDV coinfected patients. The inclusion criteria were HBsAg or HBV DNA positivity, anti-HDV or HDV RNA positivity, and at least one follow-up visit. The median follow-up was 6.2 years (IQR 3.3–10.2). At baseline, 68/152 (44.7%) patients were diagnosed with advanced liver fibrosis. Forty patients (24.7%) had at least one severe liver-related outcome during follow-up. HDV viremia was detectable in 92 patients (64.3%) at last evaluation and was more frequently detectable in patients of European origin (p < 0.001). HDV RNA-positive patients had a 4.7-fold higher risk for severe liver-related outcomes (p < 0.001) and were more frequently diagnosed with advanced fibrosis at baseline (p = 0.007) compared to HDV RNA-negative patients. Multivariate analyses identified HDV RNA positivity, as well as several markers for liver disease severity, such as INR, platelet count, and advanced fibrosis at baseline, and age at admission as independent risk factors for severe liver-related outcomes. In conclusion, almost one in four HBV-HDV coinfected patients developed a severe liver-related outcome during follow-up. Several markers for liver disease severity and HDV RNA positivity were the strongest predictors for outcomes.