Changes in the Liver Transplant Waiting List after Expanding to the 'Up-to-Seven' Criteria for Hepatocellular Carcinoma.

We aimed to assess changes in the composition of the waiting list for liver transplantation (LT) after expanding from Milan to "up-to-seven" criteria in patients with hepatocellular carcinoma (HCC). A consecutive cohort of 255 LT candidates was stratified in a pre-expansion era (2016-2018; n = 149) and a post-expansion era (2019-2021; n = 106). The most frequent indication for LT was HCC in both groups (47.7% vs. 43.4%; p = 0.5). The proportion of patients exceeding the Milan criteria in the explanted liver was nearly doubled after expansion (12.5% vs. 21.1%; p = 0.25). Expanding criteria had no effect in drop-out (12.3% vs. 20.4%; p = 0.23) or microvascular invasion rates (37.8% vs. 38.7%; p = 0.93). The length on the waiting list did not increase after the expansion (172 days [IQR 74-282] vs. 118 days [IQR 67-251]; p = 0.135) and was even shortened in the post-expansion HCC subcohort (181 days [IQR 125-232] vs. 116 days [IQR 74-224]; p = 0.04). Tumor recurrence rates were reduced in the post-expansion cohort (15.4% vs. 0%; p = 0.012). In conclusion, expanding from Milan to up-to-seven criteria for LT in patients with HCC had no meaningful impact on the waiting list length and composition, thus offering the opportunity for the adoption of more liberal policies in the future.

Enumeration and Characterization of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Circulating tumor cells (CTCs), and particularly circulating cancer stem cells (cCSC), are prognostic biomarkers for different malignancies and may be detected using liquid biopsies. The ex vivo culture of cCSCs would provide valuable information regarding biological aggressiveness and would allow monitoring the adaptive changes acquired by the tumor in real time. In this prospective pilot study, we analyzed the presence of EpCAM+ CTCs using the IsoFlux system in the peripheral blood of 37 patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE). The average patient age was 63.5 ± 7.9 years and 91.9% of the patients were men. All patients had detectable CTCs at baseline and 20 patients (54.1%) showed CTC aggregates or clusters in their peripheral blood. The increased total tumor diameter (OR: 2.5 (95% CI: 1.3-4.8), p = 0.006) and the absence of clusters of CTCs at baseline (OR: 0.2 (95% CI: 0.0-1.0), p = 0.049) were independent predictors of a diminished response to TACE. Culture of cCSC was successful in five out of thirty-three patients, mostly using negative enrichment of CD45- cells, ultra-low adherence, high glucose, and a short period of hypoxia followed by normoxia. In conclusion, the identification of clusters of CTCs before TACE and the implementation of standardized approaches for cCSC culture could aid to predict outcomes and to define the optimal adjuvant therapeutic strategy for a true personalized medicine in hepatocellular carcinoma.

Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices / Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme

Objetivo: El consenso de Baveno VI para el cribado endoscópico de varices esofagogástricas recomienda evitar la endoscopia en algunos pacientes. Bajo esta estrategia, podrían pasar desapercibidas lesiones no relacionadas con hipertensión portal, algunas de ellas potencialmente graves. El objetivo de este estudio es determinar la prevalencia de dichas lesiones e identificar los factores clínicos asociados a las mismas. Pacientes y métodos: Estudio transversal unicéntrico sobre una cohorte consecutiva de pacientes cirróticos sometidos a endoscopia digestiva alta en el contexto de un programa de cribado de varices esofagogástricas entre noviembre del 2013 y noviembre del 2018. Se analizaron los factores de riesgo para la presencia de lesiones no relacionadas con hipertensión portal mediante regresión logística uni y multivariante. Resultados: Se incluyó a 379 pacientes. La etiología mayoritaria de la cirrosis fue etílica (n=229; 60,4%). La prevalencia de lesiones endoscópicas no relacionadas con hipertensión portal fue del 39,6% (n=150). Entre los 96 pacientes con enfermedad péptica (25,3%) se tomó test de ureasa en 54 (56,2%), siendo positiva en 24 (44,4%). La presencia de lesiones endoscópicas no relacionadas con hipertensión portal no estuvo influida por la edad (p=1), el género (p=0,28), la función hepática (MELD p=0,20, Child-Pugh p=0,77) o la presencia de datos ecográficos de hipertensión portal (p=0,14). Los pacientes fumadores presentaron tendencia a mayor prevalencia de lesiones endoscópicas no relacionadas con la hipertensión portal (43,2% vs. 34,6%; p=0,09), particularmente úlcera péptica (6,4% vs. 0,6%; p=0,05) y duodenitis péptica (17,3% vs. 6,3%; p=0,002). El tabaquismo activo fue el único factor predictivo independiente de ulcus o duodenitis péptica (odds ratio=2,56; intervalo de confianza del 95%: 1,18-5,56; p=0,017).(AU)

Aim: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. Patients and methods: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. Results: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). Conclusion: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.(AU)

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Impact of MELD Allocation System on Waiting List and Early Post-Liver Transplant Mortality.

BACKGROUND AND AIMS: MELD allocation system has changed the clinical consequences on waiting list (WL) for LT, but its impact on mortality has been seldom studied. We aimed to assess the ability of MELD and other prognostic scores to predict mortality after LT. METHODS: 301 consecutive patients enlisted for LT were included, and prioritized within WL by using the MELD-score according to: hepatic insufficiency (HI), refractory ascites (RA) and hepatocellular carcinoma (HCC). The analysis was performed to predict early mortality after LT (8 weeks). RESULTS: Patients were enlisted as HI (44.9%), RA (19.3%) and HCC (35.9%). The major aetiologies of liver disease were HCV (45.5%). Ninety-four patients (31.3%) were excluded from WL, with no differences among the three groups (p = 0.23). The remaining 207 patients (68.7%) underwent LT, being HI the most frequent indication (42.5%). HI patients had the shortest length within WL (113.6 days vs 215.8 and 308.9 respectively; p<0.001), but the highest early post-LT mortality rates (18.2% vs 6.8% and 6.7% respectively; p<0.001). The independent predictors of early post-LT mortality in the HI group were higher bilirubin (OR = 1.08; p = 0.038), increased iMELD (OR = 1.06; p = 0.046) and non-alcoholic cirrhosis (OR = 4.13; p = 0.017). Among the prognostic scores the iMELD had the best predictive accuracy (AUC = 0.66), which was strengthened in non-alcoholic cirrhosis (AUC = 0.77). CONCLUSION: Patients enlisted due to HI had the highest early post-LT mortality rates despite of the shortest length within WL. The iMELD had the best accuracy to predict early post-LT mortality in patients with HI, and thus it may benefit the WL management.

Lack of agreement for defining 'clinical suspicion of rejection' in liver transplantation: a model to select candidates for liver biopsy.

The gold standard to diagnose acute cellular rejection (ACR) after liver transplantation (LT) is histological evaluation, but there is no consensus to select patients for liver biopsy. We aimed to evaluate the agreement among clinicians to select candidates for liver biopsy early after LT. From a protocol biopsy population (n = 690), we randomly selected 100 LT patients in whom the biopsy was taken 7-10 days after LT. The clinical information between LT and protocol biopsy was given to nine clinicians from three transplant centres who decided whether a liver biopsy was needed. The agreement among clinicians to select candidates for liver biopsy was poor: κ = 0.06-0.62, being κ < 0.40 in 76% of comparisons. The concordance between indication for liver biopsy and moderate-severe ACR in the protocol biopsy was κ < 0.30 in all cases. A multivariate model based on the product age-by-MELD (OR = 0.81; P = 0.013), delta eosinophils (OR = 1.5; P = 0.002) and mean tacrolimus trough concentrations <6 ng/ml within the prior 4 days (OR = 11.4; P = 0.047) had an AUROC = 0.84 to diagnose moderate-severe histological ACR. In conclusion, the agreement among clinicians to select patients for liver biopsy is very poor. If further validated the proposed model would provide an objective method to select candidates for liver biopsy after LT.

Reduced exposure to calcineurin inhibitors early after liver transplantation prevents recurrence of hepatocellular carcinoma.

BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) is a major complication after liver transplantation (LT). The initial immunosuppression protocol may influence HCC recurrence, but the optimal regimen is still unknown. METHODS: 219 HCC consecutive patients under Milan criteria, who received an LT at 2 European centres between 2000 and 2010, were included. Median follow-up was 51 months (IQR 26-93). Demographic characteristics, HCC features, and immunosuppression protocol within the first month after LT were evaluated against HCC recurrence by using Cox regression. RESULTS: In the explanted liver, 110 patients (50%) had multinodular HCC, and largest nodule diameter was 3±2.1cm. Macrovascular invasion was incidentally detected in 11 patients (5%), and microvascular invasion was present in 41 patients (18.7%). HCC recurrence rates were 13.3% at 3 years and 17.6% at 5 years. HCC recurrence was not influenced by the use/non-use of steroids and antimetabolites (p=0.69 and p=0.70 respectively), and was similar with tacrolimus or cyclosporine (p=0.25). Higher exposure to calcineurin inhibitors within the first month after LT (mean tacrolimus trough concentrations >10ng/ml or cyclosporine trough concentrations >300ng/ml), but not thereafter, was associated with increased risk of HCC recurrence (27.7% vs. 14.7% at 5 years; p=0.007). The independent predictors of HCC recurrence by multivariate analysis were: high exposure to calcineurin inhibitors defined as above (RR=2.82; p=0.005), diameter of the largest nodule (RR=1.31; p<0.001), microvascular invasion (RR=2.98; p=0.003) and macrovascular invasion (RR=4.57; p=0.003). CONCLUSIONS: Immunosuppression protocols with early CNI minimization should be preferred in LT patients with HCC in order to minimize tumour recurrence.

Perforación esofágica tras biopsia en paciente con esofagitis eosinofílica / Esophageal perforation following a biopsy in a patient with eosinophilic esophagitis

La esofagitis eosinofílica (EE) es una enfermedad infradiagnosticada que hay que sospechar ante todo paciente con disfagia e impactación alimentaria. Aunque estos son los síntomas guía, el espectro clínico y endoscópico es muy variable. Es obligatorio tomar conciencia sobre las posibles complicaciones derivadas de las maniobras diagnósticas y terapéuticas en la EE. Un manejo cuidadoso de los procedimientos endoscópicos conseguirá extremar las precauciones necesarias para evitar iatrogenia. Presentamos el caso de un varón joven con disfagia y estenosis esofágica que en el curso de su diagnóstico sufre como complicación una perforación esofágica (AU)

Eosinophilic esophagitis is an underdiagnosed disease that should be suspected in all patients with dysphagia and food impaction. Although these are the leading symptoms, the clinical and endoscopic spectrum is highly varied. Clinicians should be aware of the risk of endoscopy-related complications in this disorder. Precautions should be maximized in endoscopic examinations to avoid iatrogenic damage. We describe the case of a young patient with esophageal stricture and dysphagia who suffered a perforation following a biopsy (AU)

[Esophageal perforation following a biopsy in a patient with eosinophilic esophagitis]. / Perforación esofágica tras biopsia en paciente con esofagitis eosinofílica.

Eosinophilic esophagitis is an underdiagnosed disease that should be suspected in all patients with dysphagia and food impaction. Although these are the leading symptoms, the clinical and endoscopic spectrum is highly varied. Clinicians should be aware of the risk of endoscopy-related complications in this disorder. Precautions should be maximized in endoscopic examinations to avoid iatrogenic damage. We describe the case of a young patient with esophageal stricture and dysphagia who suffered a perforation following a biopsy.

Hepatitis aguda grave por azatioprina / Severe acute hepatitis due to azathioprine

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