Discontinuation of immunosuppression in patients with immune-mediated drug-induced liver injury or idiopathic autoimmune hepatitis: A case-control study.

Background and Aim: Drug-induced liver injury (DILI) may present with autoimmune features and require immunosuppressive therapy (IST) to reach biochemical response. Discontinuation of IST without hepatitis relapse may be more frequent in these patients as compared to patients with classical autoimmune hepatitis (AIH). We aimed to determine baseline characteristics and outcome of patients with immune-mediated drug induced liver injury (IMDILI) with particular emphasis on IST during follow-up. Methods: We performed a single-center retrospective study of consecutive patients presenting at a tertiary care center between January 2005 and December 2019 either with IMDILI or with classical AIH, for whom full baseline characteristics and a close follow-up were available over a 12-month period. Results: Overall, 31 patients (IMDILI n = 16, mean age 59 [34-74] years; AIH n = 15, mean age 47 [15-61] years) were included, showing similar biochemical, serological, and histological characteristics. Incriminating drugs in IMDILI patients were mostly represented by nonsteroidal antiinflammatory drugs and sartans. Initial corticosteroids combined with IST led to biochemical response in all patients. Compared to idiopathic AIH, more patients with IMDILI were weaned off corticosteroids at the end of follow-up (11/16 [68.7%] vs 4/15 [26.6%], P < 0.02). At 1 year of follow-up, more patients in the IMDILI group compared to the classical AIH group were off any type of IST (13/16 [81%] vs 15/15 [100%], P = 0.08). Conclusions: Although presenting with similar baseline biochemical and histological characteristics as idiopathic AIH, patients with IMDILI may not require long-term IST.

High prevalence of cholestasis, with increased conjugated bile acids in inflammatory bowel diseases patients.

AIM: To investigate the prevalence and causes of cholestasis in patients with inflammatory bowel diseases in the Swiss Inflammatory Bowel Diseases Cohort. METHODS: A retrospective cohort study was performed of all the patients in the Swiss Inflammatory bowel disease Cohort. Total bile acid was measured for all patients and cholestasis was defined as a concentration > 8 µmol/L. The characteristics of patients with or without cholestasis were compared. Bile acid profiles were then determined for 80 patients with high total bile acid and 80 matched patients with low total bile acid. Bile acid profiles were compared for smokers vs nonsmokers, ileal vs colonic disease, and inflammatory vs non inflammatory diseases. RESULTS: Ninety-six patients had more than 8 µmol/L total bile acid, giving a prevalence of 7.15%. Patients with an obvious cause of cholestasis, such as primary sclerosing cholangitis, were then excluded, leaving 1190 participants with total bile acid < 8 µmol/L and 80 with total bile acid > 8 µmol/L. In multivariate analysis, calcium supplementation was significantly associated with cholestasis (odds ratio, 2.36, 95%CI: 1.00-5.21, P = 0.040) whereas current smoking significantly reduced the risk of cholestasis (odds ratio, 0.42, 95%CI: 0.17-0.91, P = 0.041). Levels of all conjugated bile acids were higher in the cholestasis group than in the control group. When we compared patients with ileal vs colonic disease, the former had higher levels of primary, secondary, and tertiary bile acids whereas patients with colonic disease had higher levels of conjugated bile acids. CONCLUSION: Prevalence of cholestasis is high. Smoking appears to reduce cholestasis. Conjugated bile acids are higher in cholestasis and in colonic disease whereas unconjugated in ileal disease.

Alcoholic liver disease in Nepal: identifying homemade alcohol as a culprit.

BACKGROUND: Though the type of alcohol consumed is not thought to be associated with alcoholic liver disease (ALD), some studies have shown a beverage-specific effect. In the present study, we aim to study the effects of locally brewed alcoholic beverages on the development of liver disease. PATIENTS AND METHODS: This cross-sectional study was conducted at the internal medicine department of a university hospital in Nepal. All patients classified as having either alcohol abuse or alcohol dependence by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition were evaluated for the presence of ALD. RESULTS: A total of 1,500 patients were screened, of which, 447 patients had ALD. Chronic liver disease (CLD) was detected in 144 patients (9.6%). Most of the patients consumed homemade locally brewed alcohol. On multivariate analysis, the following variables were found to be significantly associated with CLD: male sex (odds ratio [OR]: 1.81; 95% confidence interval [CI]: 1.12-2.94; P=0.02): rakshi consumption ≥30 units (OR: 2.53; 95% CI: 1.07-6.01; P=0.04); and tongba consumption (OR: 3.02; 95% CI: 1.22-7.50; P=0.02). CONCLUSION: There was a significant increase in the risk of developing ALD with the consumption of rakshi and tongba after adjusting for total units consumed. The absence of striking differences between our patients with CLD and non-CLD patients with regards to the amount of alcohol consumed demonstrates that, although alcohol consumption is a prerequisite for the development of ALD, other factors like type of alcoholic beverage consumed may be involved.

Hepatic cell proliferation plays a pivotal role in the prognosis of alcoholic hepatitis.

BACKGROUND & AIMS: The role of liver progenitor cell (LPC) expansion, known as a marker of disease severity, as well as the impact of macrophage activation on liver regeneration remains unclear in humans. We aimed to characterize the LPC and macrophage compartments in alcoholic hepatitis (AH), as well as gene expression patterns to identify predictors of a good prognosis in this setting. METHODS: Immunohistochemical studies for macrophages, proliferative hepatocytes, total and proliferative LPC, as well as whole liver microarray gene expression were performed on baseline liver biopsies of 58 AH patients early after admission. Abstinent cirrhotic patients were used as controls. Patients were qualified as "improvers" or "non-improvers" based on the change in MELD score three months after baseline. RESULTS: Compared to controls, AH patients demonstrated a significant expansion of macrophages, invasion of LPC and a higher number of proliferating hepatocytes and LPC. In AH patients, total LPC expansion (total Keratin7(+) cells) was associated with liver disease severity. The group of improvers (n=34) was characterized at baseline by a higher number of proliferating hepatocytes, proliferative LPC (double Keratin7(+)Ki67(+) cells) and liver macrophages as compared to non-improvers (n=24), despite similar clinical and biological variables. Upregulated genes in improvers were associated with cell cycle mitosis together with a major expression of SPINK1. CONCLUSIONS: Higher liver macrophage expansion, increased proliferative hepatocyte but also LPC number, as well as an upregulation of cell proliferation-related genes are associated with a favourable outcome. These new findings open novel therapeutic targets in AH.

Use of glasgow-blatchford bleeding score reduces hospital stay duration and costs for patients with low-risk upper GI bleeding.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal (UGI) bleeding is a frequent cause of hospitalization. Its severity may be assessed before endoscopy using the Glasgow-Blatchford Bleeding Score (GBS), a score validated to identify patients requiring clinical intervention. The aim of this study was to assess whether the GBS was effective for shortening hospital stay and reducing costs in patients with an UGI bleeding predicted at low risk of requiring clinical intervention. PATIENTS AND METHODS: Consecutive outpatients presenting with UGI bleeding at our hospital were prospectively included. In the observational study phase, UGI endoscopy was performed in all patients according to routine clinical practice. In the interventional study phase, patients with a GBS of 0 were discharged with an appointment for an outpatient UGI endoscopy. All patients had follow-up at 7 and 30 days. Need for clinical intervention was defined as performance of endoscopic hemostasis, blood transfusion or surgery. Results Two-hundred and eight patients were included, 104 in each study phase; complete follow-up was obtained in 201 patients. GBS varied from 0 to 18, with 15 (14 %) and 11 (11 %) patients having a GBS of 0 in the observational and interventional study phase, respectively. For patients with a GBS of 0, hospital stay was shorter (6 versus 19 h, P < 0.01), and costs were lower (845 EUR versus 1272 EUR, P = 0.002) in the interventional versus the observational study phase. For patients with a GBS > 0, hospital stay duration did not significantly differ between study phases (189 versus 207 h, P = 0.726). No adverse event was observed in the patients sent home with a GBS of 0 during the interventional study phase. Conclusions Implementing the GBS as a tool for triage of hospital outpatients who present with UGI bleeding allowed us to identify those who could safely be discharged for ambulatory management. Implementing this change in the hospital strategy significantly shortened hospital stay and decreased management costs.

The role of transient elastography in the detection of liver disease in patients with chronic pancreatitis.

BACKGROUND & AIMS: Quantification of liver stiffness with transient elastography (TE) is validated for staging hepatic fibrosis in chronic hepatitis C infection. The current study was aimed to assess the diagnostic performance of liver stiffness measurement for the determination of fibrosis stage in patients with chronic pancreatitis. METHODS: Thirty consecutive patients with chronic pancreatitis and increased liver enzyme were enrolled over a 2.5-year period. Eight liver living donor candidates were recruited to serve as internal controls. The TE values were compared with non-invasive fibrosis scoring systems including aspartate transaminase (AST)/alanine aminotransferase (ALT) ratio, APRI, non-alcoholic fatty liver disease NAFLD score, FIB-4 index and to liver histology. RESULTS: TE was successful in all patients. Stiffness values ranged from 3.1 to 69 kPa (mean 16.9). Liver stiffness was correlated with fibrosis stage (Spearman's correlation 0.73, P < 0.0001). Areas under receiver operator characteristics curves for fibrosis F = 4 were 0.92 for TE, 0.87 for FIB-4 index, 0.81 for APRI, 0.73 for NAFLD score and 0.71 for AST/ALT ratio. Optimal stiffness cut-off values for diagnosis fibrosis F = 4 was 10.9 kPa, with 90% sensitivity, 85% specificity and 86% accuracy. CONCLUSION: Our study provides for the first time evidence that liver stiffness in patients with chronic pancreatitis and concomitant cholestasis can be measured by TE.

Good long-term outcome of Budd-Chiari syndrome with a step-wise management.

UNLABELLED: Budd-Chiari syndrome (BCS) is a rare, life-threatening disease caused by obstruction of hepatic venous outflow. The aim of the study was to assess long-term outcome and identify prognostic factors in BCS patients managed by a step-wise approach using anticoagulation, angioplasty/thrombolysis, transjugular intrahepatic portosystemic shunting (TIPS), and orthotopic liver transplantation (OLT). We reviewed long-term data on 157 patients previously included by the European Network for Vascular Disorders of the Liver, a multicenter prospective study of newly diagnosed BCS patients in nine European countries. Patients were followed for a median of 50 months (range, 0.1-74.0). During the study, 88 patients (56%) received at least one invasive intervention (22 patients angioplasty/thrombolysis, 62 TIPS, and 20 OLT) and 36 (22.9%) died. Most interventions and/or deaths occurred in the first 2 years after diagnosis. The Rotterdam score was excellent in predicting intervention-free survival, and no other variable could significantly improve its prognostic ability. Moreover, BCS-TIPS prognostic index (PI) score (based on international normalized ratio, bilirubin, and age) was strongly associated with survival and had a discriminative capacity, which was superior to the Rotterdam score. CONCLUSIONS: The current study confirms, in a large cohort of patients with BCS recruited over a short period, that a step-wise treatment approach provides good long-term survival. In addition, the study validates the Rotterdam score for predicting intervention-free survival and the BCS-TIPS PI score for predicting survival.

Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD). We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT) improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy) were randomized early after hospital admission to standard medical therapy (SMT) alone (n = 30), including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28). Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC) compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64%) from the BMMCT group and 18 patients (53%) from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4) in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001), and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively). CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN83972743.

The alcohol use disorders identification test (AUDIT): validation of a Nepali version for the detection of alcohol use disorders and hazardous drinking in medical settings.

BACKGROUND: Alcohol problems are a major health issue in Nepal and remain under diagnosed. Increase in consumption are due to many factors, including advertising, pricing and availability, but accurate information is lacking on the prevalence of current alcohol use disorders. The AUDIT (Alcohol Use Disorder Identification Test) questionnaire developed by WHO identifies individuals along the full spectrum of alcohol misuse and hence provides an opportunity for early intervention in non-specialty settings. This study aims to validate a Nepali version of AUDIT among patients attending a university hospital and assess the prevalence of alcohol use disorders along the full spectrum of alcohol misuse. METHODS: This cross-sectional study was conducted in patients attending the medicine out-patient department of a university hospital. DSM-IV diagnostic categories (alcohol abuse and alcohol dependence) were used as the gold standard to calculate the diagnostic parameters of the AUDIT. Hazardous drinking was defined as self reported consumption of ≥21 standard drink units per week for males and ≥14 standard drink units per week for females. RESULTS: A total of 1068 individuals successfully completed the study. According to DSM-IV, drinkers were classified as follows: No alcohol problem (n=562; 59.5%), alcohol abusers (n= 78; 8.3%) and alcohol dependent (n=304; 32.2%). The prevalence of hazardous drinker was 67.1%. The Nepali version of AUDIT is a reliable and valid screening tool to identify individuals with alcohol use disorders in the Nepalese population. AUDIT showed a good capacity to discriminate dependent patients (with AUDIT ≥11 for both the gender) and hazardous drinkers (with AUDIT ≥5 for males and ≥4 for females). For alcohol dependence/abuse the cut off values was ≥9 for both males and females. CONCLUSION: The AUDIT questionnaire is a good screening instrument for detecting alcohol use disorders in patients attending a university hospital. This study also reveals a very high prevalence of alcohol use disorders in Nepal.

Age, smoking and overweight contribute to the development of intestinal metaplasia of the cardia.

AIM: To assess the role of Helicobacter pylori (H. pylori), gastroesophageal reflux disease (GERD), age, smoking and body weight on the development of intestinal metaplasia of the gastric cardia (IMC). METHODS: Two hundred and seventeen patients scheduled for esophagogastroduodenoscopy were enrolled in this study. Endoscopic biopsies from the esophagus, gastroesophageal junction and stomach were evaluated for inflammation, the presence of H. pylori and intestinal metaplasia. The correlation of these factors with the presence of IMC was assessed using logistic regression. RESULTS: IMC was observed in 42% of the patients. Patient age, smoking habit and body mass index (BMI) were found as potential contributors to IMC. The risk of developing IMC can be predicted in theory by combining these factors according to the following formula: Risk of IMC = a + s - 2B where a = 2,…6 decade of age, s = 0 for non-smokers or ex-smokers, 1 for < 10 cigarettes/d, 2 for > 10 cigarettes/d and B = 0 for BMI < 25 kg/m² (BMI < 27 kg/m² in females), 1 for BMI > 25 kg/m² (BMI > 27 kg/m² in females). Among potential factors associated with IMC, H. pylori had borderline significance (P = 0.07), while GERD showed no significance. CONCLUSION: Age, smoking and BMI are potential factors associated with IMC, while H. pylori and GERD show no significant association. IMC can be predicted in theory by logistic regression analysis.

Transjugular intravascular ultrasound for the evaluation of hepatic vasculature and parenchyma in patients with chronic liver disease.

BACKGROUND: The evaluation of the hepatic parenchyma in patients with chronic liver disease is important to assess the extension, localization and relationship with adjacent anatomical structures of possible lesions. This is usually performed with conventional abdominal ultrasound, CT-scan or magnetic resonance imaging. In this context, the feasibility and the safety of intravascular ultrasound in the liver have not been assessed yet. METHODS: We tested the safety and performance of an intracardiac echography (ICE) catheter applied by a transjugular approach into the hepatic veins in patients with chronic liver disease undergoing hepatic hemodynamic measurements. RESULTS: Five patients were enrolled in this pilot study. The insertion of the ICE catheter was possible into the right and middle, but not into the left hepatic vein. The position of the ICE was followed using fluoroscopy and external conventional ultrasound. Accurate imaging of focal hepatic parenchymal lesions, Doppler ultrasound of surrounding blood vessels and assessment of liver surface and ascites were achieved without complications. CONCLUSIONS: This study demonstrated that a diagnostic approach using an ICE device inserted in the hepatic veins is feasible, safe and well tolerated. However, it remains for the moment only an experimental investigative tool. Whether ICE adds further information regarding parenchymal lesions and associated vascular alterations as compared to other techniques, needs additional investigation.

A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis.

BACKGROUND: Hepatic encephalopathy (HE) is a frequent and severe complication of cirrhosis. A single determination of ammonia in venous blood correlates poorly with neurological symptoms. Thus, a better biological marker is needed. AIM: To make a diagnosis of HE, we explored the value of ammonia in capillary blood, an equivalent to arterial blood, measured at bedside following an oral glutamine challenge. METHODS: We included 57 patients (age 56 yrs; M/F: 37/20) with cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and previous episodes of HE (n = 19), but without neurological deficits at time of examination, and 13 healthy controls (age 54 yrs). After psychometric tests and capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30'). Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric tests. Follow-up lasted 12 months. RESULTS: The test was well tolerated (nausea = 1; dizziness = 1). Patients showed higher values of capillary blood ammonia over time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78 umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38 patients (67%) met the criteria for HE at 60 minutes (chi2: p < 0.01). For the diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%) developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12 [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary blood ammonia, were independent predictors of event. CONCLUSIONS: In patients with cirrhosis and normal neurological examination, bedside determination of ammonia in capillary blood following oral glutamine load is well tolerated and achieves a better diagnostic performance for minimal HE than basal capillary ammonia levels. However, capillary blood ammonia is a poor predictor of development of clinically overt HE.

Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis.

BACKGROUND: Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear. METHODS: We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model. RESULTS: 43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001). CONCLUSIONS: In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.

[Gut microflora in liver and intestinal diseases: a revolution in the making]. / Le microbiote dans les maladies du foie et du tube digestif: la révolution annoncée.

After the era of classical bacteriology, the exploratory techniques of the gut microbiota have been revolutionized by the sequencing of microbial 16S rRNA. The data obtained are substantial and have led us to formulate novel hypotheses in multiple domains of medicine. This article briefly outlines these hypotheses with particular regard to the fields of steatohepatitis and inflammatory bowel diseases.

Primary aortodigestive fistula: a rare and potentially lethal cause of gastrointestinal hemorrhage.

Primary aortodigestive fistulas (PAFs) are a rare cause of gastrointestinal bleeding, with an incidence of 0.04-0.07% in autopsy series. The diagnosis of PAF is difficult and should be considered in patients with gastrointestinal hemorrhage of obscure origin. Because of its high mortality rate, clinical recognition of prodromal symptoms for early diagnosis is crucial for effective treatment. We report on the case of a 79-year-old patient with a PAF who was admitted for hematochezia and melena. The PAF was suspected during upper gastrointestinal endoscopy and confirmed by CT angiography.

[High frequency of cutaneous adverse effects under infliximab. Geneva experience, 1999-2008]. / Fréquence elevée d'effets secondaires cutanés sous infliximab. Expérience a Genève, 1999-2008.

Geneva experience, 1999-2008 Infliximab has been used for 10 years in the treatment of chronic inflammatory bowel diseases in the gastroenterology and hepatology department at the University Hospitals of Geneva. This retrospective study shows the follow-up of these patients treated with infliximab and reveals a high rate of cutaneous adverse events, which, although often mild, can sign a definitive intolerance to treatment.

A step further in the analysis of human bile proteome.

Bile was shown to collect proteins known as potential cancer biomarkers. Thorough proteomic analysis of bile is of particular interest to search for new, more sensitive and more specific, biomarkers of cancers affecting the biliary tract and surrounding organs, such as the pancreas and the liver. Therefore, extending the knowledge of the bile proteome is highly relevant, but this has proved technically difficult. In this study, we describe a strategy that circumvents problems related to the biochemical complexity of this sample and the presence of high concentrations of interfering substances. Bile collected from a patient suffering from a biliary stenosis caused by a pancreatic adenocarcinoma was fractionated by a differential centrifugation scheme, involving a stepwise increase in centrifugation speeds. Pellets and the final supernatant were further fractionated by polyacrylamide gel electrophoresis and proteins were in-gel digested prior to LC-MS/MS analysis. This approach allowed the identification of 445 unique proteins with at least two peptides (812 proteins if single-hit proteins were included), which represents a 3-fold increase in the knowledge of bile proteome. The subsequent literature comparison revealed that numerous biliary proteins identified in this sample were related to pancreas cancer. Immunoblot analysis of some known tumor markers revealed that they were preferentially associated with the soluble fraction rather than with pellets containing cellular components.

Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

BACKGROUND AND AIMS: Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4. METHODS: The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining. RESULTS: The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates. CONCLUSIONS: These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.

[Phosphate nephropathy: how to avoid it?]. / Néphropathie au phosphate: comment l'éviter?

Colonoscopy is a commonly used procedure for colon cancer screening. The ideal bowel preparation for a good visualization of the colonic mucosa would be effective and well tolerated. Sodium phosphate (NaP) and polyethylen glycol (PEG) are the two most frequently used solutions in this indication. However, although NaP has been described as more effective and better tolerated, it can cause severe acute electrolytes disturbances and, in rare cases, lead to irreversible renal failure, called phosphate nephropathy. NaP should therefore be prescribed with caution and be formally banned for patients with risk factors.