Reproductive and pregnancy control in Wilson disease patients in Spain.

BACKGROUND AND AIM: Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives. METHODS: This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry. RESULTS: The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician's recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient. CONCLUSION: Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations.

COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

OBJECTIVES: Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in PBC patients improve with OCA therapy. METHODS: Patients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score-weighted EC group was derived from a US healthcare claims database. RESULTS: In the RCT, the primary endpoint occurred in 28.6% of OCA (n=168) and 28.9% of placebo patients (n=166; intent-to-treat [ITT] analysis hazard ratio [HR]=1.01, 95% CI=0.68-1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting (IPCW) and as-treated analyses shifted the HR to favor OCA. In the EC (n=1051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR=0.39; 95% CI=0.22-0.69; P=0.001). No new safety signals were identified in the RCT. CONCLUSIONS: Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the ITT estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC.

Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update.

Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.

Profile of plasma microRNAs as a potential biomarker of Wilson's disease.

BACKGROUND: Wilson's disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs. METHODS: We conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b-/- mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age. RESULTS: In patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b-/- mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream. CONCLUSIONS: The upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD.

Validation of MELD3.0 in 2 centers from different continents.

BACKGROUND: MELD3.0 has been proposed to stratify patients on the liver transplant waiting list (WL) to reduce the historical disadvantage of women in accessing liver transplant. Our aim was to validate MELD3.0 in 2 unique populations. METHODS: This study is a 2-center retrospective cohort study from Toronto, Canada, and Valencia, Spain, of all adults added to the liver transplant WL between 2015 and 2019. Listing indications whose short-term survival outcome is not adequately captured by the MELD score were excluded. All patients analyzed had a minimum follow-up of 3 months after inclusion in the WL. RESULTS: Six hundred nineteen patients were included; 61% were male, with a mean age of 56 years. Mean MELD at inclusion was 18.00 ± 6.88, Model for End-Stage Liver Disease Sodium (MELDNa) 19.78 ± 7.00, and MELD3.0 20.25 ± 7.22. AUC to predict 90-day mortality on the WL was 0.879 (95% CI: 0.820, 0.939) for MELD, 0.921 (95% CI: 0.876, 0.967) for MELDNa, and 0.930 (95% CI: 0.888, 0.973) for MELD3.0. MELDNa and MELD3.0 were better predictors than MELD (p = 0.055 and p = 0.024, respectively), but MELD3.0 was not statistically superior to MELDNa (p = 0.144). The same was true when stratified by sex, although the difference between MELD3.0 and MELD was only significant for women (p = 0.032), while no statistical significance was found in either sex when compared with MELDNa. In women, AUC was 0.835 (95% CI: 0.744, 0.926) for MELD, 0.873 (95% CI: 0.785, 0.961) for MELDNa, and 0.886 (95% CI: 0.803, 0.970) for MELD3.0; differences for the comparison between AUC in women versus men for all 3 scores were nonsignificant. Compared to MELD, MELD3.0 was able to reclassify 146 patients (24%), the majority of whom belonged to the MELD 10-19 interval. Compared to MELDNa, it reclassified 68 patients (11%), most of them in the MELDNa 20-29 category. CONCLUSIONS: MELD3.0 has been validated in centers with significant heterogeneity and offers the highest mortality prediction for women on the WL without disadvantaging men. However, in these cohorts, it was not superior to MELDNa.

Use of HBsAg-positive donors in liver transplantation: An ILTS-EASL-AASLD multisociety survey.

The gap between organ supply and demand in liver transplantation remains large in most parts of the world. One strategy to increase the donor pool is to use grafts infected with HCV, HBV, and/or HIV viruses. We aimed to explore the current use of HBsAg-positive liver grafts worldwide. A prospective cross-sectional web-based survey was designed, with a total of 28 queries, assessing national and local regulations, center experience, and center-specific experience related to the topic, and sent to all members of International Liver Transplantation Society, European Association for the Study of the Liver, and American Association for the Study of the Liver, and promoted on social media. A total of 135 liver transplant centers answered the survey: 38% from WHO European Regions, 39% from American regions, and 9.7% from South-East Asian regions. Most of the participating centers (67.3%) had been performing liver transplantation for over 15 years, with a mean of 66.5 liver transplants per year, and 54% also performed living-donor liver transplants. HBV-related disease was the indication for liver transplantation in an average of 15% of all liver transplantation cases. Regarding national and/or regional regulations, 40% of the centers reported that the use of HBsAg-positive donors was permitted, and an additional 20% could use them under special circumstances. Thirty-two centers (31%) had previously used HBsAg-positive donors. Among these centers, 62.5% conducted living-donor liver transplants and showed an increased inclination toward the use of HBsAg-positive grafts in centers with elevated waitlist mortality. HBsAg-positive donors are underutilized worldwide. The use of HBsAg-positive liver grafts could help to increase the donor pool, particularly in highly endemic areas.

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

External validation of models to predict hepatocellular carcinoma in Hepatitis C Virus cured F3-F4 patients.

BACKGROUND & AIMS: Several hepatocellular carcinoma (HCC) risk-models have been developed to individualise patient surveillance following sustained viral response (SVR) in Hepatitis C Virus patients. Validation of these models in different cohorts is an important step to incorporate a more personalised risk assessment in clinical practice. We aimed at applying these models to stratify the risk in our patients and potentially determine cost-saving associated with individualised HCC risk-stratification screening strategy. METHODS: Patients with baseline F3-4 fibrosis treated with new oral direct-acting antivirals who had reached a SVR were regularly followed as part of the HCC surveillance strategy. Six models were applied: Pons, aMAP, Ioannou, HCC risk, Alonso and Semmler. Validation of the models was performed based on sensitivity and the proportion of patients labelled as "high risk". RESULTS: After excluding 557 with less than 3 fibrosis, 12 without SVR, 18 with a follow up (FU) <1 year, 17 transplant recipients, 16 lost to FU and 31 with HCC at time of antiviral therapy, our cohort consisted of 349 F3-4 SVR patients. Twenty-three patients (6.6%) developed HCC after a median FU of 5.12 years. The sensitivity of the different models varied between 0.17 (Semmler7noalcohol) and 1 (Alonso A and aMAP). The lowest proportion of high-risk patients corresponded to the Semmler-noalcohol model (5%). Sixty-three and 90% of the Alonso A and aMAP patients, respectively were labelled as high risk. The most reliable HCC risk-model applied to our cohort to predict HCC development is the Alonso model (based on fibrosis stage assessed by liver stiffness measurements or Fibrosis-4 index (FIB-4) at baseline and after 1 year, and albumin levels at 1 year) with a-100% sensitivity in detecting HCC among those at high risk and 63% labelled as high risk. The application of the model would have saved the cost of 1290 ultrasound no longer being performed in the 37% low-risk group. CONCLUSION: In our cohort, the Alonso A model allows the most reliable reduction in HCC screening resulting in safely stopping life-long monitoring in about a third of F3-F4 patients achieving SVR with DAAs.

Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.

Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.

Frailty Changes After Liver Transplantation. Results From a Spanish Multicenter Prospective Cohort Study.

Introduction: Until now, there has been limited evidence, primarily from US cohorts, focusing on frailty as a patient-oriented outcome after liver transplantation (LT). Our study aimed to explore the relationship between pre- and post-LT frailty in a multicenter European cohort of outpatients with cirrhosis undergoing LT. Methods: We conducted a prospective analysis of data from 180 LT recipients recruited between 2018 and 2020 from 5 Spanish centers. Participants underwent objective and subjective frailty assessments using the Liver Frailty Index (LFI) and the Subjective Clinician Assessment (SCA) pretransplant and at 3- and/or 6-mo posttransplant. Results: The median pretransplant LFI was 3.9, showing minimal change at 3 mo (3.8; P = 0.331) and improvement at 6-mo post-LT (3.6; P = 0.001). Conversely, the SCA significantly improved early post-LT: at 3 mo, poor SCA decreased from 11% to 1%, and good SCA increased from 54% to 89% (P < 0.001), remaining stable between 3- and 6-mo post-LT. Multivariable analysis revealed that each 0.1 increase in pretransplant LFI correlated with a reduced probability of being robust at 3-mo (odds ratio [OR] = 0.75; P < 0.001) and 6-mo post-LT (OR = 0.74; P < 0.001). There was poor concordance between SCA and LFI, with SCA underestimating frailty both pre- and post-LT (Kappa < 0.20). Conclusion: In our European cohort, incomplete improvement of physical frailty was observed, with <20% achieving robust physical condition within 6-mo post-LT. The pretransplant LFI strongly predicted posttransplant frailty. As the SCA tends to overestimate physical function, we recommend using both subjective and objective tools for frailty assessment in LT candidates and recipients.

Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

BACKGROUND AND AIMS: Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS: Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS: Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION: In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Effect of Cysteine with Essential Oils on Quality Attributes and Functional Properties of 'Blanca de Tudela' Fresh-Cut Artichoke.

The commercialisation of fresh-cut artichokes with optimal quality and appearance and a maximum shelf-life is a great challenge for the artichoke market. The use of different anti-browning agents has been previously studied; however, their effect is still limited. Therefore, the objective of this study is the evaluation of the effect of L-cysteine and, in combination with a mixture of essential oils components (eugenol, thymol and carvacrol) on browning, quality and bioactive compounds of fresh-cut artichokes stored for 9 days at 2 °C. Four different treatments were applied to 'Blanca de Tudela' fresh-cut artichokes: cysteine and cysteine with 75, 150 and 300 µL of the essential oils components (EOs) mixture. After 2, 4 and 9 days of storage, physicochemical parameters (weight loss, colour, respiration rate) and functional (total phenolic content, antioxidant activity) were studied. A descriptive sensorial analysis was also carried out to evaluate sensory attributes. Results showed that the application of cysteine and 150 µL of EOs displayed the lowest browning and highest antioxidant properties, as well as the best quality and sensory parameters. The use of this post-harvest treatment on fresh-cut artichokes would result in a natural and eco-friendly solution to improve artichoke quality and shelf-life.

Influence of Artichoke Antioxidant Activity in Their Susceptibility to Suffer Frost Injury.

In the northern hemisphere countries, artichoke harvest occurs in winter months; consequently, they are exposed to cold temperatures. This can lead to frost injury, such as triggering the blistering of the cuticle and detachment of outer bracts, which eventually could display brown or black discolouration. This can cause major economic and production losses. As far as we know, no literature is available about this problem in artichokes. Thus, the main aim of this study was to evaluate the effect of total phenolic content and the antioxidant potential of 'Blanca de Tudela' artichokes in their capacity to tolerate frost injury when they are exposed to low temperatures. Several factors were analysed, including floral head order, weight and size of artichokes, total phenolic content, phenolic profile and total antioxidant activity. Results showed that tertiary heads, which are the smallest in size, exhibited a greater amount of total phenolic content and antioxidant activity. As a result, these characteristics offered enhanced protection to the artichoke against frosting temperatures. In contrast, the largest artichokes, especially the primary heads, were more susceptible to suffer frostbite. Therefore, artichokes with robust antioxidant systems, characterized by elevated phenolic content, are crucial to reduce their susceptibility to frost injury.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). METHODS: A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. RESULTS: It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. CONCLUSIONS: Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. METHODS: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. RESULTS: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. CONCLUSIONS: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

Management of Established Small-for-size Syndrome in Post Living Donor Liver Transplantation: Medical, Radiological, and Surgical Interventions: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) following living donor liver transplantation is a complication that can lead to devastating outcomes such as prolonged poor graft function and possibly graft loss. Because of the concern about the syndrome, some transplants of mismatched grafts may not be performed. Portal hyperperfusion of a small graft and hyperdynamic splanchnic circulation are recognized as main pathogenic factors for the syndrome. Management of established SFSS is guided by the severity of the presentation with the initial focus on pharmacological therapy to modulate portal flow and provide supportive care to the patient with the goal of facilitating graft regeneration and recovery. When medical management fails or condition progresses with impending dysfunction or even liver failure, interventional radiology (IR) and/or surgical interventions to reduce portal overperfusion should be considered. Although most patients have good outcomes with medical, IR, and/or surgical management that allow graft regeneration, the risk of graft loss increases dramatically in the setting of bilirubin >10 mg/dL and INR>1.6 on postoperative day 7 or isolated bilirubin >20 mg/dL on postoperative day 14. Retransplantation should be considered based on the overall clinical situation and the above postoperative laboratory parameters. The following recommendations focus on medical and IR/surgical management of SFSS as well as considerations and timing of retransplantation when other therapies fail.

European Society for Organ Transplantation Consensus Statement on Biomarkers in Liver Transplantation.

Currently, one-year survival following liver transplantation (LT) exceeds 90% in large international registries, and LT is considered definitive treatment for patients with end-stage liver disease and liver cancer. Recurrence of disease, including hepatocellular carcinoma (HCC), significantly hampers post-LT outcomes. An optimal approach to immunosuppression (IS), including safe weaning, may benefit patients by mitigating the effect on recurrent diseases, as well as reducing adverse events associated with over-/under-IS, including chronic kidney disease (CKD). Prediction of these outcome measures-disease recurrence, CKD, and immune status-has long been based on relatively inaccurate clinical models. To address the utility of new biomarkers in predicting these outcomes in the post-LT setting, the European Society of Organ Transplantation (ESOT) and International Liver Transplant Society (ILTS) convened a working group of experts to review literature pertaining to primary disease recurrence, development of CKD, and safe weaning of IS. Summaries of evidence were presented to the group of panelists and juries to develop guidelines, which were discussed and voted in-person at the Consensus Conference in Prague November 2022. The consensus findings and recommendations of the Liver Working Group on new biomarkers in LT, clinical applicability, and future needs are presented in this article.