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Backgrounds/aims: Thirty percent of liver grafts in donors after brain death (DBD) in Spain are rejected by procurement surgeons owing to marginal graft quality. Poor donor indocyanine green (ICG) clearance has been associated with graft discard and malfunction. This study aimed to internally and externally validate the predictive value of ICG-plasma disappearance rate (ICG-PDR) to reject grafts before donation and set a cut-off to avoid missing any potential effective donors., Methods: Between March 2017 and August 2023, ICG clearance test was performed immediately before procurement in 71 DBD. The surgeon was blinded to test results. Univariate and multivariate analyses were performed to detect independent predictors of graft discard. Discrimination and calibration of predictors were assessed and a cut-off with 100% specificity was set. External validation was performed on 17 donors evaluated by three other transplantation teams., Results: In the training cohort, 30 of 71 grafts were discarded for transplantation. ICG-PDR was the only donor variable independently associated with graft discard. The area under receiver operating characteristic curve for ICG-PDR was 0.875 (95% confidence interval: 0.768-0.947) and good calibration was observed. Below a PDR of 13.5%/min, no graft was accepted for transplantation. These results were successfully validated using the external cohort of donors., Conclusions: ICG clearance test performed in DBD was internally and externally validated to predict liver graft discard. It could be used as a screening tool before donation to avoid unnecessary costs of travel and human resources.

Objective: Advances in hepatic radioembolization are based on a selective approach with radical intent and the use of multicompartment dosimetric analysis. The objective of this study is to assess the utility of voxel-based dosimetry in the quantification of actual absorbed doses in radiation segmentectomy procedures and to establish cutoff values predictive of response., Methods: Ambispective study in hepatocarcinoma patients treated with radiation segmentectomy. Calculated dosimetric parameters were mean tumor-absorbed dose, maximum tumor AD, minimal tumor AD in 30, 50, and 70% of tumor volume and mean AD in non-tumor liver. The actual absorbed dose (aAD) was calculated on the Y-90-PET/CT image using 3D voxel-based dosimetry software. To assess radiological response, localized mRECIST criteria were used. The objective response rate (ORR) was defined as CR or PR., Results: Twenty-four HCC patients, BCLC 0 (5), A (17) and B (2) were included. The mean yttrium-90 administered activity was 1.38 GBq in a mean angiosome volume of 206.9 cc and tumor volume 56.01 cc. The mean theoretical AD was 306.3 Gy and aAD 352 Gy. A very low concordance was observed between both parameters (rho_c 0.027). ORR at 3 and 6 m was 84.21% and 92.31%, respectively. Statistically significant relationship was observed between the maximum tumor-absorbed dose and complete radiological response at 3 m (p 0.022)., Conclusion: A segmental approach with radical intention leads to response rates greater than 90%, being the tumor maximum absorbed dose the dosimetric parameter that best predicts radiological response in voxel-based dosimetry., (© 2023. The Author(s).)

Background & Aims: Clinically significant portal hypertension (CSPH) is a landmark in the natural history of cirrhosis, influencing clinical decisions in patients with hepatocellular carcinoma (HCC). Previous small series suggested that splanchnic volume measurements may predict portal hypertension. We aimed to evaluate whether volumetry obtained by standard multidetector computerised tomography (MDCT) can predict CSPH in patients with HCC., Methods: We included 175 patients with HCC, referred for hepatic venous pressure gradient (HVPG) evaluation, in whom contemporary MDCT was available. Liver volume, spleen volume (SV) and liver segmental volume ratio (LSVR: volume of the segments I-III/volume of the segments IV-VIII) were calculated semi-automatically from MDCT. Other non-invasive tests (NITs) were also employed., Results: Volume parameters could be measured in almost 100% of cases with an excellent inter-observer agreement (intraclass correlation coefficient >0.950). SV and LSVR were independently associated with CSPH (HVPG ≥10 mmHg) and did not interact with aetiology. The volume Index (VI), calculated as the product of SV and LSVR, predicted CSPH (AUC 0.83; 95% CI 0.77-0.89). Similar results were observed in an external cohort (n = 23) (AUC 0.87; 95% CI 0.69-1.00). Setting a sensitivity and specificity of 98%, VI could have avoided 35.9% of HVPG measurements. The accuracy of VI was similar to that of other NITs. VI also accurately predicted HVPG greater than 12, 14, 16 and 18 mmHg (AUC 0.81 [95% CI 0.74-0.88], 0.84 [95% CI 0.77-0.91], 0.85 [95% CI 0.77-0.92] and 0.87 [95% CI 0.79-0.94], respectively)., Conclusions: Quantification of liver and spleen volumes by MDCT is a simple, accurate and reliable method of CSPH estimation in patients with compensated cirrhosis and HCC., Impact and Implications: An increase in portal pressure strongly impacts outcomes after surgery in patients with early hepatocellular carcinoma (HCC). Direct measurement through hepatic vein catheterization remains the reference standard for portal pressure assessment, but its invasiveness limits its application. Therefore, we evaluated the ability of CT scan-based liver and spleen volume measurements to predict portal hypertension in patients with HCC. Our results indicate that the newly described index, based on quantification of liver and spleen volume, accurately predicts portal hypertension. These results suggest that a single imaging test may be used to diagnose and stage HCC, while providing an accurate estimation of portal hypertension, thus helping to stratify surgical risks., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)

Hepatocellular carcinoma (HCC) is the most frequent liver primary cancer and represents the sixth malignant neoplasm and the fourth cause of cancer associated deaths worldwide. Despite improvements across the last years in therapeutic options, it is still associated with a high mortality. Therefore, HCC represents a major health problem and a challenge for clinicians in terms of management of patient care.

Background: Determination of indocyanine green (ICG) plasma disappearance rate (PDR) is a simple, inexpensive, and noninvasive tool to assess liver perfusion, absorption, and elimination. Its application in the liver transplant process has not been widely incorporated in clinical practice. This study aims to assess the usefulness of ICG PDR in the donor selection setting and in the early post-transplant phase and to analyze its variation between these 2 time points., Methods: We performed a single-center prospective observational study. ICG clearance test was performed in 50 brain-dead donors (T0-PDR) to assess concordance with graft suitability. Rejected grafts biopsy specimens were analyzed to correlate histology with T0-PDR. In the recipients, ICG PDR was performed before wound closure (T1-PDR). The association of T0, T1, and T0-T1 variation with the development of early allograft dysfunction (EAD) was investigated., Results: A total of 23 of 50 grafts were discarded because of poor macroscopic quality. A T0-PDR below 15.5%/min could predict graft rejection with 100% specificity and 69.6% sensitivity. All the biopsy specimens from donors with PDR < 10 %/min showed liver fibrosis. A total of 25 of the remaining 27 grafts were implanted; 5 patients (20%) developed EAD. T1-PDR performed better than T0-T1 variation to predict dysfunction., Conclusions: ICG PDR could be used in the donors as a filter to discard poor-quality grafts before procurement and, in the early post-transplant phase, to predict EAD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Cirrhosis is characterized by the complex interplay among biological, histological and haemodynamic events. Liver and spleen remodelling occur throughout its natural history, but the prognostic role of these volumetric changes is unclear. We evaluated the relationship between volumetric changes assessed by multidetector computerised tomography (MDCT) and landmark features of cirrhosis., Methods: We included consecutive cirrhotic patients who underwent liver transplantation (LT) or hepatocellular carcinoma (HCC) resection in whom dynamic MDCT was available. Different volumetric indices were calculated. Fibrosis was evaluated by the collagen proportional area and Laennec sub-stages. Correlation and logistic regression analysis were performed to explore associations of volumetric indexes and fibrosis with key prognostic features across the clinical stages of cirrhosis., Results: 185 patients were included (146 LT; 39 HCC); the predominant aetiology was viral hepatitis (51.35%); 65.9% had decompensated disease and 85.08% clinically significant portal hypertension (CSPH). The standardised liver volume and liver-spleen volume ratio negatively correlated with Model for End-stage Liver Disease (MELD), albumin and hepatic venous pressure gradient (HVPG) and were significantly lower in decompensated patients. The liver segmental volume ratio (segments I-III/segments IV-VIII) best captured the characteristic features of the compensated phase, showing a positive correlation with HVPG and a good discrimination between patients with and without CSPH and varices. Volumetric changes and fibrosis severity were independently associated with key prognostic events, with no association between these two parameters., Conclusions: Liver and spleen volumetric indices evolve differently along the natural history of cirrhosis and are associated with key prognostic factors in each phase, regardless of fibrosis severity and portal hypertension., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population., Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded., Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE., Conclusions: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The prevalence and management of coronary artery disease (CAD) in liver transplantation (LT) candidates are not well characterized. The aims of this study were to evaluate the impact on clinical outcomes of a specifically designed protocol for the management of asymptomatic CAD in LT candidates and to investigate noninvasive risk profiles for obstructive and nonobstructive CAD for 202 LT candidates. Those with high baseline cardiovascular risk (CVR; defined by the presence of classic CVR factors and/or decreased ejection fraction) received coronary angiography and significant arterial stenosis and were treated with percutaneous stents. Patients were followed up after LT until death or coronary event (CE). There were 78 patients who received coronary evaluation (62 direct angiography, 14 computed tomography coronary angiography, and 2 both). Of them, 39 (50%) patients had CAD of any severity, and 6 (7.7%) had significant lesions (5 were amenable to be treated with stents, whereas 1 patient had diffuse lesions which contraindicated the LT). Insulin-dependent diabetes was the only factor related to CAD of any severity (odds ratio, 3.44; 95% confidence interval [CI], 1.00-11.97). A total of 69 patients (46 with coronary evaluation) received LT. The incidence of CEs and overall survival after LT were similar between patients with and without coronary evaluation. Furthermore, no differences occurred between these groups in a multivariate competing risk model (subhazard ratio, 0.84; 95% CI, 0.27-2.61; P = 0.76). In conclusion, the application of an angiographic screening protocol of CAD in a selected high-risk Mediterranean population is safe and effective. The short- and medium-term incidence rates of CEs and death after LT in this population are similar to that observed in low-risk patients., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Background: Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatmentof choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application., Material and Methods: A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C)., Results: Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an "on-demand" basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria., Conclusion: Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised.

Background: Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown., Aim: This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension., Methods: Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score., Results: HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11)., Conclusions: AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by loss of balance and motor coordination due to dysfunction of the cerebellum and its afferent and efferent connections. Despite a well-described clinical and pathological phenotype, the molecular and cellular events that underlie neurodegeneration are still poorly understood. Compelling evidence points to major aetiological roles for interference with transcriptional regulation, protein aggregation and clearance, the ubiquitin-proteasome system and alterations of calcium homeostasis in the neuronal loss observed during the neurodegenerative process. But novel molecular routes that might be disrupted during disease progression are also being identified. These pathways could act independently or, more likely, interact and enhance each other, triggering the accumulation of cellular damage that eventually leads to dysfunction and, ultimately, the demise of neurons through a series of multiple events. This suggests that simultaneous targeting of several pathways might be therapeutically necessary to prevent neurodegeneration and preserve neuronal function. Understanding how dysregulation of these pathways mediates disease progression is leading to the establishment of effective therapeutic strategies in vivo, which may prove beneficial in the treatment of SCAs. Herein, we review the latest evidence for the proposed molecular processes to the pathogenesis of dominantly inherited spinocerebellar ataxias and the current therapeutic strategies.