Association of serum lactate dehydrogenase levels with the severity of microvascular invasion in hepatocellular carcinoma: a retrospective cross-sectional study.

Background: Microvascular invasion (MVI) is an important factor affecting the prognosis of hepatocellular carcinoma (HCC) after hepatectomy. Current preoperative predictors, including alpha-fetoprotein (AFP) and imaging modalities, show limited sensitivity for identifying MVI, highlighting the need for additional accessible biomarkers. Glycolysis can produce lactic acid to promote cancer cell invasion, metastasis, and angiogenesis. Meanwhile, lactate dehydrogenase (LDH) can catalyze the conversion between lactate and pyruvate, is easily measurable, and may provide complementary value. We aim to explore the relationship between serum LDH levels and the severity of MVI in HCC patients. Methods: We retrospectively analyzed 621 HCC patients who underwent hepatectomy. Patients were stratified by the upper limit of normal (ULN) for serum LDH: group A (≤ ULN, n=461) and group B (> ULN, n=160). MVI was graded as M0, M1, or M2. The association between LDH level and MVI grade was assessed using Spearman's rank correlation. Variables with P<0.2 in univariate analysis were included in a multivariable ordinal logistic regression model to identify independent factors associated with MVI severity, adjusting for key clinicopathological confounders including tumor size, number, differentiation, and baseline liver function parameters. Statistical analyses were performed using SPSS version 25.0, with a two-tailed P<0.05 considered significant. Results: MVI grades were distributed as M0: 55.7% (n=346), M1: 27.2% (n=169), and M2: 17.1% (n=106). Median LDH was significantly higher in the M2 group (232 U/L) than in M1 (212 U/L, P=0.003) or M0 (196 U/L, P=0.007). A positive correlation was found between MVI grade and LDH level (r=0.212, P<0.001). The proportion of severe MVI (M2) was higher in group B (30.6%) than in group A (12.4%) (r=0.223, P<0.001). In multivariable ordinal logistic regression, LDH remained independently associated with higher MVI grade after adjustment for tumor burden and other covariates. ROC analysis showed limited discrimination of LDH for the presence of MVI (M1+M2) [area under the curve (AUC) =0.610]. Conclusions: Serum LDH is independently associated with MVI severity of HCC. Although the strength of association and discrimination is modest, LDH may provide complementary information to established predictors and could be considered as an adjunct variable in preoperative risk assessment models, pending further external and prospective validation.