Volume 70 - 2007 - Fasc.3 - Original articles
Insulin resistance and metabolic syndrome in patients with NAFLD but without diabetes : effect of a 6 month regime intervention
Background and study aims : Non-alcoholic fatty liver disease (NAFLD) and the metabolic syndrome are two intertwined diseases sharing the same factor in their pathogenesis ; insulin resistance. The aim of the study was to establish a link between glucose tolerance and NAFLD.
Patients and methods : Fifty-two non-diabetic NAFLD patients were included in the study. Inclusion criteria were elevated alanine aminotransferase (ALT), hyperechogenic liver detected at ultra- sonography, and exclusion of other causes of liver disease. Hepatobiliary ultrasonography and laboratory tests including biochemical and metabolic profiles were performed; HOMA insulin resistance was calculated.
Results : The mean age was 43 years, and 61% were male. More than a two fold increase in alanine aminotransferase levels was seen in 37% of the patients. Serum levels of aspartate aminotrans- ferase, gamma-glutamyl transferase, alkaline phosphatase (ALP) were elevated in 36%, 46%, and 30% of patients respectively. Low HDL-C levels were found in 46% and high LDL-C levels in 25%. Other results of note were elevated lipoprotein-a levels in 40%, impaired fasting glucose in 23%, impaired glucose tolerance in 26%, elevated fasting c-peptide levels in 61%, and elevated fasting serum insulin levels in 11% of patients. In 30% of patients, body mass index was over 30 kg/m2 and 78% had a waist-hip ratio more than 0.9. HOMA insulin resistance was significantly related with elevated ALP levels and hepatomegaly. Following a 6 months treatment with a standard diet, liver enzymes and metabolic parameters both improved. Only 7 patients had persistently high liver enzymes.
Conclusions : Basal insulin levels and the oral glucose tolerance test should be an integral part of the evaluation of patients with NAFLD. The association between NAFLD and metabolic syn- drome as well as the benefits of dieting on preventing progression of NAFLD should be stressed. (Acta gastroenterol. belg., 2007, 70, 253-259).
Association of the prevalence and grade of steatosis in patients with chronic hepatitis C with the host and viral factors
Aim : The aim of this study was to investigate the prevalence of hepatosteatosis in chronic hepatitis C patients, evaluate the poten- tial impact of some host- and virus-related factors on its occur- rence and possible influence of steatosis on the consequences of hepatitis.
Patients and methods : The case records of 387 patients with hepatitis C and cirrhosis were studied. The prevalence and grade of steatosis were investigated and evaluated by logistic regression analysis as dependent variable to age, gender, alcohol consump- tion, body mass index, hepatitis C virus (HCV) genotypes, liver enzymes activity, histological activity index and fibrosis.
Results : Steatosis was found in 47.3% of the patients. It was more prevalent in males, alcohol abusers, overweight and obese patients, and in those with HCV genotypes 3 and 2. Multivariate analysis confirmed body mass index as an independent risk factor for steatosis in the overall patient cohort and in those with geno- type1 without any correlation with the steatosis grade. The preva- lence and grade of steatosis were associated with alcohol con- sumption and higher fibrosis stage. The age of the patients showed converse association.
Conclusions : The male gender, body mass index, alcohol con- sumption, genotype 2 and 3 were confirmed as risk factors for hepatosteatosis. Older patients had a lesser steatosis grade.
The correlation of histological activity index and fibrosis scores with the prevalence and higher grade of steatosis suggested a possibility to worsen the course of hepatitis C and to accelerate disease progression. (Acta gastroenterol. belg., 2007, 70, 260-266
Acute septic cholelithiasic cholecystitis and adenocarcinoma of the gallbladder ; an interesting association
Background and study aims : Primary carcinoma of the gall- bladder may present as acute lithiasic cholecystitis that leads to severe septic complications. The correlation between severe sepsis of the gallbladder and primary carcinoma is unclear. The goal of the present study is to examine the relation between severe septic complications of lithiasic cholecystitis and primary carcinoma of the gallbladder.
Patients and methods : A group of 72 patients (22 males, 50 females, age range : 45-99, mean age : 68.6 years), with severe septic cholelithiasic cholecystitis was treated with emergency surgery after failure of conservative treatment, and patients found with primary carcinoma of the gallbladder were registered. The resectability and operability of the tumor were studied, as well as tumor staging and overall patient survival.
Results : During urgent surgery for severe septic lithiasic chole- cystitis, 12 patients (12/72, 16.6%) were found with gallbladder carcinoma. Patients with septic acute lithiasic cholecystitis and carcinoma had a higher mean age compared to those without carcinoma (74.8 vs. 67.4yrs). Eleven of 12 (91.6%) carcinomas were inoperable, despite resectability of 8 out of 12 (66.6%), and overall patient survival was limited to a few months after surgery.
Conclusions : Severe septic complications in elderly patients with a long-standing history of gallbladder stones may co-exist with primary carcinoma of the gallbladder. The percentage of a gallbladder carcinoma detected in septic patients reaches up to 16.6%. Even if these patients have a poor general health, surgical intervention is a solution when they appear with severe septic clinical symptoms caused by gallstones or carcinoma, in order to avoid lethal sepsis. The possibility of a carcinoma hidden in the gallbladder must be in mind during surgery. Imaging studies before surgery may detect the carcinoma; in most cases carcino- mas are inoperable, although colecystectomy may be performed during surgery. (Acta gastroenterol. belg., 2007, 70, 267-270).
Are humoral factors involved in the colonic mucosal lesion in portal hypertensive rats ?
Aims : With a prehepatic portal hypertensive rat model, we explored the involvement of humoral factors to the occurrence of portal hypertensive colopathy (PHC), another clinical entity besides portal hypertensive gastropathy (PHG) in portal hyper- tension, by investigating the expression of inducible nitric oxide synthase (iNOS), endothelial constitutive NOS (ecNOS), endothe- lin-1 (ET-1), tumour necrosis factor alpha (TNF-a) and vascular endothelial growth factor (VEGF) in the colonic and gastric mucosa.
Methods : Portal hypertension was produced by a two-stage lig- ation of portal vein plus ligation of the left adrenal vein in male Sprague-Dawley rats. Two weeks after complete obstruction of the portal vein, the portal pressure was measured and the expression of iNOS, ecNOS, ET-1, TNF-a and VEGF in the colonic and gas- tric mucosa were detected by RT-PCR and immunohistochemistry methods.
Results : A 1.8fold (P < 0.01) elevation of the portal pressure was detected in the portal hypertensive rats as compared to control. Significantly up-regulation of the mRNA levels of iNOS (P < 0.01), ET-1 (P < 0.05) and TNF-a (P < 0.01), but not ecNOS and VEGF, were detected in the colonic mucosa of portal hypertensive rats compared with control. The mRNA of iNOS, ecNOS, ET-1, TNF-a and VEGF were all significantly increased at varied levels in the gastric mucosa as compared to control (P all < 0.05). No difference of the appearance and localization of immunostaining of iNOS, ecNOS, ET-1, TNF-a and VEGF in the colonic and gastric mucosa were seen between two groups.
Conclusions : These data suggest the involvement of the up- regulation of iNOS, ET-1 and TNF-a in the colonic mucosal lesion of portal hypertensive rats. (Acta gastroenterol. belg., 2007, 70, 271- 276).
Clinical, biochemical and histological correlations in a group of non-drinker subjects with non-alcoholic fatty liver disease
The correlation between biochemistry, imaging-studies and histology is a matter of controversy in non-alcoholic fatty liver disease (NAFLD) and the major pathophysiology of non-alcoholic steatohepatitis (NASH) is still unknown. We aimed to perform a comparative analysis between clinical, biochemical and his- tological variables of NAFLD. One-hundred and five NAFLD patients (F/M : 51/54), were studied, all with no-alcohol intake. The groups were followed-up for six months.
Necroinflammation and fibrosis were more severe in patients with diabetes (p = 0.002, and p = 0.0001, respectively). In compar- ing NAFL to NASH, plasma nitric-oxide and malondialdehyde levels were significantly higher (p = 0.05, for-both), and vitamin-E and-C levels were significantly lower in NASH (p = 0.002, and 0.001, respectively). The serum ferritin levels were higher in NASH patients (p = 0.016). While the ultrasonographic grade was significantly higher, the liver-spleen density gradient was signifi- cantly lower in NASH group (p = 0.017, and 0.005, respectively). Within a six month period, serum ALT levels dropped into the normal range in 23/76 (30.3%) patients and serum ALT in the 6th month correlated significantly with the severity of steatosis, inflammation and fibrosis in initial biopsy(p = 0.023, 0.035, 0.011, respectively).
In conclusion, the probability of severe liver disease is higher in patients with elevated-ALT in NAFLD. Serum ferritin levels have some prognostic significance in liver damage and fibrosis. Overt diabetes is predictive of advanced fibrosis and inflammation. However impaired glucose-tolerance is not. The advice on diet and exercise for six months after diagnosis may be a good strategy in NAFLD. The patients with normal-ALT without hepatomegaly, morbid-obesity and diabetes seem to have a good prognosis, however some of these patients may still require liver biopsy. (Acta gastroenterol. belg., 2007, 70, 277-284).
Expression of Bax protein in gastric carcinomas. A clinicopathological and immunohistochemical study
Background and study aims : Reduced Bax protein expression has been shown to be a negative prognostic factor in patients with breast, ovarian, colorectal, esophageal and pancreatic cancer. Our aim was to immunohistochemically study Bax protein expression in gastric carcinomas and correlate its expression with clinico- pathological parameters and prognosis.
Patients and methods : Immunohistochemistry was performed, using a monoclonal antibody against bax, in paraffin-embedded tumor specimens from 47 cases of gastric cancer.
Results : Positive staining for the Bax protein was found in 20/47 (42.4%) adenocarcinomas examined. Negative Bax protein expres- sion in tumour cells was correlated with lymph node metastasis (P < 0.05), and degree of differentiation (p<0.05). Univariate analysis showed that the variables with a significant negative impact on survival were : high TNM tumour stage, depth of penetration in the gastric wall, lymph node involvement, and Bax protein expression. Multivariate analysis showed that the only variable with an impact on survival was Bax protein expression (p<0.05, Relative Risk : 3.34). Kaplan-Meier curves showed that the 5-year survival was 36.8% in cases with positive compared with 16% in cases with negative Bax protein expression (p=0.0427).
Conclusion : Negative Bax expression in gastric cancer is asso- ciated with de-differentiation, lymph node metastases, and poor clinical prognosis. Bax protein expression might play an important role in the development and phenotypic differentiation of gastric carcinomas and tumor progression. (Acta gastroenterol. belg., 2007, 70, 285-289).