12-Hydroxyheptadecatrienoic Acid Predicts Hepatocellular Carcinoma Development During Nucleos(t)ide Analogue Therapy

Area of Science:

• Hepatology
• Oncology
• Metabolomics

Background:

• Alterations in polyunsaturated fatty acid (PUFA) metabolites are implicated in hepatocellular carcinoma (HCC) development.
• The role of PUFA metabolites in HCC development during nucleos(t)ide analogue (NUC) therapy for chronic hepatitis B virus (HBV) infection is not well understood.

Purpose of the Study:

• To investigate the association between PUFA metabolites and HCC development in NUC-naïve patients with chronic HBV infection receiving NUC therapy.
• To identify potential predictive biomarkers for HCC development during NUC treatment.

Main Methods:

• Serum samples from 195 NUC-naïve patients were analyzed for 158 PUFA metabolites using targeted lipidomics.
• Statistical analyses, including variable importance in projection and log-rank tests, were used to evaluate associations with HCC development.
• Multivariate analysis identified independent predictors of HCC.

Main Results:

• Nineteen patients developed HCC during follow-up, with 5- and 10-year cumulative incidences of 7.7% and 12.4%, respectively.
• 12-hydroxyheptadecatrienoic acid (12-HHT) was the top metabolite differentiating HCC development.
• Low pre-treatment 12-HHT levels (≤3.82 ng/mL) were significantly associated with increased HCC risk (HR, 4.28; 95% CI, 1.18-15.55), alongside a high FIB-4 index (≥4.08).

Conclusions:

• Pre-treatment serum 12-HHT concentration is a novel predictive biomarker for HCC development in patients with chronic HBV receiving NUC therapy.
• 12-HHT levels, combined with FIB-4 index, can aid in risk stratification for HCC in this patient population.