Ausloos, Floriane MD; Hillaire, Sophie MD, PhD; Bedossa, Pierre MD, PhD; Bert, Fréderic MD, PhD; Moreno, Christophe MD, PhD; Geubel, André MD; Plessier, Aurélie MD; Valla, Dominique MD Author Information

BACKGROUND/AIMS:Idiopathic pancreatitis is considered to be a multigenic and multifactorial disease. Genetically determined pancreatitis is associated with mutations in the PRSS1,SPINK1 and CFTR genes. This study aimed at examining the clinical and morphological characteristics of patients diagnosed with genetically determined sporadic pancreatitis.METHODS:Inclusion criteria were the presence of PRSS1,CFTR or SPINK1 gene mutations in patients with idiopathic recurrent or chronic pancreatitis. Patients with hereditary pancreatitis were excluded. Age- and sex-matched patients with idiopathic pancreatitis and negative genetic testing served as controls (n = 68).RESULTS:Genetic testing was performed in 351 probands referred to our centre since 1999. Sixty-one patients (17.4%) carried at least 1 detected mutation in 1 of the 3 tested genes (34 CFTR, 10 PRSS1 and 13 SPINK1 mutations), and 4 patients showed a combination of mutations. Follow-up has been currently extended to a median of 5 years (range 1-40). Similar clinical features were noted in the case and matched groups except for an earlier age of onset of pancreatic symptoms and a higher incidence of pancreatic cancer in the case group and in patients with CFTR mutations compared to the control group (p < 0.05). The standardized incidence ratio, the ratio of observed to expected pancreatic cancers, averaged 26.5 (95% confidence interval 8.6-61.9). All pancreatic cancer patients were smokers.CONCLUSION:Clinical parameters of patients with sporadic idiopathic pancreatitis and gene mutations are similar to those of age- and sex-matched patients without gene mutations, except for the age of pancreatic disease onset. A significantly higher occurrence of pancreas cancer was observed in the case group, particularly in those patients carrying CFTR mutations. We therefore suggest to include patients with CFTR variants presenting with risk factors in a screening and surveillance programme and to strongly advise them to stop smoking.

Background. Hypoalbuminemia commonly observed in cirrhosis is considered to be mainly related to hepatocellular dysfunction. However, the correlation between the decrease in serum albumin and liver function is far from linear and arguments in favor of an additive role of protein-losing enteropathy have been brought by a few studies. Aim. To assess the potential role of protein-losing enteropathy in a group of patients with cirrhosis, portal hypertension, and hypoalbuminemia. Design and methods. Eleven patients with documented cirrhosis, portal hypertension, and a low serum albumin level compared to liver function underwent an In-111-transferrin scintigraphy. Results. Using this sensitive method of investigation, nine exhibited features suggestive of exudative enteropathy. Serum albumin level and digestive protein loss were even correlated (Pearson's coefficient = -0.529, one-sided p = 0.047). Protein loss were however not correlated with the degree of portal hypertension or with the extent of liver dysfunction evaluated by the aminopyrine breath test. Conclusions. Our preliminary data obtained in a small group of selected patients with cirrhosis, portal hypertension, and hypoalbuminemia indicate that protein-losing enteropathy may represent an appreciable and underestimated cause of hypoproteinemia.

This document analyzes the reasons for organizing an abdominal ultrasound training for Belgian trainees in hepatogastroenterology. The hepatogastroenterology speciality should implement, together with the radiology speciality and the national scientific and professional associations, the minimum training requirements which are proposed by the European Board of Gastroenterology and Hepatology and the European Federation of Societies for Ultrasound in Medicine and Biology. Trainees in hepatogastroenterology should acquire the same theoretical and practical training as radiologists, they should be taught and supervised by competent instructors and have their expertise evaluated.

We report the case of a 41 year old Peruvian pregnant woman who presented at 31 weeks of pregnancy with a disabling cholestatic pruritus of two weeks duration appeared shortly after the initiation of a treatment with a micronized progesterone preparation. She had a previous history of stillbirth at 37 weeks of pregnancy, an occurrence also preceded by pruritus. Withdrawal of the hormonal preparation and the prescription of ursodeoxycholic acid resulted in a prompt clinical and biochemical improvement as well as in a uneventful delivery. Current knowledge about patho-physiology and management of cholestatis of pregnancy is reviewed.

In spite of the fact that severe side effects have been reported, black cohosh [Actaea racemosa (syn. Cimifuga racemosa)] is likely to be one of the most popular herbs used in the treatment of postmenopausal symptoms and menstrual dysfunction. We report the cases of two patients, one with submassive liver necrosis and the other with chronic hepatitis most likely related to the use of two different preparations containing black cohosh. This represents another advice for caution concerning this popular preparation of inconsistent therapeutic value.

Background. IgG4-associated cholangitis (IAC) can mimic primary sclerosing cholangitis although, in contrast to the latter, it is highly responsive to steroid therapy. IAC is known to be associated with autoimmune pancreatitis and has also been shown to be part of a more complex autoimmune IgG4 syndrome. However, an association with inflammatory bowel disease (IBD), a condition in which its identification may have therapeutic and prognostic importance, has not yet been described.Case reports: We report the cases of two H LA identical siblings both DRB*1501 positive exhibiting features of IAC together with ulcerative colitis. Subsequent high resolution HLA typing performed by sequence-based-typing showed similar alleles in both siblings: A*0301 A*3201 B*07 (0702/62) B*1401 C*0702 C*0802 DRB1*1501. There is indirect evidence that this hitherto undescribed association, likely to be strongly linked to a genetic background, might account for a proportion of the cases of cholangitis associated with IBD.Conclusion: Appropriate investigation for I BD-associated cholangitis is mandatory to identify IAC, the recognition of which has particular therapeutic and prognostic implications. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

epithelium using an In Vitro model of the epithelial barrier.Methods: Caco-2 monolayers grown on semipermeable filter supports were stimulated with varying concentrations of endogenous and synthetic glucocorticoids and tight junction function was assessed by measuring transepithelial electrical resistance as well as permeability of fluorophore-coupled tracer compounds.Basic tight junction structure was analyzed by immunofluorescence against ZO-1 and occludin as well as phalloidin staining.Real time rt-PCR was employed to assess transcriptional changes of different claudin genes; in addition, expression of claudin-2 and claudin-4 was analyzed by Western blotting.Results: Upon glucocorticoid stimulation, fully differentiated Caco-2 monolayers exhibited a dose dependent significant increase in transepithelial electrical resistance that could be completely reversed by the glucocorticoid receptor antagonist RU-486.Basic tight junction architecture as assessed by localization of ZO-1 and occludin was not altered upon steroid stimulation.Phalloidin staining of the actin cytoskeleton displayed no alterations in these cells.Using real time rt-PCR, we observed a significant down-regulation of the pore forming tight junction component claudin-2, whereas claudin-4 displayed a significant upregulation upon glucocorticoid stimulation on the RNA level.Western blotting confirmed these results on the protein level.Conclusions: Our data suggest that glucocorticoid signaling regulates intestinal barrier function by controlling claudin expression within the intestinal epithelium.We thereby identified a novel mode of action potentially contributing to the well established anti-inflammatory potency of these compounds.The elucidation of the molecular mechanisms involved in this regulation may not only enhance our understanding of glucocorticoid effects on the intestinal epithelium, but also allow for the validation of novel drug targets aiming to enhance or re-establish intestinal barrier function.

The case of a patient under tibolone therapy for two years who developed a mixed-type liver injury with prolonged cholestasis and features of the vanishing bile duct syndrome following a ten weeks treatment with St. John wort (Hypericum Perforatum) infusions is reported. In the absence of evidence of a potential role for concomitant medication i.e. hydroxychloroquine sulfate to play a role in the clinical, biochemical and morphological picture, an interaction between the herbal preparation and tibolone was suspected as the likely cause of liver damage.

La maladie de Von Recklinghausen ou neurofibromatose de type 1 (NF1) est la plus frequente des phacomatoses (1/3000 naissances) et elle se revele souvent a l'adolescence. La maladie est caracterisee par le developpement de nombreuses tumeurs, principalement des taches « cafe-au-lait », des neurofibromes cutanes, sous-cutanes et profonds. On peut parfois assister a une transformation maligne de neurofibromes profonds. Le risque de survenue de neurofibrosarcome est d'environ 5%. Le cas clinique rapporte ici est celui d'un patient de 16 ans chez qui a ete observe un neurofibrosarcome survenu dans le cadre d'une maladie de Von Recklinghausen. La particularite de cette obser-vation clinique tient a la localisation atypique de la tumeur dans le tube digestif, localisation rapportee une seule fois dans la lit-terature a ce jour (1). Sept ans apres avoir subi une gastrectomie de type Billroth II (BII) realisee dans le cadre du traitement de la formation tumorale intergastro-colique, le patient a presente une hemorragie digestive liee a la survenue d'un ulcere anastomoti-que benin.

The case of a 76-year-old retired surgeon and lover of green tea (camellia sinensis) infusions who developed a clinical, sero-biochemical and histological picture of severe subacute hepatitis is reported. The clinical presentation was that of jaundice with asthenia and weight loss. Abnormal liver function tests were associated with hyper-gammaglobulinemia, and the transient presence of anti-smooth-muscle antibodies and ANCA. Liver histology showed mixed features of lobular hepatitis with central collapses, portal inflammatory cells infiltration and interface hepatitis. All other potential causes of hepatitis were excluded on the basis of clinical, biochemical and serological data. Herbal preparation withdrawal resulted in a slow and continuous improvement with a complete clinical and sero-biochemical resolution after 7 months.

Background/Aims: Surgical resection is a standard treatment of hepatocellular carcinoma, but liver cirrhosis is known to be associated to a high tumor recurrence rate.Methodology: A retrospective study of 55 consecutive patients (37 males, 18 females) suffering from hepatocellular carcinoma having undergone surgical resection. Hepatocellular carcinoma developed in 29 patients with normal liver (group A) and in 26 patients with chronic liver disease (CLD) (group B). Patients were significantly older and at high-risk in Group B.Results: Radical liver resection was achieved in 98% (100% in group A; 96% in group B). Overall 2-month mortality was 2% (0% in group A; 4% in group B). The 5-year overall and disease-free survival was respectively 55% and 35%. However, the 5-year overall and disease-free survival was significantly better in Group A (71% and 59%) compared to Group B (37% and 6%) (p<0.001), respectively. Multivariate statistical analysis demonstrated that age > 50 years, poor tumor differentiation and presence of satellite nodules were significant independent adverse predictive factors of overall and disease-free survival.Conclusions: Resection of HCC is safe and effective with satisfactory overall and disease-free survival rates, except when underlying chronic liver disease and poor tumor differentiation are present.

Cytomegalovirus infection of the gastro-intestinal tract is frequent and may be serious in the immunocompromised patient. We report a case of cytomegalovirus infection in an immunocompetent young man who presented total food intolerance, pleural effusion and oedema as the result of severe protein losing hypertrophic gastropathy. Hypertrophic gastropathy with severe mucosal protein loss has been described in Menetrier's disease, a condition of unknown cause which involves foveolar hyperplasia of the gastric mucosa. Related hypoalbuminemia is responsible for a clinical picture of diffuse edema. In adults, the natural course of the disease is marked by a chronic course and carries a bad prognosis. In our case, the disease ran a protracted disabling course, likely shortened by ganciclovir therapy, followed by slow clinical, endoscopic and biochemical resolution after several' months course.

OBJECTIVES: Hepatic hydrothorax is a rare but challenging complication of cirrhosis. The Transjugular Intrahepatic Portosystemic Shunt (TIPS) appears as one of the most successful approach of therapy. METHODS: To assess long-term efficacy and safety, we reviewed 28 patients (Child B/C: 43/57%) who underwent TIPS placement for refractory hepatic hydrothorax in our institution between 1992 and 2001. RESULTS: The 30-days mortality was 14%, reaching 25% at 90 days. The one-year survival without liver transplantation was 41.2%. Reduction in the volume of pleural effusion and improvement in clinical symptoms was observed in 68% while a complete radiological and echographic disappearance of hydrothorax was documented in 57%. Statistical analysis showed that poor liver function was predictive of mortality and non-response. Of the different liver function parameters and in this small series, the Child-Pugh score was more discriminating than the recently described Mayo risk score. CONCLUSION: This study shows that TIPS is effective in the treatment of hepatic hydrothorax for selected patients. Poor liver function is a strong predictive of bad outcome.