K.A. Hosny

miR‐615‐5p is restrictedly expressed in cirrhotic and cancerous liver tissues and its overexpression alleviates the tumorigenic effects in hepatocellular carcinoma

microRNAs aberrant behavior in heptocellular carcinoma (HCC) plays a major role in HCC pathogenesis. miR‐615‐5p expression has never been evaluated in HCC. We showed that miR‐615‐5p was preferentially expressed in HCC, cirrhotic liver tissues and HCC cell lines, but undetected in normal livers. Forced miR‐615‐5p expression in HCC cell lines led to significant decrease in cell growth and migration. In‐silico predication revealed insulin‐like growth factor‐II (IGF‐II) as a potential downstream target for miR‐615‐5p. Forcing the expression of miR‐615‐5p showed downregulation of IGF‐II mRNA, as well as inhibition of the luciferase activity in a luciferase reporter vector harboring the IGF‐II‐3′UTR target sequence. miR‐615‐5p acts as tumor‐suppressor in HCC through targeting IGF‐II.

Endovascular management of early hepatic artery thrombosis after living donor liver transplantation

To study the feasibility of endovascular management of early hepatic artery thrombosis (HAT) after living‐donor liver transplantation (LDLT) and to clarify its role as a less invasive alternative to open surgery. A retrospective review of 360 recipients who underwent LDLT. Early HAT developed in 13 cases (3.6%). Diagnosis was performed using Doppler, CT angiography, and digital subtraction angiography. Intra‐arterial thrombolysis (IAT) was performed using streptokinase or tPA. In case of underlying stricture, PTA was attempted. If the artery did not recanalize, continuous infusion was performed and monitored using Doppler US. Initial surgical revascularization was successful in 2/13 cases. IAT was performed in 11/13 cases. The initial success rate was 81.8% (9/11), the failure rate was 18.2% (2/11). Rebound thrombosis developed in 33.3% (3/9). Hemorrhage developed after IAT in 2/11 cases (18.2%). Definite endovascular treatment of HAT was achieved in 6/11 cases (54.5%) and definite treatment (surgical, endovascular or combined) in 9/13 cases (69%). (Follow‐up 4 months–4 years). Endovascular management of early HAT after LDLT is a feasible and reliable alternative to open surgery. It plays a role as a less invasive approach with definite endovascular treatment rate of 54.5%.

miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma

This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin‐like growth factor‐2‐mRNA‐binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR‐1275 to simultaneously target the three IGF2BPs, and screening revealed miR‐1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH‐7 cells with miR‐1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR‐1275. Ectopic expression of miR‐1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR‐1275. These findings indicate that the tumor‐suppressor miR‐1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R.

Repression of miR-17-5p with elevated expression of E2F-1 and c-MYC in non-metastatic hepatocellular carcinoma and enhancement of cell growth upon reversing this expression pattern

E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In this study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread.

Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth.

Abstract IGF2BP 1, 2 and 3 control the fate of many transcripts. Immunoprecipitation studies demonstrated the IGF2BPs to bind to IGF1R mRNA, and our laboratory has recently shown them to post-transcriptionally regulate IGF1R. This study sought to identify a microRNA regulating the IGF2BPs and consequently IGF1R. All three IGF2BPs were among the top-ranked predicted targets of let-7i. Let-7i was downregulated in HCC tissues, and transfection of HuH-7 with let-7i inhibited malignant cell behaviors and decreased IGF2BPs transcripts. Direct binding of let-7i to IGF2BP2 and IGF2BP3 3′UTRs was confirmed, and the effect of let-7i caused a decrease in the IGF2BPs’ target gene, the IGF1R. IGF1R mRNA was inversely correlated with let-7i in HCC tissues and was reduced upon let-7i transfection into HuH-7. Reporter assays validated IGF1R as a target of let-7i. Therefore, let-7i may control HCC tumorigenesis by regulating IGF1R directly and indirectly by interrupting the interplay between IGF1R and the IGF2BPs.

A retrospective evaluation of causes of exempting living liver donors in an Egyptian centre

BACKGROUND AND STUDY AIMS Living-related liver transplantation has helped to solve the problem of shortage of deceased organ donors. However, studies showed significant donor complications occurring with adult living liver donation. This study aims at assessing different causes of exclusion of potent living donor transplantation in Egypt. PATIENTS AND METHODS The data of 158 living donors (corresponding to 50 consecutive transplanted cases) were retrospectively studied. RESULTS Only 50 donors were found to meet all the preoperative assessment criteria while 108 potential donors were excluded at various assessment steps. Majority of the excluded potential donors were due to anatomical variations (52/108) followed by hepatic steatosis (19/108) and positive hepatitis B or C virus serology (11/108). Regarding the anatomic variations, biliary anomalies were ranked as the first cause to exclude donors with the majority of them having the type C biliary variant. Portal vein variations were the second most common cause of exclusion due to portal vein trifurcation. Hepatic artery variations were detected in a lesser number of excluded donors. No donors were excluded for hepatic vein anomalies. CONCLUSION Anatomical variations are the most common causes to exempt living liver donors. Preoperative evaluation of anatomical variations, viral serology and hepatic steatosis plays the major role to accept or exclude the potential donors.

268 MIR-155 IS AN INDUCER FOR THE INSULIN-LIKE GROWTH FACTOR II MITOGENIC SIGNALING PATHWAY IN HCV-PROGRESSED HEPATOCELLULAR CARCINOMA

268 MIR-155 IS AN INDUCER FOR THE INSULIN-LIKE GROWTH FACTOR II MITOGENIC SIGNALING PATHWAY IN HCV-PROGRESSED HEPATOCELLULAR CARCINOMA H.M. El Tayebi, K.A. Hosny, G. Esmat, K. Breuhahn, A.I. Abdelaziz. The Molecular Pathology Research Group, German University Cairo, Department of General Surgery, Faculty of Medicine, Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany E-mail: hend.saber@guc.edu.eg

Portal venous pressure and proper graft function in living donor liver transplants in 69 patients from an Egyptian center

BACKGROUND Several studies have defined the optimal portal pressure suitable for adequate graft renewal in liver transplantation (LT) but none have studied an Egyptian population to our knowledge. OBJECTIVES Determine the level of portal venous pressure (PVP) for adequate graft function, and study the effect of PVP modulation on the outcome of LT in an Egyptian population. DESIGN Cross-sectional, prospectively collected data. SETTING Liver transplantation unit. PATIENTS AND METHODS The study included adult cirrhotic patients who underwent right lobe liver donor living transplantation (LDLT) at our transplantation center. Intraoperative Doppler was performed on all LDLT patients. Two PVP measurements were obtained during the recipient operation: before PV clamping and after graft reperfusion. These PVP measurements were correlated with the results of intraoperative and postoperative Doppler findings and graft function. Mortality in the early postoperative period (<1 month) and development of small-for-size syndrome (SFSS) were recorded. MAIN OUTCOME MEASURES PVP, graft injury, and the effect of PVP modulation on the outcome of LT were the primary outcome measures. Secondary outcome measures were to correlate PVP to portal vein hemodynamics and intraoperative mean hepatic artery, peak systolic velocity, and also to correlate PVP with the postoperative graft function and mean postoperative platelet count. SAMPLE SIZE AND CHARACTERISTICS 69 adult patients with end-stage liver disease. RESULTS Post-reperfusion PVP was lower than pre-clamping PVP. The mean pre-clamping and post-reperfusion values were higher in patients who experienced early mortality and in patients with smaller grafts. A PVP greater than 16.5 mm Hg at the end of the operation predicted the development of SFSS (sensitivity=91.7% and specificity=50.5%). Cases of high PVP that were modulated to a lower level had a smooth and uneventful postoperative outcome. CONCLUSION PVP is a significant hemodynamic factor that influences the functional status of the transplanted liver, including the development of SFSS, in the Egyptian population. PVP modulation may improve the outcome of LDLT. LIMITATIONS Further study with a larger sample is needed to confirm these results.