Revising the criteria for the predictors of variceal haemorrhage outcome

Background and study aims: There are many criteria and definitions used to evaluate the failure to control and prevent variceal bleeding. Baveno criteria were developed in Baveno consensus workshops I-III. Some of these criteria are fairly difficult to apply and do not adequately reflect common situations that are observed in clinical practice. Therefore, new criteria were developed at the Baveno-IV workshop. In the present study, we aimed to evaluate the validity of Baveno II-IV criteria in the prediction of bleeding recurrence among patients with liver cirrhosis who presented with bleeding oesophageal varices

Patients and methods: Fifty patients with liver cirrhosis and acute variceal bleeding were divided into two groups according to treatment response. Group I consisted of 44 patients for whom treatment to control bleeding was successful, and Group II included 6 patients for whom treatment failed. Baveno criteria were used in the evaluation of treatment outcome in these patients

Results: The overall accuracy of Baveno II and III criteria was 87.3% within the first 6 h and 76.5% after 6 h, with a mean accuracy 81.9%. The overall accuracy of Baveno IV criteria in this study was 83%. The criterion of death was also very specific [100%], with 100% PPV, but its sensitivity was very low [16.7%]

Conclusion: Baveno IV criteria are less complicated, much easier to apply and have nearly the same accuracy as Baveno II/III criteria. However, there are some criteria that need to be modified, such as the adjusted blood requirement index [ABR1], among others

Association of type 2 diabetes mellitus and glutathione S transferase [GSTM1 and GSTT1] genetic polymorphism

Oxidative stress, arising as a result of an imbalance between free radicals and anti-oxidant defenses, is associated with damage to lipids, proteins and nucleic acids, which could contribute to cellular dysfunctions leading to the pathophysiology of various diseases including atherosclerosis, Lancer and diabetes mellitus. Glutathione S-transferases [GSTs] belong to a group of multigene and multifunctional doioxification enzymes, which defend cells against a wide variety of toxic insults. An important condition affecting GST expression is oxidative stress, usually observed in diabetes. To assess whether the glutathione S-transferase T1 [GSTT1] and M1[GSTM1] genotypes are associated with type 2 diabetes mellitus and to ascertain whether the levels of blood lipids given exposure to diabetes are modified by the specific genetic polymorphisms of GSTT1 and GSTM1. Using a multiplex polymerase chain reaction, GSTT1 and GSTM1 gene polymorphisms were analyzed in 29 patients with type 2 diabetes mellitus compared to 16 healthy age and sex matched control group. The association between genotypes and blood lipids were assessed separately for all the study subjects [type 2 diabetes mellilus group and the control group] with GSTT1 null and also for GSTM1 null compared to GSTT1 present and GSTM1 present genotypes respectively. The proportion of GSTT1 null genotypes was higher in diabetic patients as compared to controls [17.24% versus 6.25%]. No significant difference of the frequency of GSTM1 null was observed between cases and controls [58.6% versus 62.5%]. The GSTT1 present genotype conferred a statistically significant 0.39 fold reduction in risk of type 2 diabetes mellitus relative to the null genotype of the GSTT1 genotype but the GSTM 1 genotype did not differ with respect to their association with risk of type 2 diabetes mellitus. Among individuals with GSTT1 null and GSTM1 null, the serum cholesterol, triglycerides and high density lipoprotein were not significantly different from GSTT1 present or GSTM 1 present genotypes. GSTT1 gene polymorphisms may play an important role in type 2 diabetes mellitus pathogenesis. The potential role of GSTM1 polymorphism as a marker of susceptibility to type 2 diabetes mellitus needs further studies in a larger number of patients. GSTT1 and GSTM1 null genotype do not have an effect on blood lipids

Altered BANKL/OPG system in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy was established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. To evaluate bone mineral density [BMD] and OPG/RANKL system in cirrhotic patients with backache. This study included 50 subjects suffering from backache, divided into 4 groups as follows: Group I: 10 subjects with normal BMD, Group II: 10 patients with pathological BMD but otherwise healthy considered as control, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD. The lowest BMD values are estimated at the lumber spine, femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic/ osteoporotic non cirrhotic patients compared to control group, while it is significantly higher than control in both osteopenic/osteoporotic and patients with normal BMD of cirrhotic groups. RANKL, was significantly higher in non cirrhotic patients with pathological BMD compared to control group, but lower than control in cirrhotic groups both with normal and pathological BMD, with significant difference in cirrhotic with pathological BMD and non significant in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and International Normalized Ratio [INR], but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. In cirrhotic patients, low BMD has tendency to affect axial bone early, which is similar to postmenopausal osteoporosis. On the contrary, higher OPG and lower RANKL levels are opposite to postmenopausal osteoporosis. This difference indicates that: OPG/RANKL system is activated in a different way in cirrhosis, suggesting a role for OPG/RANKL system in pathogenesis of hepatic osteodystrophy

Expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha in hepatocellular carcinoma

To investigate the expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha [HIF-1 alpha] genes in hepatocellular carcinoma and correlate their expression with clinicopathological data. Liver biopsy samples of 30 hepatocellular carcinoma [HCC] subjects. 20 chronic hepatitis C [CHC] and 20 liver biopsy samples from non cancerous tissue [i.e control samples] of HCC were assessed by polymerase chain reaction [RT-PCR] and restriction enzyme analysis for the three genes; wild p53 gene, mutations in p53 at codon 249, exon 7 and hypoxia inducible factor-1 alpha gene. Wild p53 gene was detected in 18/30cases of HCC [60%], 16/20 cases of CHC [80%] and 15/20 cases of control samples [75%] with no significant difference between the studied groups. Mutated p53 gene was detected in 12/30 cases of HCC [40%], 4/20 cases of CHC [20%] and 5/20 cases of control samples [25%], also with no statistically significant difference between the studied groups while HIF-lalpha gene was expressed in 20/30 cases of HCC [66.7%] in comparison to 2/20 cases of CHC [10%] and 3/20 of control samples [15%] with a highly statistically significant difference [p<0.001]. The expression of both wild p53 and the mutated p53 correlated with tumor size but did not correlate with grade of malignancy nor serum alpha fetoprotein level, while the expression of HIF-1 alpha correlated with grade of malignancy and alpha fetoprotein level but not with tumor size. No correlation between expression of all genes and capsule infiltration or presence of cirrhosis was found in all groups. HIF-1 alpha is highly expressed in HCC and is related to grade of malignancy and serum alpha fetoprotein level

Rankl/OPG system is altered in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy has been established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. The Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. In this study we aim to evaluate OPG/RANKL system in cirrhotic patients with backache. This study includes 50 subjects suffering backache, divided into 4 groups as follows: Group I:10 subjects with normal bone mineral density [BMD] as control, Group II: 10 patients with pathological BMD but who are otherwise healthy, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD estimation. The lowest BMD values were estimated at the lumber spine, then femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic non cirrhotic patients compared to the control group, while it was significantly higher than controls in both osteopenic and non osteopenic patients of the cirrhotic groups. SRANKL was significantly higher in non cirrhotic patients with pathological BMD compared to the control group, but lower than controls in cirrhotic groups both with normal and pathological BMD, with a significant difference in cirrhotics with pathological BMD, and a non significant difference in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and INR, but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. OPG/RANKL system plays a role in the pathogenesis of hepatic Osteodystrophy. In cirrhotic patients, low BMD has a tendency to affect axial bone earlier, which is similar to postmenopausal osteoporosis. However in cirrhosis there are higher OPG and lower sRANKL levels which are opposite to postmenopausal osteoporosis. This difference indicates that: either OPG/RANKL system is working in a different way in cirrhosis, which might be due to an increased RANK/RANKL affinity which is not measurable, and consumes part of total RANKL leaving a smaller amount of measurable soluble RANKL to be assessed, which would explain its lower level in serum despite increased osteoporotic changes in bone, or there are other factors associated with this process to make their mechanism of action different than in postmenopausal osteoporosis

Risk factors for development of peripheral neuropathy in type I diabetes mellitus

This study was done to investigate the role of some risk factors for development of peripheral neuropathy in children and young adolescents with type I diabetes mellitus [type I DM]. Diabetic patients were divided into three groups: Group I included 10 diabetic patients with clinically and electrophysiologically evident peripheral neuropathy. Group II included 20 diabetic patients with subcIinicaI peripheral neuropathy evident only by measuring the motor nerve conduction velocity [MCV], and Group III included 30 diabetic patients with neither clinical nor subclinical peripheral neuropathy. The patients included were 33 females and 27 males, their age ranged from 5-20 years. Ten normal healthy individuals of matched age and sex served as a control group [Group IV]. All the studied groups were subjected to full clinical and neurological examination, measuring [MCV] of the common peroneaI and median nerves, estimation of egcosyIated hemoglobin level [HbA1c], assay of erythrocyte superoxide dismutase [SOD] as well as molecular genetic study of the manganese superoxide dismutase [MnSOD] gene polymorphism. Our results showed a significant increase in HbA1c level and a significant decrease' In SOD level as well as MCV of common peroneaI and median nerves in group I and group II as compared with group III and group IV. There were significant negative correlations between HbA1c when compared with SOD and MCV as well as signiticant positive correlations between SOD levels and MCV in all the diabetic groups. The frequencies of Ala allele and the AIa/Ala genotype of the Mn-SOD gene were significantly lower in neuropathic diabetic patients. In contrast, the Val allele and VaWaI genotype were significantly more frequent in neuropathic diabetic patients than in diabetic subjects without peripheral neuropathy

Conclusion: EIectrophysioIogicaI studies should be done in all type-I diabetic patients regardless their age or duration of the disease for early diagnosis and following the progression of diabetic neuropathy before start of clinical manifestations [subcIinicaI peripheral neuropathy]. Poor glycemic control, low levels of the key antioxidant enzyme SOD, and the Val allele with Ala/ VaI genotype of the Mn-SOD gene Were signiticant risk factors for the development of diabetic neuropathy in type 1 diabetic patients which may necessitate appropriate support for enhancing antioxidant supply to act against the rapid onset and progression of diabetic neuropathy, by reducing the excess of oxygen free radicals [OFR] and peroxide

Biological therapy as a natural modality in management of hepatocellular carcinoma

Biological therapy as a natural modality in management of hepatocellular carcinoma ABST: The aim of this study was to evaluate the efficacy of Viscum Fraxini as a biological therapy in the management of hepatocellular carcinoma. Thirty patients with primary hepatocellular carcinoma were subjected to weekly injection of 3 ml of Viscum Fraxini extract. According to the duration of treatment, they were divided into four groups. The impact of the drug on liver enzymes, liver and kidney function tests, blood picture, alpha fetoprotein level, quality of life and tumor size was investigated and compared between the individual groups. The drug significantly affected the quality of life with a considerable improvement of the appetite, increase in sleeping hours and remarkable decrease in pain in right hypochondrium. The drug led to a reduction in alpha fetoprotein level, improved Hb level and RBCs count; and its effect on the tumor size was promising, but not significant. It was concluded that Viscum Fraxini is safe and valuable therapy for the management of hepatocellular carcinoma