Recipient donor sex combinations in solid organ transplantation and impact on clinical outcome: A scoping review.

INTRODUCTION: Solid organ transplantation (SOT) is a lifesaving treatment for end-stage organ failure. Although many factors affect the success of organ transplantation, recipient and donor sex are important biological factors influencing transplant outcome. However, the impact of the four possible recipient and donor sex combinations (RDSC) on transplant outcome remains largely unclear. METHODS: A scoping review was carried out focusing on studies examining the association between RDSC and outcomes (mortality, graft rejection, and infection) after heart, lung, liver, and kidney transplantation. All studies up to February 2023 were included. RESULTS: Multiple studies published between 1998 and 2022 show that RDSC is an important factor affecting the outcome after organ transplantation. Male recipients of SOT have a higher risk of mortality and graft failure than female recipients. Differences regarding the causes of death are observed. Female recipients on the other hand are more susceptible to infections after SOT. CONCLUSION: Differences in underlying illnesses as well as age, immunosuppressive therapy and underlying biological mechanisms among male and female SOT recipients affect the post-transplant outcome. However, the precise mechanisms influencing the interaction between RDSC and post-transplant outcome remain largely unclear. A better understanding of how to identify and modulate these factors may improve outcome, which is particularly important in light of the worldwide organ shortage. An analysis for differences of etiology and causes of graft loss or mortality, respectively, is warranted across the RDSC groups. PRACTITIONER POINTS: Recipient and donor sex combinations affect outcome after solid organ transplantation. While female recipients are more susceptible to infections after solid organ transplantation, they have higher overall survival following SOT, with causes of death differing from male recipients. Sex-differences should be taken into account in the post-transplant management.

Surgical site infections after kidney transplantation are independently associated with graft loss.

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND & AIMS: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.

Humoral response to SARS-CoV-2 infection among liver transplant recipients.

OBJECTIVE: Immunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19. DESIGN: Prospective multicentre case-control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT). RESULTS: Overall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024). CONCLUSIONS: Our findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.

Final safety and efficacy results from a 106 real-world patients registry with an ascites-mobilizing pump.

BACKGROUND AND AIMS: Patients with cirrhotic refractory ascites ineligible for transjugular intrahepatic shunt (TIPSS) have limited treatment options apart from repeated large volume paracentesis. The alfapump® is an implantable device mobilizing ascites from the peritoneal cavity to the bladder, from where it can be excreted. The aim of this observational cohort study was to prospectively investigate safety and efficacy of the device in a real-world cohort with cirrhotic refractory ascites and contraindications for TIPSS. METHODS: A total of 106 patients received an implant at 12 European centres and were followed up for up to 24 months. Complications, device deficiencies, frequency of paracentesis, clinical status and survival were recorded prospectively. RESULTS: Approximately half of the patients died on-study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow-up. The most frequent causes of on-study death and complication-related explant were progression of liver disease and infection. The device reduced the requirement for large-volume paracentesis significantly, with more than half of patients not having required any post-implant. Survival benefits were not observed. Device-related reinterventions were predominantly caused by device deficiencies. A post-hoc comparison of the first 50 versus the last 50 patients enrolled revealed a decreased reintervention rate in the latter, mainly related to peritoneal catheter modifications. CONCLUSIONS: The device reduced paracentesis frequency in a real-world setting. Technical complications were successfully decreased by optimization of management and device modification (NCT01532427).

The MELD upgrade exception: a successful strategy to optimize access to liver transplantation for patients with high waiting list mortality.

BACKGROUND: MELD exceptions are designed to equipoise liver transplant waiting list survival. We aimed to analyze the impact of the MELD Upgrade rule and all other MELD exceptions on the liver transplant waiting list outcomes during 2012-2017 in Switzerland. METHODS: We conducted a nationwide cohort study including all adult patients registered on the Swiss liver transplant waiting list between 2012 and 2017. Waiting list mortality and access to transplantation were analyzed, considering MELD exceptions as time-dependent covariates. RESULTS: 730 patients were included. Patients with MELD Upgrade exceptions had a higher risk of dying while on the waiting list (OR 2.13; CI 95% 1.30-3.47) and also an increased likelihood of receiving a liver transplantation, when compared to patients without MELD exceptions. Patients with any type of MELD exceptions were more likely to be transplanted when compared to patients without MELD exceptions. The proportion of patients with MELD exceptions increased from 2012 to 2017 (44% vs 88%). Allocation MELD at the time of transplantation showed an annual increase (23 ± 8 points vs 32 ± 5 points, p < 0.001). CONCLUSION: Only patients with MELD Upgrade exceptions had the expected combination of higher waiting list mortality and quicker access to liver transplantation.

Effects of structured intraoperative briefings on patient outcomes: multicentre before-and-after study.

BACKGROUND: Operations require collaboration between surgeons, anaesthetia professionals, and nurses. The aim of this study was to determine whether intraoperative briefings influence patient outcomes. METHODS: In a before-and-after controlled trial (9 months baseline; 9 months intervention), intraoperative briefings were introduced in four general surgery centres between 2015 and 2018. During the operation, the responsible surgeon (most senior surgeon present) briefed the surgical team using the StOP? protocol about: progress of the operation (Status), next steps (Objectives), possible problems (Problems), and encouraged asking questions (?). Differences between baseline and intervention were analysed regarding surgical-site infections (primary outcome), mortality, unplanned reoperations, and duration of hospital stay (secondary outcomes), using inverse probability of treatment (IPT) weighting based on propensity scores. RESULTS: In total, 8256 patients underwent surgery in the study. Endpoint data were available for 7745 patients (93.8 per cent). IPT-weighted and adjusted intention-to-treat analyses showed no differences in surgical-site infections between baseline and intervention (9.8 versus 9.6 per cent respectively; adjusted difference (AD) -0.15 (95 per cent c.i. -1.45 to 1.14) per cent; odds ratio (OR) 0.92, 95 per cent c.i. 0.83 to 1.15; P = 0.797), but there were reductions in mortality (1.6 versus 1.1 per cent; AD -0.54 (-1.04 to -0.03) per cent; OR 0.60, 0.39 to 0.92; P = 0.018), unplanned reoperations (6.4 versus 4.8 per cent; AD -1.66 (-2.69 to -0.62) per cent; OR 0.72, 0.59 to 0.89; P = 0.002), and fewer prolonged hospital stays (21.6 versus 19.8 per cent; AD -1.82 (-3.48 to -0.15) per cent; OR 0.87, 0.77 to 0.98; P = 0.024). CONCLUSION: Short intraoperative briefings improve patient outcomes and should be performed routinely.

Outcomes of surgery depend on patient characteristics and surgeon expertise, but also on teamwork, notably communication. The present study introduces the StOP? protocol, in which the surgeon informs the team about the current status (St), objectives regarding next steps (O), and potential problems (P), and encourages the team to ask questions and raise concerns (?). The results suggest an effect of the StOP? intervention on patient mortality, risk of unplanned reoperation, and duration of hospital stay, but not on surgical-site infections. The study is promising regarding the effect of structured intraoperative communication on important patient outcomes. The study compared patient outcomes at baseline and after implementation of the StOP? protocol, which enhances exchange of structured information within the interdisciplinary surgical team during the course of the operation. The intention-to-treat analyses in this multicentre before-and-after study of 8256 patients undergoing general surgery showed no differences between baseline and intervention for surgical-site infections, but revealed reduced mortality and unplanned reoperations, and fewer prolonged hospital stays during the intervention period.

Stereotactic image-guided microwave ablation of hepatocellular carcinoma using a computer-assisted navigation system.

BACKGROUND & AIMS: Ablation plays an important role in the treatment of hepatocellular carcinoma. Because image-guided navigation technology has recently entered the clinical setting, we aimed to analyse its safety, therapeutic and procedural efficiency. METHODS: Retrospective analysis of patients treated with stereotactic image-guided microwave ablation (SMWA) between January 2015 and December 2017. Interventions were performed using computertomography-guidance with needle trajectory, ablation planning and automatic single-marker patient registration. Needle placement and ablation coverage was controlled by image fusion under general anaesthesia with jet-ventilation. RESULTS: In total 174 ablations were performed in 88 patients during 119 interventions. Mean age was 66 (46-84) years, 74 (84.1%) were men and 74% were Child Pugh Class A. Median tumour size was 16 (4-45) mm, 62.2% were BCLC A. Median lateral and longitudinal error of needle placement were 3.2 (0.2-14.1) and 1.6 (0-15.8) mm. Median one tumour (1-4) was ablated per session. One patient developed a Dindo IIIb (0.8%) complication, six minor complications. After re-ablation of 12 lesions, an efficacy rate of 96.3% was achieved. Local tumour progression was 6.3% (11/174). Close proximity to major vessels was significantly correlated with local tumour progression (P < .05). Median overall follow-up was 17.5 months after intervention and 24 months after initial diagnosis. BCLC stage, child class and previous treatment were significantly correlated with overall survival (P < .05). CONCLUSION: Stereotactic image-guided microwave ablation is a safe and efficient treatment for HCC offering a curative treatment approach in general and in particular for lesions not detectable on conventional imaging or untreatable because of difficult anatomic locations.

A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts.

BACKGROUND: Clinical risk factors for postoperative nausea and vomiting (PONV) are well described, whereas genetic findings are conflicting. OBJECTIVE: The aim of this study was to investigate a possible association of genetic variants and nongenetic variables with the incidence and severity of PONV. DESIGN: A prospective observational study in two independent and different patient cohorts. SETTING: Two independent patient cohorts differing in surgical procedures were enrolled in two tertiary care hospitals between 2008 and 2016. PATIENTS: Consecutive patients of European origin undergoing elective surgery in two university hospitals. Clinical data were collected up to 24 h after surgery, and blood was drawn for genotyping. Of 2773 patients enrolled, 918 (Cohort A) and 1663 (Cohort B) with complete data sets were analysed. MAIN OUTCOME MEASURE: Patients were allocated to one of three groups (No PONV, Intermediate PONV or Severe PONV) depending on the frequency of vomiting, the severity of nausea and the need for antiemetics. Clinical variables and 13 genetic variants of seven candidate genes were evaluated for association with these three phenotypes. The cohorts were analysed separately by ordinal logistic regression analysis, treating PONV as a dependent ordinal three-stage variable. Odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: In Cohort A, the main predictors for PONV were female sex [OR (95% CI): 3.6 (2.7 to 4.8), P < 0.0001], nonsmoking status 1.8 (1.3 to 2.5), P < 0.001, the SS genotype (5-HTTLPR, rs4795541) of the promoter polymorphism in the serotonin transporter 1.5 (1.1 to 2.1), P = 0.019, and patient age 0.99 (0.98 to 0.99), P = 0.013. Analysis of Cohort B was consistent with these findings [5-HTTLPR: 1.8 (1.4 to 2.3), P < 0.00001]. Sex-specific regression models confirmed this 5-HTTLPR association in women and men. CONCLUSION: In two independent cohorts, in addition to the well known clinical factors, a polymorphism of 5-HTTLPR in the serotonin transporter was independently associated with PONV. A possible evaluation of this biomarker to improve risk prediction within the scope of precision medicine should be considered. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03490175.

A sustaining rod increases necrosis of loop ileostomies: a randomized controlled trial.

PURPOSE: Defunctioning loop ileostomies (LI) are commonly used in colorectal surgery to reduce the potentially detrimental consequences of anastomotic leakages. However, stoma-related morbidity is high with up to 75% of patients having local complications. The aim of this study was to investigate the effect of a sustaining rod on the local complication rate. METHODS: In this prospective, multi-center, randomized controlled trial, subjects were allocated to either a rod or a rod-less protocol (NCT00959738). The primary outcome was local morbidity as measured by a stoma specific morbidity score (SSMS) during the first 3 months postoperatively. RESULTS: Between August 2008 and July 2014, a total of 122 patients were enrolled in the study, of which 78 (63.8%) completed the study [44 (56.4%) rod, 34 (43.6%) rod-less]. There was no significant difference in the SSMS between the two groups. The incidence of necrosis or partial necrosis, however, was significantly increased in the rod group: 13 (29.5%) vs. 1 (2.9%) in the rod-less group (p < 0.01). The retraction rate did not differ significantly between the groups: two (4.5%) in the rod vs. five (14.7%) in the rod-less group (p = 0.13). High body mass index (BMI > 26) was associated with an odds ratio of 5 (p < 0.01) for severe stoma complications. CONCLUSIONS: A rod-less technique for loop ileostomies reduces the risk of stomal necrosis, with a high BMI being an independent risk factor for stomal complications.

Laparoscopic image-based navigation for microwave ablation of liver tumors-A multi-center study.

BACKGROUND: Stereotactic navigation technology has been proposed to augment accuracy in targeting intrahepatic lesions for local ablation therapy. This retrospective study evaluated accuracy, efficacy, and safety when using laparoscopic image-guided microwave ablation (LIMA) for malignant liver tumors. METHODS: All patients treated for malignant liver lesions using LIMA at two European centers between 2013 and 2015 were included for analysis. A landmark-based registration technique was applied for intraoperative tumor localization and positioning of ablation probes. Intraoperative efficiency of the procedure was measured as number of registration attempts and time needed to achieve sufficient registration accuracy. Technical accuracy was assessed as Fiducial Registration Error (FRE). Outcome at 90 days including mortality, postoperative morbidity, rates of incomplete ablations, and early intrahepatic recurrences were reported. RESULTS: In 34 months, 54 interventions were performed comprising a total of 346 lesions (median lesions per patient 3 (1-25)). Eleven patients had concomitant laparoscopic resections of the liver or the colorectal primary tumor. Median time for registration was 4:38 min (0:26-19:34). Average FRE was 8.1 ± 2.8 mm. Follow-up at 90 days showed one death, 24% grade I/II, and 4% grade IIIa complications. Median length of hospital stay was 2 days (1-11). Early local recurrence was 9% per lesion and 32% per patient. Of these, 63% were successfully re-ablated within 6 months. CONCLUSIONS: LIMA does not interfere with the intraoperative workflow and results in low complication and early local recurrence rates, even when simultaneously targeting multiple lesions. LIMA may represent a valid therapy option for patients with extensive hepatic disease within a multimodal treatment approach.

Intraoperative image-guided navigation system: development and applicability in 65 patients undergoing liver surgery.

BACKGROUND: Image-guided systems have recently been introduced for their application in liver surgery. We aimed to identify and propose suitable indications for image-guided navigation systems in the domain of open oncologic liver surgery and, more specifically, in the setting of liver resection with and without microwave ablation. METHOD: Retrospective analysis was conducted in patients undergoing liver resection with and without microwave ablation using an intraoperative image-guided stereotactic system during three stages of technological development (accuracy: 8.4 ± 4.4 mm in phase I and 8.4 ± 6.5 mm in phase II versus 4.5 ± 3.6 mm in phase III). It was evaluated, in which indications image-guided surgery was used according to the different stages of technical development. RESULTS: Between 2009 and 2013, 65 patients underwent image-guided surgical treatment, resection alone (n = 38), ablation alone (n = 11), or a combination thereof (n = 16). With increasing accuracy of the system, image guidance was progressively used for atypical resections and combined microwave ablation and resection instead of formal liver resection (p < 0.0001). CONCLUSION: Clinical application of image guidance is feasible, while its efficacy is subject to accuracy. The concept of image guidance has been shown to be increasingly efficient for selected indications in liver surgery. While accuracy of available technology is increasing pertaining to technological advancements, more and more previously untreatable scenarios such as multiple small, bilobar lesions and so-called vanishing lesions come within reach.

A Novel Ultrasound-Based Registration for Image-Guided Laparoscopic Liver Ablation.

Background Patient-to-image registration is a core process of image-guided surgery (IGS) systems. We present a novel registration approach for application in laparoscopic liver surgery, which reconstructs in real time an intraoperative volume of the underlying intrahepatic vessels through an ultrasound (US) sweep process. Methods An existing IGS system for an open liver procedure was adapted, with suitable instrument tracking for laparoscopic equipment. Registration accuracy was evaluated on a realistic phantom by computing the target registration error (TRE) for 5 intrahepatic tumors. The registration work flow was evaluated by computing the time required for performing the registration. Additionally, a scheme for intraoperative accuracy assessment by visual overlay of the US image with preoperative image data was evaluated. Results The proposed registration method achieved an average TRE of 7.2 mm in the left lobe and 9.7 mm in the right lobe. The average time required for performing the registration was 12 minutes. A positive correlation was found between the intraoperative accuracy assessment and the obtained TREs. Conclusions The registration accuracy of the proposed method is adequate for laparoscopic intrahepatic tumor targeting. The presented approach is feasible and fast and may, therefore, not be disruptive to the current surgical work flow.

Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors.

BACKGROUND & AIMS: Sporadic pancreatic neuroendocrine tumors (pNETs) are rare and genetically heterogeneous. Chromosome instability (CIN) has been detected in pNETs from patients with poor outcomes, but no specific genetic factors have been associated with CIN. Mutations in death domain-associated protein gene (DAXX) or ATR-X gene (ATRX) (which both encode proteins involved in chromatin remodeling) have been detected in 40% of pNETs, in association with activation of alternative lengthening of telomeres. We investigated whether loss of DAXX or ATRX, and consequent alternative lengthening of telomeres, are related to CIN in pNETs. We also assessed whether loss of DAXX or ATRX is associated with specific phenotypes of pNETs. METHODS: We collected well-differentiated primary pNET samples from 142 patients at the University Hospital Zurich and from 101 patients at the University Hospital Bern (both located in Switzerland). Clinical follow-up data were obtained for 149 patients from general practitioners and tumor registries. The tumors were reclassified into 3 groups according to the 2010 World Health Organization classification. Samples were analyzed by immunohistochemistry and telomeric fluorescence in situ hybridization. We correlated loss of DAXX, or ATRX, expression, and activation of alternative lengthening of telomeres with data from comparative genomic hybridization array studies, as well as with clinical and pathological features of the tumors and relapse and survival data. RESULTS: Loss of DAXX or ATRX protein and alternative lengthening of telomeres were associated with CIN in pNETs. Furthermore, loss of DAXX or ATRX correlated with tumor stage and metastasis, reduced time of relapse-free survival, and decreased time of tumor-associated survival. CONCLUSIONS: Loss of DAXX or ATRX is associated with CIN in pNETs and shorter survival times of patients. These results support the hypothesis that DAXX- and ATRX-negative tumors are a more aggressive subtype of pNET, and could lead to identification of strategies to target CIN in pancreatic tumors.

Vascular cell adhesion molecule 1 expression by biliary epithelium promotes persistence of inflammation by inhibiting effector T-cell apoptosis.

UNLABELLED: Chronic hepatitis occurs when effector lymphocytes are recruited to the liver from blood and retained in tissue to interact with target cells, such as hepatocytes or bile ducts (BDs). Vascular cell adhesion molecule 1 (VCAM-1; CD106), a member of the immunoglobulin superfamily, supports leukocyte adhesion by binding α4ß1 integrins and is critical for the recruitment of monocytes and lymphocytes during inflammation. We detected VCAM-1 on cholangiocytes in chronic liver disease (CLD) and hypothesized that biliary expression of VCAM-1 contributes to the persistence of liver inflammation. Hence, in this study, we examined whether cholangiocyte expression of VCAM-1 promotes the survival of intrahepatic α4ß1 expressing effector T cells. We examined interactions between primary human cholangiocytes and isolated intrahepatic T cells ex vivo and in vivo using the Ova-bil antigen-driven murine model of biliary inflammation. VCAM-1 was detected on BDs in CLDs (primary biliary cirrhosis, primary sclerosing cholangitis, alcoholic liver disease, and chronic hepatitis C), and human cholangiocytes expressed VCAM-1 in response to tumor necrosis factor alpha alone or in combination with CD40L or interleukin-17. Liver-derived T cells adhered to cholangiocytes in vitro by α4ß1, which resulted in signaling through nuclear factor kappa B p65, protein kinase B1, and p38 mitogen-activated protein kinase phosphorylation. This led to increased mitochondrial B-cell lymphoma 2 accumulation and decreased activation of caspase 3, causing increased cell survival. We confirmed our findings in a murine model of hepatobiliary inflammation where inhibition of VCAM-1 decreased liver inflammation by reducing lymphocyte recruitment and increasing CD8 and T helper 17 CD4 T-cell survival. CONCLUSIONS: VCAM-1 expression by cholangiocytes contributes to persistent inflammation by conferring a survival signal to α4ß1 expressing proinflammatory T lymphocytes in CLD.

Factors affecting screening for hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a frequent cancer. Its prognosis is highly dependent on early diagnosis. Patients at risk for developing HCC should be enrolled in a surveillance programme. Nevertheless, many patients at risk are not regularly screened. We aimed at exploring the characteristics that affect enrolment in a surveillance programme. MATERIAL AND METHODS: The characteristics of the patients included in the prospective Bern HCC cohort between August 2010 and August 2011 were analysed according to their participation in a surveillance programme. RESULTS: Among the 82 patients included in the cohort during this period of time, 48 were in a surveillance program before the diagnosis of HCC. Thirty five percent of cirrhotic patients were not screened. Age, sex, level of education, Child-Pugh status and MELD score were similar between the patients who were screened and those who were not screened. Patients with a private insurance and patients treated by a liver specialist were more frequently enrolled in a surveillance program. Sixty seven percent of the screened patients were eligible for curative treatment whereas only 15% of the non-screened patients were. CONCLUSIONS: In conclusion the surveillance of patients at risk for developing HCC increases their chances to be diagnosed at an early stage to allow curative treatment. More than one third of cirrhotic patients were not regularly screened. Patients with chronic liver disease should be referred to identify those at risk and enrol them in a surveillance program.