Studying the frequency of aberrant DNA methylation of APC, P14, and E-cadherin genes in HCV-related hepatocarcinogenesis.

BACKGROUND: Data about the molecular pathogenesis of hepatitis C-related hepatocellular carcinoma (HCC) are still challenging. OBJECTIVES: Therefore, we tried to investigate the epigenetic study of three nominated genes (APC, P14, and E-cadherin) in the pathogenesis of HCV-related HCC in Egyptian. METHODS: Between March 2016 and March 2017, the DNA methylation, and quantification using (epigenetic ELISA kit) for E-cadherin, APC, and P14 genes were studied in three groups of patients: HCV related liver cirrhosis without HCC group (LC-group; n= 20), HCC on top of HCV-related cirrhosis (HCC-group; n= 20), and a third apparently healthy control group (control-group; n= 10). RESULTS: E-cad methylation showed non-significant differences between groups. P14 methylation was occurred only in HCC-group (45%). APC methylation was the highest in HCC group (70%). Methylation level was high in HCC group in comparison to both LC and control groups (P< 0.001). DNA methylation at a cutoff point > 2.9 ng/ml predicts HCC in LC-group with 90% sensitivity and 80% specificity and at level > 2.3 ng/ml had 95% sensitivity and 90% specificity in control-group. The pooled sensitivity, specificity, positive and negative predictive values and accuracy were 90%, 60%, 69.2, 85.7 and 75% respectively. CONCLUSION: Aberrant DNA methylation of multiple genes is associated with disease progression in HCV related cirrhosis. Moreover, early detection of promotor methylation of these may sever as good biomarker for early detection and therapeutic targets in high risk patients.

Outcomes and predictors of in-hospital mortality among cirrhotic patients with non-variceal upper gastrointestinal bleeding in upper Egypt.

BACKGROUND/AIMS: Variceal bleeding is one of the most frequent causes of morbidity and mortality among cirrhotic patients. Clinical endoscopic features and outcomes of cirrhotic patients with non-variceal upper gastrointestinal bleeding (NVUGIB) have been rarely reported. Our aim is to identify treatment outcomes and predictors of in-hospital mortality among cirrhotic patients with non-variceal bleeding in Upper Egypt. MATERIALS AND METHODS: A prospective study of 93 cirrhotic patients with NVUGIB who were admitted to the Tropical Medicine and Gastroenterology Department, Assiut University Hospital (Assiut, Egypt) over a one-year period (November 2011 to October 2012). Clinical features, endoscopic findings, clinical outcomes, and in-hospital mortality rates were studied. Patient mortality during hospital stay was reported. Many independent risk factors of mortality were evaluated by means of univariate and multiple logistic regression analyses. RESULTS: Of 93 patients, 65.6% were male with a mean age of 53.3 years. The most frequent cause of bleeding was duodenal ulceration (26.9%). Endoscopic treatment was needed in 45.2% of patients, rebleeding occurred in 4.3%, and the in-hospital mortality was 14%. Hypovolemic shock was the most common cause of death (46.2%). Independent risk factors of in-hospital mortality among cirrhotic patients with NVUGIB in our study were bacterial infection during hospitalization [odds ratio (OR) =0.32, 95% confidence interval (CI) =0.03-0.89], shock (OR =1.12, 95% CI =0.68-1.54), early rebleeding (OR =2.26, 95% CI =1.85-3.21), low serum albumin (OR =3.81, 95% CI =2.35-4.67), low baseline hemoglobin (OR =0.714, 95% CI =0.32-1.24), and the need for endoscopic treatment (OR =2.96, 95% CI =0.62-3.63). CONCLUSION: Bacterial infection during hospitalization, shock, early rebleeding, low serum albumin, low baseline hemoglobin, and the need for endoscopic treatment were independent risk factors of in-hospital mortality among cirrhotic patients with NVUGIB in Upper Egypt.