Volume 72 - 2009 - Fasc.4 - Original articles
Treatment of chronic hepatitis C in patients with human immunodeficiency virus (HIV) with weekly peginterferon alpha-2b plus ribavirin: a multi-centred Belgian study
Background and study aims : In Belgium, 10-15% of patients infected with the human immunodeficiency virus (HIV) are co- infected with hepatitis C virus (HCV). Because of increased inci- dence of antiretroviral drug-related hepatotoxicity and more rapid clinical evolution towards end-stage liver disease, treatment of chronic hepatitis C becomes a priority. We report the results of a multi-centred Belgian study evaluating efficacy and safety of peginterferon alpha-2b plus ribavirin in HIV-HCV co-infected patients without AIDS and without decompensated liver disease.
Patients and methods : Forty-one patients, all genotypes, were screened to participate. Eventually 37 received treatment with peginterferon alpha-2b (1.5 µg/kg/week) plus daily weight-based ribavirin for 52 weeks. About one third of the patients were geno- types 1, 2/3, and genotype 4, most of the latter being of Central African origin. About 56% of the patients had severe fibrosis (Metavir score ?? F3).
Results : Sustained viral response (SVR) at 24 weeks of follow-up was observed in 10/37 (27%) of patients. SVR was higher in geno- type 2/3 compared to genotype 1/4 (46.7% versus 13.6% ; p = 0.06) and in low (F0-F1) versus high (F2-F4) grade fibrosis (p = 0.06). Treatment was withdrawn for side effects in 11/37 patients (30%). One Child A cirrhosis patient at the start of therapy died 7 months after treatment withdrawal as a result of severe haemolytic anaemia.
Conclusions : It can be concluded that weight-based peginterfer- on alpha-2b plus ribavirin can be successful in selected HIV-HCV co-infected patients. Caution should be applied in patients with advanced liver disease. (Acta gastroenterol. belg., 2009, 72, 389-393).
Microalbuminuria in inflammatory bowel diseases using immunoturbidimetry and high-performance liquid chromatography
Background and study aims : To measure urinary albumin excre- tion using immunoturbidimetry (IT) and high-performance liquid chromatography (HPLC) in inflammatory bowel diseases.
Patients and methods : A cross-sectional study was carried out on 60 selected patients with Crohn's disease (CD), 57 with ulcerative colitis (UC) and 22 healthy volunteers, as controls. Urinary albumin excretion was measured by IT and HPLC, and albumin-creatinine ratio was calculated. This ratio was compared in patients with active and inactive CD and UC and in healthy volunteers.
Results: Patients with CD and UC had higher albumin- creatinine ratio compared to controls using both IT and HPLC (p < 0.05). We measured higher albumin-creatinine ratio in patients with active compared to inactive CD (p < 0.05). Albuminuria did not correlate with disease duration of CD or UC, but patients with more extended CD according to the Montreal classification had higher HPLC-albumin-creatinine ratio. In CD, we found a significant correlation between HPLC-albumin- creatinine ratio and some inflammatory markers i.e. white blood cells (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). In UC, there was no significant correlation between HPLC-albumin- creatinine ratio and the above markers of systemic inflammation or activity of UC. Albumin-creatinine ratio measured by HPLC was higher in both active and inactive CD and UC groups than albumin-creatinine ratio measured by IT. Using a receiver operat- ing characteristics curve analysis, in case of HPLC-albumin- creatinine ratio cut-off values of the activity of CD were 2.46 mg/mmol for men, 5.30 mg/mmol for women.
Conclusions : HPLC-urinary albumin-creatinine ratio is associ- ated with the clinical and laboratory disease activity indices in CD, but not in UC. Using HPLC we found a more sensitive method compared to IT to measure albuminuria that would be a sensitive activity marker in CD. (Acta gastroenterol. belg., 2009, 72, 394-401).
Incidence of adult form of autoimmune hepatitis in Valencia (Spain)
Background and study aims : There is little information on the incidence of autoimmune hepatitis (AIH) because on many occa- sions the disease can progress asymptomatically, different diagnos- tic criteria have been proposed during the last 20 years, and many epidemiological studies are based on retrospective clinical series. The aim of this study was to determine the incidence of AIH in the province of Valencia, Spain, during the year 2003.
Patients and Methods : The Services of Gastroenterology of eight acute-care reference hospitals in the province of Valencia, Spain, covering 1,774,736 inhabitants over 14 years of age, participated in a prospective study. All newly diagnosed patients with AIH between January 1, 2003 and December 31, 2003 were eligible. The diagnosis was based on criteria of the International Autoimmune Hepatitis Group revised in 1999.
Results : There were 19 new cases of AIH, 18 females and 1 male [mean (SD) age of 54.3 (11.2) years, range 23-73]. Incidence peaked in the 45-54 year age group. Eighteen cases were classified as AIH type 1 and one case as AIH type 2. The incidence rate of AIH for the year 2003 in people older than 14 years of age was 1.07 new cases per 100,000 inhabitants, with 1.96 cases per 100,000 inhabi- tants in females and 0.12 cases per 100,000 inhabitants in males.
Conclusions : The 2003 annual incidence of AIH in Valencia, Spain, was similar to that reported in other European countries. AIH occurred more frequently in women and in the 45-54 year age group, type 1 being the most common. (Acta gastroenterol. belg., 2009, 72, 402-406).
Expression of claudin-4 and b-catenin in gastric premalignant lesions
Background and study aims : Abnormal expression of claudin-4 and b-catenin play a role in carcinogenesis. The purpose of the present study was to examine claudin-4 and b-catenin expression in normal and precancerous gastric mucosa.
Patients and methods : Endoscopic biopsy specimens [normal gastric mucosa (n = 22), intestinal metaplasia (n = 24), dysplasia (n = 18), Helicobacter pylori (H. pylori)-associated chronic gastritis (n=32) and remnant gastric mucosa (n=18)] obtained from different 114 patients were examined by immunohistochemistry.
Results : Claudin-4 expression was present in 94.4% of dyspla- sia, 87.5% of intestinal metaplasia, 62.5% H. pylori-associated chronic gastritis, and 88.9% remnant gastric mucosa but only 18.2% of normal gastric mucosa biopsies. Decreased expression of b-catenin was present in 27.8% of dysplasia, 8.3% of intestinal metaplasia, 15.6% of H. pylori-associated chronic gastritis, and 22.2% of remnant gastric mucosa biopsies, but was not present in normal gastric mucosa. When compared with normal gastric mucosa, there was a significant difference in claudin-4 expression in all groups (P < 0.05), but a significant difference was detected in dysplasia and remnant gastric mucosa for b-catenin (P < 0.05).
Conclusions : Our results suggest that claudin-4 expression is upregulated in premalignant gastric alterations. (Acta gastro- enterol. belg., 2009, 72, 407-412).
Usefulness of histopathological markers in diagnosing Barrett's intraepithelial neoplasia (dysplasia)
The incidence of oesophageal adenocarcinoma has significantly increased in Europe over the last 30 years. The progression from normal mucosa to adenocarcinoma has been associated with genetic and morphological traits regrouped under the term "intra- epithelial neoplasia" (IEN) according to the Vienna classification. The early detection of such lesions represents the first step in the identification of high-risk patients. The morphological criteria of IEN are the gold standard to identify such patients.
Firstly described by Riddell et al in 1983, IEN is based on mor- phological criteria including both cytological and architectural alterations and is classified into different stages of severity. However, large studies have clearly demonstrated the lack of repro- ducibility, with large inter-individual discrepancies for both dis- crete and severe lesions.
Discrepancies between high grade IEN and adenocarcinoma can be minimized by using the Vienna classification, which groups both of these lesions under the "stage IV".
Discrepancies between low-grade IEN and uncertain lesions remain too important. Erroneous and overstated diagnosis of low grade IEN induces an unnecessary follow-up of patients with obvi- ous psychological and economic consequences. Recent studies have demonstrated that the reading of the slides by 2 to 3 gastrointesti- nal (GI) pathologists significantly decreases interpretation mis- takes.
Because of these interpretation problems, scientists have looked for non-morphological criteria to confirm the pre-cancerous state. The current PubMed literature proposes many putative biomark- ers. However, none of these has been correctly validated in large prospective case-control studies, which hampers their use in clini- cal routine.
DNA quantification by flux cytometry and morphometry repre- sent alternative methods of documenting IEN but these techniques are complex and expensive. The use of the proliferation marker Ki67 needs deep sampling with correct orientation and standard- ized cell counting. P504 S has been studied in Barrett's disease and might be a novel tool. The only promising tool thus far is the over- expression of p53 as shown in prospective studies demonstrating a nice correlation with clinical evolution and is easy to use in clinical routine. (Acta gastroenterol. belg., 2009, 72, 425-432)
