Imbalances in NET homeostasis linked to portal vein thrombosis in CHB-related decompensated cirrhosis

Background and aims

Portal vein thrombosis (PVT) is a challenging complication in liver cirrhosis, with no currently available sensitive diagnostic markers. This study aimed to investigate the potential of neutrophil extracellular traps (NETs) and Deoxyribonuclease (DNase) as diagnostic indicators for PVT in chronic hepatitis B (CHB)-related decompensated cirrhosis.

Methods

We analyzed 145 CHB-related decompensated cirrhosis patients from the Ditan study and 33 from the Changgung validation study, categorizing them based on PVT occurrence. Plasma samples were assessed for NET markers, including cell-free DNA (cfDNA) and histone-DNA complexes, along with DNase activity.

Results

PVT patients exhibited elevated levels of cfDNA and histone-DNA complexes, and reduced DNase activity. This pattern persisted regardless of hepatocellular carcinoma (HCC) status. Histone-DNA levels, DNase activity, and hemoglobin were identified as independent risk factors for PVT. Receiver operating characteristic curve analysis revealed that high histone-DNA levels may serve as a potential diagnostic marker for PVT, with an area under the curve of 0.8628 in the Ditan study and 0.7521 in the Changgung study. When combined with cfDNA and DNase activity, the area under the curve improved to 0.8774 in the Ditan study and 0.7975 in the Changgung study.

Conclusions

Imbalances in NET homeostasis are associated with PVT in CHB-related decompensated cirrhosis, including cases involving HCC. Histone-DNA complexes, a significant risk factor for PVT, show potential as a diagnostic marker for PVT in decompensated cirrhosis, particularly in HBV-related HCC.