Research progress on molecular markers related to the donor kidney injury from organ donation after citizen's death / 器官移植

Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.

Expression and significance of L-FABP in hilar cholangiocarcinoma / 中华消化外科杂志

Objective To explore the expression of liver fatty acid binding protein (L-FABP) in tissues of hilar cholangiocarcinoma and the relationship between expression of L-FABP and clinicopathological factors and prognosis of the patients.Methods The retrospective case-control study was conducted.The clinicopathological data of 132 patients with hilar cholangiocarcinoma who were admitted to the Navy General Hospital between January 2003 and January 2013 were collected.The expression of L-FABP in tumor tissues and adjacent tissues of hilar cholangiocarcinoma and normal bile duct tissues were respectively detected by immunohistochemistry.Observation indicators:(1) expression of L-FABP by immunohistochemistry;(2) relationship between clinicopathological factors of patients and expression of L-FABP in tumor tissues;(3) follow-up and survival situations;(4) prognostic analysis of patients after radical resection of hilar cholangiocarcinoma.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival time up to June 2017.Count data were described as percentage and compared using the chi-square test.The survival time was calculated by the Kaplan-Meier method.Measurement data with skewed distribution were described as M (range).The univariate analysis and multivariate analysis were respectively done using the nonparametric test and COX regression model.Results (1) Expression of L-FABP by immunohistochemistry:the positive expressions of L-FABP were located in the cytoplasm.The low,moderate and high expression rates of L-FABP in tumor tissues were respectively 11.36％ (15/132),71.97％ (95/132) and 16.67％ (22/132),and positive-staining cells showed platy and / or diffuse distribution;the low,moderate and high expression rates of L-FABP in adjacent tissues of hilar cholangiocarcinoma were respectively 77.27％ (102/132),7.58％ (10/132) and 15.15％ (20/132),and positive-staining cells showed scattered or platy distribution,with a weaker staining intensity compared with tumor tissues;there was no positive expression in normal bile duct tissues.There was a statistically significant difference in expressions of L-FABP among tumor tissues and adjacent tissues of hilar cholangiocarcinoma and normal bile duct tissues (x2=5.423,P ＜ 0.05).(2) Relationship between clinicopathological factors of patients and expression of L-FABP in tumor tissues:cases with low,moderate and high expressions of L-FABP in tumor tissues were respectively 10,30,5 in 45 patients with tumor diameter ＜ 3 cm and 4,29,9 in 42 patients with 3 cm ≤ tumor diameter ≤ 5 cm and 1,36,8 in 45 patients with tumor diameter ＞ 5 cm,with a statistically significant difference (x2 =10.171,P＜ 0.05).(3) Follow-up and survival situations:132 patients were followed up for 5-90 months,with a median time of 33 months.During the followup,postoperative overall median survival time of 132 patients was 31 months.(4) Prognostic analysis of patients after radical resection of hilar cholangiocarcinoma:results of univariate analysis showed that tumor differentiation,lymph node metastasis and expressions of L-FABP in tumor tissues were related factors affecting prognosis of patients after radical resection of hilar cholangiocarcinoma (Z =1.845,3.156,1.243,P＜0.05).Results of multivariate analysis showed that tumor differentiation,lymph node metastasis and expressions of L-FABP in tumor tissues were independent factors affecting prognosis of patients after radical resection of hilar cholangiocarcinoma (odds ratio =0.431,1.806,3.692,95％ confidence interval:0.292-0.693,0.974-2.973,1.875-11.364,P＜0.05).Conclusions The high expression of L-FABP in tumor tissues is significantly correlated with the tumor diameter.Tumor differentiation,lymph node metastasis and expressions of L-FABP in tumor tissues are independent factors affecting prognosis of patients after radical resection of hilar cholangiocarcinoma.

Gene polymorphisms in non-alcoholic fatty liver disease: a review of research progress / 临床肝胆病杂志

Non-alcoholic fatty liver disease (NAFLD) is considered one of the most common chronic liver diseases throughout the world. The incidence of NAFLD is closely associated with ethnicity, nationality, family, and region. In recent years, the association between NAFLD and gene has grown to be paid more attention. It is of great significance for inhibiting the prevalence of fatty liver disease to understand NAFLD and the gene polymorphisms associated with its pathogenesis. In this review, we summarize the gene polymorphisms associated with glucose metabolism, fatty acid metabolism, and oxidative stress in the pathogenic mechanisms of NAFLD and point out that NAFLD is a genetic-environment-metabolic stress disorder.

Loss of Liver Fatty Acid Binding Protein Expression in Hepatocellular Carcinomas is Associated with a Decreased Recurrence-Free Survival

BACKGROUND/AIMS: Loss of liver fatty acid binding protein (LFABP) expression by immunohis-tochemistry is a useful marker for the identification of hepatocyte nuclear factor 1alpha (HNF1alpha)-inactivated hepatocellular adenomas; however, the expression status of LFABP in hepatocel-lular carcinomas (HCCs) is still unclear. We aimed to investigate the expression status of LFABP in HCCs and examine the clinicopathological characteristics of LFABP-negative HCCs. METHODS: Immunohistochemical stains LFABP, K19 (mouse monoclonal, Dako, Glostrup, Den-mark) and EpCAM (mouse monoclonal, Calbiochem, Darmstadt, Germany) were performed on tissue microarray sections from 188 surgically resected HCCs, and the association between LFABP expression status and the clinicopathological features, survival and "stemness"-related marker expression status were analyzed. RESULTS: Loss of LFABP expression was noted in 30 (16%) out of 188 HCCs. LFABP-negative HCCs were associated with a decreased recurrence-free survival (LFABP-negative: 17.0 +/- 4.84 months [95% confidence interval [CI]: 7.5-26.5 months] versus LFABP-positive: 51.0 +/- 8.7 months [95% CI: 34.0-68.0 months]; P=0.004). HCCs with LFABP expression loss were more frequently larger and showed more frequent vascular invasion, although not statistically sig-nificant; and an inverse correlation was seen between LFABP expression and K19 expression status (P=0.001). CONCLUSIONS: Loss of LFABP expression is seen in HCCs, and is associated with a decreased recurrence-free survival.

Common Carotid Intima-media Thickness in Patients with Non-alcoholic Fatty Liver Disease: A Population-based Case-control Study / 대한소화기학회지

BACKGROUND/AIMS: Metabolic syndrome is a well-known risk factor for atherosclerosis. Non-alcoholic fatty liver disease (NAFLD) has features of metabolic syndromes. This study aimed to investigate the association between NAFLD and atherosclerosis. METHODS: In a population-based study in southern Iran, asymptomatic adult inhabitants aged more than 20 years were selected through cluster random sampling, and were screened for the presence of fatty liver and common carotid intima-media thickness (CIMT), with abdominal and cervical ultrasonography, respectively. Those with fatty liver were compared to the same number of individuals without fatty liver. RESULTS: Two hundred and ninety individuals were found to have fatty change on abdominal ultrasonography, and were labeled NAFLD. Compared to normal individuals, NAFLD patients had significantly higher prevalence of increased CIMT (OR, 1.66; p<0.001). Those with hypertension (HTN), diabetes mellitus (DM), higher waist circumference (WC) and older ages had significantly higher prevalence of thick CIMT. Through adjusting the effects of different variables, we indicated that NAFLD could be an independent risk factor for thick common carotid intima-media (OR, 1.90; 95% CI, 1.17-3.09; p=0.009). It was also shown that age could be another independent risk factor for thick CIMT. CONCLUSIONS: Individuals with risk factors such as HTN, DM, and high WC are prone to develop atherosclerosis of the carotid artery. The presence of NAFLD should be considered as another probable independent factor contributing to the development of carotid atherosclerosis.

Value of urinary L-FABP and NGAL in the diagnosis of acute kidney injury caused by obstructive nephropathy and the prediction of renal outcome / 中华肾脏病杂志

Objective To evaluate the values of urinary liver-fatty acid binding protein (uL-FABP) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in diagnosis of acute kidney injury (AKI) caused by obstructive nephropathy and in the prediction of renal prognosis.Methods Clinical data of 30 patients with obstructive nephropathy were collected prospectively.uL-FABP and uNGAL were measured by ELISA at various time points.Risk factors of the renal outcome were evaluated.The patients were followed up for at least one year.Results Patients with AK1 had higher levels of uL-FABP and uNGAL compared to those without AKI [700.00(154.62-1216.14) μg/g· Cr vs 26.90 (16.77-41.38) μg/g·Cr; 1266.69 (671.57-3396.07) μg/g·Cr vs 179.12 (90.98-215.16) μg/g·Cr,all P ＜ 0.01].Positive correlations of uL-FABP and uNGAL with serum creatinine were found (r =0.552,0.553,all P ＜ 0.01).The AUCs of uL-FABP and uNGAL to detect AKI were 0.925 and 0.900.Patients with non complete renal recovery had higher levels of uL-FABP before operation and 72-hour after operation compared to those with complete renal recovery (all P ＜ 0.01).Before operation,the AUC of uL-FABP to detect renal prognosis was 0.948,sensitivity was 85.7％ and specificity was 90.9％.72-hour after operation,the AUC of uL-FABP to detect renal prognosis was 0.935,sensitivity was 85.7％ and specificity was 90.9％.Kaplan-Meier analysis revealed that uL-FABP before operation over 366.57 μg/g · Cr or uL-FABP 72-hour after operation over 223.60 μg/g · Cr were closely related to the poor progression of renal function.Conclusions uL-FABP and uL-NGAL have good accuracy in detecting AKI.The level of uL-FABP before operation and 72-hour after operation is helpful to predict the renal outcome of obstructive nephropathy.

Hepatic Hemangiomas with Peritumoral Sparing of Fatty Infiltration in Hepatic Steatosis: Findings on Contrast-enhanced MR Imaging and on Sonography

PURPOSE: We wanted to determine the frequency of peritumoral sparing of fatty infiltration (PTSF) around hepatic hemangioma in hepatic steatosis and to evaluate the finding of these tumors on dynamic contrast-enhanced MR imaging and on sonography. MATERIALS AND METHODS: This study included 76 hemangiomas in 67 patients suffering with hepatic steatosis. A diagnosis of hemangioma was based on the histologic findings, hemangioma SPECT or a compatible enhancement pattern on the dynamic contrast-enhanced MR study. For chemical shifting, PTSF was defined when there wasn't any decrease in signal intensity of the liver parenchyma on the opposed-phase images as compared with the in-phase images, and this intensity appeared as a hyperintense area around the tumor. We evaluated the frequency of PTSF and we analyzed if the presence of PTSF was related to the tumor size, the rapidity of enhancement or an associated arterioportal shunt. Among those, sonographic images were available in 55 hemangiomas. We also evaluated the sonographic appearances of hemangiomas with PTSF. RESULTS: Of the 76 hemangiomas, PTSF was noted on the MR chemical-shift images in 57 hemangiomas (75%). There was no significant relationship between tumor size and the presence of PTSF (p=.578). However, this finding was more frequently found in high-flow hemangiomas than in the slow-flow ones (p=.0038) and it was also related to the presence of associated arterioportal shunt (p=.0158). Sonographically, hemangiomas with PTSF were commonly surrounded by a peritumoral low-echoic area (28/41, 68%); these tumors more frequently showed a thin high-echoic rim on sonography than did the tumors without this finding (p=.0055). CONCLUSION: PTSF is commonly seen in hemangiomas in hepatic steatosis patients. Hepatic hemangiomas with PTSF tend to show rapid enhancement on dynamic MR imaging and this is accompanied by arterioportal shunt. They tend to be seen as an iso- or low-echoic mass with a thin high-echoic rim on sonography, and the mass is commonly surrounded by a peritumoral low-echoic area.

Focal Sparing in Fatty Liver: Mimicking Hypervascular Tumor on Gadolinium-Enhanced Opposed-Phase Gradient-Echo Images

We describe the magnetic resonance imaging findings in a case of focal sparing in fatty liver that showed homogeneous hyperintensity on gadolinium-enhanced opposed-phase gradient-echo images and mimicked a hypervascular mass due to paradoxical suppression of signal intensity of surrounding liver parenchyma with fatty infiltration.