Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM: To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS: Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS: Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, a P < 0.001 and r = 0.270, b P < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively; P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION: The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

A correction formula for neuron-specific enolase measurement in hemolyzed neonatal serum samples.

As a specific biomarker in neonatal hypoxic-ischemic encephalopathy (HIE), the measurement of neuron-specific enolase (NSE) has been advocated as a predictor of outcome in neurological injury. However, the measured levels of NSE may be influenced by hemolysis. In the current study, the change in the concentration of NSE in serum was measured by chemiluminescence prior to and following the addition of individual frozen and thawed red blood cells from 86 neonates that were collected within 24 h of birth. The changes in the concentration of NSE were compared with the changes in the concentration of hemoglobin (Hb), measured by the hemoglobin cyanide (HiCN) method, to establish a correction formula. The performance of the correction formula was evaluated by comparing the corrected concentration of NSE using the individual constants and the correction formula. The average individual constant of NSE from the 86 hemolyzed neonatal serum samples was 25.15±3.94 mg/g Hb. The concentration variation between NSE and Hb in neonatal sera could be described by the equation ΔNSEserum=1.8594+24.0670 xΔHbHiCN (r2=0.8045, P<0.001). There was no statistically significant difference in the NSE corrected results between the individual constant group and the correction formula group (Z=-1.645, P=0.100). The linear regression formula of Hb measured with the instrumental method compared with the HiCN method was Hbinstr=0.9816×HbHiCN+0.5596 (r2=0.9924, P<0.001). Based on these regression analyses, the correction formula for NSE in hemolyzed neonatal serum was determined as NSEcorr=NSEmeas-24.0670×HbHiCN-1.8594 or NSEcorr=NSEmeas-24.5181×Hbinstr+11.8609. In conclusion, hemolysis has a substantial influence on the accurate measurement of NSE in neonatal serum samples. For hemolyzed neonatal serum samples, correcting the NSE results using a correction formula is essential to evaluate the severity of neonatal hypoxic ischemic encephalopathy.

Diagnostic value of urinary-to-serum human epididymis protein 4 ratio in ovarian cancer.

Human epididymis protein 4 (HE4) is one of the best-known tumor markers for ovarian cancer (OC). Emerging evidence indicates that the evaluation of serum HE4 (S-HE4) levels may be problematic when patients have chronic kidney disease (CKD). Assaying urine for HE4 levels is non-invasive alternative for the diagnosis of OC. However, whether the combined detection of S- and urinary HE4 (U-HE4) levels distinguishes OC from CKD remains unknown. To investigate this issue, the present study recruited 31 female patients with OC, 38 female patients with CKD, and 36 healthy control (HC) females. Serum and urine samples were preoperatively collected for HE4 level detection. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance of S-HE4 level, U-HE4 level and the ratio of urinary-to-serum HE4 level (R-HE4). Data from the current study indicated that serum HE4 levels in the OC and CKD groups were significantly higher than that in the HC group. The U-HE4 level in the OC group was significantly higher than that in the CKD and HC groups. The highest R-HE4 was observed in the HC group, followed by the OC group, and the lowest R-HE4 was observed in the CKD group. ROC analysis demonstrated that the R-HE4 was useful in differentiating OC from CKD and HC. Based on the diagnostic interval of optimal cut-off values from 36.85 to 96.15, the sensitivity and specificity of R-HE4 in differentiating OC patients from non-OC patients were 82.6 and 85.4%, respectively. Thus, the combined detection of S- and U-HE4 levels facilitates the diagnosis of OC, and R-HE4 is an effective marker for differentiating OC from CKD.

Aberrant production of soluble inducible T-cell co-stimulator (sICOS) and soluble programmed cell death protein 1 (sPD-1) in patients with chronic hepatitis C.

Previous studies have indicated that immune dysregulation is an important cause of HCV­mediated damage to the liver. Co­stimulation signals, including programmed cell death protein 1 (PD­1) and inducible T­cell co­stimulator (ICOS), have been demonstrated to be involved in the pathogenesis of HCV. The purpose of this study was to investigate the soluble PD­1 (sPD­1) and soluble ICOS (sICOS) serum levels in chronic HCV patients, and to elucidate the association of sPD­1 and sICOS levels with pathological injury of chronic HCV infection. Sixty­three patients with chronic HCV and 30 normal controls were recruited for this study. The serum concentration levels of sPD­1 and sICOS were measured by enzyme­linked immunosorbent assay, and the mRNA levels of PD­1 and ICOS were detected using real­time RT­PCR. The serum sPD­1 and sICOS levels were significantly elevated in the chronic HCV patient group compared with the normal control group. Furthermore, the relative mRNA expression levels of these proteins were also increased in chronic HCV patients. sPD­1 and sICOS serum levels were significantly correlated with anti­HCV antibody levels, but not with HCV RNA. Aberrant sPD­1 and sICOS serum levels may reflect the dysregulation of T­cell activation, and are associated with the pathological injury of chronic HCV infection.