Abstract
Background and aim:Hepatocellular carcinoma (HCC) biomarkers are limited, as even the best studied, alpha-fetoprotein (AFP), is elevated in no more than 50% of HCC patients. The aim was to evaluate several serum liver function tests in relation to survival and tumor characteristics in a large cohort of Turkish HCC patients.Methods:We retrospectively examined the serum levels of gamma glutamyl transpeptidase (GGT) in relation to patient survival.Results:Kaplan-Meier analysis showed that only GGT and albumin amongst liver function tests, were significantly associated with survival. Survival worsened with increase in GGT levels semi-quantitatively. Increase in GGT levels was also found to significantly correlate with an increase in maximum tumor diameter from 4.5 to 7 cm, a 20-fold increase in serum alpha-fetoprotein level, an increase in tumor multifocality from 20 to 54% of patients, and a doubling in percent of patients with portal vein thrombosis (PVT) from 20 to 40%. Serum GGT levels also showed significant survival differences for patients with low AFP levels. A doublet combination of serum GGT with albumin levels was associated with higher hazard ratios in a Cox regression analysis, as compared with single parameter GGT. The combination parameter pair was also prognostically useful in the low-AFP patient subcohort and was associated with significant differences in patient tumor characteristics.Conclusions:Serum GGT levels and especially combination serum GGT plus albumin levels, were significantly associated both with HCC patient survival and tumor aggressiveness characteristics, regardless of AFP levels in a large Turkish cohort. This might be especially useful since the majority of HCC patients do not have elevated levels of AFP.
Highlights
Hepatocellular carcinoma (HCC) prognosis has in general been shown to depend on 2 separate yet related considerations, namely tumor and non-tumor characteristics. The former includes tumor size and multiplicity, presence or absence of portal vein invasion by tumor (PVT), degree of tumor differentiation, serum levels of serum alphafetoprotein [1,2,3,4] and an immature form of prothrombin called desgamma carboxy prothrombin or DCP [5], which in turn is associated with increased incidence of portal vein thrombosis (PVT) [6]
Patient data: We retrospectively analyzed a database of 470 prospectively-accrued non-transplant HCC patients who had both survival data and baseline tumor parameter data, including Computerized axial tomography (CT) scan information on HCC maximum tumor diameter (MTD), number of tumor nodules and presence or absence of macroscopic portal vein thrombosis (PVT), as well as serum alpha-fetoprotein (AFP) levels; complete blood count; routine serum liver function tests
Database management conformed to legislation on privacy and this study conforms to the ethical guidelines of the Declaration of Helsinki and approval for this retrospective study on de-identified HCC patients was obtained by the Institutional Review Board of each participating institution, as previously reported [22]
Summary
Hepatocellular carcinoma (HCC) prognosis has in general been shown to depend on 2 separate yet related considerations, namely tumor and non-tumor characteristics The former includes tumor size and multiplicity, presence or absence of portal vein invasion by tumor (PVT), degree of tumor differentiation, serum levels of serum alphafetoprotein [1,2,3,4] and an immature form of prothrombin called desgamma carboxy prothrombin or DCP [5], which in turn is associated with increased incidence of PVT [6]. The aim was to evaluate several serum liver function tests in relation to survival and tumor characteristics in a large cohort of Turkish HCC patients
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