Prophylaxis of post-ERC infectious complications in patients with biliary obstruction by adding antimicrobial agents into ERCcontrast media- a single center retrospective study

Background: Patients with biliary obstruction are at high risk to develop septic complications after endoscopic retrograde cholangiography (ERC). We evaluated the benefits of local application of antimicrobial agents into ERC contrast media in preventing post-ERC infectious complications in a high-risk study population. Methods: Patients undergoing ERC at our tertiary referral center were retrospectively included. Addition of vancomycin, gentamicin and fluconazol into ERC contrast media was evaluated in a case-control design. Outcomes comprised infectious complications within 3 days after ERC. Results: In total, 84 ERC cases were analyzed. Primarily indications for ERC were sclerosing cholangitis (75%) and malignant stenosis (9.5%). Microbial testing of collected bile fluid in the treatment group was positive in 91.4%. Detected organisms were sensitive to the administered antimicrobials in 93%. The use of antimicrobials in contrast media was associated with a significant decrease in post-ERC infectious complications compared to non-use (14.3% vs. 33.3%; odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.114-0.978). After adjusting for the variables acute cholangitis prior to ERC and incomplete biliary drainage, the beneficial effect of intraductal antibiotic prophylaxis was even more evident (OR = 0.153; 95% CI: 0.039-0.598, p = 0.007). Patients profiting most obviously from intraductal antimicrobials were those with secondary sclerosing cholangitis. Conclusion: Local application of a combination of antibiotic and antimycotic agents to ERC contrast media efficiently reduced post-ERC infectious events in patients with biliary obstruction. This is the first study that evaluates ERC-related infectious complications in patients with secondary sclerosing cholangitis. Our first clinical results should now be prospectively evaluated in a larger patient cohort to improve the safety of ERC, especially in patients with secondary sclerosing cholangitis

Frequency and significance of the novel single nucleotide missense polymorphism Val109Asp in the human gene encoding omentin in Caucasian patients with type 2 diabetes mellitus or chronic inflammatory bowel diseases

BACKGROUND: The omental adipose tissue is pathogenetically involved in both type 2 diabetes mellitus (T2D) and chronic inflammatory bowel diseases (IBD) such as Ulcerative colitis (UC) and Crohn's Disease (CD). Thus, adipokines secreted from omental adipose tissue might play an important role in these diseases. Omentin represents a new adipokine expressed in and secreted by omental adipose tissue. Therefore, it was the aim to investigate the putative role of a newly described sequence missense variation in the human omentin gene. METHODS: The Val109Asp single nucleotide miss-sense polymorphism and the His86His polymorphism in exon-4 of the omentin gene were newly identified by random sequencing. Only the miss-sense polymorphism was investigated further. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis of amplified DNA fragments. Three different cohorts of well-characterized individuals were included in the study. 114 patients suffering from T2D, 190 patients suffering from IBD (128 with CD and 62 with UC) and 276 non-diabetic healthy controls without any history for IBD were analyzed. RESULTS: The following allelic frequencies were determined: controls: Val-allele: 0.26, Asp-allele: 0.74; T2D: Val-allele: 0.3, Asp-allele: 0.7; IBD: Val-allel: 0.31, Asp-allele: 0.69. UC and CD patients did not differ in regard to the allelic frequency. Similarly, controls, T2D patients and IBD patients did not show significant differences in genotype distribution among each other. Disease manifestation and pattern of infestation were not related to genotype subgroups, neither in CD nor in UC. Furthermore, there was no significant association between genotype subgroups and anthropometric or laboratory parameters in T2D patients. CONCLUSION: Based on sequence comparisons and homology searches, the amino acid position 109 is conserved in the omentin gene of humans, mice and chimpanzee but is not completely conserved between other omentin homologous genes. Moreover, position 109 lies outside the fibrinogen domain. Due to these structural features and based on the present data, the Val109Asp sequence variation is more a single nucleotide polymorphism than a real disease-causing mutation

Suitability of the simplified autoimmune hepatitis score for the diagnosis of autoimmune hepatitis in a German cohort

Background: Several years ago the International Autoimmune Hepatitis Group simplified the previous revised original scoring system for diagnosis of autoimmune hepatitis (AIH) into a scoring system based on only four instead of 13 parameters. Objective: We aimed to evaluate the suitability of the simplified AIH score for diagnosis of AIH in a German cohort with chronic liver diseases. Methods: In this retrospective single-center study, we compared the accuracy of both AIH scores in 70 patients with AIH and 211 patients with chronic liver diseases (PBC (n=52), PSC (n=27), NASH (n=67), DILI (n=15), CHB/C (n=50)). Sensitivity, specificity and predictability of each scoring system were calculated. Results: Using the simplified AIH score, the sensitivity and specificity of detecting a probable AIH (scores >= 6) were 96% and 97% with a positive and negative predictive value of 92% and 99%, respectively. For diagnosis of definite AIH (scores >= 7), the sensitivity and specificity were 43% and 100% with a positive and negative predictive value of 97% and 84%, respectively. The concordance with the revised original criteria was 63%. The specificity for excluding AIH was excellent in both scoring system. Conclusion: The simplified diagnostic criteria allow a reliable diagnosis of AIH in a German cohort

Evaluation of treatment response after chemoembolisation (TACE) in hepatocellular carcinoma using real time image fusion of contrast-enhanced ultrasound (CEUS) and computed tomography (CT)--preliminary results.

OBJECTIVE To evaluate treatment response of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with a new real-time imaging fusion technique of contrast-enhanced ultrasound (CEUS) with multi-slice detection computed tomography (CT) in comparison to conventional post-interventional follow-up. MATERIAL AND METHODS 40 patients with HCC (26 male, ages 46-81 years) were evaluated 24 hours after TACE using CEUS with ultrasound volume navigation and image fusion with CT compared to non-enhanced CT and follow-up contrast-enhanced CT after 6-8 weeks. Reduction of tumor vascularization to less than 25% was regarded as "successful" treatment, whereas reduction to levels >25% was considered as "partial" treatment response. Homogenous lipiodol retention was regarded as successful treatment in non-enhanced CT. RESULTS Post-interventional image fusion of CEUS with CT was feasible in all 40 patients. In 24 patients (24/40), post-interventional image fusion with CEUS revealed residual tumor vascularity, that was confirmed by contrast-enhanced CT 6-8 weeks later in 24/24 patients. In 16 patients (16/40), post-interventional image fusion with CEUS demonstrated successful treatment, but follow-up CT detected residual viable tumor (6/16). Non-enhanced CT did not identify any case of treatment failure. Image fusion with CEUS assessed treatment efficacy with a specificity of 100%, sensitivity of 80% and a positive predictive value of 1 (negative predictive value 0.63). CONCLUSIONS Image fusion of CEUS with CT allows a reliable, highly specific post-interventional evaluation of embolization response with good sensitivity without any further radiation exposure. It can detect residual viable tumor at early state, resulting in a close patient monitoring or re-therapy

Dominant-negative suppression of HNF-1 alpha results in mitochondrial dysfunction, INS-1 cell apoptosis, and increased sensitivity to ceramide-, but not to high glucose-induced cell death

Maturity onset diabetes of the young (MODY) 3 is a monogenic form of diabetes caused by mutations in the transcription factor hepatocyte nuclear factor (HNF)-1 alpha. We investigated the involvement of apoptotic events in INS-1 insulinoma cells overexpressing wild-type HNF-1 alpha (WT-HNF-1 alpha) or a dominant-negative mutant (DN-HNF-1 alpha) under control of a doxycycline-dependent transcriptional activator. Forty-eight h after induction of DN-HNF-1 alpha, INS-1 cells activated caspase-3 and underwent apoptotic cell death, while cells overexpressing WT-HNF-1 alpha remained viable. Mitochondrial cytochrome c release and activation of caspase-9 accompanied DN-HNF-1 alpha-induced apoptosis, suggesting the involvement of the mitochondrial apoptosis pathway. Activation of caspases was preceded by mitochondrial hyperpolarization and decreased expression of the anti-apoptotic protein Bcl-xL. Transient overexpression of Bcl-xL was sufficient to rescue INS-1 cells from DN-HNF-1 alpha-induced apoptosis. Both WT- and DN-HNF-1 alpha-expressing cells demonstrated similar increases in apoptosis when cultured at high glucose (25 mm). In contrast, induction of DN-HNF-1 alpha highly sensitized cells to ceramide toxicity. In cells cultured at low glucose, DN-HNF-1 alpha induction also caused up-regulation of the cell cycle inhibitor p27(KIP1). Therefore, our data indicate that increased sensitivity to the mitochondrial apoptosis pathway and decreased cell proliferation may account for the progressive loss of beta-cell function seen in MODY 3 subjects

Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and the metabolic syndrome. It encompasses a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). The latter develops upon pro-inflammatory cell infiltration and is widely considered as the first relevant pathophysiological step in NAFLD-progression. The chemokine monocyte chemoattractant protein 1 (MCP-1) plays an important role in the progression of hepatic inflammation and fibrosis, and both increased hepatic expression and circulating serum levels have been described in NASH. Here, we aimed to investigate MCP-1 expression in simple hepatic steatosis. Upon feeding a high-fat diet mice developed hepatic steatosis in the absence of significant hepatic inflammation, but elevated hepatic MCP-1 expression compared to control mice fed a standard chow. Interestingly, high-fat diet fed mice had significantly higher MCP-1 serum levels, and MCP-1 mRNA expression was significantly increased in visceral adipose tissue. Furthermore, MCP-1 serum levels were also elevated in patients with ultrasound-diagnosed NAFLD and correlated with the body-mass index and fasting glucose. In conclusion, our data indicate both the liver and adipose tissue as cellular sources of elevated circulating MCP-1 levels already in the early phase of hepatic steatosis. Since MCP-1 derived from visceral adipose tissue reaches the liver via portal circulation at high concentrations it may significantly contribute to the progression of simple steatosis to NASH