miRNA-221 and miRNA-222 are promising biomarkers for progression of liver fibrosis in HCV Egyptian patients.

BACKGROUND: Current methodologies used to determine the progression of hepatic fibrosis rely heavily on liver biopsy, a dangerous and invasive procedure, with semi-subjective analysis of the results of the biopsy. Thus, a new approach is immensely needed for monitoring the progression of liver fibrosis in Hepatitis C virus (HCV) patients. AIM OF WORK: The purpose of this study was to find highly specific and sensitive miRNA biomarkers that can be used to detect different stages of liver fibrosis. METHODOLOGY: The study consisted of 42 cases of chronic hepatitis C (CHC) with early-stage fibrosis, 45 cases of CHC with late-stage fibrosis, and 40 healthy subjects with no CHC or fibrosis as controls. Expression patterns of 5 miRNAs (miR-16, miR-146a, miR-214-5p, miR-221, and miR-222) were analyzed in each group using TaqMan real-time PCR. RESULTS: Serum levels of miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 were all significantly up-regulated in early and late stages of liver fibrosis. miRNA-222 had the highest sensitivity and specificity values in early and late fibrosis. miRNA-221 had the second highest sensitivity and specificity with the late-stage fibrosis group. Furthermore, miRNA-221 showed significant positive correlations with both miRNA-16 and miRNA-146a in the early- and late-stage fibrosis groups, with the early stage having a stronger correlation. CONCLUSIONS: The results indicated that miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 can be used to detect the presence of liver fibrosis. The high sensitivity and specificity of miRNA-222 and miRNA-221 in late-stage fibrosis indicate promising prognostic biomarkers for HCV-induced liver fibrosis.

Predictors of In-Hospital Mortality in patients with hepatocellular carcinoma and Acute Variceal bleeding.

INTRODUCTION: Detection of hepatocellular carcinoma (HCC) in cirrhotic patients remains a serious, unsolved problem, and the risk factors for acute variceal bleeding (AVB) in HCC patients remain unclear. This study aimed to determine the in-hospital mortality (IHM) and factors influencing the clinical outcomes of AVB in patients with liver cirrhosis and HCC. METHODS: This was a retrospective, non-randomized, clinical study that was conducted in 2014. The study was conducted on 70 patients with liver cirrhosis and HCC presenting by acute upper gastrointestinal bleeding (AUGIH). All patients were examined endoscopically within 24 hours from presentation and bleeding varices accounted for AUGIH. Full medical history, clinical examination, and laboratory and radiologic data were collected from admission charts, and hospital medical records were statistically analyzed with SSPS version 22. RESULTS: Thirty-two patients (45.7%) survived and 38 died (54.3%). Survivors are more likely to be Child-Pugh class A or B, and the non-survivors were class C. The Model for End-Stage Liver Disease (MELD) was highly predictive of IHM at an optimized cut-off value of ≥ 12.9. Higher esophageal varices grades and presence of active bleeding on index endoscopy were significant (p < 0.01) in the non-survivors compared to survivors. Complications of liver cirrhosis and associated major comorbidity were significantly higher (p < 0.01) in the non-survivors than the survivors. Univariate logistic regression analysis identified higher Grade Esophageal Varices and number of transfused packed red blood cells units as two independent predictors of IHM. CONCLUSIONS: IHM was particularly high (54.3%) among HCC patients with AVB who had MELD score > 12.9, higher grade Esophageal Varices, active bleeding on index endoscopy, more increased needs for blood transfusion, longer hospital stay, decompensated liver disease with major comorbidity.

Impact of hyponatremia on frequency of complications in patients with decompensated liver cirrhosis.

INTRODUCTION: Hyponatremia is common in cirrhosis. The relationship between hyponatremia and severity of cirrhosis is evidenced by its close association with the occurrence of complications, the prevalence of hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, refectory ascites, and hepatic hydrothorax. The aim of this study was assess the impact of hyponatremia on the occurrence of both liver-related complications and the hemodynamic cardiovascular dysfunction. METHODS: This prospective study was conducted in 2015 on 74 patients with liver cirrhosis. The patients were from the Gastroenterology and Hepatology Department of Theodor Bilharz Research Institute in Giza, Egypt. The patients were divided into three groups according to their serum level of sodium. Group 1 included 30 patients with serum sodium >135 meq/L, group 2 included 24 patients with serum sodium between135 and 125 meq/L, and group 3 included 20 patients with serum sodium <125 meq/L. For each of the patients, we conducted aclinical examination, laboratory investigations, chest X-ray, ECG, abdominal sonar, and echocardiography. RESULTS: Hyponatremia was found in 59.46% of our cirrhotic patients, and they showed significantly increased Model for End-Stage Liver Disease (MELD) score, MELD-Na score, QTc interval, Pulmonary vascular resistance (PVR) and inferior vena cava (IVC) collapsibility, and decreased SVR and IVC diameter. Also hepatic encephalopathy, ascites, renal failure, infectious complications, and pleural effusion were significantly more common in hyponatremic cirrhotic patients. CONCLUSION: In cirrhosis, hyponatremia is more common in severe cardiovascular dysfunction and associated with increased risk of hepatic encephalopathy, ascites, illness severity scores, renal failure, infectious complications, and pleural effusion. We recommend selective oral administration of vasopressin V2-receptor antagonist, tolvaptan, which acts to increase the excretion of free water, thereby resolving hypervolemic hyponatremia and may have the potential to improve outcomes in these patients.

NON-INVASIVE PREDICTORS FOR THE PRESENCE, GRADE AND RISK OF BLEEDING FROM ESOPHAGEAL VARICES IN PATIENTS WITH POST-HEPATITIC CIRRHOSIS.

Variceal bleeding is the last step of a chain of events initiatedby an increase in portal pressure, followed by the development and progressive dilation ofvarices until these finally rupture and bleed. The ideal method to diagnose portal hypertension should be accurate, noninvasive, objective, and reproducible. The study evaluated the predictive value of two non-invasive parameters for the diagnosis of esophageal varices (EV): 1-Right liver lobe diameter/serum albumin ratios (RLLD/S. albumin), and 2-Platelet count/splenic bipolar diameter ratios (Platelets count/SBPD). This study included eighty Egyptian patients with post-hepatitic cirrhosis (45 males and 35 females). They underwent laboratory ultrasono-graphic and endoscopic examinations within one week. RLLD/S. albumin and Platelets count/SBPD ratios were calculated. The results showed that EV were not detected by upper digestive endoscopy in 25%, while grade I of EV was found in 17.5%, grade II in 17.5%, grade III in 20%, & grade IV in 20%. RLLD/S. albumin concentration ratio diagnosed the varices at cut off value of 3.43 with 95% sensitivity and 80% specificity. Also, it was positively correlated with grading of E.V, when this ratio increased the grading of E.V increases and vice versa. Besides, it predicted bleeding from E.V. at cut off value of 5.096 with 63% sensitivity and 73% specificity. Platelet count/SBPD ratio predicted the presence of varices at cut off value 1847 with 95% sensitivity and 93% specificity, and negatively correlated with grading of EV, when this ratio decreased grading of E.V increase and vice versa. It also predicted bleeding from E.V. at cut off value of 4809 with 50% sensitivity and 93% specificity.

Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma.

INTRODUCTION: Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-ß1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process. YKL-40 is a glycoprotein member of ECM and plays a role in cancer cell proliferation. The purpose of this study was to determine the serum biomarkers of EMT and its impact on the fibrogenic process and tumorigenesis in HCV-genotype 4 patients. METHODS: In this case-control study that was conducted in 2013-2014, 97 HCV-infected patients were subjected to clinical examination, laboratory investigations, and liver biopsy. According to the histopathologic examination, they were classified to F0 (14 cases), F1 (17 cases), F2 (15 cases), F3 (18 cases), F4 (22 cases), and HCC (11 cases). Fifteen age- and gender-matched subjects were included as normal controls. Serum levels of TGF-ß1, BMP-7, CTGF, YKL-40 were assessed, and the TGF-ß1/BMP-7 ratios were calculated. The data were analyzed by plotting the receiver operating characteristic curve (ROC), Pearson product-moment correlation coefficient, and Spearman's rank correlation coefficient (Spearman's rho). RESULTS: Serum levels of TGF-ß1, BMP-7, CTGF, and YKL-40 were significantly increased in all patient groups compared to controls (p < 0.001). LC exhibited the highest CTGF level and YKL-40 was highest in HCC. The TGF-ß1/ BMP-7 ratios reflected the progression of EMT from CHC to LC, however, there was no significant difference between LC and HCC. TGF-ß1/ BMP-7 ratio is considered to reflect positive correlation with CTGF in LC group (r = 0.629; p < 0.03) and YKL-40 in HCC group (r = 0.504; p < 0.04). CONCLUSION: Increased TGF-ß1/BMP-7 ratio and CTGF levels reflect the rate of EMT and provide information about fibrogenic activity. Also, this ratio, in association with YKL-40, can be used to predict malignant transformation in HCV-genotype 4 Egyptian patients.