GPR, King's Score and S-Index are superior to other non-invasive fibrosis markers in predicting the liver fibrosis in chronic Hepatitis B patients.

Background and study aims: In this study, we investigated the efficacy of nine non-invasive fibrosis markers in the assessment of the degree of fibrosis in patients with chronic Hepatitis B (CHB) in comparison with liver biopsy. Patients and methods: A total of 1454 untreated CHB patients from two different centers who underwent liver biopsy were included in the study. Laboratory results of patients were reviewed retrospectively and the pathology slides were re-evaluated in accordance with the Ishak score. Degree of fibrosis ≥ 3 was accepted as "significant fibrosis", ≥ 4 as "advanced fibrosis", and ≥ 5 as cirrhosis. The diagnostic performance of the markers Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis-4 score (FIB-4), Aspartate aminotransferase to Alanine aminotransferase Ratio (AAR), AAR to Platelet Ratio Index (AAPRI), Gamma-glutamyl transpeptidase to Platelet Ratio (GPR), King's Score, Fibro quotient (Fibro-Q), S Index and Platelet to Lymphocyte Ratio (PLR) were evaluated with ROC analysis. Results: In detecting significant fibrosis, APRI, GPR, King's Score and S Index had AUROC values over 0.70. For advanced fibrosis, all of the models except AAPRI; and for cirrhosis, all of the models had AUROC values over 0.70. In accordance with the chosen staging system, GPR, King's Score and S Index had high diagnostic efficacy whereas APRI, FIB-4, FibroQ and PLR had moderate diagnostic efficacy, AAR and AAPRI had low diagnostic efficacy. Conclusions: GPR, King's Score and S Index had moderate diagnostic performance in detecting significant fibrosis and advanced fibrosis, and high diagnostic performance in detecting cirrhosis.

Serum levels of gamma-glutamyl transpeptidase in relation to HCC human biology and prognosis.

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.

Plasma lipids, tumor parameters and survival in HCC patients with HBV and HCV.

INTRODUCTION AND AIMS: Hepatocellular carcinoma (HCC) is a consequence of chronic liver disease, particularly from hepatitis B or C and increasingly from obesity and metabolic syndrome. Since lipids are an important component of cell membranes and are involved in cell signaling and tumor cell growth, we wished to evaluate the relationship between HCC patient plasma lipids and maximum tumor diameter and other indices of HCC human biology. METHODS: We examined prospectively-collected data from a multi-institutional collaborative Turkish HCC working group, from predominantly HBV-based patients, for plasma lipid profiles, consisting of triglycerides, total cholesterol, LDL-cholesterol (LDL) and HDL-cholesterol (HDL) and compared these with the associated patient maximum tumor diameter (MTD), portal vein thrombosis, alpha-fetoprotein (AFP) and also with patient survival. RESULTS: We found that both low HDL (p=0.0002) and high LDL (p=0.003) levels were significantly associated with increased MTD, as well as in a final multiple linear regression model on MTD. The combination of low HDL combined with high HDL levels were significant in a regression model on MTD, PVT and an HCC Aggressiveness Index (Odds Ratio 12.91 compared to an Odds Ratio of 1 for the reference). Furthermore, in a Cox regression model on death, the HDL plus LDL combination had a significantly higher Hazard Ratio than the reference category. CONCLUSIONS: Low plasma HDL, high plasma LDL and especially the combination, were significantly related to more aggressive HCC phenotype and the combination was significantly related to a higher Hazard Ratio for death.

The predictive role of Paraoxonase 1 (PON1) activity on survival in patients with metastatic and nonmetastatic gastric cancer.

BACKGROUND: Oxidative stress is known to be implicated in the pathogenesis of malignancies including gastric cancer (GC). Paraoxonase 1(PON1) is a member of antioxidant defense system which acts by hydrolysing peroxidases. Our aim is to assess the levels PON1 activity in different stages and localizations of GC and analyze the predictive role of PON1 activity on overall survival in GC. MATERIALS AND METHODS: One hundred and twenty six patients with GC were enrolled to the study. Patients were divided into two groups; group I (nonmetastatic GC, n=65) and group II (metastatic GC, n=61). Paraoxonase 1 activity, albumine and lactate dehidrogenase levels and whole blood count were analyzed. Union Internationale Contre le Cancer system was used for staging procedure. RESULTS: Patients at advanced N or M stage have significantly lower levels of PON1 (34.26 U/L and 29.88 U/L, p=0.04 and p=0.03; respectively). Gender, Lauren's classification, grade, localization and T stage of tumor have nonsignificant impact on PON1 activity. PON1 activity was a significant prognostic factor in GC as well as metastasis, localization of tumor and low hemoglobine or albumine level. CONCLUSIONS: Lower levels of paraoxonase 1 activity in patients with metastatic gastric cancer may reflect the presence of enhanced oxidative stress in advanced stages of the disease. PON1 activity is a significant and independent predictor of overall survival. Identifying novel prognostic markers can help to establish appropriate therapeutic strategies, to determine preventive measures and to improve survival rates.