Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients

Clinical and Experimental Medicine - Identification of host genetic factors influencing the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV)...     

Role of Helicobacter pylori in patients with HCV-related chronic hepatitis and cirrhosis with or without hepatocellular carcinoma: possible association with disease progression

The discovery of Helicobacter hepaticus as a causal agent of hepatitis and hepatocellular carcinoma (HCC) in mice has stimulated interest in looking for Helicobacter species in human liver samples. In this study, we searched for association between H. pylori and HCV-related liver disease. Liver specimens were collected from eighty-five patients; they were divided into five different groups according to liver pathology (METAVIR system). Group I (the 1st control group) consisted of 16 patients with chronic hepatitis C without histological activity. Group II consisted of 25 patients with chronic active hepatitis C, Group III, 17 patients with HCV-related cirrhosis and Group IV, 16 patients with HCV-related cirrhosis and HCC. Group V (2nd control group) consisted of 11 patients suffering from gastro duodenal and gall bladder diseases but negative for HCV. All cases were tested by polymerase chain reaction on liver samples for the presence of H. pylori DNA Cag A gene. Routine biochemical, radiological and RT-PCR for HCV RNA were also performed for all cases. The positivity of H. pylori PCR CagA gene in liver tissue was directly proportional to the severity of liver pathology, this being 75%, 52.9% and 32% in groups IV, III and II, respectively, which was more significant than the 1st and 2nd control groups (P < 0.001). There was a significant difference between H. pylori PCR values when compared to METAVIR staging (F) in different groups (P = 0.001). Helicobacter pylori PCR (Cag A gene) was positive in about 28.2% cases of late fibrosis (F3 + F4) while positivity was (5.9%) in early fibrosis (F1 + F2) (P = 0.0001). There was significant difference between H. pylori PCR (Cag A gene) in liver tissue and METAVIR activity in different groups (P = 0.002) as most of H. pylori PCR-positive cases were METAVIR activity A1 and A2 (15.3% and 12.9%, respectively). There was no association between H. pylori PCR and quantitative HCV RNA (P = 0.531). Also there was no significant difference of Child-Pugh staging in the H. pylori PCR-positive group when compared to the negative group (P = 0.996). There may be an association between the presence of H. pylori (Cag A gene) in the liver and disease progression in HCV-related chronic hepatitis and cirrhosis with and without HCC.     

Synthesis and evaluation of some novel quinazolinone derivatives as diuretic agents

A new series of quinazolin-4(3H)-one derivatives containing either a thiazole or a 1, 3, 4-thiadiazole moiety were prepared in order to study the effect of such a heterocyclic combination on the expected diuretic activity. Synthesis of the target compounds (2, 4, and 6) has been achieved through an interaction of the starting 7-chloro-2-methyl-4H-3, 1-benzoxazin-4-one 1 with different heterocyclic amines. Alkylation of 3-(2-mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivative 4 with different alkyl halides or chloroacetic acid afforded the corresponding thioethers 5 while interaction of 2-methyl-3-(1, 3, 4-thiadiazol-5-yl or thiazol-5-yl)quinazolin-4(3H)-ones (2 and 6) with various aromatic aldehydes resulted in the formation of the arylvinyl analogs 3 and 7, respectively. On the other hand, 2-morpholinomethyl-3-(2-sulfamoyl or mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivatives 10 have also been synthesized through an interaction of the sulfonamide or thiol analog 9 with the appropriate amine. Biological evaluation of some of the target compounds as diuretic agents was carried out. The results showed that 2-[2-(4-chlorophenyl)vinyl]-7-chloro-3-(2-sulfamoyl-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one 7b exhibited significant diuretic activity. The detailed synthesis, spectroscopic and biological data are reported.     

Interrelationship between Toll-like receptors and infection after orthotopic liver transplantation

Early microbial recognition by the innate immune system is accomplished by Toll-like receptors (TLRs), with resultant initiation of a pro-inflammatory response against infecting organisms. In spite of presence of an abundance of Toll-like receptors on the surface of the liver, gut bacteria does not elicit an inflammatory reaction in healthy individuals due to tolerance to these TLRs, suggesting that the inflammatory responses seen in the liver are the result of breakdown of this tolerance. While orthotopic liver transplantation is often life saving in many instances, death following this procedure is most commonly due to infection that occurs in up to 80% of transplant recipients, most commonly due to microbial causes in up to 70% of cases and viral infections in 20%, while fungal infections affect only 8% of cases. The probability of acquiring infection following hepatic transplantation is heightened due to affection of the innate immune defense mechanisms of the host following this procedure. Single nucleotide polymorphisms of TLRs have been associated with increased likelihood of either development of post-transplant infection or eradication of infecting organism. However, conflicting reports from other studies reveal that prevalence of this single nucleotide polymorphism is not increased in infected patients.     

Percutaneous US-guided combined ethanol and tetracycline injection for treating symptomatic simple and hydatid hepatic cysts

Introduction

Percutaneous treatment of simple or hydatid liver cysts is widely used in clinical practice and ethanol is the commonest sclerosant used. Abdominal discomfort and pain commonly occurs after ethanol injection which increase with increased ethanol volume.

Predictors of hepatocyte proliferative activity in chronic hepatitis B and C vs. steatohepatitis as assessed by the monoclonal antibody MIB1-Ki-67

Background and study aimsChronic hepatitis is characterised by increased regenerative cell proliferation, a process that makes cells more susceptible to gene mutations and development of hepatocellular carcinoma (HCC). Evaluation of the proliferative index could be a useful tool for identifying patients at risk for HCC. The current study was planned to evaluate hepatocyte proliferation in predominant causes of chronic liver disease in an attempt to investigate predictors of proliferation.Patients and methodsThis study included 84 patients with chronic liver diseases, and they were classified into three groups: chronic hepatitis C (50 patients), non-alcoholic steatohepatitis (NASH) (20 patients) and chronic hepatitis B (14 patients). All cases were investigated by liver function tests, polymerase chain reaction (PCR) hepatitis C virus (HCV) and hepatitis B virus (HBV), routine abdominal ultrasound and liver biopsy with detection of the proliferative index using the monoclonal antibody MIBI-Ki-67.ResultsThe proliferative index was significantly higher in the chronic hepatitis C group than in the chronic hepatitis B group (P value = 0.007). There were significant correlations of the Ki-67 index in both zone 1 and zones 2 and 3 with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and histological activity index (HAI) score. Using the multiple regression analysis on the variables affecting proliferation, it was found that predictors of zone 1 proliferation were the following variables: ALT, age, AST and aetiological factor, in that order.ConclusionHCV aetiology had significantly higher proliferation index, whereas NASH had the least. Increased HAI score is associated with higher proliferative index in either zone 1 or zones 2 and 3. Predictors of proliferation index in zone 1 were ALT, age, AST and aetiological factor.