GEMA-Na and MELD 3.0 severity scores to address sex disparities for accessing liver transplantation: a nationwide retrospective cohort study.

Background: The Gender-Equity Model for liver Allocation corrected by serum sodium (GEMA-Na) and the Model for End-stage Liver Disease 3.0 (MELD 3.0) could amend sex disparities for accessing liver transplantation (LT). We aimed to assess these inequities in Spain and to compare the performance of GEMA-Na and MELD 3.0. Methods: Nationwide cohort study including adult patients listed for a first elective LT (January 2016-December 2021). The primary outcome was mortality or delisting for sickness within the first 90 days. Independent predictors of the primary outcome were evaluated using multivariate Cox's regression with adjusted relative risks (RR) and 95% confidence intervals (95% CI). The discrimination of GEMA-Na and MELD 3.0was assessed using Harrell c-statistics (Hc). Findings: The study included 6071 patients (4697 men and 1374 women). Mortality or delisting for clinical deterioration occurred in 286 patients at 90 days (4.7%). Women had reduced access to LT (83.7% vs. 85.9%; p = 0.037) and increased risk of mortality or delisting for sickness at 90 days (adjusted RR = 1.57 [95% CI 1.09-2.28]; p = 0.017). Female sex remained as an independent risk factor when using MELD or MELD-Na but lost its significance in the presence of GEMA-Na or MELD 3.0. Among patients included for reasons other than tumours (n = 3606; 59.4%), GEMA-Na had Hc = 0.753 (95% CI 0.715-0.792), which was higher than MELD 3.0 (Hc = 0.726 [95% CI 0.686-0.767; p = 0.001), showing both models adequate calibration. Interpretation: GEMA-Na and MELD 3.0 might correct sex disparities for accessing LT, but GEMA-Na provides more accurate predictions of waiting list outcomes and could be considered the standard of care for waiting list prioritization. Funding: Instituto de Salud Carlos III, Agencia Estatal de Investigación (Spain), and European Union.

Antimigration versus conventional fully covered metal stents in the endoscopic treatment of anastomotic biliary strictures after deceased-donor liver transplantation.

INTRODUCTION: Migration of fully covered metal stents (FCMS) remains a limitation of the endoscopic treatment of anastomotic biliary strictures (ABS) following orthotopic liver transplantation (OLT). The use of antimigration FCMS (A-FCMS) might enhance endoscopic treatment outcomes for ABS. METHODS: Single center retrospective study. Consecutive patients with ABS following OLT who underwent ERCP with FCMS placement between January 2005 and December 2020 were eligible. Subjects were grouped into conventional-FCMS (C-FCMS) and A-FCMS. The primary outcome was stent migration rates. Secondary outcomes were stricture resolution, adverse event, and recurrence rates. RESULTS: A total of 102 (40 C-FCMS; 62 A-FCMS) patients were included. Stent migration was identified at the first revision in 24 C-FCMS patients (63.2%) and in 21 A-FCMS patients (36.2%) (p = 0.01). The overall migration rate, including the first and subsequent endoscopic revisions, was 65.8% in C-FCMS and 37.3% in A-FCMS (p = 0.006). The stricture resolution rate at the first endoscopic revision was similar in both groups (60.0 vs 61.3%, p = 0.87). Final stricture resolution was achieved in 95 patients (93.1%), with no difference across groups (92.5 vs 93.5%; p = 0.84). Adverse events were identified in 13 patients (12.1%) with no difference across groups. At a median follow-up of 52 (IQR: 19-85.5) months after stricture resolution, 25 patients (24.5%) developed recurrences, with no difference across groups (C-FCMS 30% vs A-FCMS 21%; p = 0.28). CONCLUSIONS: The use of A-FCMS during ERCP for ABS following OLT results in significantly lower stent migration rates compared to C-FCMS. However, the clinical benefit of reduced stent migration is unclear. Larger studies focusing on stricture resolution and recurrence rates are needed.

Esophageal necrosis secondary to thoracic aortic aneurysm.

We present the case of a 78-year-old man with dyslipidemia with ongoing treatment with statins. He was admitted for a history of 3-month dysphagia and weight loss. The physical exam was unremarkable. Blood tests revealed anemia (hemoglobin 11,5 g/dL). Gastroscopy showed a partially stenotic bulging ulcer in the middle esophagus, with a fibrinous base and residual clot Histopathology ruled out any malignancy and confirmed the presence of transmural necrosis with infiltration of inflammatory cells. Computed tomography (CT) revealed a 11x11x12 cm thoracic aortic aneurysm, with an intramural 4 cm thrombus in the anterolateral wall. The patient was referred for urgent Vascular Surgery, but unfortunately, he presented massive hematemesis with cardiorespiratory arrest, and despite cardiopulmonary resuscitation, he died.

Postreperfusion Biopsy as a Predictor of Biliary Complication After Deceased Donor Liver Transplantation. A Retrospective Cohort Study.

BACKGROUND: Ischemia reperfusion injury (IRI) on postreperfusion biopsies is associated with worse outcomes after liver transplantation, although the influence on biliary complications (BC) remains poorly studied. Therefore, the primary aim of our study was to assess the influence of IRI on the incidence of BC. A secondary aim was to assess the influence of steatosis on biliary complications and determine factors that predictor BC. METHODS: We report a retrospective cohort study including patients with liver transplantation and postreperfusion injury. Biopsies were classified as relevant and nonrelevant ischemia reperfusion injury for assessment of BC. BC included anastomotic stricture, ischemic cholangiopathy, leaks, and bilomas. Independent predictive factors of biliary complications were assessed using univariate and multivariate analyses. RESULTS: 302 patients were included, and 125 patients fulfilled the criteria for relevant IRI (41.4%). Worse IRI was not associated with biliary complications (42.5% vs 40.1%; P = .68), nor was liver graft steatosis associated with BC (40.5% vs 41.5%, P = .95). The median time until biliary complications did not differ between the 2 groups (2 months; interquartile range = 1-15 vs 3 months; interquartile range = 1-12.5; P = .18). Hepatic artery thrombosis (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.4-8.2; P = .004), older donor age (OR = 2.1; 95% CI, 1.1-4.1; P = .024), and prolonged cold ischemia time (OR = 1.9; 95% CI, 1.1-3.2) were independent factors of biliary complications. CONCLUSION: Severe IRI on the postreperfusion injury does not predict development of biliary complications.

Postreperfusion Liver Biopsy as Predictor of Early Graft Dysfunction and Survival After Orthotopic Liver Transplantation.

Background: Postreperfusion liver biopsy (PRB) can assess the degree of ischemia/reperfusion injury (IRI) after orthotopic liver transplantation (OLT). The influence of IRI on graft outcomes and overall survival is controversial. Aim: To determine the correlation between the severity of IRI in PRB and overall graft and patient survival and, secondarily, to identify factors on PRB that predict poor graft outcomes. Methods: This is a retrospective analysis of all patients who underwent OLT using donation after brain death (DBD) with PRB. The severity of IRI in PRB was graded. Predictors of IRI were assessed using univariate and multivariate analysis and the Kaplan-Meier with log rank test for the graft and overall survival, respectively. Results: We included 280 OLTs (64.7%). The histopathological assessment of IRI severity was as follows: no IRI (N = 96, 34.3%), mild IRI (N = 65; 23.2%), moderate IRI (N = 101; 36.1%), and severe IRI (N = 18; 6.4%). The incidence rates of initial good graft function (IGGF), primary nonfunction and early allograft dysfunction (EAD) were 32.5%, 3.9%, and 18.6%, respectively. Severe IRI was associated with a lower incidence of IGGF (OR: 0.34, 95% CI 0.12-0.92; P = 0.03). Patients with severe IRI tended to have a higher incidence of EAD (33.2% vs. 18.6, P = 0.23). The cold ischemia time was an independent predictor of severe IRI on the multivariate analysis. Severe IRI was associated with poor 1- and 5-year overall survival rates (67% and 44%, respectively, compared with 84 and 68% in nonsevere IRI). Patients with severe IRI exhibited worse graft and overall survival. Conclusions: Cold ischemia time predicts the development of severe IRI. Patients with severe IRI show worse graft and overall survival and a lower incidence of IGGF, suggesting that histopathological findings could be useful for identifying patients at high risk of worse outcomes after OLT.

XI factor deficiency as cause of recurrent gastrointestinal bleeding.

We present the case of a 73-year-old woman with no relevant medical history. She was admitted for a 3-month intermittent melena. The physical exam was unremarkable. Blood tests revealed anemia (hemoglobin 7.4 g/dL), raised urea (69 mg/dL), normal platelets and coagulation. Gastroscopy was performed with active oozing bleeding in the fundus and gastric body. Endoscopic fulguration of the potential lesions with holmium laser was performed. She was discharged with resolution of the symptoms and analytical improvement. However, the patient required hospitalization two weeks later due to recurrence of melena and anemia.

Immunosuppressive Treatment With mTOR Inhibitors for Malignancies After Liver Transplantation: Long-Term Survival Retrospective Analysis.

BACKGROUND: Immunosuppressive calcineurin inhibitors have been associated with an increased risk of post-transplant malignancies. The mammalian target of rapamycin inhibitors (mTORi) is an alternative immunosuppressive regimen with an antineoplastic effect. The aim of the study was to determine the long-term survival of mTORi-treated recipients with de novo or recurring tumors after liver transplantation (LT). METHODS: This retrospective analysis included mTORi-treated LT recipients between March 2013 and March 2019. We analyzed long-term survival and mTORi indications in an oncology setting in patients with de novo and recurrent malignancies after LT. Overall survival (OS) rate was compared from the Spanish Liver Transplant Registry (SLTR) data using the Kaplan-Meier method. High-risk hepatocellular carcinoma (HCC) was defined as microvascular invasion or satellite lesions as described in the liver explant. RESULTS: A total of 237 patients underwent LT during the study period; 111 patients underwent mTORi-based immunosuppression (48%, cancer was the main indication): 24.5% high-risk HCC; 24.4% HCC recurrence; 14.3% cholangiocarcinoma; and 36.7% de novo malignancies. The 1- and 5-year OS rates after LT in the mTORi group were 83% and 65%, respectively (SLTR group, 85% and 72.6%, respectively); 30.6% patients received mTORi monotherapy, and 38.7% patients had an early switch to mTORi in the first 3 months after oncologic diagnosis. mTORi monotherapy or oncologic treatment strategies had a nonsignificant association with prognosis. The OS rate was higher when the mTORi switch occurred early, 83% and 67%, respectively. CONCLUSIONS: mTORi-based immunosuppression may be a preferred option in patients transplanted with tumors. The OS rate was comparable to data from the SLTR. An mTORi early switch improves OS rate.

Hepatocolic fistula managed with a novel Padlock® device for endoscopic closure.

Recent advances in endoscopic therapeutics allow conditions such as fistulas of the digestive system to be treated endoscopically. These cases were recently managed with surgery. The Padlock® system includes a nitinol clip that was recently introduced for endoscopic therapy. There are few reports with regard to its use in the daily clinical practice. We report a case of a colonic fistula that was endoscopically managed with this novel over-the-scope nitinol clip system.

Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease.

Current evidence suggests that gut dysbiosis drives obesity and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Toll-like receptor 2 (TLR2) and TLR6 specifically recognize components of Gram-positive bacteria. Despite the potential implications of TLR2 in NAFLD pathogenesis, the role of TLR6 has not been addressed. Our aim is to study a potential role of TLR6 in obesity-related NAFLD. Forty morbidly obese patients undergoing bariatric surgery were prospectively studied. Cell surface expression of TLR2 and TLR6 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated monocytes were cultured with specific TLR2/TLR6 agonists and intracellular production of cytokines was determined by flow-cytometry. In liver biopsies, the expression of TLR2 and TLR6 was analyzed by immunohistochemistry and cytokine gene expression using RT-qPCR. TLR6 expression in PBMCs from non-alcoholic steatohepatitis (NASH) patients was significantly higher when compared to those from simple steatosis. The production of pro-inflammatory cytokines in response to TLR2/TLR6 stimulation was also significantly higher in patients with lobular inflammation. Hepatocyte expression of TLR6 but not that of TLR2 was increased in NAFLD patients compared to normal liver histology. Deregulated expression and activity of peripheral TLR6 in morbidly obese patients can mirror the liver inflammatory events that are well known drivers of obesity-related NASH pathogenesis. Moreover, TLR6 is also significantly overexpressed in the hepatocytes of NAFLD patients compared to their normal counterparts. Thus, deregulated TLR6 expression may potentiate TLR2-mediated liver inflammation in NAFLD pathogenesis, and also serve as a potential peripheral biomarker of obesity-related NASH.