LDH and GGT/ALT Ratio as Novel Prognostic Biomarkers in Hepatocellular Carcinoma Patients after Liver Transplantation

LDH和GGT/ALT比值作为肝移植后肝细胞癌患者的新型预后生物标志物

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Abstract

BACKGROUND: Liver inflammation indices reflect its inflammatory microenvironment, which may play a role in the proliferation, invasion, and migration of carcinoma. This study is aimed at exploring the prognostic significance of serum lactate dehydrogenase (LDH) levels and gamma-glutamyl transferase (GGT)/alanine aminotransferase (ALT) ratio in hepatocellular carcinoma after liver transplant (LT). METHODS: We retrospectively analyzed data from 155 patients with a pathologically confirmed diagnosis of hepatocellular carcinoma who received LT between January 2013 and September 2017. We used receiver operating characteristics (ROC) curves to determine the optimal LDH and GGT/ALT ratio cut-off values. The Kaplan-Meier method and the logarithmic rank test were used to compare the survival curves without recurrence (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify factors associated with survival. RESULTS: Serum LDH levels were significantly associated with the Child-Pugh score (P = 0.037), largest tumor size (<50 vs. ≥50 mm) (P = 0.017), tumor count (<3 vs. ≥3) (P = 0.009), microvascular invasion (P = 0.006), and the Milan criteria (P ≤ 0.001). The serum GGT/ALT ratio was significantly correlated with alpha-fetoprotein (AFP) levels (of <400 vs. ≥400 ng/ml) (P ≤ 0.001), largest tumor size (of <50 vs. ≥50 mm) (P ≤ 0.001), the Edmondson grade (I-II vs. III-IV) (P = 0.028), microvascular invasion (P ≤ 0.001), and the Milan (P = 0.002) and Hangzhou criteria (P = 0.018). The survival curves showed that the patients with high LDH and the GGT/ALT ratio were associated with poor RFS and OS (P < 0.05). Univariate and multivariate analyses showed that AFP levels of ≥400 ng/ml, largest tumor size of ≥50 mm, microvascular invasion, LDH levels of ≥213.5 U/l, and the GGT/ALT ratio of ≥3.1338 were factors independently associated with RFS. CONCLUSION: Elevated LDH levels and the GGT/ALT ratio before LT were associated with poor OS and RFS in the present study. These factors could be used in the prognostication of patients with hepatocellular carcinoma undergoing LT.

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