Aldehyde dehydrogenase 2 polymorphism: possibly a predisposing factor to hepatocellular carcinoma in hepatitis C cirrhotics?

Hepatocellular carcinoma [HCC] is considered as a long term multistage disease with multiple genetic alteration. Aldehyde dehydrogenase 2 [ALDH2] polymorphism may modify the risk of HCC. The aim of the present work was to evaluate the role of ALDH2 polymorphism as a predisposing factor for HCC in chronic hepatitis C virus [HCV] infected patients with cirrhosis for early detection. This study included fifty five subjects divided into three groups; twenty chronic hepatitis C patients with cirrhosis [group A], twenty chronic hepatitis C patients with cirrhosis and HCC [group B] and fifteen control subjects [group C]. The included patients were subjected to history taking, clinical examination, abdominal ultrasonography and liver biopsy [whenever possible]. All the subjects enrolled in this study were analysed for ALDH2 gene polymorphism. Genomic DNA prepared from leucocytes were used for polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] technique. In addition, mitöchondrial ALDH activity was estimated in leucocytes. Of all fifty five subjects included in this study, six were heterozygous for ALDH2 gene mutation [ALDH2*1/*2] representing 10.9%, and the others were homozygous for the normal allele [ALDH2*11*1]. Non was detected to have homozygous mutant allele. The distribution among the patients groups was the same; three patients out of twenty in each group were heterozogous for the mutant gene [15%]. All the control subjects had normal homnozygous gene [ALDH2*1/*1]. The two patients' groups showed significantly higher percent of heterozygous mutant; ALDH2*1/*2 [X[2]=11.92,P=0.0027] and lower mitochondrial ALDH activity towards acetaldehyde [F=24.32, P=0.0002] in comparison to control group. However, non significant changes in both parameters were observed between the two patients' groups [P>0.05]. ALDH2 gene mutation could not be considered as a possible predictor for HCC in non alcoholic HCV-cirrhotic patients. However, these data did not exclude completely the relation to HCV infection and/or cirrhosis. Follow-up large scale studies are needed to investigate the exact link between ALDH2 mutation and cancer

Association of CagA and VacA genotypes of helicobacter pylori with gastroduodenal diseases

Helicobacter pylori [H. pylori] infects the majority of the population in developing countries. However, the rate of gastrointestinal complications has no parallel with the infection. In the present study our aim was to detect and type the cagA [cytotoxin associated gene] status and the vacA [vacuolating cytotoxin] genotypes directly from biopsy DNA, and to further define the relationship between H. pylori genotypes and gastroduodenal pathology. Antral gastric biopsies were obtained for molecular analysis and histopathological diagnosis from 105 patients with dyspeptic symptoms undergoing upper gastrointestinal endoscopy. H. pylori DNA, cagA status and vacA s and m types were detected by polymerase chain reaction [PCR]. H. pylori DNA was detected in 100 [95.2%] of gastric biopsy specimens, of those, 43 [43%] were cagA positive and all [100%] were vacA positive. The vacA s2/m2 genotype was the most prevalent [54%] followed by s1/m2 [27%], then s1/m1 [16%] and 3% showed multiple genotypes. We found 90.5% and 75% of cases with peptic ulcer disease [PUD] and gastric adenocarcinoma respectively to be cagA positive in contrast to only 28% of gastritis cases. The vacA s1 allele was the commonest in PUD and gastric adenocarcinoma cases [85.7% and 75% respectively], while the vacA s2 allele was the commonest in gastritis cases [70.7%]. In conclusion, we suggest the possibility of a genotype-phenotype association of H. pylori disease. Determination of cagA status and vacA genotypes may contribute to the potential clinical identification of patients at different levels of risk. We recommend further studies involving other virulence genes

role of prostaglanidin E2 [PGE2] in refractory ascites in patients with hepatic cirrhosis

To determine the effect of the prostaglandin E2 in the pathogenesis of refractory ascites in liver cirrhosis. The study is consisted of three groups. Group I: consisted of twenty patients having liver cirrhosis with refractory ascites. Group II: comprised ten patients having liver cirrhosis with ascites. Group III: included ten normal subjects as controls. All the groups were subjected to thorough history taking and physical examination, routine blood examination, liver function tests, renal function tests including serum urea. creatinine, creatinine clearance, serum sodium and potassium, 24hs urinary sodium and potassium, 24hs urinary volume, estimation of PGE2 in the urine using ELISA technique. liver function tests showed a significant affection in group I, II particularly serum albumin, AIG ratio and prothrombin activity. Renal functions showed deterioration in glomerular filtration rate as shown by creatinine clearance values in group I, II, III. Other parameters, save 24hs urinary potassium levels were found to be statistically significant affected on comparing the three groups. Urinary PGE2 levels showed a statistically significant difference on comparing the three groups. renal prostaglandins play an important role in the preservation of renal function in all situations with known elevation of vasconstriction mediators, as occurs in decompensated liver disease