Predictors of early re-bleeding and mortality after acute variceal haemorrhage

Oesophageal variceal haemorrhage is a devastating complication of portal hypertension [PHT]. This study was done to determine the risk factors for re-bleeding within 5 days and mortality up to 6 weeks in patients with cirrhosis and acute variceal haemorrhage [AVH]. The study included 100 patients presenting with haematemesis and/or melena due to bleeding varices. All patients were subjected to full clinical assessment, routine laboratory investigations, calculation of the Child-Turcotte-Pugh [CTP] and model for end stage liver disease [MELD] scores, abdominal ultrasound and emergency upper gastrointestinal endoscopy. The patients were followed up since admission and up to 6 weeks for the occurrence of rebleeding [in the first 5 days] and mortality [up to 6 weeks] after the acute attack. The patients were grouped into three groups: Group I: patients who survived more than 6 weeks following endoscopic management and did not rebleed during this period [75 patients]. Group II: patients who died within 6 weeks of AVH [10 patients]. Group III: patients who rebled or died within 5 days of AVH [15 patients]. The mean MELD score was significantly higher in group II [18.29 +/- 0.66] and group III [18.73 +/- 0.89] as compared to group I [12.8 +/- 2.1] [p = 0.001]. Active bleeding at time of endoscopy was present in 8% of group I, 70% of group II and 53.3% of group III and the difference was statistically significant [p = 0.003], while white nipple sign was present in 10.6% of group I, 90% of group II and 73.3% of group III and the difference was statistically significant [p = 0.05]. In conclusion high MELD score [>18], presence of active bleeding or white nipple sign at time of endoscopy are significant predictors for early rebleeding and mortality after AVH

Genetic polymorphism of uridine-diphosphoglucuronosyl transferase 1A7 gene in chronic viral hepatitis and hepatocellular carcinoma

Hepatocellular Carcinoma [HCC] is the most common cause of primary liver neoplasm and the fourth most frequent type of cancer worldwide causing one million deaths per year. Genetic polymorphisms of UDP-glucuronosyltransferases [UGTs], which detoxifies endogenous and environmental carcinogen, have been reported to be associated with HCC. The present study aimed to elucidate the role of UGT1A7 SNP [622 T-C] in the pathogenesis of Hepatocellular Carcinoma [HCC] and whether this polymorphism is associated with elevated bilirubin level or not. This study was conducted on 22 patients with HCC, 25 patients with chronic viral hepatitis B and/ or C and 16 apparently healthy controls. All subjects underwent laboratory tests for Liver and Kidney functions, serological markers [HBV and HCV] and serum AFP as a tumor marker, Genomic DNA from the blood was analyzed for UGT1A7 polymorphism using PCR-RFLP. The prevalence of HCV infection was higher in HCC group compared to other groups. AFP-level significantly increased in HCC than in viral hepatitis and control [p<0.0005]. A statistically significant increase was found in the frequency of risky genotypes [TC, CC] in HCC group as compared to the protective genotype [TT] [P<0.01]. UGT1A7 T allele and C allele were designated as H [high activity] and L [low activity] alleles, respectively. A statistically significant increase was found in frequency of L allele in HCC group [54%] as compared to control group [25%] p=0.03. On the other hand, the H allele showed statistically significant decrease in HCC group [46%] compared to control group [75%] p=0.03. Increase in total bilirubin level in cases harboring UGT 1A7 Polymorphism compared to wild genotype [p<0.01] was observed demonstrating its role in the pathogenesis of hyperbilirubineamia. The UGT1A7 polymorphism was associated with elevated bilirubin level and may play a role in the pathogenesis of HCC

Non-invasive fibrosis seromarkers as a predictor of liver fibrosis in chronic hepatitis C and/or non-alcoholic steatohepatitis

In patients with chronic hepatitis C, the precise stage of hepatic fibrosis is the most important predictor of disease progression and it determines the need for antiviral therapy. Although liver biopsy is acknowledged as the gold standard for evaluating fibrosis, it is occasionally prone to sampling error and complications. We aimed to correlate an index of biochemical markers with histological features of fibrosis to predict hepatic fibrosis in patients with chronic hepatitis C virus, patients with combined hepatitis C virus and non-alcoholic steatohepatitis and those with non-alcoholic steatohepatitis, aiming to reduce the use of the liver biopsy. Out of those attending our out patient clinic for clinical, haematological, biochemical, virological, histological and ultrasonographic assessment prior to interferon therapy for hepatitis C virus, we enrolled 41 patients and grouped them according to histopathological examination of their liver biopsies into: Group I: 21 chronic hepatitis C virus patients as defined by positive 3rd generation ELISA; Group II: 20 patients with combined hepatitis C virus and NASH. We added a third group [Group III] of 15 patients having non alcoholic steatohepatitis as defined clinically, biochemically and through diagnostic percutanous liver biopsy. There were 33 male 23 female patients; 35 [62.5%] of them were from rural areas and 21 [37.5%] were from urban areas; the mean ages were 40.5 +/- 9, 46.6 +/- 7.7 and 42.13 +/- 11.06 in Group I, II and III respectively. Twenty apparently healthy individuals served as the control group. All the patients and the control group were submitted to full clinical history and examination, abdominal ultrasonography, CBC, liver biochemical profile and fibrosis biomarkers [apolipoprotein A1, haptoglobin, alpha2 marcoglobulin, GGT]. Liver biopsy was done for suitable patients after taking a consent and the results of fibrosis seromarkers were compared with the results of liver biopsy using the Metavir scoring system, We also estimated patients' body mass index, fasting and post prandial blood glucose. We excluded patients with other causes of chronic liver disease and co-morbidities that could confound the results of the non-invasive markers adopted, including schistosomiasis which was excluded by serological test. 43% of Group I and 40% of Group II had advanced fibrosis. None of Group III had advanced fibrosis; mild fibrosis was detected in 80% of them. gamma-GT was found positively correlated to the degree of hepatic fibrosis in Groups I, II and III [r = 0.667, 0.656 and 0.121, respectively] with P values of 0.001, 0.002, 0.668, respectively. alpha2 macroglobulin was found to be a reliable predictor of fibrosis [r = 0.30, P = 0.02] with ROC curve [area under the curve = 0.70] best cutoff value 2.55 g/L with sensitivity of 0.80 and specificity of 0.50. The results of haptoglobin were negatively related to the degree of hepatic fibrosis in Group I and II with ROC curve area under the curve of 0.33 and P value of 0.04. Significant direct correlation was seen in Group III [r = 0.55, P = 0.03], so by regression analysis, haptoglobin can be used as a good predictor for fibrosis in Group III [r = 0.54, P=0.04]. Apolipoprotein A1 has negative correlation to the stage of fibrosis in Groups I and II although the results were statistically insignificant. APRI index was found significantly directly correlated to the fibrosis stage and the grade of inflammation of all studied groups [r= 0.57, P< 0.01 and r = 0.36, P< 0.01, respectively] with a best cutoff value of 0.62, with sensitivity of 0.86 and specificity of 0.57. In patients with advanced fibrosis the best cutoff value was found to be 0.72 with sensitivity of 0.94 and specificity of 0.67. Mordified APRI test showed AUC of 0.79 [P<0.01] with a best cutoff value of 0.067 at which sensitivity and specificity were 0.82 and 0.61, respectively. Alpha macroglobulin, haptoglobin, apolipoprotein A1, APRI index and a modified APRI index, were found be significant predictors of hepatic fibrosis and were reprocessed by stepwise logistic regression

Alterations in colonic mucosal lesions in patients with portal hypertension

Portal hypertensive colopathy [PHC] is a clinical entity in liver cirrhosis. The frequency and profile of colonic mucosal lesions of this entity are not well studied. The aim of this study is to evaluate the prevalence of colonic mucosal changes in patients with liver cirrhosis and their clinical significance. Forty patients with post-viral liver cirrhosis and portal hypertension [PHT] underwent upper gastrointestinal endoscopy as well as a full length colonoscopy to detect changes in colonic mucosa. PHC was diagnosed endoscopically by the presence of vascular ectasia, diffuse hyperaemic mucosa and rectal varices. Biopsies were obtained from the recto-sigmoid area as well as from any abnormal mucosal lesions apart from angiodysplastic areas. Diffuse hyperaemia, angiodysplasia and rectal varices were found in 40%, 32.5% and 17.5% of patients while haemorrhoids in 42.5%, respectively. The prevalence of PHC increased with worsening Child-Pugh class, the mere presence of oesophageal varices while platelet count was significantly associated with angiodysplastic lesions only. None of other upper endoscopic features of PHT was significantly related to PHC. Moreover, history of lower gastrointestinal [GI] bleeding was significantly associated with the presence of rectal varices and haemorrhoids. Colonoscopic features of PHC were significantly associated with the histopathological diagnosis revealing 79% sensitivity and 66.6% specificity. Conclusion: PHC is a frequent finding in patients with PHT. Colonoscopic features suggestive of PHC were in concordance with the histopathological evidence. Although the presence of haemorrhoids is not a feature of colopathy, yet it should be considered together with anorectal varices as a cause of lower GI bleeding

Non invasive prediction of varices in Egyptian cirrhotic patients

Cirrhotic patients frequently undergo screening endoscopy for the presence of varices. In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aim was to develop a predictive model using independent risk factors for the presence of varices in the enrolled patients. 200 patients with liver cirrhosis with no history of variceal haemorrhage were subjected to clinical examination; laboratory investigations [CBC, Liver biochemical profile, serum urea and creatinine], modified Child-Pugh score and MELD score were calculated. Abdominal ultrasonography and Doppler study of the portal and splenic veins studying the liver size, the presence of periportal thickening, hepatic veins flow pattern, the splenic longest axis and volume, the presence of ascites and collaterals. Portal vein and splenic vein diameter, patency, cross sectional area, mean flow velocity, blood flow volume congestion index and direction of flow of portal vein were calculated. Platelets count/Splenic diameter ratio and Right liver lobe diameter/ albumin ratio were calculated for all patients. Upper endoscopy was done where oesophageal varices were graded according to modified Thakeb classification. This study revealed that 83% of patients had oesophageal varices; 52% had small sized oesophageal varices and 31% had large sized oesophageal varices. In patients with varices; 12% had biphasic and 22.9% had monophasic hepatic veins flow pattern, with p value of 0.002. Portal vein direction of flow was bidirectional in 22.9% and Hepatofugal in 9.6% with a p value of 0.004. The portal vein velocity of 9.3 +/- 2.3cm/ sec with a p value of <0.001 and the ascites was present in 77% of patients with a p value of 0.005. In patients with large sized varices; shrunken liver was present in 83.1% of patients with a p value of 0.005 and serum albumin <2.5gm/dl with a p value of 0.008. Hepatic veins flow pattern [biphasic and monophasic], portal vein direction of flow [hepatofugal and bidirectional], decreased portal vein velocity and the presence of ascites [moderate and marked] were the significant variables for prediction of presence of varices. Shrunken liver and the low serum albumin were the significant variables for prediction of large varices

Squamous cell carcinoma antigen as a tumor marker in patients with hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is considered the fifth most common cancer in the world. Owing to its increased incidence in the last decade and the expected further increase in the next 2 decades, HCC is arousing great interest. HCC commonly develops on cirrhotic livers and therefore, surveillance programs have been suggested to identify early HCC, at a stage suitable for surgical or interventional therapy and has a better clinical outcome. The only serologic marker used in clinical practice is alpha-fetoprotein [alpha-FP], but its sensitivity is poor. Hence, the investigation of new markers is required. To assess the clinical utility of squamous cell carcinoma antigen [SCCA] as a non invasive marker in the early diagnosis of HCC and whether the association of alpha-FP and SCCA could improves the diagnostic power. This study is conducted on 65 newly diagnosed hepatic focal lesion cases from those attending the Tropical Medicine Department, Cairo University Hospitals [Group I] as well as 20 age and sex matched healthy control subjects [Group II]. Group I was further subdivided into la [49 HCC proved untreated patients] and Ib [16 patients with Cirrhosis only] according to their histopathological findings. All patients were subjected to full history taking, clinical examination, laboratory investigations [including liver function test, hepatitis markers, alpha-FP and SCCA serum levels], triphasic abdominal CT and pathological examination. Group I included 42 males [64.7%] and 23 females [35.3%] with ages ranging between 42-70 years [60.7111.28], of them 16 patients had HBV [24.6%], 37 patients had HCV [56.9%] and 12 patients [18.4%] had mixed HBV and HCV infection. Group I was further subdivided into group la which included 49 HCC proved patients and group Ib which included 16 patients with regeneration nodules [cirrhosis only] according to their histopathologic findings. Group II [control] included 20 age and sex matched healthy subjects. Mean levels of serum alpha-FP and SCCA in group Ia was significantly higher when compared with group Ib [p<0.0005 for both of them]. At a cutoff of serum alpha-FP 200 ng/mL, the sensitivity was 35% and the specificity was 100% while at a cutoff >400ng/mL, the sensitivity decreased to 7.6%. On using the receiver operator curve [ROC], to improve the specificity and sensitivity of alpha-FP and SCCA, the cutoff value of 40ng/ml and 0.55ug/L yielded a sensitivity of 67.2% and 61.2% respectively and specificity of 100% [best cutoff]. When combined sensitivity of them was calculated at the best-chosen cutoff values, sensitivity improved to 87.7% with specificity of 100%.Combined use of alpha-FP and SCCA in the screening of patients with hepatic focal lesions may increase the chance of diagnosis of HCC patients

Study of the enhancing effect of sodium chloride injection on radiofrequency ablation of hepatocellular carcinoma

One of the potential strategies to increase the efficacy of RFA is to modulate the biologic environment of the treated tissues. Several investigators have studied increasing RFA heating by combining intra-tumoral injections of different concentrations of sodium chloride with RFA. The aim of this study is to assess the enhancing effect of normal saline [NS] on radiofrequency ablation [RFA] of hepatocellular carcinoma [HCC] using a cool-tip needle. This study included 40 patients with HCC [proved by histopathology or combined spiral CT and elevated alpha-fetoprotein]. They were randomly divided into two groups [20 patients in each group]. The first group was treated with RFA preceded by intra-tumoral normal saline injection [RFA + S]; the second group was treated with RFA only [RFA]. The procedure was successful in all patients [100%] of the RFA + S group and in 11 [55%] of the RFA group [as proved by spiral CT or pathology]. This difference between the two procedures was statistically highly significant [P = <0.01]. No major complications occurred in either group. Combined RFA and normal saline is more effective than RFA alone. Considering the reduced cost and wide availability of isotonic saline together with the easy performance of the intra-tumoral injection, the dramatic improvement in therapeutic effect of RFA to 100% could be a breakthrough in future strategies to modernize the RFA technique

study of the effect of sodium valproates on brain neurotransmitters GABA and 5HT and its teratogenic effect an experimental study

White albino rats were given sodium valproates 400mg / kgm / day for 21 days in males and till 20th day of gestation in females compared to other group of rats didn't receive any drug. The effect of the drug on rats showed significant elevation of GABA concentrations in all tested brain areas and 5HT in cerebral cortex and midbrain, while reduced 5HT in thalamus and hypothalamus. Maternal adminstration of Sodium Valproates induced non Significant change in the number of resorption and live fetuses, as well as number of implantation. Fetuses revealed spina bifida [30%], absence of angle of mandible and ossific centers in upper and lower limbs [15%] and short neck [15%]. Side effects of sodium Valproates such as sedation and weight gain could be attributed to increase of GABA concentration, whereas increased appetite may be due to decreased 5HT in hypothalamus. The anticonvulsant effect of Sodium Valproates could be due to such increase of GABA and to some extent incease of 5HT