Seroprevalence and Clinical Characteristics of Hepatitis D Virus Infection in Korean Patients with Chronic Hepatitis B, Liver Cirrhosis, and Hepatocellular Carcinoma

Background/Aims: Hepatitis delta virus (HDV) coinfection exacerbates clinical outcomes in chronic hepatitis B (CHB) patients.With emerging HDV-targeted therapeutics, accurate prevalence and clinical impact data are essential.In this study, the seroprevalence, clinical significance, and molecular characteristics of HDV were assessed in South Korean patients across the spectrum of liver disease.Methods: This two-center retrospective study included 526 patients with CHB: non-cirrhotic CHB (n=100), cirrhotic CHB (liver cirrhosis, n=100), and hepatocellular carcinoma (HCC; n=326).Serum samples (2012 to 2024) were analyzed for anti-HDV antibodies and HDV RNA using commercial assays and quantitative reverse-transcription polymerase chain reaction, followed by full-length genomic sequencing.Results: The median patient age was 58.0 years, and 71.3% of the patients were male.The overall anti-HDV seroprevalence was 2.7% (14/526).Prevalence did not differ significantly across disease groups: 2.0% in non-cirrhotic CHB, 4.0% in cirrhotic CHB, and 2.5% in HCC (p=0.733).Notably, in HCC patients, anti-HDV seroprevalence was significantly higher in advanced stages (Barcelona Clinic Liver Cancer [BCLC] C-D) than in very early-to-intermediate stages (BCLC 0-B) (5.3% vs 0.9%; p=0.024).HDV RNA was detected in only one patient (0.2% of the total cohort; 7.1% of anti-HDV-positive patients).Phylogenetic analysis characterized the first full-length HDV genotype 1 genome in South Korea, which clustered with East Asian strains.Conclusions: Anti-HDV seroprevalence in Korean CHB patients is 2.7%, whereas viremic prevalence is 0.2%.Anti-HDV positivity is linked to male sex and advanced HCC stage.These findings emphasize the need for HDV screening in patients with advanced liver disease.(Gut Liver,