The Putative Role of Natural Killer Cells in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Natural Killer (NK) cells have crucial roles in immune responses against malignant transformation including hepatocellular carcinoma (HCC). The NKG2D receptor has a critical role in the NK recognition of target cells. AIM: We assessed NKG2D receptor expression as a diagnostic biomarker for HCC detection and progression in Egyptian patients with hepatitis C virus (HCV)-related HCC. METHODS: We classified 81 patients into three groups: chronic hepatitis (21), cirrhotic (30) and HCC (30) patients, with 36 individuals enrolled to the control group. We analyzed NK levels in peripheral blood and NKG2D receptor expression in NK cells using flow cytometry. RESULTS: We observed a significant decrease in NKG2D (CD314) expression on circulating NK cells and frequency of NK cells expressing NKG2D (CD314) in HCC patients. Also, in patients, larger foci lesions significantly correlated with decreased NK cell numbers. Multiple foci numbers and patients with a Child score C significantly correlated with decreased circulating NK cells expressing NKG2D and decreased NKG2D expression. CONCLUSION: The percentage of NK cells in peripheral blood and NKG2D receptor expression could function as potential biomarkers for HCC detection and progression.

DNA Methyltransferases as Potential Biomarkers for HCV Related Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern in many countries including Egypt. The alteration in DNA methylation that was observed in HCC patients suggests a possible role of DNA methyltransferases (DNMTs) in the disease pathogenesis in addition to potential role as a disease biomarker. AIM: To study the change in DNMTs expression in chronic HCV infected patients as potential non- invasive biomarker for diagnosis of hepatocellular carcinoma. METHODS: 26 patients with HCC, 45 patients with liver cirrhosis, 20 chronic HCV patients and 20 apparently healthy individuals as a control group were enrolled in this study. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed for all study participants. RESULTS: A significant difference in DNMTs expression was observed among the studied groups. Receiver operating characteristics (ROC) curve analysis revealed that with a cutoff value of 3.16 for DNMT 3A expression, sensitivity and specificity were 80.8 and 95.6% respectively and area under curve (AUC) was 0.958, p < 0.001 for discriminating hepatocellular carcinoma among post hepatitis C cirrhotic patients. Besides DNMT 3B relative expression cutoff value of 3.10 showed 84.6% sensitivity and 77.8% specificity and AUC was 0.888, p < 0.001. On the other hand, cutoff value 0.65 for DNMT1 relative expression showed 92.3% sensitivity and 44.4% specificity and AUC was 0.72, p= 0.002. DNMT1, DNMT 3A and DNMT 3B have significant positive correlation with the level of AFP (p-value = 0.003, 0.004 and 0.008 respectively). The relative expression of DNMT3B was significantly correlated to focal lesion size (p-value = 0.015). High DNMTs expression was significantly associated with the presence of multiple focal lesions but not with the Child Pugh grade (p> 0.05). CONCLUSION: The mRNA levels of DNMTs could be a potential biomarker for early detection of HCC development.
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MicroRNA-215 as a Diagnostic Marker in Egyptian Patients with Hepatocellular Carcinoma.

Background: MicroRNAs are mentioned as a small non-coding RNAs groups and aberrant miRNA expression was found in hepatocellular carcinoma (HCC) patients. Aim: To evaluate role of plasma MicroRNA-215 as a diagnostic tool in HCC patients. Methods: A prospective study included 195 subjects: healthy controls (group I), cirrhotic patients (group II), and patients with HCC (group III). Clinical examination, radiological and laboratory investigations which included quantification of miR-215 by Real-time qPCR were done for all cases. Results: Spearman's rank correlation revealed that in HCC group, there was a negative correlation between MiRNA-215 and serum AFP levels and focal size lesion (cm) (rs = -0.72, - 0.94 respectively, p<0.001). Receiver operating characteristics analysis for discrimination between cirrhosis and HCC groups regarding microRNA-215 displayed 78.3% sensitivity, 88.0% specificity at cutoff value of ≤ 1.90. Area under the curve (AUC) was 0.87 (p< 0.001). As regards AFP, it had a sensitivity of 81.7%, a specificity of 66.7 at cutoff value of ≥ 11.50 (ng/mL). Conclusions: Plasma level of miR-215 may be a promising biomarker in HCC diagnosis. Moreover, if miR-215 combined with AFP, it can be used as a diagnostic biomarker, for early detection of HCC.

Assessment of perception of medical students in regard to links between tobacco or alcohol use and cancer.

BACKGROUND: The aim of this study was to assess cancer awareness among medical students in Saudi Arabia toward tobacco and alcohol use as risk factors. MATERIALS AND METHODS: A cross-sectional survey from October to December 2014, covering 1200 medical students, was performed. RESULTS: Of the total, 975 (81.25%) responded. The male to female ratio was 1.00:7.125. 96/975 (9.8%) had smoked tobacco in their lifetime, and 51/975 (5.23%) were alcoholic beverage consumers. On asking them whether tobacco smoking and alcohol consumption can cause cancer, only 4/975 (0.4%) and 14/975 (1.43%) answered no for smoking and alcohol, respectively. CONCLUSIONS: The prevalence of smoking and alcohol use is very low among medical students, which might be due to high female contribution besides social stigma. The prevalence of second-hand smoke (SHS) was found to be very high in Hail region.

Study of adiponectin in chronic liver disease and cholestasis.

PURPOSE: Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance. METHODS: Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed. RESULTS: Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA. CONCLUSIONS: Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.