Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Risk factors for allograft failure in liver transplant recipients.

BACKGROUND: With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. MATERIAL AND METHODS: A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death. RESULTS: The mean age of recipients at the time of LT was 50.3 ±â€Š12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ±â€Š15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p < 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis in the initial protocol biopsy during follow-up (p = 0.001) to be recipient-related significant and independent risk factors for allograft failure following LT. CONCLUSION: Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.

Training, work, and lifestyle of transplant physicians and surgeons in Germany.

BACKGROUND: International data on training, work, and lifestyle of transplant physicians and surgeons are scarce. Such data might help in development of uniform education paths and provide insights for young clinicians interested in this field. This study aimed at the evaluation of these data in all transplant-associated medical disciplines. METHODS: A survey on professional and academic training, workload, and lifestyle was generated. The questionnaire was distributed to all members of the German Transplant Association (DTG), utilizing the tool SurveyMonkey(®) . RESULTS: A total of 127 members of the DTG responded (male/female 66.1%/33.9%, 45.8±10.3 years). The majority had been working in transplant medicine for more than 10 years (61.9%). Fifteen respondents (11.8%) obtained an official European certification (European Union of Medical Specialists). A total of 57 (48.3%) respondents worked full time on research during training. The research focus was clinical for most respondents (n=72, 61.5%). An average working time of 62±1.5 h/wk was reported. Fifty-eight percent of all respondents complained of inadequate remuneration and 50% reported inadequate acknowledgment of their professional performance. CONCLUSION: This is the first study reporting characteristics of training, work, and lifestyle in an interdisciplinary cohort of German transplant physicians and surgeons. Enormous efforts in clinical and research work were reported, associated with high rates of professional and financial dissatisfaction.

Endoscopic ultrasound: valuable tool for diagnosis of biliary complications in liver transplant recipients?

BACKGROUND: Biliary complications after liver transplantation (LT) are still common and are an important cause of mortality and morbidity. Until now, endoscopic retrograde cholangiopancreatography (ERCP) has been considered the gold standard for diagnosing such complications. The aim of this study was to evaluate the diagnostic yield and therapeutic impact of endoscopic ultrasound (EUS) in the management of biliary complications after LT. METHODS: Thirty-seven liver transplant patients who presented with clinical, biochemical, sonographic, and/or histological evidence of biliary complications, and who first received EUS followed by ERCP, were enrolled into this prospective observational study. Subsequently, we evaluated the value of EUS in detecting and classifying biliary complications after LT. RESULTS: Thirty-seven biliary complications were detected in 32 patients. Endoscopic ultrasound showed an overall sensitivity and accuracy of 94.6 % each. In cases of biliary cast and ischemic cholangiopathy, EUS was found to be diagnostically superior to ERCP and has had, in these cases, a significant impact on clinical decision-making. However, EUS was less reliable when diagnosing anastomotic strictures. CONCLUSION: EUS can complement ERCP to improve diagnosis of biliary complications after LT and help guide treatment strategies to address these complications.

Mycophenolic acid induces apoptosis of hepatic stellate cells in an in vitro model of HCV.

INTRODUCTION: Hepatitis C virus (HCV) infection is an important risk factor for the development of liver fibrosis and progression to cirrhosis. Liver transplantation as terminal treatment option for liver disease requires life-long immunosuppression. However, immunomodulatory therapy may promote reinfection and renewed fibrogenesis. Immunosupressive agents may also affect the life cycle of hepatic stellate cells (HSC), the main source of extracellular matrix. We thus aimed to characterize the effects of three common immunosuppressive agents on HSC apoptosis with or without engulfment of HCV infected apoptotic bodies. MATERIAL AND METHODS: LX2 cells were incubated with three different immunosuppressants (rapamycine, mycophenolic acid or cyclosporine A) and co-incubated for 24 and 48 h with apoptotic bodies (AB), produced from Huh7 cells or from Con1 cells (Huh7-cells containing a subgenomic HCV replicon). The engulfment of AB was confirmed by immunofluorescence staining. HSC viability, apoptosis rate and expression of profibrogenic and proapoptotic genes were quantified. RESULTS: In LX2 cells that engulfed Con1 AB, the treatment with mycophenolic acid induced HSC apoptosis and reduced collagen 1alpha 1 expression compared to cylosporine A or rapamycine treatment. In conclusion mycophenolic acid is a potent inducer of HSC apoptosis and attenuates HSC activation and consecutively fibrogenesis in HCV infection. Translational studies will need to confirm these mono-culture results in vivo.

MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity.

BACKGROUND & AIMS: Oncogene polycomb group protein enhancer of zeste homolog 2 (EZH2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study was to investigate the functional role of both miR-101 and EZH2 in human hepatocellular carcinoma (HCC). METHODS: MiR-101 and EZH2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. RESULTS: MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. CONCLUSION: Tumor suppressor miR-101 represses HCC progression through directly targeting EZH2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC.

Evaluation of fibrotic liver disease with whole-liver T1ρ MR imaging: a feasibility study at 1.5 T.

PURPOSE: To test at 1.5 T whether T1ρ magnetic resonance (MR) imaging of fibrotic liver disease is feasible, to investigate whether liver T1ρ imaging allows assessment of the severity of liver cirrhosis, and to assess the normal liver T1ρ range in healthy patients. MATERIALS AND METHODS: This prospective study was approved by the institutional ethics committee. Written informed consent was obtained. Healthy volunteers (n = 25) and patients (n = 34) with cirrhosis underwent whole-liver T1ρ MR imaging at 1.5 T. Mean T1ρ values were calculated from liver regions of interest. Mean T1ρ values were correlated to clinical data and histopathologic analysis by analysis of variance. Receiver operating characteristic curves were calculated to determine the accuracy of mean T1ρ values for the assessment of Child-Pugh class. RESULTS: Mean T1ρ values of volunteers (mean, 40.9 msec ± 2.9 [standard deviation]; range, 33.9-46.3 msec) were significantly lower than those of patients who were Child-Pugh class A (P < .004), B (P < .001), or C (P < .001), and significant differences were found between each Child-Pugh stage (A vs B, P < .002; B vs C, P < .009; A vs C, P < .001). Liver cirrhosis was confirmed via histologic analysis in all patients with liver biopsy. Mean T1ρ values did not correlate with necroinflammatory activity (r = 0.31; P = .23), degree of steatosis (r = -0.016; P = .68), or presence of iron load (r = 0.22; P = .43). Mean T1ρ values performed well by assessing the Child-Pugh stage, with receiver operating characteristic areas of 0.95-0.98. Intraclass correlation coefficient values ranged between 0.890 and 0.987, which indicated excellent imaging and reimaging reproducibility and interobserver and intraobserver variability. CONCLUSION: Whole-liver T1ρ MR imaging at 1.5 T to detect and assess human liver cirrhosis is feasible. Further investigation and optimization of this technique are warranted to cover the entire spectrum of fibrotic liver disease.

Hepatitis B and C in liver transplantation: new strategies to combat the enemies.

Hepatitis B immune globulin-free therapeutic regimens with a nucleos(t)ide analogue (NUC) or NUC combinations after liver transplantation (LT) are currently being investigated for their efficacy and safety as HBV re-infection prophylaxis in clinical studies. Recurrence rates differ among these studies as most of them are limited by a non-randomised study design, small sample size, lack of long-term data and varying time intervals for the switch from combined to purely virostatic prophylaxis. Post-transplant pre-emptive antiviral therapy with pegylated IFN and ribavirin is associated with low sustained virological response rates and was found to have no advantage over treatment of manifest HCV re-infection. Safety and efficacy of triple antiviral therapy including boceprevir or telaprevir in patients with manifest HCV re-infection are currently under investigation in clinical trials. Relevant drug interactions have been shown to occur during calcineurin inhibitor (CNI) and concomitant triple antiviral therapy, which vary with type of CNI and choice of HCV protease inhibitor. Newer direct-acting antivirals with lower or minimal toxicity, when used in combination with immunosuppressives, are worthy of further study in LT patients. This review focuses on hot topics in the management of hepatitis B and C patients before and after LT and offers a critical summarised selection of the corresponding relevant studies published in the current literature or presented at recent liver congresses.

Calcineurin inhibitors in liver transplantation - still champions or threatened by serious competitors?

Current strategies for immunosuppression in liver transplant (LT) recipients include the design of protocols targeting a more individualized approach to reduce risk factors such as renal failure, cardiovascular complications and malignancies. Renal injury in LT recipients may be often multifactorial and is associated with increased risk of post-transplant morbidity and mortality. The quest for low toxicity immunosuppressive regimens has been challenging and resulted in CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil (MMF) and/or mammalian target of rapamycin inhibitor-based immunosuppressive regimens. Use of antibody induction to delay CNI administration may be an option in particular in immunocompromized, critically ill patients with high MELD scores. Protocols including MMF introduction and concomitant CNI minimization have the potential to recover renal function even in the medium and long term after LT. We review on hot topics in the prevention and management of acute and chronic renal injury in LT patients. For this purpose, we present and critically discuss results from immunosuppressive studies published in the current literature or presented at recent LT meetings.

Strategies to prevent or reduce acute and chronic kidney injury in liver transplantation.

Acute kidney injury (AKI) has a major impact on short- and long-term survival in liver transplant (LT) patients. There is no currently accepted uniform definition of AKI, which would facilitate standardization of the care of patients with AKI and to improve and enhance collaborative research efforts. New promising biomarkers such as neutrophil gelatinase-associated lipocalin or kidney injury molecule-1 have been developed for the prevention of delayed AKI treatment. Early dialysis has been shown to be beneficial in patients with AKI stage III according to the classification of the Acute Kidney Injury Network, whereas treatment with loop diuretics or dopamine is associated with worse outcome. The mainstay for the prevention of AKI seems to be avoidance of volume depletion and maintenance of a mean arterial pressure >65 mmHg. Although the aetiology of chronic kidney disease in transplant recipients may be multifactorial, calcineurin-inhibitor (CNI)-induced nephrotoxicity significantly contributes to the development of renal dysfunction over time after LT. The delayed introduction of CNI at minimal doses has shown to be safe and effective for the preservation of kidney function. Other strategies to overcome CNI nephrotoxicity include CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil or the mammalian target of rapamycin inhibitor-based immunosuppressive regimens. However, CNI avoidance may bear a higher rejection risk. Thus, more results from randomized-controlled studies are urgently warranted to determine which drug combinations are the most beneficial approaches for the potential introduction of CNI-free immunosuppressive regimens.

Genetic, immunological and clinical risk factors for biliary strictures following liver transplantation.

BACKGROUND: Biliary strictures after liver transplantation (LT) are a major cause of morbidity and reduced graft survival. AIMS: The purpose of this study was to investigate genetic, immunological and clinical risk factors for the occurrence of post-LT ischaemic type biliary lesions (ITBLs) and biliary anastomotic strictures (AS). METHODS: Clinical and laboratory data, chemokine receptor (CCR) genotypes, chemotactic cytokines and anti-major-histocompatibility complex antibodies in serum were investigated in 162 LT patients. RESULTS: In the univariate analysis, older donor and recipient age, partial LT, high peak aspartate aminotransaminase (AST) levels and CC chemokine receptor 5 delta32 loss-of-function mutation (CCR5Δ32) were associated with ITBL, whereas LT for acute liver failure (ALF), ABO-compatible non-identical LT, presence of donor-specific anti-human leucocyte antigen (HLA) class II antibodies and fractalkine receptor (CX3CR1)-249II allele were associated with AS. In the multivariate analysis, CCR5Δ32 was an independent risk factor for ITBL, whereas LT for ALF, ABO-compatible non-identical LT, and CX3CR1-249II allele remained predictive for AS. Serum levels of interferon-gamma and interleukin (IL)-6 as well as IL-10 were significantly increased in patients with biliary strictures. CONCLUSION: Specific chemokine receptor polymorphisms of the recipient are associated with development of post-LT biliary strictures. Altered cytokine profile may contribute to enhanced fibrotic tissue remodelling and biliary stricture formation. Screening of anti-HLA antibodies might be useful for early identification of at-risk patients who could benefit from closer surveillance and tailored immunosuppressive regimen. Our findings may have relevance for prediction and management of post-LT biliary strictures.

Hepatitis C virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly.

Amphiregulin (AREG) is a ligand of the epidermal growth factor (EGF) receptor and may play a role in the development of cirrhosis and hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). AREG showed an enhanced expression in HCV-infected human hepatoma cells according to gene array analysis. Therefore, we addressed the question about the role of AREG in HCV infection. AREG expression level was elevated in hepatoma cells containing a subgenomic HCV replicon or infected by HCV. Using a reporter assay, AREG promoter activity was found to be upregulated upon HCV infection. The enhanced AREG expression in hepatoma cells was partly caused by dsRNAs, HCV NS3 protein and autocrine stimulation. AREG was able to activate cellular signalling pathways including ERK, Akt and p38, promote cell proliferation, and protect cells from HCV-induced cell death. Further, knockdown of AREG expression increased the efficiency of HCV entry, as proven by HCV pseudoparticles reporter assay. However, the formation and release of infectious HCV particles were reduced by AREG silencing with a concomitant accumulation of intracellular HCV RNA pool, indicating that the assembly and release of HCV progeny may require AREG expression. Blocking the MAPK-ERK pathway by U0126 in Huh7.5.1 cells had a similar effect on HCV replication. In conclusion, HCV infection leads to an increase in AREG expression in hepatocytes. AREG expression is essential for efficient HCV assembly and virion release. Due to the activation of the cellular survival pathways, AREG may counteract HCV-induced apoptosis of infected hepatocytes and facilitate the development of liver cirrhosis and hepatocellular carcinoma.

Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival.

UNLABELLED: Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium-90 (Y-90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (± 18) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome. CONCLUSION: Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted.

Liver transplantation with donors over the expected lifespan in the model for end-staged liver disease era: is Mother Nature punishing us?

BACKGROUND: The lack of sufficient donors to satisfy the waiting list requirements has prompted many to expand the acceptance criteria. The purpose of this study was to evaluate our liver transplantation (LT) experience with donors beyond the average lifespan. PATIENTS AND METHODS: From January 2008 to December 2009, we received 75 liver offers involving donors ≥ 75 years of age. Donor and recipient data were analysed by both uni- and multivariate Cox proportional hazard model analyses. RESULTS: We performed 32 adult liver transplants (43%). Half of the patients received organs through rescue allocations. Seven recipients (22%) developed initial poor function. Two had primary graft non-function (PNF). Four recipients were re-transplanted (two PNF and two ischaemic-type bile lesions). One- and 3-year cumulative survival was 62 and 51% respectively. PNF, lab model for end-staged liver disease (MELD), post-LT haemodialysis, post-LT re-operations and post-LT sepsis were significant predictors by univariate analysis. Only PNF reached multivariate significance (P = 0.0307). Rescue offer allocation reached significance as a predictor of PNF by general linear model forward analysis. One- and 3-year 'MELD based allocation' (n = 16) vs 'rescue allocation' (n = 16) survival rates were 44 and 29% vs 82 and 76% respectively (P = 0.0197). CONCLUSIONS: Although grafts from donors ≥ 75 years allow for an expansion of the donor pool, long-term recipient survival is inferior to that encountered with younger donors. Acceptable results could be obtained by identifying 'preferred' recipients for rescue allocations.

Efficacy and safety of subcutaneous human HBV-immunoglobulin (Zutectra) in liver transplantation: an open, prospective, single-arm phase III study.

Hepatitis B re-infection prophylaxis is crucial for graft and recipient survival for transplanted patients and is administered routinely after liver transplantation for hepatitis B. Aim of the current study was the investigation of efficacy, safety and feasibility of home-treatment of a novel human hepatitis B immunoglobulin BT088 (Zutectra) after weekly subcutaneous application in liver-transplanted patients. A total of 23 patients (5 female, 18 male, median age 51 years) were enrolled and switched from monthly IV to weekly SC hepatitis B immunoglobulin administration. During a period of 18 weeks (optional 24 weeks) anti-HBs levels, signs of re-infection, adverse events and feasibility of self-administration were studied. After 8 weeks of training patients showing good compliance and stable antibody titres were allowed to start self-administration at home. All patients maintained a safety level of >100 U/l anti-HBs. No failure was noted, no re-infection occurred. A total of 10 treatment-emergent events were assessed as related to study drug application (injection-site haematoma, headache, abdominal pain, fatigue and haematuria). High numbers of self-administration (287 vs. 122 by staff) demonstrated general feasibility of SC administration. Weekly subcutaneous administration of BT088 (Zutectra - registered trade mark in the EU) is effective, safe and presents an easy-to-apply treatment option for combined hepatitis B virus re-infection prophylaxis in liver transplant patients (Eudra CT Number: 2005-003737-40).

High brain-natriuretic peptide level predicts cirrhotic cardiomyopathy in liver transplant patients.

Cirrhotic cardiomyopathy may appear following liver transplantation. Brain-natriuretic peptide (BNP) values exceeding 391 pg/ml or 567 pg/ml may partially reflect ventricular stress because of cardiac dysfunction or indicate cirrhotic cardiomyopathy, respectively. The aim of the study was to assess cardiac dysfunction in liver transplant patients and its correlation with BNP as a biomarker. From 1/2008 to 7/2009, 157 adult liver transplant recipients with proven cirrhosis were recruited for the study. BNP and liver enzymes were recorded upon admission, on the first postoperative day (POD) and 1 week after transplantation. Patients with ischemic heart attacks were excluded from the study. We identified two groups of patients. Group 1 was characterized by a BNP <391 pg/ml and Group 2 by a BNP >391 pg/ml. Group 2 had a significantly higher model of end-stage liver disease score than Group 1 (median 30, range 10-40 versus median 22, range 10-40, respectively; P = 0.003), required significantly more dialysis treatments and had a significantly higher mortality rate. Postoperative echocardiography in patients with a BNP >391 pg/ml indicated diastolic dysfunction in all of the patients and systolic dysfunction in 10 of the patients. Increased serum-BNP was associated with an overall higher mortality rate.

Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation.

The aim of this study was to determine the efficacy, safety, and immunosuppressant adherence in 125 stable liver transplant (LT) patients converted from twice-daily tacrolimus (TAC BID) to once-daily TAC (TAC OD). Tacrolimus trough levels, laboratory parameters, metabolic disorders, selected patient reported outcomes, and adverse events were assessed. Mean TAC trough level concentration was 6.1 ± 2.3 ng/ml at study entry, decreased to 5.5 ± 2.1 ng/ml (P = 0.016) and 5.5 ± 2.2 ng/ml (P = 0.019) after 1 and 2 weeks, respectively, and tended to equal the baseline value during further follow-up. At week 1, TAC concentrations were lower in 62.4% of patients and higher in 36.0% when compared with baseline. Renal and cardiovascular risk factors remained stable and no rejection episodes occurred over 12 months. Adverse events were consistent with the safety profile known from previous studies with TAC BID. Nonadherence measured by the "Basel Assessment of Adherence Scale to Immunosuppressives" was evident in 66.4% at study entry and decreased to 30.9% postconversion (P < 0.0001). Prevalence of nonadherence at baseline was significantly higher in patients converted >2 years after LT and in those ≤60 years of age. Conversion to TAC OD is safe, enhances immunosuppressant adherence and should be accompanied by a close TAC level monitoring during the initial period.

Changes in staging for hepatocellular carcinoma after radiofrequency ablation prior to liver transplantation as found in the explanted liver.

BACKGROUND/AIMS: To analyze the efficacy of radiofrequency ablation (RFA) prior to liver transplantation (LT) in liver explants. METHODOLOGY: We reviewed pathological findings in the explanted livers of 13 patients with histologically proven HCC and liver cirrhosis who underwent RFA as bridging treatment prior to LT. Eight patients had solitary nodules with a median diameter of 4cm, whereas five patients had two tumors each with a median total diameter of 3.3cm prior to RFA. One session of RFA was performed by all patients. RESULTS: Tumor regression was proved in 3/13 patients whereas steady disease was observed in 5/13 patients (38%). Tumor regression was observed only in one of the five patients having two tumors prior to RFA. Pathology proved a multifocal tumor in four patients, including one patient with a radiological presumed solitary tumor. Tumor progression was observed in 5/13 patients (38%). CONCLUSIONS: Although the majority of our patients (8/13, 62%) had a solitary tumor at the beginning of treatment, tumor progression was observed in a large proportion (38%) among them. The underestimation of tumor lesions in radiology and partial necrosis of the tumor achieved in most patients limit the role of RFA as bridging treatment prior to LT.

Drainage patterns of right and accessory hepatic veins: anatomical-functional classification derived from 3-dimensional CT reconstructions.

BACKGROUND/AIMS: Inadequate knowledge of the right (RHV) and accessory (IHV) hepatic 'venous drainage' territories can lead to severe postoperative venous congestion after right graft live donor liver transplantation. The purpose of our study was to define the anatomical-functional RHV and IHV drainage territories. METHODOLOGY: One hundred and forty consecutive live liver donor candidates were evaluated by means of 3-D CT reconstructions and 3-D virtual hepatectomies. Three RHV/IHV drainage patterns were identified and 'risky' configurations for right graft resections were defined. RESULTS: Livers with 'small' IHV drainage volumes (90.1±63.2mL) had dominant type IRHV/ IHV or non-dominant type III-RHV/IHV total liver (TL) complexes. All other cases had 'large' IHV volumes (294.7±115.5mL, p<0.001) with dominant type II-RHV/IHV TL complexes. Loss of IHV drainage volume (such as with no IHV reconstruction) in these cases was associated with a 'dominance transition' from right (RHV) to middle (MHV) hepatic veins, placing the grafts at 'high risk' for venous congestion. CONCLUSIONS: Type II-RHV/IHV complexes with large IHV drainage volumes are at 'high risk' for venous congestion in live donor liver transplantation.

Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation.

Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.