Dilatation Therapy and Demographic Characteristics Significantly Influence the Amount of Propofol for Therapeutic Endoscopic Retrograde Cholangiography.

BACKGROUND AND STUDY AIMS: Patients undergoing therapeutic endoscopic retrograde cholangiography (ERC) may require different amounts of sedative agents depending on demographic characteristics, indication of ERC, and/or endoscopic intervention. PATIENTS AND METHODS: We retrospectively analyzed all patients undergoing therapeutic ERC from 2008 - 2014 who received deep sedation with propofol ± midazolam. RESULTS: A total of 2448 ERC procedures were performed in 781 patients. The cumulative per procedure propofol dose in the different groups was as follows: PSC 479 mg (±256), bile duct stones 356 mg (±187), benign stenosis/cholestasis 395 mg (±228), malignant stenosis 401 mg (±283), and postliver transplant complications 391 mg (±223) (p < 0.05). Multivariable analysis showed that dilatation therapy (p = 0.001), age (p = 0.001), duration of the intervention (p = 0.001), BMI (p = 0.001), gender (p = 0.001), platelet count (p = 0.003), and bilirubin (p = 0.043) influence independently the propofol consumption. CONCLUSIONS: Demographic characteristics and endoscopic interventions have a distinct influence on the amount of sedation required for therapeutic ERC. Although the sedation-associated complication rate is low optimization of sedative regimens is a prime goal to further reduce adverse events of therapeutic ERC.

The Role of Endoscopic Retrograde Cholangiopancreatography in the Diagnosis of Biliary Atresia: 14 Years' Experience.

INTRODUCTION: Biliary atresia (BA) is a rare destructive inflammatory obliterative cholangiopathy of neonates. Early diagnosis is important in disease management. The aim was to evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) in diagnosing BA in a large cohort. In addition, we evaluated whether parameters such as bile trace, GGT, bilirubin, and laboratory values in combination can be used to develop a risk score that could indicate the referral to specialized centers. MATERIALS AND METHODS: All infants with neonatal cholestasis (2000-2014) who presented to our endoscopy unit for suspected BA were included. Demographics, laboratory parameters, ultrasound findings, liver biopsy results, ERCP diagnosis, and surgical outcome were collected. Value and safety of ERCP and risk factors for BA were retrospectively analyzed. RESULTS: We included 251 infants in our cohort (55% males, median age: 53 days). BA was intraoperatively diagnosed in 155 (83.4%) patients and was excluded in 30 (16.2%). Fifty-six cases were not operated due to the ERCP findings. ERCP was successful in 224/251 patients (89.2%) with no procedure-related complications. The operative and endoscopic diagnosis matched in 96.6% of the patients (positive predictive value: 92.2%, negative predictive value: 97.1%). In comparison to cases with excluded BA, the ones with this disease were significantly associated with absence of duodenal bile traces (98.4 vs. 1.6%, p < 0.001), higher bilirubin (p < 0.001, cutoff 7.3 mg/dL), and higher GGT (p < 0.001, cutoff 250 U/L). CONCLUSION: ERCP is safe and accurate in the hands of experts in diagnosing BA if the cause of cholestasis is unclear. While evaluating the role of ERCP for diagnosing this disease, we found that the secondary parameters GGT > 250 U/L, bilirubin > 7.3 mg/dL (125 µmol/L), and the absence of bile traces are risk factors.

A combined bile and urine proteomic test for cholangiocarcinoma diagnosis in patients with biliary strictures of unknown origin.

BACKGROUND: Detection of cholangiocarcinoma (CC) remains a diagnostic challenge particularly in patients with primary sclerosing cholangitis (PSC). We recently established diagnostic peptide marker models in bile and urine to detect CC. Our aim was to combine both models to reach a higher diagnostic accuracy of CC diagnosis. METHODS: Bile (BPA) and urine (UPA) proteome analysis by capillary electrophoresis mass spectrometry was performed in a case-control phase II study on 87 patients (36 CC including 13 with CC on top of PSC, 33 PSC and 18 other benign disorders). A logistic regression model with both analyses was developed and subsequently validated in a prospective cohort of 45 patients. RESULTS: In the retrospective study, single BPA and UPA showed sensitivities of 83 and 89 % and specificities of 80 and 86 % with an area under the curve (AUC) value of 0.85 and 0.93. If CC was defined as positive UPA and BPA the combination resulted in a sensitivity of 72 % and a specificity of 96 %. The logistic regression model resulted in an increase in sensitivity to 92 % at 84 % specificity with an AUC of 0.96. Applied to the prospective study cohort, the logistic regression model was superior in its sensitivity (94%) and specificity (76%) over single BPA (63% sensitivity, 69% specificity) and UPA (81% sensitivity, 72% specificity) with an AUC of 0.84. CONCLUSION: Our logistic regression model enables CC diagnosis with a higher accuracy than currently available diagnostic tools leading potentially to an earlier diagnosis.

NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients.

Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive cholestatic disease of unknown aetiology characterized by chronic biliary infections. Hence we hypothesized that common NOD2 (nucleotide-binding oligomerisation domain containing 2) gene variants, known risk factors for Crohn's disease and bacterial translocation in liver cirrhosis, increase the odds of developing SC-CIP. Screening of 4,641 endoscopic retrograde cholangiography procedures identified 17 patients with SC-CIP, who were then genotyped for the three common NOD2 mutations (Cohort 1, discovery cohort). To validate the association, we subsequently tested these NOD2 variants in 29 patients from SC-CIP cohorts of three additional medical centers (Cohort 2, replication cohort). In Cohort 1, the NOD2 variants were present in 5 of 17 SC-CIP patients (29.4%), which is twice the frequency of the general population. These results were replicated in Cohort 2 with 8 patients (27.6%) showing NOD2 mutations. In contrast, polymorphisms of hepatocanalicular transporter genes did not have major impact on SC-CIP risk. This first study on genetic susceptibility in SC-CIP patients shows an extraordinary high frequency of NOD2 variation, pointing to a critical role of inherited impaired anti-bacterial defense in the development of this devastating biliary disease.

Patients with primary sclerosing cholangitis require more sedation during endoscopic retrograde cholangiography.

Background and study aims Patients with primary sclerosing cholangitis (PSC) require repeated endoscopic retrograde cholangiography (ERC). Our aim was to evaluate whether patients with PSC require higher doses of sedation during ERC. Patients and methods We retrospectively analyzed all patients undergoing ERC from 2006 to 2013 who received conscious sedation with propofol and midazolam. The duration of the intervention and a potential progression of propofol consumption or intervention time by visit number were analyzed. Univariable and multivariable analyses were performed to identify independent factors which influence propofol consumption. Results A total of 2962 ERC procedures were performed in 1211 patients. Patients with PSC (n = 157) underwent 461 ERC procedures whereas patients without PSC (n = 1054) had 2501 ERC examinations. The total median propofol dose was 450 mg (290 - 630 mg) for patients with PSC and 300 mg (200 - 450 mg) for the non-PSC group (P < 0.05). The propofol consumption in patients with PSC was increased by a factor of 1.24 (P = 0.0071) independent of intervention time. Younger age (< 60.8 years) and duration of the intervention were associated with a higher need for sedation by factors of 1.21 and 1.71, respectively (P < 0.0001). The robustness of the results was tested in a sensitivity analysis which confirmed the results (P < 0.0001). Conclusions Patients with PSC may require higher doses of sedation for ERC compared to other patient groups independent of age and duration of ERC. The higher dosage of sedation has to be taken into account when using ERC to treat a patient with PSC.

Clinical Impact of Liver Biopsies in Liver Transplant Recipients.

BACKGROUND Percutaneous liver biopsy is an established diagnostic procedure for the assessment of liver pathologies. Limited data are available on the clinical impact of liver biopsies in liver transplant recipients. MATERIAL AND METHODS Liver transplant recipients undergoing liver biopsy between 2000 and 2013 were analyzed. Demographic characteristics and transplantation data were extracted from the transplantation database. RESULTS A total of 496 liver biopsies were performed in 312 patients. The main biopsy indications were suspected rejection (66%, 327/496), protocol biopsy (22%, 108/496), and suspected recurrence of the primary disease (7%, 34/496). Histological findings showed acute cellular rejection in 36% (179/496), idiopathic chronic hepatitis in 28% (141/496), and normal histology in 11% (54/496). Liver biopsies in patients with clinically suspected rejection showed histological findings compatible with acute or chronic rejection in 46% (151/327). In 41% (205/496) of the patients, the immunosuppressive therapy was adjusted due to the biopsy result. For alanine-aminotransferase and bilirubin, significant differences were detected between baseline and week 4 and 12 after treatment modification (p<0.05). CONCLUSIONS Liver biopsies in liver transplant recipients have potential impact on the modification of the immunosuppressive therapy. The correlation between suspected rejection and histological findings is limited; therefore, a liver biopsy is indicated in unclear cases.

Acute gastrointestinal bleeding cases presenting to the emergency department are associated with age, sex and seasonal and circadian factors.

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the most common emergencies in gastroenterology. The aim of this study was to investigate the association between the incidence of GIB and seasonal, circadian and meteorological patterns in the emergency department (ED) of a tertiary hospital. PATIENTS AND METHODS: From January 2007 until December 2012, we retrospectively evaluated patients presenting to the ED with respect to the number and location of GIB, season, time of day and weather. RESULTS: Of 45 458 patients, 578 (1.3%) presented with a GIB. Of these, 62.5% were men compared with 54.7% of all patients in the ED (χ, P=0.0002). Patients with GIB were on average 4.4 years older than those without GIB (95% confidence interval 2.76-5.98, t-test, P<0.001). In addition, 304 (52.6%) patients had upper GIB and 138 (23.9%) had lower GIB. In total, 136 (23.5%) patients required no endoscopy because of initial laboratory and circulatory stability. In univariate analysis, meteorological parameters, including air temperature, cloud cover, relative humidity, vapour pressure, amount of precipitation, sunshine duration and snow height, were each associated with an increased risk of acute GIB (all P-values<0.05). In the 6-year study period, patients with GIB presented to the ED mainly during the winter months. Independent predictors of GIB on multivariate logistic regression were older age, male sex, season and daytime, all P less than 0.005. Emergency admissions during the night were associated with a 54 and 35% higher risk of GIB compared with daytime (8 a.m. to 4 p.m., P=0.0002) and late evening hours (4 p.m. to midnight, P=0.0142), respectively. CONCLUSION: Presentation of patients with acute GIB in the ED is age and sex specific and shows seasonal and circadian differences in distribution, with an increased incidence in winter months and during night-time. This should be considered when determining possible emergency endoscopic interventions and the availability of emergency endoscopy services.

Urinary Peptide Analysis Differentiates Pancreatic Cancer From Chronic Pancreatitis.

OBJECTIVES: Differentiation of pancreatic cancer (PCA) from chronic pancreatitis (CP) is challenging. We searched for peptide markers in urine to develop a diagnostic peptide marker model. METHODS: Capillary electrophoresis-mass spectrometry was used to search for peptides in urine of patients with PCA (n = 39) or CP (n = 41). Statistical different peptides were included in a peptide multimarker model. Peptide markers were sequence identified and validated by immunoassay and immunohistochemistry (IHC). RESULTS: Applied to a validation cohort of 54 patients with PCA and 52 patients with CP, the peptide model correctly classified 47 patients with PCA and 44 patients with CP (area under the curve, 0.93; 87% sensitivity; 85% specificity). All 5 patients with PCA with concomitant CP were classified positive. Urine proteome analysis outperformed carbohydrate antigen 19-9 (area under the curve, 0.84) by a 15% increase in sensitivity at the same specificity. From 99 healthy subjects, only four were misclassified. Fetuin-A was the most prominent peptide marker source for PCA as verified by immunoassay and IHC. In silico protease mapping of the peptide markers' terminal sequences pointed to increased meprin-A activity in PCA, which in IHC was associated with neoangiogenesis. CONCLUSIONS: Urinary proteome analysis differentiates PCA from CP and may serve as PCA screening tool.

Efficacy and safety of bovine activated factors IIa/VIIa/IXa/Xa in patients with active gastrointestinal bleeding: a proof of concept study.

BACKGROUND AND STUDY AIMS: Endoscopic treatment of active gastrointestinal bleeding often remains difficult, and considerable technical expertise is required. Our aim was to assess the efficacy and safety of endoscopic hemostasis with a liquid combination of bovine activated factors IIa/VIIa/IXa/Xa (SeraSeal). METHODS: Patients with active gastrointestinal bleeding were prospectively included. In group A, 5 mL of bovine activated factors IIa/VIIa/IXa/Xa was topically applied via catheters to the bleeding site as initial hemostasis; group B received a similar application but as rescue therapy after failure of conventional endoscopic hemostasis. RESULTS: In group A, bleeding was stopped by the agent in 15 /22 patients (68 %) and by conventional endoscopic hemostasis in 5 of the other 7, with coiling and surgery required for definitive hemostasis in 2. In group B, the addition of the agent definitively stopped bleeding in 13 /15 patients (87 %), with hemostasis in the remaining 2 achieved with fibrin glue. Rebleeding was observed in 1 patient. CONCLUSIONS: Our proof of concept study suggests that the use of bovine activated factors IIa/VIIa/IXa/Xa might be a safe and effective addition to current endoscopic hemostatic strategies, but further studies are necessary.ClinicalTrials.gov identifier: NCT02349490.

MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.

BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) are at high risk for the development of cholangiocarcinoma (CC). Analysis of micro ribonucleic acid (MiRNA) patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC. METHODS: Serum and bile from consecutive patients with PSC (n = 40 (serum), n = 52 (bile)), CC (n = 31 (serum), n = 19 (bile)) and patients with CC complicating PSC (PSC/CC) (n = 12 (bile)) were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12). The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation. RESULTS: Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile. CONCLUSIONS: Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

Liver transplantation for critically Ill patients with secondary sclerosing cholangitis: Outcome and complications.

Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a destructive cholangiopathy with a poor prognosis. Liver transplantation (LT) is an established therapeutic option in end-stage liver disease but is insufficiently evaluated in patients with SSC-CIP. Our aim was the retrospective analysis of the outcome and complications of patients with SSC-CIP undergoing LT between 2002 and 2012. Demographic characteristics, laboratory, transplantation, and follow-up data were compared to sex- and age-matched patients undergoing LT because of other reasons. Quality of life (QoL) before and after LT was assessed in a retrospective telephone interview. LT was performed in 21 patients with SSC-CIP. The main causes for intensive care unit admission comprised cardiothoracic surgery interventions (10/21, 48%), polytrauma (6/21, 29%), and pneumonia (3/21, 14%). Median follow-up period after LT was 82 months (interquartile range [IQR], 37-129) for patients with SSC-CIP and 83 months (IQR, 55-104) for control patients. Biopsy-proven rejection episodes in patients with SSC-CIP (4/21, 19%) were similar compared to control patients (12/60, 20%; P = 0.93). Cytomegalovirus infections were equal in both groups (10/21, 48% versus 25/60, 42%; P = 0.64). The 1-, 3-, and 5-year survival rates of patients with SSC-CIP versus control patients were 100% versus 98%, 86% versus 92%, and 76% versus 87%, respectively (P > 0.05). The QoL improved significantly after LT in SSC-CIP. In conclusion, LT is a valid option for patients with SSC-CIP with excellent long-term outcome and improvement of QoL.

Endoscopic diagnosis of cholangiocarcinoma: From endoscopic retrograde cholangiography to bile proteomics.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer. In clinical practice, the diagnosis remains challenging and often requires endoscopic approaches. Endoscopic retrograde and percutaneous transhepatic cholangiography are the first-line endoscopic procedures for the evaluation of indeterminate bile duct strictures. Tissue acquisition via brush cytology and forceps biopsies allows the cytological and/or histological confirmation of the disease. Due to the low sensitivity of these techniques, repetitive examinations and/or alternative approaches are required. Cholangioscopy, endoscopic and intraductal ultrasound and confocal laser endomicroscopy are additional methods which can be applied for the diagnosis of CCA. Particularly, new experimental approaches like bile and urine proteomic analyses show promising results which have to be evaluated prospectively for further integration in diagnostic algorithms.

Microbiological analysis of fluids in postsurgical gastroesophageal intrathoracic leaks obtained by endoscopy: a new way to optimize antibiotic therapy.

BACKGROUND/AIMS: Postsurgical gastroesophageal intrathoracic leakage is a potentially life-threatening condition that is frequently accompanied by mediastinitis and subsequent sepsis. Aspiration of fluids from intrathoracic leaks during endoscopy for microbiological analysis is rarely performed in clinical routine. The aim was to evaluate the role of routine microbiological analysis of intrathoracic leaks via endoscopy and its impact on antibiotic therapy. METHODS: This is a prospective, observational single-center study. Seventeen consecutive patients who presented for endoscopic treatment of intrathoracic leaks were included. Concomitantly, fluids from intrathoracic leaks during endoscopic intervention and blood cultures were obtained and a microbiological analysis was performed. RESULTS: Bacteria and/or fungi were detected by culture of fluid aspirated from intrathoracic leaks in 88% cases, but in none of the blood cultures. In 15 patients, microbial colonization of the leakage was detected despite previous empiric antibiotic therapy; treatment had to be adjusted in all patients according to the observed antibiotic susceptibility profile. CONCLUSIONS: The microbiological colonization of postsurgical gastroesophageal intrathoracic leaks in patients is frequent. Only the direct microbiological analysis of fluids from intrathoracic leaks, but not of blood cultures, is effective for optimizing an antibiotic therapy in such patients.

Microbiological analysis of bile and its impact in critically ill patients with secondary sclerosing cholangitis.

OBJECTIVES: Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is an emerging disease entity with unfavourable outcome. Our aim was to analyze the microbial spectrum in bile of patients with SSC-CIP and to evaluate the potential impact on the empiric antibiotic treatment in these patients. METHODS: 169 patients (72 patients with SSC-CIP and 97 patients with primary sclerosing cholangitis (PSC)) were included in a prospective observational study between 2010 and 2013. Bile was obtained during endoscopic retrograde cholangiography (ERC) and microbiologically analyzed. RESULTS: Patients with SSC displayed a significantly different microbiological profile in bile. Enterococcus faecium, Pseudomonas aeruginosa and non-albicans species of Candida were more frequent in SSC compared to patients with PSC (p < 0.05). Patients with SSC showed a higher incidence of drug or multi-drug resistant organisms in bile (p = 0.001). The antimicrobial therapy was adjusted in 64% of patients due to resistance or presence of microorganisms not covered by the initial therapy regimen. CONCLUSIONS: Patients with SSC-CIP have a distinct microbial profile in bile. Difficult to treat organisms are frequent and an ERC with bile fluid collection for microbiological analysis should be considered in case of insufficient antimicrobial treatment.

Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells.

Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a(+)DX5(-) NK cells with adaptive-like features. Development of this NK cell lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet(+)Eomes(-)CD49a(+) NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a(+) NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56(bright), and express low levels of CD16, CD57, and perforin. After stimulation, CD49a(+) NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a(+) NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.

Gastrointestinal Endoscopy Is Safe in Patients Before and After Lung or Heart Transplantation.

BACKGROUND: Gastrointestinal complications are common in patients after lung and heart transplantation. Endoscopy is a standard method for the assessment of gastrointestinal morbidities. The aim of this study was to analyze the number and type of complications during endoscopic procedures in patients before and after lung or heart transplantation. METHODS: A retrospective single centre analysis of endoscopic procedures in patients before and after lung and heart transplantation from May 1999 to September 2012 was performed compared to a control group. RESULTS: Four hundred fifty-nine endoscopic procedures were performed in 175 patients after transplantation (84 lung and 91 heart) and 213 procedures in 160 transplant candidates on the waiting list for lung (n = 126) or heart (n = 34) transplantation. In 26% (n = 56/214) of the endoscopic examinations, an intervention was necessary in the lung transplant group compared to 32% (n = 79/245) in the heart transplant group and 27% (n = 43/160) and 21% (n = 11/53) in the lung and heart transplant candidates, respectively. In the control group, endoscopic interventions were performed in 24% (n = 195/805) of the examinations. Overall, 14 (1%) complications resulted from 1,477 endoscopic examinations. Only four (0.9%) of 459 endoscopic examinations were followed by complications in the transplant recipients, whereas in the control group, 10 complications (1.2%) of 805 endoscopies were documented. No endoscopic complication occurred in the lung and heart transplant candidates. CONCLUSION: Diagnostic and therapeutic endoscopies can be safely performed after lung and heart transplantation and in patients on the waiting list for these organs.

Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma.

BACKGROUND: The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis. AIM: To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC. METHODS: Bile and serum Angpt-2 levels were measured in patients with CC (n=45), PSC (n=74), CC complicating PSC (CC/PSC) (n=11) and patients with bile duct stones (n=37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2. RESULTS: Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74-0.93 versus 0.65-0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature. CONCLUSIONS: Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.

MicroRNAs in the bile of patients with biliary strictures after liver transplantation.

Biliary complications after liver transplantation remain a major cause of morbidity and reduced graft survival. Ischemic-type biliary lesions (ITBLs) are common and difficult to treat. The pathophysiology of ITBLs remains unclear, and diagnostic markers are still missing. The analysis of microRNA (miRNA) profiles is an evolving field in hepatology. Our aim was to identify specific miRNA patterns in the bile of patients with ITBLs after liver transplantation. Liver transplant patients with biliary complications were included in a cross-sectional study. Patients with ITBLs (n = 37), anastomotic strictures (ASs; n = 39), and bile duct stones (BDSs; n = 12) were compared. Patients with ITBLs were categorized by disease severity. The miRNA concentrations in bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation. The concentrations of microRNA 517a (miR-517a), miR-892a, and miR-106a* in bile were increased for patients with ITBLs versus patients with ASs or BDSs (P < 0.05). Categorization by ITBL severity showed higher median concentrations in patients with intrahepatic and extrahepatic strictures (P > 0.05). miR-210, miR-337-5p, miR-577, and miR-329 displayed no statistical differences. In conclusion, miR-517a, miR-892a, and miR-106a* are increased in the bile fluid of patients with ITBLs versus patients with ASs or BDSs. An analysis of miRNA profiles may be useful in the diagnosis and management of patients with ITBLs. Future studies are needed to prove the potential prognostic value of these miRNAs.

Safety and performance of liver biopsies in liver transplant recipients.

BACKGROUND: Liver biopsy in patients after liver transplantation (OLT) serves as a diagnostic tool to establish the cause of liver pathology. However, liver biopsy may cause life-threatening complications. Very limited information is available about complications and success rates of liver biopsies in patients after OLT. Our aim was to investigate biopsy-related complications and quality of specimen obtained by liver biopsy after OLT and to evaluate risks and benefits of this procedure. METHODS: Retrospective analysis of patients after OLT presenting for liver biopsy between January 2000 and October 2012. All patients were observed for 24 h after intervention. Twelve or more portal tracts were required for liver biopsy specimens to be considered as adequate. RESULTS: Of 703 liver biopsies were performed in 409 patients. Thirteen (1.9%) liver biopsies did not have an adequate number of portal tracts. Only 10 (1.4%) liver biopsies caused complications. Five patients suffered from pain, three patients developed post-procedural fever, and three patients had subcapsular/intercostal bleeding. One patient suffered from a vasovagal reaction. Pain was treated by analgesics; none of the patients required blood transfusion or surgery. CONCLUSIONS: Liver biopsy is a safe and adequate diagnostic tool in patients after OLT.

Changes in liver stiffness using acoustic radiation force impulse imaging in patients with obstructive cholestasis and cholangitis.

BACKGROUND: Acoustic radiation force impulse imaging is used to assess stages of liver fibrosis. The aim of our study was to evaluate liver stiffness changes in patients with biliary obstruction with or without sclerosing cholangitis after biliary drainage. METHODS: A total of 71 patients were enrolled in this prospective study (cohort N=51, control group N=20); 51 patients with obstructive cholestasis, indicated for endoscopic retrograde cholangiography, received stiffness measurement by acoustic radiation force impulse imaging before and 1-2 days after endoscopic retrograde cholangiography. Seventeen patients with obstructive cholestasis had primary or secondary sclerosing cholangitis. Forty one patients had a follow-up acoustic radiation force impulse imaging measurement after 3.0 ± 9.31 weeks. RESULTS: In all patients with obstructive cholestasis, stiffness decreased significantly after biliary drainage (p<0.001). The main decrease was observed within 2 days after endoscopic retrograde cholangiography (1.92-1.57 m/s, p<0.001) and correlated with the decrease of bilirubin and alkaline phosphatase (p=0.04 and p=0.002, respectively). In patients with sclerosing cholangitis, the initial decrease of stiffness after biliary drainage was weaker than in those without (2.1-1.85 m/s vs. 1.81-1.43 m/s, p=0.016). CONCLUSION: Acoustic radiation force impulse imaging elastography shows that liver stiffness is increased by biliary obstruction, and decreases after endoscopic retrograde cholangiography irrespective of the aetiology. In patients with sclerosing cholangitis the reduction in stiffness after biliary drainage is impaired.