Abstract / Summary
Background and Aim: Hepatitis delta virus (HDV) infection is among the most aggressive forms of chronic viral hepatitis: fibrosis advances quickly, and cirrhosis, hepatocellular carcinoma (HCC) and hepatic decompensation develop more often than with other hepatitis viruses. Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading chronic liver disorder worldwide, and it may add to liver damage when it occurs alongside viral hepatitis. To date, however, data on hepatic steatosis in patients with chronic HDV infection remain scarce. We therefore aimed to describe the frequency of hepatic steatosis, assessed by the controlled attenuation parameter of transient elastography (FibroScan), in patients with chronic HBV infection and persistent anti-HDV seropositivity, and to examine whether it was associated with liver fibrosis. Methods: A total of 125 patients with chronic HBV infection and anti-HDV antibodies documented for at least six months were enrolled in this cross-sectional study between March and September 2024. HDV-RNA was tested in all participants. FibroScan provided liver stiffness measurement (LSM, kPa) and the controlled attenuation parameter (CAP, dB/m). We used CAP ≥ 248 dB/m to identify steatosis and LSM ≥ 12.5 kPa to identify cirrhosis. Because cardiometabolic risk factors were not systematically recorded, the criteria for MASLD could not be applied, and steatosis is reported as CAP-defined hepatic steatosis. Multivariable logistic regression was used to look for factors linked to LSM-defined advanced fibrosis (LSM ≥ 9.5 kPa), with sensitivity analyses accounting for ALT elevation. Results: The mean age was 39.0 years, and 74.4% (n = 93) of patients were male. HDV-RNA was detectable in 68.0% (n = 85). Of the 85 patients previously treated with pegylated interferon-alpha, 26 (30.6%) had a sustained virological response (SVR). Median LSM was 10.1 kPa (IQR 9.1–10.7) and median CAP 218 dB/m (IQR 211–239); cirrhosis was present in 15.2% (n = 19). CAP-defined steatosis was found in 24.0% (n = 30). Patients with and without steatosis were similar in age, sex, HDV-RNA status, liver stiffness, cirrhosis rate and SVR rate (36.4% vs. 28.6%, p = 0.593). After adjustment, detectable HDV-RNA was associated with advanced fibrosis (adjusted odds ratio [aOR] 4.89, 95% CI 2.13–11.26, p < 0.001), including after further adjustment for ALT. No significant association was found for steatosis (aOR 0.82, 95% CI 0.32–2.12, p = 0.684), although the confidence interval was wide. Conclusions: About one in four anti-HDV-positive patients had CAP-defined hepatic steatosis. Detectable HDV-RNA was associated with LSM-defined advanced fibrosis, whereas no significant association with steatosis was found; the precision of this estimate was limited, and the exploratory cirrhosis analysis was underpowered. Whether steatosis in this setting reflects metabolic dysfunction, and whether it affects long-term outcomes, warrants prospective study with full metabolic phenotyping.