CD44 is a key player in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Cluster of differentiation (CD)44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. We aimed to evaluated the contribution of CD44 to non-alcoholic steatohepatitis (NASH) development and liver injury in mouse models and in patients at various stages of non-alcoholic fatty liver disease (NAFLD) progression. METHODS: The role of CD44 was evaluated in CD44-/- mice and after injections of an αCD44 antibody in wild-type mice challenged with a methionine- and choline-deficient diet (MCDD). In obese patients, hepatic CD44 (n=30 and 5 NASH patients with a second liver biopsy after bariatric surgery) and serum sCD44 (n=64) were evaluated. RESULTS: Liver inflammation (including inflammatory foci number, macrophage and neutrophil infiltration and CCL2/CCR2 levels), liver injury and fibrosis strongly decreased in CD44-/- mice compared to wild-type mice on MCDD. CD44 deficiency enhanced the M2 polarization and strongly decreased the activation of macrophages by lipopolysaccharide (LPS), hepatocyte damage-associated molecular patterns (DAMPs) and saturated fatty acids. Neutralization of CD44 in mice with steatohepatitis strongly decreased the macrophage infiltration and chemokine ligand (CCL)2 expression with a partial correction of liver inflammation and injury. In obese patients, hepatic CD44 was strongly upregulated in NASH patients (p=0.0008) and correlated with NAFLD activity score (NAS) (p=0.001), ballooning (p=0.003), alanine transaminase (p=0.005) and hepatic CCL2 (p<0.001) and macrophage marker CD68 (p<0.001) expression. Correction of NASH was associated with a strong decrease in liver CD44+ cells. Finally, the soluble form of CD44 increased with severe steatosis (p=0.0005) and NASH (p=0.007). CONCLUSION: Human and experimental data suggest that CD44 is a marker and key player of hepatic inflammation and its targeting partially corrects NASH. LAY SUMMARY: Human and experimental data suggest that CD44, a cellular protein mainly expressed in immune cells, is a marker and key player of non-alcoholic steatohepatitis (NASH). Indeed, CD44 enhances the non-alcoholic fatty liver (NAFL) (hepatic steatosis) to NASH progression by regulating hepatic macrophage polarization (pro-inflammatory phenotype) and infiltration (macrophage motility and the MCP1/CCL2/CCR2 system). Targeting CD44 partially corrects NASH, making it a potential therapeutic strategy.

Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis.

Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed well-differentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n=8; STAT3, n=1; and GNAS, n=1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

Primary biliary cirrhosis: proposal for a new simple histological scoring system.

BACKGROUND & AIMS: A simple and reproducible evaluation of non diagnostic histological lesions related to prognosis remains crucial in primary biliary cirrhosis (PBC). Presently there is no satisfactory simple scoring system analysing them reliably. We elaborated a semi-quantitative scoring system that assesses fibrosis, lymphocytic interface hepatitis (LIH) and ductopenia, separately. This study was aimed to evaluate its intra/interobserver reproducibility and its correlation with the main biochemical data. METHODS: Liver biopsies from 33 consecutive newly diagnosed PBC patients were independently analysed by five liver pathologists. Fibrosis was classified into five stages (portal/periportal fibrosis/few septa/numerous septa/cirrhosis) and LIH into four grades. The bile duct ratio (BDR), i.e. ratio of the number of portal tracts with ducts to total number of portal tracts, Ludwig's and Scheuer's stages were evaluated. Intra and interobserver agreements were assessed. Histological results were correlated to the biochemical data. RESULTS: Most patients had an early disease on clinical and biological parameters. The biopsies measured 23 mm on average (range 12 - 40 mm). Intraobserver reproducibility was substantial for fibrosis (κ = 0.68), LIH (κ = 0.69) and BDR (ICC = 0.69). Interobserver agreement for fibrosis was fair with the 5-class system (κ = 0.36), moderate with a 4-class system (κ = 0.56). moderate for LIH (κ = 0.59) and BDR (ICC = 0.50). Ludwig's and Scheuer's staging showed a fair interobserver agreement (κ = 0.32, κ = 0.31 respectively). Our system showed better correlations with biochemistry than Ludwig's and Scheuer's systems did. CONCLUSIONS: This simple scoring system, assessing fibrosis, LIH and BDR separately, has a substantial intraobserver and a moderate interobserver reproducibility. Its prognostic relevance has to be evaluated.

Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of Alcoholic Steatohepatitis.

BACKGROUND: Among its pleiotropic effects, vitamin D may protect the liver from fibrosis and/or inflammation. However, the impact of vitamin D on liver pathology in hepatitis C remains unclear, and very few studies including alcoholic patients with liver pathologies have been performed. Here we compared the levels of 25-OH vitamin D in the blood of alcoholic patients with the occurrence of alcoholic steatohepatitis (ASH) or bridging fibrosis. METHODS: One hundred and one alcoholic patients were included. All the patients received a liver biopsy, and the levels of 25-OH vitamin D were evaluated with the Liaison 25-OH vitamin D assay. Logistic regression analyses were performed to obtain predictive factors of liver histology. RESULTS: Among alcoholic patients, 40.6% presented ASH and 39.6% presented bridging fibrosis. A severe deficiency in 25-OH vitamin D (<10 ng/ml) was seen in 60.4% of patients. This deficiency was frequent in patients with ASH (85.4%) and in those with bridging fibrosis (80%) but was independently associated only with ASH (odds ratio = 8.46 [95% confidence interval 2.05 to 34.89], p = 0.003). CONCLUSIONS: In alcoholic patients, a severe deficiency in 25-OH vitamin D was independently associated with the occurrence of ASH.

Preventive cancer stem cell-based vaccination reduces liver metastasis development in a rat colon carcinoma syngeneic model.

Cancer stem cells (CSCs) represent a minor population of self-renewing cancer cells that fuel tumor growth. As CSCs are generally spared by conventional treatments, this population is likely to be responsible for relapses that are observed in most cancers. In this work, we analyzed the preventive efficiency of a CSC-based vaccine on the development of liver metastasis from colon cancer in a syngeneic rat model. We isolated a CSC-enriched population from the rat PROb colon carcinoma cell line on the basis of the expression of the aldehyde dehydrogenase-1 (ALDH1) marker. Comparative analysis of vaccines containing lysates of PROb or ALDH(high) cells by mass spectrometry identifies four proteins specifically expressed in the CSC subpopulation. The expression of two of them (heat shock protein 27-kDa and aldose reductase) is already known to be associated with treatment resistance and poor prognosis in colon cancer. Preventive intraperitoneal administration of vaccines was then performed before the intrahepatic injection of PROb cancer cells. While no significant difference in tumor occurrence was observed between control and PROb-vaccinated groups, 50% of the CSC-based vaccinated animals became resistant to tumor development. In addition, CSC-based vaccination induced a 99.5% reduction in tumor volume compared to the control group. To our knowledge, this study constitutes the first work analyzing the potential of a CSC-based vaccination to prevent liver metastasis development. Our data demonstrate that a CSC-based vaccine reduces efficiently both tumor volume and occurrence in a rat colon carcinoma syngeneic model.

Core needle versus standard needle for endoscopic ultrasound-guided biopsy of solid pancreatic masses: a randomized crossover study.

BACKGROUND AND STUDY AIMS: A new core biopsy needle for endoscopic ultrasound (EUS)-guided sampling has recently been developed. The aim of this prospective multicenter study was to compare this needle with a standard needle in patients with solid pancreatic masses. PATIENTS AND METHODS: Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included. Each patient had two passes with a standard 22G needle and a single pass with a 22G core needle performed in a randomized order. Samples from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists. The primary endpoint was the accuracy of the detection of malignancy. The reference standard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning, endoscopic or surgical guidance, and/or by clinical follow-up with repeated imaging examinations for at least 12 months. The secondary endpoints were the rate of technical failure and the quality of the cytohistological samples obtained. RESULTS: Of the 80 patients included (49 men; mean age 67.1 ±â€Š11.1), 87.5 % had final malignant diagnoses (adenocarcinoma n = 62, 77.5 %). There was no difference between the needles in diagnostic accuracy (standard needle 92.5 % vs. core needle 90 %; P = 0.68) or technical failure. Both pathologists found the overall sample quality significantly better for the standard needle (expert 1, P = 0.009; expert 2, P = 0.002). CONCLUSIONS: The diagnostic accuracy of EUS sampling for solid pancreatic masses using standard and core needles seems comparable but with a better overall histological sample quality for the former. ClinicalTrial.gov identifier: NCT01479803.

Gastrojejunal Anastomosis Exclusively Using the "NOTES" Technique in Live Pigs: A Feasibility and Reliability Study.

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) could reduce procedure-associated morbidity and mortality. The aim of this study was to determine the feasibility of performing a simple model of gastrojejunal anastomosis in a living porcine model exclusively using NOTES. METHODS: It was a prospective experimental animal study concerning pigs weighing between 25 and 30 kg. Endoscopies were performed using a double-channel gastroscope. A preliminary phase allowed for the development of the technique on 3 animals that were immediately euthanized. The experimental phase included the implementation of a gastrojejunal anastomosis in 9 animals. Antibiotic therapy was continued for 7 days with gradual feeding. Surviving animals were euthanized after 3 weeks. Anastomosis permeability in each animal was confirmed by opacification, endoscopy, and histopathological analysis. The main outcome measurements were the feasibility and animal survival at 3 weeks postsurgery. RESULTS: The entire procedure was performed on 9 animals (4 males and 5 females). Anastomosis required 4.7 ± 1.2 stitches (range 4-7). The average total length of the procedure was 143 ± 50.8 minutes (range 87-225 minutes). One bleeding, 2 suture dehiscences, and a poor stomach incision were the immediate complications endoscopically resolved. At 3 weeks, 5 animals had survived. Three animals died as a result of anastomotic leakage confirmed at necropsy and histopathology. In the surviving animals, histology confirmed permeable anastomoses with collagen scar tissue and continuity of the mucosa and mucosa muscle layers. CONCLUSION: Successful gastrojejunal anastomosis by NOTES is technically feasible but is subject to a learning curve.

Regular coffee but not espresso drinking is protective against fibrosis in a cohort mainly composed of morbidly obese European women with NAFLD undergoing bariatric surgery.

BACKGROUND & AIMS: The aim of this study was to determine the influence of coffee and other caffeinated drinks on liver fibrosis of severely obese European patients. METHODS: A specific questionnaire exploring various types of coffee (regular filtrated coffee and espresso), caffeinated drinks, and chocolate was filled in by 195 severely obese patients. All patients had liver biopsies that were analyzed according to the NASH Clinical Research Network Scoring System. Univariate and multivariate analyses of significant fibrosis were performed. RESULTS: Caffeine came mainly from coffee-containing beverages (77.5%). Regular coffee and espresso were consumed in 30.8% and 50.2% of the patients, respectively. Regular coffee, espresso, and total caffeine consumption was similar between patients with and without NASH. While consumption of espresso, caffeinated soft drinks, and chocolate was similar among patients, with respect to the level of fibrosis, regular coffee consumption was lower in patients with significant fibrosis (F ≥2). According to logistic regression analysis, consumption of regular coffee was an independent protective factor for fibrosis (OR: 0.752 [0.578-0.980], p=0.035) in a model including level of AST (OR: 1.04 [1.004-1.076], p=0.029), presence of NASH (OR: 2.41 [1.007-5.782], p=0.048), presence of the metabolic syndrome (NS), and level of HOMA-IR (NS). Espresso, but not regular coffee consumption was higher in patients with lower HDL cholesterol level, higher triglyceride level, and the metabolic syndrome. CONCLUSIONS: Consumption of regular coffee but not espresso is an independent protective factor for liver fibrosis in severely obese European patients.

GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation.

BACKGROUND & AIMS: Mosaic G-protein alpha-subunit (GNAS)-activating mutations are responsible for the McCune-Albright (MCA) syndrome. This oncogene that activates the adenylate cyclase is also mutated in various tumor types leading to the accumulation of cyclic-AMP. Identification of a hepatocellular adenoma (HCA) in two MCA patients led us to search for GNAS activation in benign and malignant hepatocellular carcinogenesis. METHODS: GNAS mutations were screened by sequencing 164 HCA, 245 hepatocellular carcinoma (HCC), and 17 fibrolamellar carcinomas. Tumors were characterized by quantitative RT-PCR, gene mutation screening and pathological reviewing. The consequences of wild type and mutant GNAS expression were analyzed in hepatocellular cell lines. RESULTS: A somatic GNAS-activating mutation was identified in 5 benign tumors and in 2 HCC. In benign tumors, GNAS mutations were exclusive from HNF1A, CTNNB1, and IL6ST mutations whereas one HCC demonstrated both CTNNB1 and GNAS mutations. Quantitative RT-PCR showed an activation of the IL-6 and interferon pathways in GNAS-mutated tumor tissues. Accordingly, pathological reviewing identified in GNAS-mutated tumors an inflammatory phenotype characterized by fibrosis and STAT3 activation. We further demonstrated in HCC cell lines that GNAS mutant expression induced inflammatory response and STAT3 activation. CONCLUSIONS: We identified for the first time the association between two rare diseases, MCA syndrome and HCA occurrence, but also that somatic GNAS-activating mutations in sporadic benign and malignant liver tumors are characterized by an inflammatory phenotype. These results showed a cross-talk between cyclic-AMP and JAK/STAT pathways in liver tumors and they reinforce the role of STAT3 activation in liver tumorigenesis.

The pig as a preclinical model for intestinal ischemia-reperfusion and transplantation studies.

Small bowel transplantation has become an established procedure for treatment of irreversible intestinal failure. In this procedure, primary ischemia and reperfusion is inevitable and will lead to some level of tissue injury. Both clinical and experimental data demonstrate that events occurring at the time of transplantation, called ischemia reperfusion injury (IRI), may have deleterious short- and long-term effects, manifesting as increased episodes of acute rejection and chronic allograft dysfunction. Recently, the acute phase of IRI has been increasingly viewed as part of the innate immune response to the lack of vascular perfusion and oxygen. Research on intestinal IRI that aims to understand its mechanisms and the means to reduce its impact on morbidity and mortality related to intestinal transplantations is considered important because a link has been suggested between innate immunity, adaptive immune responses and organ regeneration, and thus long-term graft function. This article provides an overview of porcine models commonly used to study intestinal reperfusion injury and to evaluate intestinal transplant protocols. It also updates the current knowledge obtained from this model, establishing the pig as a reference standard in intestinal transplantation research.

Anti-apoptotic pro-survival effect of clotrimazole in a normothermic ischemia reperfusion injury animal model.

BACKGROUND: Increasing evidence suggests that apoptosis plays a critical role in ischemia reperfusion (IR)-mediated liver injury. Clotrimazole (CTZ) is a potent antimycotic drug that also has a free radical scavenger activity. This study investigated the possible anti-apoptotic, pro-survival role of CTZ in hepatic IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into three groups: sham, control, and CTZ-treated (n = 10 each). Control and CTZ-treated animals were subjected to 60 min of normothermic ischemia of the left lateral lobe of the liver followed by 6 h of reperfusion. Animals were then sacrificed, the liver excised, and blood samples collected. RESULTS: CTZ induced a significant increase in expression of anti-apoptotic Bcl-xL protein. Serum levels of aspartate transaminase and alanine transaminase were significantly lower in CTZ-treated animals than in controls. Histopathologically, tissue damage in the form of apoptosis was significantly lower in CTZ-treated animals than in controls. Expression of the activated form of caspase-3 and the cleaved form of its substrate, poly-ADP-ribose polymerase, decreased significantly in the CTZ-treated group compared with controls. CTZ increased the expression of phospho-p 44/42 ERK1/2 and decreased the phosphorylated form of JNK, without affecting p38 MAPK. CONCLUSION: CTZ protects the liver against IR apoptosis in rats through overexpression of the anti-apoptotic protein Bcl-xL. Other pro-survival pathways such as phospho-p 44/42 ERK1/2 kinase are also activated while JNK is down-regulated.

KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications.

BACKGROUND: KRAS and BRAF mutations in primary colorectal tumors (PT) are predictive of nonresponse to anti-epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). The question of primary resistance to anti-EGFR treatment as a result of the presence of KRAS or BRAF mutations only in metastases has been raised but not resolved. METHODS: We analyzed the mutational status of KRAS and BRAF in 64 new patients with mCRC and performed a systematic review of published data from 285 patients. RESULTS: A total of 285 and 95 matched PT/metastases were available for the analysis of the KRAS and the BRAF status, respectively. An identical mutational pattern of KRAS in PT and the matching metastases were reported in all the cases but 14 (5%). In six cases (2%), KRAS was mutated in the PT and wild type in the metastatic site, whereas in eight cases (3%), KRAS was wild type in the PT and mutated in the metastatic site. An identical mutational pattern of BRAF in PT and the matching metastases was reported in all but two cases (3%). In one case (1.5%), BRAF was mutated in the PT and wild type in the metastatic site, whereas in one case (1.5%), BRAF was wild type in the PT and mutated in the metastatic site. CONCLUSIONS: The acquisition by metastases of a KRAS or a BRAF mutation that was not present in the PT is a rare event, occurring in 5% of cases of mCRC. This is not a frequent mechanism of primary resistance to anti-EGFR treatments in mCRC.

Matrix metalloproteinase inhibition protects rat livers from prolonged cold ischemia-warm reperfusion injury.

UNLABELLED: Matrix metalloproteinases (MMPs) have been implicated in the hepatic injury induced after cold ischemia-warm reperfusion (CI-WR), by altering the extracellular matrix (ECM), but their precise role remains unknown. The hepatic MMP expression was evaluated after 2 conditions of CI (4 degrees C for 24 and 42 hours: viable and nonviable livers) followed by different periods of WR, using isolated perfused rat livers. CI-WR induced moderate changes in hepatic MMP transcript levels not influenced by CI duration, whereas gelatinase activities accumulated in liver effluents. Therefore, the protective effect of a new phosphinic MMP inhibitor, RXP409, was tested after prolonged CI. RXP409 (10 microM) was added to the University of Wisconsin solution, and livers were preserved for 42 hours (4 degrees C), then reperfused for 1 hour in Krebs solution (37 degrees C), containing 20% erythrocytes. Liver viability parameters were recorded, and the extent of cell necrosis was evaluated on liver biopsies, using trypan blue nuclear uptake. Treatment with RXP409 significantly improved liver function (transaminase release and bile secretion) and liver injury. In particular, the MMP inhibitor significantly modified the extent of cell death from large clusters of necrotic hepatocytes as found in control livers (2%-60% of liver biopsies; mean, 26% +/- 9%) to isolated necrotic hepatocytes as found in treated livers (0.2%-12%; mean, 3% +/- 2%) (P < 0.05). CONCLUSION: These data demonstrate that MMPs, by altering the ECM, play a major role in liver CI-WR injury leading to extensive hepatocyte necrosis and that their inhibition might prove to be a new strategy in improving preservation solutions.

Bariatric surgery can correct iron depletion in morbidly obese women: a link with chronic inflammation.

BACKGROUND: Obesity is associated with a chronic and low-grade inflammation which may cause hypoferremia as seen in patients with chronic inflammatory diseases. The aim of the present study was to investigate the relationship between iron status and markers of inflammation in morbidly obese women and the effect of bariatric surgery. METHODS: Our cohort of patients consisted of 178 morbidly obese females selected for bariatric surgery. Clinical and biochemical data were recorded before surgery, and histopathological studies were carried out on preoperative liver biopsy samples. Fifty-five patients have been followed up after bariatric surgery. RESULTS: A high prevalence of iron depletion was present in this cohort, with 53% having a transferrin saturation ratio below 0.20. Iron depletion was significantly correlated with raised levels of indices of inflammation, C-reactive protein (CRP), orosomucoid and haptoglobin), and with the white blood cell count. In multivariate analysis, orosomucoid and CRP were independently associated with iron depletion. Moreover, 6 months after bariatric surgery, inflammation level decreased, which was inversely correlated with the increase in transferrin saturation. CONCLUSIONS: Iron depletion is common in morbidly obese women. Low-grade chronic inflammation associated with obesity could be a modulator of iron uptake and utilization. Bariatric surgery may reduce chronic inflammation and improve iron status.

Glucose intolerance and hypoadiponectinemia are already present in lean patients with chronic hepatitis C infected with genotype non-3 viruses.

OBJECTIVES: Steatosis and metabolic abnormalities seem to be frequent and deleterious in chronic hepatitis C. Changes in glucose homeostasis and in adiponectin levels, an adipokine with anti-inflammatory and insulin-sensitive properties, were evaluated in patients with chronic hepatitis C according to steatosis, liver fibrosis and body mass index. METHODS: Seventy-three patients with chronic hepatitis C (40 men, 33 women) infected with genotypes non-3 and 22 healthy controls (11 men and 11 women) were included in the study and all had a biochemical evaluation, including metabolic parameters, adiponectin measurement, and a liver biopsy. Insulin sensitivity was assessed with the HOMA 1-IR insulin resistance model. RESULTS: Steatosis was found in 65.7% of the patients and significant fibrosis (METAVIR F2-F4) was present in 28.7%. The presence of steatosis could only be predicted by fibrosis, whereas significant fibrosis could be predicted by steatosis and age. Adiponectin levels were significantly decreased (-32%) with the severity of the steatosis. Although overweight chronic hepatitis C patients (body mass index>or=25 kg/m2) had insulin resistance and hypoadiponectinemia, lean chronic hepatitis C patients (body mass index<25 kg/m2) had already significantly higher glycemia and lower adiponectin levels than in controls. CONCLUSIONS: This study confirms the high incidence of steatosis in patients infected by hepatitis C virus genotypes non-3, well linked to the development of fibrosis and metabolic abnormalities. Importantly, the present findings put emphasis on the early development of these metabolic abnormalities as they were already found in lean patients with chronic hepatitis C. The direct implication of hepatitis C virus is thus further stressed in the development of steatosis and insulin resistance, with or without involvement of host factors.

[Intestinal transplantation]. / La greffe intestinale.

Even though surgical techniques for isolated intestine, liver-intestine, and multivisceral transplantations were developed in the 1960's, very few patients were transplanted before 1990 because initial immunosuppression regimens were insufficient, making intestine transplantation impossible. Intestine transplantation resulted in death in most patients within days or months. The discouraging results of the first clinical trials were due to technical complications, sepsis, and the failure of conventional immunosuppression to control rejection. By 1990 the development of tacrolimus-based immunosuppression and improved surgical techniques, the increased array of potent immunosuppressive medications, infection prophylaxis, and suitable patient selection helped improve actuarial graft and patient survival rates for all types of intestine transplantation. The aims of this review are to describe the current status of intestine transplantation including the underlying diseases and conditions that may be indications for intestine transplantation, to identify patient populations for this indication, to provide key steps for patient evaluation, to summarize current recommendations for immunosuppression, to list the most common postoperative complications, and to discuss the international experience of small bowel transplantation compiled and analyzed by the International Intestine Transplant Registry since 1985.

Hepatitis C awareness among adolescents in the Alpes-Maritimes area of France.

OBJECTIVES: Certain practices with a potential risk of hepatitis C virus (HCV) transmission begin early, during adolescence. In 2004, primary prevention interventions targeting adolescents aged 13-17 years attending school in the Alpes-Maritimes region of France were conducted by the "Réseau Hépatite C Ville Hôpital Côte d'Azur". The aim of this study was to assess the adolescents' knowledge about HCV and to evaluate the impact of such interventions. METHODS: A random sample of secondary state schools in the Alpes-Maritimes was invited to participate in the study. Before and after presenting a slide show about HCV in the selected classrooms, the investigators asked the students to complete an anonymous self-administered questionnaire designed to assess their knowledge about HCV infection. RESULTS: The intervention concerned a study population of 2,946 students, mean age 14.4 +/- 2.5 years. Before the interventions, 21% had good knowledge of HCV infection and 24% had good know-ledge of disease contagion. These percentages increased significantly after the interventions to 95% and 84% respectively. Knowledge improvement was more significant among high school students and among students whose parents had an employment. CONCLUSIONS: Adolescents are poorly informed about HCV infection. The present intervention enabled significant improvement in their knowledge about the infection and disease contagion, independently of gender, age and geographical area.

Atypical MRI features of a biliary cystadenoma revealed by jaundice.

We report on the case of a patient admitted for epigastric pain. An abdominal ultrasound revealed a voluminous cystic lesion of the left hepatic lobe. In magnetic resonance imaging, the mass had a liquid-liquid level that was spontaneously hyperintense on T(1)-weighted images and hypointense on T(2)-weighted images. Magnetic resonance cholangiography identified bilateral intrahepatic bile duct dilatation. A left hepatectomy finally revealed a mucinous cystadenoma with pseudo-ovarian stroma that had a pedunculated intraductal extension to the biliary convergence.