Independent association of the LNG index with extrahepatic metastasis in hepatocellular carcinoma

Extrahepatic metastasis (EHM) indicates a poor prognosis in hepatocellular carcinoma (HCC). This study evaluated the association of the logarithmically transformed neutrophil-to-lymphocyte ratio–gamma-glutamyl transferase index (LNG) with EHM at initial assessment and its incremental discriminative value. This single-center retrospective cross-sectional study included 678 adults with newly diagnosed HCC. LNG was calculated as the natural logarithm of the product of its components. Associations were assessed using multivariable logistic and linear regression and restricted cubic splines. Model performance was evaluated using receiver operating characteristic, reclassification, and decision curve analyses. EHM was present in 270 patients (39.8%). The adjusted odds ratio (OR) per unit increase in LNG was 1.25 (95% confidence interval [CI]: 1.06–1.48; p = 0.007). Adjusted spline analysis indicated nonlinearity (p = 0.009). Compared with the lowest tertile, adjusted ORs were 2.45 (95% CI: 1.45–4.17) and 2.59 (95% CI: 1.44–4.69) in the middle and highest tertiles, respectively. LNG yielded an area under the receiver operating characteristic curve (AUC) of 0.748 (95% CI: 0.711–0.785). In an exploratory analysis, the AUC was 0.717 (95% CI: 0.652–0.783) among patients with alpha-fetoprotein (AFP) levels <20 ng/mL. Adding LNG to a baseline model, which included age, sex, tumor size, AFP, multifocality, and cirrhosis, increased the AUC from 0.762 to 0.797 (p < 0.001). This also improved reclassification and led to a greater estimated net benefit. Among patients with EHM, LNG was positively associated with albumin-bilirubin and Controlling Nutritional Status scores and platelet-to-lymphocyte ratio. LNG may complement initial EHM assessment in HCC, though external validation is required.