The Significance of Circulating Cell-Free DNA Markers in Chronic Hepatitis B Patients with Hepatocellular Carcinoma

(1) Background: Hepatocellular carcinoma (HCC) is the most serious complication of chronic hepatitis B (CHB). Recently, the detection of circulating cell-free (cf) DNA and nucleosomes has found numerous applications in oncology. This study aimed to examine the levels of serum cfDNA markers and nucleosomes in CHB patients with and without HCC and assess their potential association with HCC patients’ survival. (2) Methods: Nineteen patients with CHB and HCC and 38 matched patients with CHB without cancer development during 5 years of antiviral therapy were included. Stored serum samples were analyzed for cfDNA species, including the cfDNA concentration and levels of Alu115, Alu247, and nucleosomes. DNA integrity was expressed as the Alu247/Alu115 ratio. (3) Results: Compared to controls, HCC patients had higher median Alu247 levels (64.2 vs. 23.2 genomic equivalent, p = 0.004) and DNA integrity (1.0 vs. 0.7, p < 0.001) and a trend for a higher median cfDNA concentration (36.0 vs. 19.5 ng/mL, p = 0.064). Increased DNA integrity (Alu247/Alu115 > 1) was associated with an increased risk of death during the first year after HCC diagnosis (p = 0.016). (4) Conclusions: Levels of Alu247 and DNA integrity in serum cfDNA are elevated in CHB patients with HCC, whereas increased DNA integrity seems to be associated with a worse short-term prognosis in this setting.