Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis

AIM: To determine the prognostic value of alkaline phosphatase(ALP) and γ-glutamyltransferase(GGT) for hepatocellular carcinoma(HCC).METHODS: We analyzed the outcome of 172 HCC patients who underwent liver resection. Receiver operating characteristic(ROC) curve analysis was performed to determine the cut-off value of ALP and GGT. Then, preoperative risk factors for survival were evaluated by multivariate analysis. Based on the significant factors, aprognostic score model was established.RESULTS: By ROC curve analysis, ALP > 120 U/L and GGT > 115 U/L were considered elevated. Overall survival(OS) and tumor-free survival(TFS) for patients with elevated ALP and GGT were significantly worse than for patients with ALP and GGT within the normal range. Multivariate analysis showed that the elevated levels of ALP, GGT and tumor size were independent prognostic factors. Giving each positive factor as a score of 1, we established a preoperative prognostic score model. The 5-year OS for patients with a score of 0, 1, 2 and 3 were 84.0%, 45.9%, 44.1% and 0%, respectively, while the TFS was 80.6%, 40.0%, 38.8% and 0%, respectively. When combining patients with scores of 1 and 2 into the middle risk group, and patients with scores of 0 and 3 into the low-risk and highrisk groups, respectively, different outcomes would be significantly distinguished by the risk groups.CONCLUSION: Elevated ALP and GGT levels were risk predictors in HCC patients. Our prognostic model might vary the outcomes of patients from different risk groups.

Kinetic analysis of γ-glutamyltransferase reaction process for measuring activity via an integration strategy at low concentrations of γ-glutamyl p-nitroaniline

At 0.12 mmol/L γ-glutamyl p-nitroaniline(GGPNA),an improved integrated method was developed for kinetic analysis of γ-glutamyltransferase(GGT) reaction process and the integration with the classical initial rate method to measure serum GGT.For the improved integrated method,an integrated rate equation,which used the predictor variable of reaction time and considered inhibitions by both GGPNA and products,was nonlinearly fit to GGT reaction processes.For the integration strategy,classical initial rates were estimated when GGPNA consumption percentages were below 50%;otherwise,maximal reaction rates of GGT were estimated by the improved integrated method and converted into initial rates according to the differential rate equation at 0.11 mmol/L GGPNA.The inte-gration strategy was validated using optimized GGT kinetic parameters and 10-s intervals to record reaction curves within 8.0 min.By the integration strategy,there was a linear response from 0.9 to 32.0 U/L GGT,coefficients of variation were below 3.5%for GGT from 8.0 to 32.0 U/L(n=5) ,and GGT activities in clinical sera responded linearly to their classical initial rates at 2.00 mmol/L GGPNA with an expected slope.Therefore,the integration strategy was successful in measuring GGT at 0.12 mmol/L GGPNA.

Serological diagnostic factors for liver metastasis in patients with colorectal cancer

AIM:To investigate the serological diagnostic factors for liver metastasis in patients with colorectal cancer.METHODS:One hundred and six adult in-patients with colorectal cancer were studied and divided into patients with liver metastasis(n = 56) and patients without liver metastasis(n = 50).Serum levels of tumor and biochemical markers for liver were measured at the time of diagnosis.RESULTS:The mean survival time was 55.9 mo,36.8 mo and 68.3 mo for the overall patients,patients with liver metastasis and patients without liver metastasis,respectively.Lactate dehydrogenase(LDH) level was significantly correlated with the survival time of colorectal cancer patients.The levels of alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase(GGT),LDH and carcinoembryonic antigen(CEA) were significantly higher in patients with liver metastasis than in those without liver metastasis.Patients with lymph node metastasis had a higher risk of liver metastasis than those without lymph node metastasis.The cut points of LDH,GGT and CEA for screening liver metastasis were 180 U/L,30 U/L and 5.0 μg/L,respectively.The sensitivity was 64.3%,69.6% and 70.4%,and the specificity was 64.0%,60.0% and 52.4%,respectively.The sensitivity of parallel test was 85.2% for LDH and CEA,and 92.6% for GGT and CEA,respectively.The specificity of serial test was 85.7% for LDH(or GGT) and CEA.CONCLUSION:Early diagnosis of liver metastasis is of great significance.The sensitivity and specificity of combined tumor and biochemical markers are rather good in screening colorectal liver metastasis.

Monitoring the level of serum paraoxonase 1 activity in liver transplantation patients

BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.

Carbohydrate antigen 19-9 as a novel prognostic biomarker in distal cholangiocarcinoma

BACKGROUND Distal cholangiocarcinoma(DCC)presents as one of the relatively rare malignant tumors in the digestive system and has a poor long-term prognosis.Curative resection is currently the most appropriate therapy for patients with DCC because of the lack of effective adjuvant therapies.Therefore,it is important to accurately predict the prognosis for formulating a reasonable treatment plan and avoiding unnecessary surgical trauma.AIM To minimize the interference of obstructive jaundice on carbohydrate antigen 19-9(CA19-9)level by adapting CA19-9 toγ-glutamyltransferase(GGT)as an indicator,to determine the strong associations between CA19-9/GGT and postoperative neoplasm recurrence and long-term outcome of DCC.METHODS We enrolled 186 patients who were diagnosed with DCC between January 2010 and December 2019 and performed radical excision with strict criteria as follows in our hospital.Receiver operating characteristic curves were drawn according to preoperative CA19-9/GGT and 1-year survival.Based on this,patients were divided into two groups(group 1,low-ratio,n=81;group 2,high-ratio,n=105).Afterwards,by the way of univariate and multivariate analysis,the risk factors influencing postoperative tumor recrudesce and long-term prognosis of patients with DCC were screened out.RESULTS Optimum cut-off value of CA19-9/GGT was 0.12.Patients in group 2 represented higher CA19-9 and lymphatic metastasis rate accompanied by lower GGT,when compared with group 1(P<0.05).The 1-,3-and 5-year overall survival rates of patients in groups 1 and 2 were 88.3%,59.2%and 48.1%,and 61.0%,13.6%and 13.6%,respectively(P=0.000).Multivariate analysis indicated that CA19-9/GGT,lymphatic metastasis and tumor differentiation were independent risk factors for tumor recurrence and long-term prognosis of DCC.CONCLUSION Elevation of CA19-9/GGT performed better as a biomarker of aggressive carcinoma and predictor of poor clinical outcomes by reducing the effect of obstruction of biliary tract on CA19-9 concentration in patients with DCC.

Correlation of Liver Enzymes with Diabetes and Pre-diabetes in Middle-aged Rural Population in China

The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus（T2DM） and pre-diabetes（pre-DM） in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test（OGTT） was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases（ALT and GGT）, Hb A1 C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose（IFG）, impaired glucose tolerance（IGT）, impaired fasting glucose combined with impaired glucose tolerance（IFG＋IGT） and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio（WHR）, blood pressure, fasting blood glucose（FBG）, high density lipoprotein-cholesterol（HDL-C）, and liver enzymes（ALT and GGT）. Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance（IR） in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.