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

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.

The aMAP Score is an Independent Risk Factor for Intermediate-stage Hepatocellular Carcinoma: A Large Retrospective Cohort Study

“…There is increasing evidence that poor prognosis and poor treatment response are associated with elevated LDH levels [34]. Zhang et al also found a negative correlation between the OS and LDH levels [35].…”

Establishment and validation of nomogram model for the diagnosis of AFP-negative hepatocellular carcinoma

“…Serum GGT combined with the AST/ALT and GGT/ALT ratios have been shown to be of great value in predicting the prognosis of HCC ( 34 , 36 , 37 ). However, the utility of the GGT/AST for diagnosing AFP-negative HCC patients has not been reported.…”

“…Our nomogram model showed a high performance in the diagnosis of AFP-negative HCC in both training (AUC=0.838) and validation (AUC=0.840) sets. Few previous studies have focused on the construction of a nomogram model based on serological indicators for the diagnosis of AFP-negative HCC, with most limited to the analysis of single- or several-factor ROC diagnostic curves showing incomplete consideration of factors and a single study sample of diseases that may bias the results( 30 , 37 , 38 ).…”

Circulating biomarkers of mortality prediction in patients undergoing liver transplantation due to hepatocellular carcinoma

“…High blood levels of DCP have been associated with an increased risk of HCC recurrence in patients with HCC undergoing LT. [30][31][32][33] In addition, high blood DCP levels were associated with mortality in patients with HCC undergoing LT in a study of 213 patients [34] and in another study of 246 patients. [35] Lactate dehydrogenase A study of 155 HCC patients undergoing LT [36] has found an association between high blood lactate dehydrogenase (LDH) and mortality.…”