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Background: Metamizole is one of the most used analgesic, antipyretic, and spasmolytic agents in many countries worldwide. While metamizole-induced agranulocytosis is an, albeit seldom, well-known adverse event, metamizole-associated drug-induced liver injury has been reported rarely in the literature and hence often remains unconsidered. Here, we present a unique case where metamizole-induced hepatotoxicity got unmasked by the simultaneous development of characteristic agranulocytosis. Case Report: A 22-year-old woman without known conditions presented with a new onset of fever, jaundice, and maculopapular rash and explicitly denied intake of any new substances. Laboratory tests showed liver injury, granulopenia, and positive anti-nuclear and anti-mitochondrial (AMA-M2) antibodies. Liver biopsy revealed a histological pattern characteristic of drug-induced liver injury and bone marrow biopsy, the classical picture of metamizole-induced agranulocytosis. Indeed the in-depth interview of the patient unveiled metamizole consumption over the last two months. Therefore, we could diagnose metamizole-induced hepato- and myelotoxicity. Accordingly, steroid therapy led to normalization of liver parameters and stimulation with granulocyte colony- stimulating factor to leukocyte recovery. Conclusion: This case report is intended to increase the awareness of metamizole-associated druginduced liver injury which should always be kept in mind due to its occasionally life-threatening course. Diagnosis can be difficult particularly if anamnesis and written records are without hints for prior metamizole intake.

Background and aims Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension. Impact of administration of aspirin on transplant-free survival after TIPS remains unknown. Methods A multicenter retrospective analysis including patients with TIPS implantation between 2011 and 2018 at three tertiary German Liver Centers was performed. N = 583 patients were included. Survival analysis was performed in a matched cohort after propensity score matching. Patients were grouped according to whether aspirin was (PSM-aspirin-cohort) or was not (PSM-no-aspirin-cohort) administered after TIPS. Primary endpoint of the study was transplant-free survival at 12 months after TIPS. Results Aspirin improved transplant-free survival 12 months after TIPS with 90.7% transplant-free survival compared to 80.0% (p = 0.001) after PSM. Separated by TIPS indication, aspirin did improve transplant-free survival in patients with refractory ascites significantly (89.6% vs. 70.6% transplant-free survival, p p = 0.797). Conclusion This retrospective multicenter study provides first data indicating a beneficial effect of aspirin on transplant-free survival after TIPS implantation in patients with refractory ascites.

Background and aims Adenoma detection rate (ADR) in colon cancer screening is most important for cancer prophylaxis. This work is the first three‐armed randomised controlled clinical trial aimed at comparing a head‐to‐head setting standard colonoscopy (SC) with Endocuff‐assisted colonoscopy (EC) and cap‐assisted colonoscopy (CAC) for improvement of ADR. Methods Patients from Poland and Germany with independent indication for colonoscopy were randomised into three arms of this trial: EC, CAC and SC. Exclusion criteria were age

Surgery has become well established for patients with colorectal and neuroendocrine liver metastases. However, the value of this procedure in non-colorectal and non-neuroendocrine metastases (NCRNNELMs) remains unclear. We analyzed the outcomes of patients that underwent liver surgery for NCRNNELMs and for colorectal liver metastases (CRLMs) between 2012 and 2017 at our institution. Prognostic factors of overall and recurrence-free survival were analyzed, and a comparison of survival between two groups was performed. Seventy-three patients (30 NCRNNELM and 43 CRLM) were included in this study. Although the mean age, extrahepatic metastases, and rate of reoperation were significantly different between the groups, recurrence-free survival was comparable. The 5-year overall survival rates were 38% for NCRNNELM and 55% for CRLM. In univariate analysis, a patient age of ≥60 years, endodermal origin of the primary tumor, and major complications were negative prognostic factors. Resection for NCRNNELM showed comparable results to resection for CRLM. Age, the embryological origin of the primary tumor, and the number of metastases might be the criteria for patient selection.

Purpose To compare the safety and outcome of transjugular versus percutaneous technique in recanalization of non-cirrhotic, non-malignant portal vein thrombosis. Methods We present a retrospective bicentric analysis of 21 patients with non-cirrhotic, non-malignant PVT, who were treated between 2016 and 2021 by interventional recanalization via different access routes (percutaneous [PT] vs. transjugular in transhepatic portosystemic shunt [TIPS] technique). Complication rates with a focus on periprocedural bleeding and patency as well as outcome were compared. Results Of the 21 patients treated (median age 48 years, range of 19–78), seven (33%) patients had an underlying prothrombotic condition. While 14 (57%) patients were treated for acute PVT, seven (43%) patients had progressive thrombosis with known chronic PVT. Nine patients underwent initial recanalization via PT access and twelve via TIPS technique. There was no significant difference in complete technical success rate according to initial access route (55.5% in PT group vs. 83.3% in TIPS group, p = 0.331). However, creation of an actual TIPS was associated with higher technical success in restoring portal venous flow (86.6% vs. 33.3%, p = 0.030). 13 (61.9%) patients received thrombolysis. Nine (42.8%) patients experienced hemorrhagic complications. In a multivariate analysis, thrombolysis (p = 0.049) and PT access as the first procedure (p = 0.045) were significant risk factors for bleeding. Conclusion Invasive recanalization of the portal vein in patients with PVT and absence of cirrhosis and malignancy offers a good therapeutic option with high recanalization and patency rates. Bleeding complications result predominantly from a percutaneous access and high amounts of thrombolytics used; therefore, recanalization via TIPS technique should be favored.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.

Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective measure to treat complications of portal hypertension. However, liver function may deteriorate after TIPS. Predictors of liver function and outcome after TIPS are therefore important for management of TIPS patients. The study aimed to evaluate the impact of liver volume on transplant-free survival (TFS) after TIPS, as well as the evolution of liver volume and its relationship with liver function after TIPS. A retrospective analysis of all consecutive patients who underwent TIPS in a tertiary care university liver center between 2012 and 2017 (n = 216) was performed, n = 72 patients with complete prior and follow-up (FU) computed tomography (CT) imaging studies were included in the study. Volumetry of the liver was performed by a semi-automatic 9-lobe image segmentation algorithm at baseline and FU (FU 1: 90–180 d, FU 2: 180–365 d, FU 3: 365–545 d, FU 4: 545–730 d, FU 5: &gt, 730 d). Output variables were total liver volume (TLV, cm3), left liver volume (LLV, cm3), right liver volume (RLV, cm3) and TLV/body weight ratio. CT derived liver volumes were correlated with liver function tests, portosystemic pressure gradient (PPG) measurements and survival. To assess predictors of liver volume change over time we fitted linear mixed models. Kaplan–Meier analysis was performed and validated by matched pair analysis followed by Cox regression to determine independent prognostic factors for survival. The median TLV at baseline was 1507.5 cm3 (773.7–3686.0 cm3). Livers with higher baseline liver volumes and larger TLV/weight ratios retained their volume after an initial loss while smaller livers continuously lost volume after TIPS. At the first follow-up period (90–180 d post-TIPS) lower liver volumes and TLV/weight ratios were associated with higher bilirubin levels. Within the final multivariable model containing time (days since TIPS), baseline INR and baseline TLV, the average loss of liver volume was 0.74 mL per day after TIPS. Twelve-month overall transplant-free survival was 89% and median overall TFS was 33 months. The median TFS for a baseline TLV/body weight ratio &gt, 20 was significantly higher compared with ≤ 20 (40.0 vs. 27.0 months, p = 0.010) while there were no differences regarding the indication for TIPS or etiology of liver disease in the matched pair analysis. Lower TLV/weight ratios before TIPS were associated with shorter TFS and should therefore be critically considered when selecting patients for TIPS. In addition, this study provides first evidence of an effect of TIPS on subsequent liver volume change and associated liver function.

The life expectancy of unresectable hilar cholangiocellular carcinomas (CCCs) is very limited and endoscopic radiofrequency ablation (ERFA) of the biliary tract may prolong survival. Our single-center-study retrospectively analysed all CCC cases, in whom ERFAs of the biliary tract were performed between 2012 and 2017 and compared these to historical control cases who received the standard treatment of sole stent application. ERFA was performed in 32 patients with malignant biliary strictures that were mainly caused by Bismuth III and IV hilar CCCs (66%). 14 of these patients received repeated ERFAs, for an overall performance of 54 ERFAs. Stents were applied after examination of all patients (100%). Adverse events occurred in 18.5% of examinations. Case-control analysis revealed that the survival time of cases with unresectable Bismuth type III and IV hilar CCCs (n = 20) treated with combined ERFA and stent application significantly increased compared to controls (n = 22) treated with sole stent application (342 +/− 57 vs. 221 +/− 26 days; p = 0.046). In conclusion, ERFA therapy significantly prolonged survival in patients with unresectable Bismuth type III and IV hilar CCC. As an effective and safe method, ERFA should be considered as a palliative treatment for all these patients.

Simple Summary Among multiple other functional roles of tissue factor (TF) and other coagulation proteins in the development and targeting of malignant disease, some scientific groups are attempting to modify TF and target the molecule or truncated forms of the molecule to tumor vasculature to selectively induce local blood vessel thromboembolic occlusion resulting in tumor infarction. This review briefly describes the characteristics and development of some of these proteins and structures, including tTF-NGR, which as the first drug candidate from this class has entered clinical trials in cancer patients. Abstract Besides its central functional role in coagulation, TF has been described as being operational in the development of malignancies and is currently being studied as a possible therapeutic tool against cancer. One of the avenues being explored is retargeting TF or its truncated extracellular part (tTF) to the tumor vasculature to induce tumor vessel occlusion and tumor infarction. To this end, multiple structures on tumor vascular wall cells have been studied at which tTF has been aimed via antibodies, derivatives, or as bifunctional fusion protein through targeting peptides. Among these targets were vascular adhesion molecules, oncofetal variants of fibronectin, prostate-specific membrane antigens, vascular endothelial growth factor receptors and co-receptors, integrins, fibroblast activation proteins, NG2 proteoglycan, microthrombus-associated fibrin-fibronectin, and aminopeptidase N. Targeting was also attempted toward cellular membranes within an acidic milieu or toward necrotic tumor areas. tTF-NGR, targeting tTF primarily at aminopeptidase N on angiogenic endothelial cells, was the first drug candidate from this emerging class of coaguligands translated to clinical studies in cancer patients. Upon completion of a phase I study, tTF-NGR entered randomized studies in oncology to test the therapeutic impact of this novel therapeutic modality.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.

Background: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT). Methods: This prospective, observational study enrolled 65 patients with acute (

Background Portal hypertension is a major complication of liver cirrhosis. Transjugular intrahepatic portosystemic shunt is effective in treatment of portal hypertension. However, decreased parenchymal portal venous flow after transjugular intrahepatic portosystemic shunt insertion favours ischaemic liver injury which has been discussed to induce hepatocarcinogenesis causing hepatocellular cancer. Aim This study aimed to explore the association between transjugular intrahepatic portosystemic shunt placement and the development of hepatocellular cancer. Methods A total of 1338 consecutive liver cirrhosis patients were included in this retrospective study between January 2004–December 2015. Data were analysed with regard to development of hepatocellular cancer during follow-up. Binary logistic regression and Kaplan-Meier analyses were conducted for the assessment of risk factors for hepatocellular cancer development. In a second step, to rule out confounders of group heterogeneity, case-control matching was performed based on gender, age, model of end-stage liver disease score and underlying cause of cirrhosis (non-alcoholic steatohepatitis, alcoholic liver disease and viral hepatitis). Results Besides established risk factors such as older age, male gender and underlying viral hepatitis, statistical analysis revealed the absence of transjugular intrahepatic portosystemic shunt insertion as a risk factor for hepatocellular cancer development. Furthermore, matched-pair analysis of 432 patients showed a significant difference ( p = 0.003) in the emergence of hepatocellular cancer regarding transjugular intrahepatic portosystemic shunt placement versus the non-transjugular intrahepatic portosystemic shunt cohort. Conclusion In patients with end-stage liver disease, transjugular intrahepatic portosystemic shunt insertion is significantly associated with reduced rates of hepatocellular cancer development.

Purpose: To evaluate predictive parameters for the development of Hepatic Encephalopathy (HE) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement and for success of shunt modification in the management of shunt-induced HE. Methods: A retrospective analysis of all patients with TIPS (n = 344) has been performed since 2011 in our university liver center. n = 45 patients with HE after TIPS were compared to n = 48 patients without HE after TIPS (case-control-matching). Of n = 45 patients with TIPS-induced HE, n = 20 patients received a reduction stent (n = 18) or TIPS occlusion (n = 2) and were differentiated into responders (improvement by at least one HE grade according to the West Haven classification) and non-responders (no improvement). Results: Older patient age, increased serum creatinine and elevated International Normalized Ratio (INR) immediately after TIPS placement were independent predictors for the development of HE. In 11/20 patients (responders, 55%) undergoing shunt modification, the HE grade was improved compared with nine non-responders (45%), with no relevant recurrence of refractory ascites or variceal bleeding. A high HE grade after TIPS insertion was the only positive predictor of treatment response (p = 0.019). A total of 10/11 responders (91%) survived the 6 months follow-up after modification but only 6/9 non-responders (67%) survived. Discussion: Older patient age as well as an increased serum creatinine and INR after TIPS are potential predictors for the development of HE. TIPS reduction for the treatment of TIPS-induced HE is safe, with particular benefit for patients with pronounced HE.

Aim Research has identified patients with chronic liver disease as a risk group for colorectal neoplasia. In this study, we aimed to identify liver disease subgroups at enhanced risk of developing colorectal neoplasia, as well as causal factors. Methods The present retrospective study included patients with chronic liver disease undergoing colonoscopy during liver transplantation evaluations, and liver-healthy patients as part of the German screening protocol. We assessed inflammatory laboratory values, Model for End-stage Liver Disease score, portal hypertension, and liver disease etiologies as explanatory variables. Outcomes included polyps, adenomas, high-risk situations, and colorectal cancer, tested in uni- and multivariable analyses. Results A total of 1046 patients were included, 407 with liver disease, 639 without. Alcohol-toxic, metabolic, cryptogenic, non-alcoholic fatty liver disease, and hepatocellular carcinoma were significantly associated with colorectal neoplasia, as were low compared with high Model for End-stage Liver Disease scores. Portal hypertension showed no associations with neoplasia. Inflammatory markers were associated with colorectal neoplasia, independent of liver disease severity. Conclusions Low Model for End-stage Liver Disease score, inflammatory markers, and certain etiologies were associated with colorectal neoplasia. Our findings suggest that inflammation may play an important role in the development of colonic adenomas in patients with chronic liver disease. Findings need to be confirmed in prospective studies, but may allow risk stratification and, possibly, development of prophylactic treatments.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. Results: MTD was 3 mg/m2 tTF-NGR/day &times, 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t1/2(terminal) of 8 to 9 h without accumulation in daily administrations. Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.

BACKGROUND The level of suffering of chronically ill patients does not necessarily correlate with illness severity. In this study, we evaluated the burden of suffering and its impact on health-related quality of life in liver transplant recipients and liver cirrhosis patients. MATERIAL AND METHODS The Pictorial Representation of Illness and Self Measure (PRISM) was used to explore levels of suffering in outpatients of Münster University Hospital, Germany. Self-illness separation scores were analyzed as a measure of disease-specific burden of suffering. Health-related quality of life was measured using the Short Form Health Survey (SF-36). RESULTS Data from 201 subjects were statistically analyzed. Median Self-illness separation scores for liver transplant recipients and patients with liver cirrhosis were 13.5 (minimum/maximum: 0.2/25.6) cm and 6.3 (0.1/25.6) cm (p0.001), respectively. The median SF-36 Mental Component Summary and Physical Component Summary scores were 46.4 (12.5/66.2) and 40.1 (12.3/61.1), respectively. Higher health-related quality of life was associated with greater self-illness separation. Liver transplant recipients showed normal Mental Component Summary scores compared with the general German population; patients with liver cirrhosis had significantly lower Mental Component Summary scores. Physical Component Summary scores were significantly higher in liver transplant recipients than in patients with liver cirrhosis, but still lower than in the general population. CONCLUSIONS PRISM is a novel, simple tool for measuring the illness burden in liver transplant recipients and patients with liver cirrhosis. This measure may help to identify patients at a higher risk of psychological disorders.

Background Research increasingly focuses on identifying individuals at greater risk of colorectal cancer (CRC) to enhance colonoscopy screening efficacy. Objective The objective of this article is to determine associations between chronic liver disease and lesions along the colorectal adenoma-carcinoma sequence. Methods This retrospective study encompasses consecutive liver disease patients (LDPs) of all etiologies evaluated for liver transplantation at a single institution and a control group of liver-healthy patients (LHPs) undergoing colonoscopy as part of the German CRC screening program. Rates of polyps, adenomas, high-risk situations (HRS) and CRC were analyzed in univariable and multivariable settings adjusting for age, gender, body mass index and number of colonoscopies. Differences between LHPs and LDPs and between cirrhotic and noncirrhotic hepatopathy were assessed. Results In total, 1046 patients (52.6% male, median age 59.6 years) were included, of whom 38.9% had liver disease. A total of 41.0% of all patients showed polyps, 23.2% adenomas, 10.0% HRS, and 0.5% CRC. LDPs were more likely to develop polyps, adenomas and HRS than LHPs, both in univariable and multivariable analysis. There were no significant differences between cirrhotic and noncirrhotic patients. Conclusion Chronic liver disease of any etiology is associated with colonic lesions of the colorectal adenoma-carcinoma sequence, independent of cirrhosis. LDPs should receive intensified, and earlier, colonoscopy screening.

Summary Background Early differentiation of malignant from benign bile duct obstruction is of utmost importance. Aim To identify biochemical and clinical predictors for malignancy in patients with bile duct obstruction, and establish a predictive model by combining pre-treatment patient characteristics. A web-based application was developed for easy assessment of malignant bile duct probability (www.pmal-score.org). Methods One thousand hundred and thirty-five patients [median age 66 (52–75) years, 53% male] with bile duct obstruction of various aetiologies were retrospectively evaluated at our tertiary referral centre. Multivariate logistic regression analysis identified factors as independently significant for malignant bile duct obstruction. A predictive risk score was established using ROC analysis and applied to an external validation cohort of 101 patients. Results Three hundred and ninety-four patients had malignant bile duct obstruction proven by surgery, while in 741 patients benign obstruction was observed. Multivariate analysis identified various clinical factors to be predictive for malignancy. On the basis of eight predictors, a risk score for malignancy was developed [X = 0.025 * [age] + 1.239 * [1 if weight loss, otherwise 0] − 0.235 * [1 if pain, otherwise 0] + 0.649 * [1 if diabetes, otherwise 0] + 0.896 * [1 if jaundice, otherwise 0] + 0.109 * [bilirubin] + 0.0007 * [γ-GT] + 0.0003 * [AP] − 4.374]: A significant correlation between the predicted malignancy and the actual malignancy was found by ROC (AUC: 0.862; 95% CI 0.838–0.886, P

Background Therapy for HCV-infected patients after orthotopic liver transplantation (OLT) is based on interferon (IFN) as the gold standard, but sustained virologic response (SVR) and safety profiles of the IFN-based therapies are very unsatisfactory. The aim of this continuing analysis is evaluation of the impact of an IFN-free sofosbuvir (SOF)-based therapy in HCV-infected liver transplant recipients. Material and methods Post-OLT patients with a proven recurrence of HCV were treated with SOF and ribavirin (RBV) for 24 weeks (n=10). Laboratory parameters and FibroScan® are continuously evaluated at weeks 0, 12, 24, and 36. A retrospectively analyzed HCV patient cohort who received antiviral therapy with pegylated INF and RBV± telaprevir (TLV) were used as a control group. Results All patients who finished their treatment with SOF/RBV at least 12 weeks ago showed an SVR. The SOF-based therapy showed a significantly higher rate of rapid virologic response (RVR) and sustained virologic response (SVR) compared to the IFN-based therapies (RVR: p=0.007; SVR: p=0.009). According to temporary data on FibroScan® analysis, regression of fibrosis was observed in 8 patients treated with SOF/RBV. No premature termination of SOF became necessary. Conclusions In this small group of patients, the preliminary results indicate that a regression of fibrosis is achievable within 24 weeks of therapy with SOF after OLT. SOF seems to be effective and safe in the treatment of OLT patients infected with HCV and will likely improve patient and transplant survival.

Background & Aims Chronic hepatitis C virus (HCV) infection is a major burden on individuals and health care systems. The Extension for Community Healthcare Outcomes (Project ECHO) enables primary care providers to deliver best-practice care for complex conditions to underserved populations. The US Congress passed the ECHO Act in late 2016, requiring the Department of Health and Human Services to investigate the model. We performed a cost-effectiveness analysis to assess diagnosis and treatment of HCV infection in a primary care patient panel with and without the implementation of Project ECHO. Methods We used Markov models to simulate disease progression, quality of life, and life expectancy among individuals with HCV infection and for the general population. Data from the University of New Mexico's ECHO operation for HCV show an increase in treatment rates. Corresponding increases in survival, quality-adjusted life years (QALYs), costs, and resulting budget impact between ECHO and non-ECHO patients with HCV were then compared. Results Project ECHO increased costs and QALYs. The incremental cost-effectiveness ratio of ECHO was $10,351 per QALY compared with the status quo; >99.9% of iterations fell below the willingness-to-pay threshold of $100,000 per QALY. We were unable to confirm whether the increase in rates of treatment associated with Project ECHO were due to increased or more targeted screening, higher adherence, or access to treatment. Our sensitivity analyses show that the results are largely independent of the cause. Budget impact analysis shows payers would have to invest an additional $339.54 million over a 5-year period to increase treatment by 4446 patients, per 1 million covered lives. Conclusion Using a simulated primary care patient panel, we showed that Project ECHO is a cost-effective way to find and treat patients with HCV infection at scale using existing primary care providers. This approach could substantially reduce the burden of chronic HCV infection in the United States, but high budgetary costs suggest that incremental rollout of ECHO may be best.

Background and Aims Pneumocystis jirovecii pneumonia also known as pneumocystis pneumonia (PCP) is an opportunistic respiratory infection in human immunodeficiency virus (HIV) patients that may also develop in non-HIV immunocompromised persons. The aim of our study was to evaluate mortality predictors of PCP patients in a tertiary referral centre. Methods Fifty-one patients with symptomatic PCP were enrolled in the study. The patients had either HIV infection (n = 21) or other immunosuppressive conditions (n = 30). Baseline characteristics (e.g. age, sex and underlying disease) were retrieved. Kaplan–Meier analysis was employed to calculate survival. Comparisons were made by log-rank test. A multivariate analysis of factors influencing survival was carried out using the Cox regression model. Chi-squared test and Wilcoxon–Mann–Whitney test was applied as appropriate. Results The median survival time for the HIV group was >120 months compared with 3 months for the non-HIV group (P = 0.009). Three-month survival probability was also significantly greater in the HIV group compared with the non-HIV group (90% vs 41%, P = 0.002). In univariate log-rank test, intensive care unit (ICU) necessity, HIV negativity, age >50 years, haemoglobin 5 mg/dL and multiple comorbidities were significant negative predictors of survival. In the Cox regression model, ICU and HIV statuses turned out to be independent prognostic factors of survival. Conclusion PCP is a serious problem in non-HIV immunocompromised patients in whom survival outcomes are worse than those in HIV patients.

Perihilar cholangiocarcinomas are often considered incurable. Late diagnosis is common. Advanced disease therefore frequently causes questioning of curative surgical outcome.This study aimed to develop a prediction model of curative surgery in patients suffering from perihilar cholangiocarcinomas based on preoperative endosonography and computer tomography.A cohort of 81 patients (median age 67 (54-75) years, 62% male) with perihilar cholangiocarcinoma was retrospectively analyzed. Multivariate logistic regression analysis of staging variables taken from the European Staging System was performed and applied to ROC analysis.The correlation of predicted rates of eligibility for surgery with actual rates reached AUC values between 0.652 and 0.758 for endosonography and computer tomography (Our predictive web-based model pSurg with inclusion of T, N, M, B, PV, HA and V stage of the recently published European Staging System for perihilar cholangiocarcinoma results in highly significant predictability for curative surgery when combining preoperative endosonography and computer tomography, thus allowing for better patient selection in terms of possibility of curative surgery.

BACKGROUND This study evaluated the effect of liver transplantation (LTX) and STACE on overall survival in palliative patients with HCC exceeding Milan criteria. MATERIAL AND METHODS At a single center 63 HCC patients exceeding Milan criteria were retrospectively analyzed. Forty patients underwent STACE as palliative therapy modality and 23 palliative patients were scheduled for LTX. The primary endpoint was overall patient survival. Statistical analysis included Kaplan-Meier method, log rank, chi squared tests and Cox regression model for the identification of prognostic factors. RESULTS There was no significant difference when comparing the 2 groups (LTX vs. no LTX) in terms of Child classification, co-morbidities, underlying disease, and sex. Overall survival was significantly prolonged after LTX was performed (p=0.012). In the Cox regression model, LTX (p=0.021), LTX

Patient: Male, 37 Final Diagnosis: Chronic HCV-infection • hepatic decompensation Symptoms: Esophageal varices • portal-hypertensive gastropathy • splenomegaly • recurrent ascitic decompensation • hepatorenal syndrome • hepatic encephalopathy Medication: — Clinical Procedure: Liver transplantation • antiviral therapy Specialty: Gastroenterology and Hepatology Objective: Unusual setting of medical care Background: Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. Case Report: The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated. Conclusions: Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant interactions with the patient’s immunosuppressive regimens. Still, the peritransplant setting is a very demanding environment for anti-HCV therapy, and further studies are needed.

Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients.Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months.Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6-8.7 mL/min, p0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion.Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs.

Cronkhite-Canada syndrome (CCS) is a rare non-familial disorder with multiple gastrointestinal polyps and ectodermal changes. Adenomatous and carcinomatous changes have been reported. Video capsule endoscopy is a useful non-invasive tool to reveal polypoid lesions of the gastrointestinal tract suspicious for malignancy. We report a case of a patient with CCS with excessively elongated intestinal villi resembling dense sea grass under water as well as multiple polyps of the intestinal mucosa revealed by video capsule endoscopy. This report presents for the first time small bowel video sequences of CCS qualifying video capsule endoscopy for screening purposes and early detection of malignancy.

AIM: To compare endoscopic retrograde cholangio-pancreatography (ERCP), intraductal ultrasound (IDUS), endosonography (EUS), endoscopic transpapillary forceps biopsies (ETP) and computed tomography (CT) with respect to diagnosing malignant bile duct strictures. METHODS: A patient cohort with bile duct strictures of unknown etiology was examined by ERCP and IDUS, ETP, EUS, and CT. The sensitivity, specificity, and accuracy rates of the diagnostic procedures were calculated based on the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery. For each of the diagnostic measures, the sensitivity, specificity, and accuracy rates were calculated. In all cases, the gold standard was the histopathologic staging of specimens or long-term follow-up of at least 12 mo. A comparison of the accuracy rates between the localization of strictures was performed by using the Mann-Whitney U-test and the χ2 test as appropriate. A comparison of the accuracy rates between the diagnostic procedures was performed by using the McNemar’s test. Differences were considered statistically significant if P < 0.05. RESULTS: A total of 234 patients (127 males, 107 females, median age 64, range 20-90 years) with indeterminate bile duct strictures were included. A total of 161 patients underwent operative exploration; thus, a surgical histopathological correlation was available for those patients. A total of 113 patients had malignant disease proven by surgery; in 48 patients, benign disease was surgically found. In these patients, the decision for surgical exploration was made due to the suspicion of malignant disease in multimodal diagnostics (ERCP, CT, or EUS). Fifty patients had a benign diagnosis and were followed by a surveillance protocol with a follow-up of at least 12 mo; the median follow-up was 34 mo. Twenty-three patients had extended malignant disease, and thus were considered palliative. A comparison of the different diagnostic tools for detecting bile duct malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92% (IDUS + ETP), 74% (EUS), and 73% (CT), respectively. In the subgroup analysis, the accuracy rates (%, ERCP + IDUS/ETP/IDUS + ETP; EUS; CT) for each tumor entity were as follows: cholangiocellular carcinoma: 92%/74%/92%/70%/79%; pancreatic carcinoma: 90%/68%/90%/81%/76%; and ampullary carcinoma: 88%/90%/90%/76%/76%. The detection rate of malignancy by ERCP/IDUS was superior to ETP (91% vs 59%, P < 0.0001), EUS (91% vs 74%, P < 0.0001) and CT (91% vs 73%, P < 0.0001); EUS was comparable to CT (74% vs 73%, P = 0.649). When analyzing accuracy rates with regard to localization of the bile duct stenosis, the accuracy rate of EUS for proximal vs distal stenosis was significantly higher for distal stenosis (79% vs 57%, P < 0.0001). CONCLUSION: ERCP/IDUS is superior to EUS and CT in providing accurate diagnoses of bile duct strictures of uncertain etiology. Multimodal diagnostics is recommended. peerReviewed

AIM To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography (ERCP) for management of biliary complications after liver transplantation (LT). METHODS Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December 2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing. RESULTS Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14 (53.8%) patients, non-anastomotic strictures in seven (26.9%), biliary cast in three (11.5%), and stones in six (23.1%). A benefit of cholangioscopy was seen in 12 (46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive (43.2%), 12 (32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics. CONCLUSION Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications.

The aim of our study was to compare colon capsule endoscopy (CCE) with standard colonoscopy (SC) in the assessment of mucosal disease activity and localization of inflammatory colonic mucosa in patients with known ulcerative colitis (UC).Thirteen symptomatic patients (8 males, 5 females, mean age 38.5 ± 12.0 years) with known UC (mean duration of colitis: 9.7 ± 8.1 years) and indication for endoscopy due to suspected disease activity were included. All patients underwent CCE (first generation capsule, Given Imaging Ltd., Yokneam, Israel) on day 1 followed by SC on day 2 in a single center non-randomized, non-placebo-controlled diagnostic study (NCT00837304). SC and CCE were video recorded, and analysis was independently performed by 6 experienced endoscopists. The modified Rachmilewitz score was calculated, and Wilcoxon signed-rank test was used for analysis. Difference in recognition of disease activity by the endoscopists was assessed by application of the Kruskal-Wallis test.Assessment of disease activity revealed a significantly higher Rachmilewitz score of 7.3 ± 2.9 in the SC group compared to 4.8 ± 3.4 in the CCE group. Significantly, more detection of vessel vulnerability, granulated mucosa and mucosal damage was seen by SC. Disease extension was underestimated by CCE compared to SC. Disease activity assessment by means of SC or CCE did not differ statistically between the investigators (p = 0.26 and p = 0.1, respectively). After CCE, the capsule egestion rate was 77 %. The overall acceptance of both procedures was similar.Considering the significantly different assessment of disease activity and significantly more appropriate assignment of the horizontal spread of inflammation by SC versus CCE, we recommend the preferential use of SC in the assessment of inflammation in UC patients.

To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct.A patient cohort with bile duct strictures of unknown etiology was examined by IDUS. Sensitivity, specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery. Analysis of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 patients. IDUS staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity, specificity and accuracy rates for T and N stages. The endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160, Olympus, Ltd., Tokyo, Japan). All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines. For IDUS, a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co., Tokyo, Japan).A total of 397 patients (210 males, 187 females, mean age 61.43 ± 13 years) with indeterminate bile duct strictures were included. Two hundred and sixty-four patients were referred to the department of surgery for operative exploration, thus surgical histopathological correlation was available for those patients. Out of 264 patients, 174 had malignant disease proven by surgery, in 90 patients benign disease was found. In these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan, endoscopic ultrasound or magnetic resonance imaging). Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in sensitivity, specificity and accuracy rates of 93.2%, 89.5% and 91.4%, respectively. In the subgroup analysis of malignancy prediction, IDUS showed best performance in cholangiocellular carcinoma as underlying disease (sensitivity rate, 97.6%) followed by pancreatic carcinoma (93.8%), gallbladder cancer (88.9%) and ampullary cancer (80.8%). A total of 133 patients were not surgically explored. 32 patients had palliative therapy due to extended tumor disease in IDUS and other imaging modalities. Ninety-five patients had benign diagnosis by IDUS, forceps biopsy and radiographic imaging and were followed by a surveillance protocol with a follow-up of at least 12 mo; the mean follow-up was 39.7 mo. Tumor localization within the common bile duct did not have a significant influence on prediction of malignancy by IDUS. The accuracy rate for discriminating early T stage tumors (T1) was 84% while for T2 and T3 malignancies the accuracy rates were 73% and 71%, respectively. Relating to N0 and N1 staging, IDUS procedure achieved accuracy rates of 69% for N0 and N1, respectively.Pre-test likelihood of 52% may not rule out bias and over-interpretation due to the clinical scenario or other prior performed imaging tests.IDUS shows good results for accurate diagnostics of bile duct strictures of uncertain etiology thus allowing for adequate further clinical management.

Gallstone-induced ileus is a rare complication of cholelithiasis. Since localization of gallstones impacted in the small bowel, especially in the ileum, prevents access by conventional endoscopy in most cases, the mainstay of treatment remains surgical. Recent invention of double- and single-balloon enteroscopy has added much to the ability of imaging the small bowel and enables endoscopically directed therapy. Herein, for the first time, we report a successful endoscopic calculus removal via peroral single-balloon enteroscopy in an 81-year-old woman suffering from gallstone ileus of the ileum.

was seen in 12, 10, and 25 patients respectively. The modalities of diagnosis of bone metastasis were computer tomography (CT) (16 cases), magnetic resonance imaging (MRI) (10), bone scintigram (5), operation (1) and positron emission tomography (PET)-CT (1). The sites of bone metastasis were vertebra (17 cases), rib (12), pelvis (10), cranial bone (4), femur (4), sternum (3), and others (2). The average (SD) duration from the diagnosis of HCC to bone metastasis was 713 (±570) days. During the study period, 30 (91%) patients died (mean(SD) 355(±93) days from the diagnosis of bone metastasis). There was no significant difference in age, gender, stage, platelet count and serum tumor marker levels except for AFP between the two groups. Factors indicating a significant difference were serum AFP level, Child-Pugh classification and control of intrahepatic HCC by univariate analysis (p