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Background: End-stage liver diseases (ESLDs) are a significant global health challenge due to their high prevalence and severe health impacts. Despite the severe outcomes associated with ESLDs, therapeutic options remain limited. Targeting the activation of hepatic stellate cells (HSCs), key drivers of extracellular matrix accumulation during liver injury presents a novel therapeutic approach. In ESLDs patients, branched-chain amino acids (BCAAs, leucine, isoleucine and valine) levels are decreased, and supplementation has been proposed to attenuate liver fibrosis and improve regeneration. However, their effects on HSCs require further investigation. Objective: To evaluate the efficacy of BCAAs and their metabolites, branched-chain α-keto acids (BCKAs), in modulating HSCs activation in human and rat models. Methods: Primary HSCs from rats and cirrhotic and non-cirrhotic human livers, were cultured and treated with BCAAs or BCKAs to assess their effects on both preventing (from day 1 of isolation) and reversing (from day 7 of isolation) HSCs activation. Results: In rat HSCs, leucine and BCKAs significantly reduced fibrotic markers and cell proliferation. In human HSCs, the metabolite of isoleucine decreased cell proliferation around 85% and increased the expression of branched-chain ketoacid dehydrogenase. The other metabolites also showed antifibrotic effects in HSCs from non-cirrhotic human livers. Conclusion: BCAAs and their respective metabolites inhibit HSC activation with species-specific responses. Further research is needed to understand how BCAAs influence liver fibrogenesis. BCKAs supplementation could be a strategic approach for managing ESLDs, considering the nutritional status and amino acid profiles of patients. The antifibrotic effects of BCAAs and BCKAs in various conditions are depicted for human HSCs (left) and rat HSCs (right) The symbol ‘↓’ indicates a downregulation or a decrease. α-SMA alpha-smooth muscle actin, BCAAs branched-chain amino acids, BCKAs branched-chain keto acids, HSCs hepatic stellate cells, KMV α-keto-β-methylvalerate. Figure created with Biorender.com [ABSTRACT FROM AUTHOR]

The prevalence and mortality related to end-stage liver disease (ESLD) continue to rise globally. Liver transplant (LT) recipients continue to be older and have inherently more comorbidities. Among these, cardiac disease is one of the three main causes of morbidity and mortality after LT. Several reasons exist including the high prevalence of associated risk factors, which can also be attributed to the rise in the proportion of patients undergoing LT for metabolic dysfunction-associated steatohepatitis (MASH). Additionally, as people age, the prevalence of now treatable cardiac conditions, including coronary artery disease (CAD), cardiomyopathies, significant valvular heart disease, pulmonary hypertension, and arrhythmias rises, making the need to treat these conditions critical to optimize outcomes. There is an emerging body of literature regarding CAD screening in patients with ESLD, however, there is a paucity of strong evidence to support the guidance regarding the management of cardiac conditions in the pre-LT and perioperative settings. This has resulted in significant variations in assessment strategies and clinical management of cardiac disease in LT candidates between transplant centres, which impacts LT candidacy based on a transplant centre's risk tolerance and comfort level for caring for patients with concomitant cardiac disease. Performing a comprehensive assessment and understanding the potential approaches to the management of ESLD patients with cardiac conditions may increase the acceptance of patients, who appear too complex, but rather require extra evaluation and may be reasonable candidates for LT. The unique physiology of ESLD can profoundly influence preoperative assessment, perioperative management, and outcomes associated with underlying cardiac pathology, and requires a thoughtful multidisciplinary approach. The strategies proposed in this manuscript attempt to review the latest expert experience and opinions and provide guidance to practicing clinicians who assess and treat patients being considered for LT. These topics also highlight the gaps that exist in the comprehensive care of LT patients and the need for future investigations in this field. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a frequent complication following liver transplantation (LT) that has a multifactorial etiology. While some perioperative risk factors have been associated with postoperative AKI, the impact of liver graft weight to recipient body weight ratio (GW/RBW) has been poorly explored. We hypothesized that a high GW/RBW ratio would be associated with AKI after LT. Methods: This single‐center historical cohort study included all consecutive adults who had LT at Paul Brousse Hospital between 2018 and 2022. Patients requiring preoperative renal replacement therapy, combined solid organ transplantation, retransplantation, split or domino graft were excluded, as well as those with missing graft weight and creatinine values during the first postoperative week. The primary exposure was GW/RBW ratio expressed as a proportion. The primary outcome was the incidence of postoperative AKI within 7 days after surgery, defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcome was the AKI severity (KDIGO grades). We estimated logistic and ordinal regression models adjusted for potential confounding factors and explored nonlinear associations. Results: Of 467 patients analyzed, 211 (45%) developed AKI. A high GW/RBW ratio was associated with both the risk of postoperative AKI and the severity of AKI (KDIGO grades), especially above a threshold of 2.5% (non‐linear effect). Conclusion: A high GW/RBW ratio was associated with an exponential increase in the risk of AKI after LT. A high GW/RBW ratio was also associated with an increased AKI severity. Our findings may help improve graft allocation in patients undergoing LT. [ABSTRACT FROM AUTHOR]

Background: Data to guide dialysis decision-making for transplant-ineligible patients with cirrhosis are lacking. Aims: We aimed to describe the processes, predictors, and outcomes of renal replacement therapy (RRT) initiation for transplant-ineligible patients with cirrhosis at a single liver transplantation center. Methods: We conducted a mixed-methods study of a retrospective cohort of 372 transplant-ineligible inpatients with cirrhosis with acute kidney injury (AKI) due to hepatorenal syndrome (HRS-AKI) or acute tubular necrosis (ATN) between 2008 and 2015. We performed survival analyses to evaluate 6-month survival and renal recovery and examined end-of-life care outcomes. We used a consensus-driven medical record review to characterize processes leading to RRT initiation. Results: We identified 266 (71.5%) patients who received RRT and 106 (28.5%) who did not receive RRT (non-RRT). Median survival was 12.5 days (RRT) vs. 2.0 days (non-RRT) (HR 0.36, 95%CI 0.28–0.46); 6-month survival was 15% (RRT) vs. 0% (non-RRT). RRT patients were more likely to die in the intensive care unit (88% vs. 32%, p < 0.001). HRS-AKI patients were more likely to be RRT dependent at 6 months than ATN patients (86% vs. 27%, p = 0.007). The most common reasons for RRT initiation were unclear etiology of AKI on presentation (32%) and belief of likely reversibility of ATN (82%). Conclusion: Most transplant-ineligible patients who were initiated on RRT experienced very short-term mortality and received intensive end-of-life care. However, approximately 1 in 6 were alive at 6 months. Our findings underscore the critical need for structured clinical processes to support high-quality serious illness communication and RRT decision-making for this population. [ABSTRACT FROM AUTHOR]

Background and Aim: The Model for End‐Stage Liver Disease (MELD) is a reliable prognostic tool for short‐term outcome prediction in patients with end‐stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD‐Na, in patients with alcoholic liver cirrhosis. Methods: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD‐Na, and MELD 3.0, for 30‐day and 90‐day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. Results: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD‐Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD‐Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90‐day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. Conclusion: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Introduction: Ascites, a severe complication of cirrhosis, significantly impacts patient morbidity and mortality especially in Black patients. Access to disease optimizing care has been proposed as a potential driver of this disparity. In this study, we evaluate TIPS utilization across racial and ethnic groups. Methods: We examined data from a 20% random sample of US Medicare enrollees with continuous Part D coverage. We required 180 days of continuous outpatient enrollment prior to cirrhosis diagnosis and all patients had ≥1 paracentesis within 180 days of their cirrhosis diagnosis. Time zero was the date of the first paracentesis. We assessed the likelihood of TIPS placement. Analyses were conducted to determine the independent associations between each outcome and race/ethnicity. Results: 5915 patients (average age 68.2, 64.4% male) were included in the analysis. 439 (7.4%) patients were identified as Black, 223 (3.8%) as Hispanic, and 4942 (83.6%) as white. When compared to white patients in a multivariable analysis, Black patients were less likely to receive a TIPS procedure (hazard ratio 0.4; 95% confidence interval (CI) 0.2–0.8) and had less days alive outside of the hospital (−100.5; 95% CI −189.4 – −11.6). There were no significant differences in transplant-free survival or number of paracenteses per year between ethnic and racial groups. Conclusion: Black patients are less likely to receive a TIPS procedure when controlling for common patient- and disease-specific variables. Access to optimal specialized services may be a significant driver for disparities in outcomes of patients with cirrhosis between racial and ethnic groups. [ABSTRACT FROM AUTHOR]

Background and Aims: Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes. Methods: 593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan–Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes. Results: The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted. Conclusion: Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT. [ABSTRACT FROM AUTHOR]

Purpose of Review: This paper aims to investigate the crucial role of palliative care in the management of chronic liver disease (CLD) and cirrhosis. Faced with a global surge in liver-related morbidity and mortality, our goal is to understand the impact of early engagement with palliative care specialists on symptom management, quality of life, and the overall trajectory of advanced liver disease. Recent Findings: While strides have been made in preventing and treating specific etiologies of CLD, such as viral infections, the escalating rates of alcohol use and obesity present new challenges for physicians. Despite advancements, liver transplantation unfortunately remains an elusive solution for many due to various constraints. Our review underscores the underutilization of palliative care in this context, emphasizing its potential to mitigate symptoms and enhance the overall well-being of patients and their caregivers. Summary: Implementing palliative care early during CLD proves instrumental in reducing symptoms, hospitalizations, and resource utilization. This not only improves the quality of life for patients but also signifies a paradigm shift in approaching the uncertainties surrounding advanced liver disease. Urging further research and global initiatives, our findings advocate for a comprehensive integration of palliative care in the holistic management of patients with advanced liver disease. [ABSTRACT FROM AUTHOR]

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Background: Persons with HIV (PWH) with end-stage kidney disease (ESKD) who are eligible for kidney transplantation have post-transplantation outcomes similar to those without HIV infection. However, barriers to referral for care, evaluation, and receipt of transplants remain for PWH. We sought to identify PWH with ESKD or end-stage liver disease (ESLD) who would be candidates for organ transplant and to review their clinical outcomes. Methods: We analyzed data from participants in the HIV Outpatient Study (HOPS) between January 1, 2009, and June 30, 2023, with a diagnosis of ESKD or ESLD. We identified a subset of PWH who would otherwise meet the general criteria for kidney or liver transplantation. Targeted clinical outcomes included dialysis, transplantation, and death. Results: Among 5215 PWH in the HOPS, 258 with ESKD and 23 with ESLD would otherwise meet the criteria for transplant. However, only 9 kidney and 2 liver transplants were performed. Conclusions: Low transplantation rates among eligible PWH suggest that timely referral for care and evaluation for kidney and liver transplantation often does not occur. Expanding access for PWH with ESKD to both deceased and living donor kidney allografts is needed. Kidney and liver transplant centers also need to seek ways to broaden access for eligible PWH with ESKD or ESLD. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic liver disease (CLD) in children, often leads to cirrhosis and end-stage liver disease (ESLD). CLD poses significant challenges in management and prognosis. Assessing body composition, including sarcopenia, is increasingly recognized as important in understanding outcomes in this population. Methods We conducted a prospective observational study, involving children aged 2 to 18 years with ESLD awaiting liver transplantation. Socio-demographic, clinical, and laboratory data were collected, and body composition was assessed using Bioelectrical Impedance Analysis (BIA). Sarcopenia was defined using age-specific cut-off points for appendicular skeletal muscle mass (aSMM) and fat-free mass (FFM). Results The study included 57 children (42.1% girls, 57.9% boys; median age: 10.9 years) with liver cirrhosis. Of them 11 (19.3%) died during the study. The mean duration of living with end-stage liver disease prior to participation was 5.43 years [IQR: 3.32, 8.39]. The most common etiology was biliary atresia (24.6%), followed by cryptogenic (22.8%). Deceased children exhibited significantly higher sarcopenia prevalence, lower basal metabolic rate and growth scores compared to survivors (P

Background : Living donor liver transplantation (LDLT) is an effective treatment for patients with end-stage liver disease. This study was performed to evaluate the outcomes of the initial series of LDLT procedures performed in the Republic of Uzbekistan and to demonstrate that liver transplantation is viable under the conditions in this country. Methods : Between October 2021 and December 2023, we performed 40 LDLTs. We evaluated both immediate and long-term outcomes. Results : Thrombosis of the hepatic artery developed in one case (2.5%). Arterial anastomotic stenoses were diagnosed in three cases (7.5%) and were successfully treated with endovascular balloon vasodilation. Splenic artery steal syndrome arose in three patients (7.5%) and was managed with endovascular embolization of the splenic artery. One patient (2.5%) developed portal vein thrombosis. Portal vein stenosis occurred in two patients (5%) at 10 months posttransplantation and was addressed with endovascular balloon angioplasty, yielding good clinical outcomes. Biliary complications were observed in 45% of the cases, with bile leakages accounting for 89% of these issues and strictures of the biliary anastomoses for 11%. The in-hospital mortality rate was 12.5%. Conclusions: Our research findings and analysis of complications align with the international literature, and the results are deemed acceptable during this implementation phase of the liver transplantation program. Accordingly, liver transplantation is feasible in the Republic of Uzbekistan; however, improvements in surgical and therapeutic methods are necessary to minimize the development of both early and late postoperative complications.

Background: Chronic liver disease (CLD) in children, often leads to cirrhosis and end-stage liver disease (ESLD). CLD poses significant challenges in management and prognosis. Assessing body composition, including sarcopenia, is increasingly recognized as important in understanding outcomes in this population. Methods: We conducted a prospective observational study, involving children aged 2 to 18 years with ESLD awaiting liver transplantation. Socio-demographic, clinical, and laboratory data were collected, and body composition was assessed using Bioelectrical Impedance Analysis (BIA). Sarcopenia was defined using age-specific cut-off points for appendicular skeletal muscle mass (aSMM) and fat-free mass (FFM). Results: The study included 57 children (42.1% girls, 57.9% boys; median age: 10.9 years) with liver cirrhosis. Of them 11 (19.3%) died during the study. The mean duration of living with end-stage liver disease prior to participation was 5.43 years [IQR: 3.32, 8.39]. The most common etiology was biliary atresia (24.6%), followed by cryptogenic (22.8%). Deceased children exhibited significantly higher sarcopenia prevalence, lower basal metabolic rate and growth scores compared to survivors (P < 0.05), (771.0 vs. 934.0, P = 0.166) (65.0 vs. 80.5, P = 0.005). Total body and limb-specified lean mass were lower in deceased children, although not statistically significant. Similarly, total mineral (90% normal) and bone mineral content were lower in deceased children, with a significant difference observed only in water-to-FFM percentage (72.5 vs. 73.1, P = 0.009). Conclusion: This study highlights the high prevalence of sarcopenia among children with ESLD and its association with adverse outcomes, including mortality. Bioimpedance analysis emerges as a promising, non-invasive method for assessing body composition in pediatric ESLD, warranting further investigation and integration into clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive impairment (CI) is common in both end‐stage kidney disease (ESKD) and alcohol‐related liver cirrhosis. The aim of this study was to assess the prevalence and patterns of CI in patients awaiting kidney and liver transplantation, and to identify its determinants. Methods: In this cross‐sectional, prospective study, 31 consecutive patients with ESKD and 31 consecutive patients with alcohol‐related liver cirrhosis, all currently on transplant waiting lists, were screened for cognitive decline using the Addenbrooke's Cognitive Examination. Medical history, demographics, and laboratory test results were also collected. Results: The prevalence of CI among patients with ESKD and alcohol‐related liver cirrhosis was 26% and 90%, respectively. In both groups, memory was the most affected cognitive domain, along with verbal fluency in patients with ESKD, and visuospatial abilities in patients with alcoholic cirrhosis. The most statistically significant increase in the prevalence of CI was found in patients with lower educational attainment, in both alcohol‐related liver cirrhosis and ESKD populations as well as in older patients with alcoholic cirrhosis. Furthermore, better cognitive functioning in ESKD patients was associated with higher levels of total lymphocyte count and alanine transaminase (ALT), and in alcohol‐related liver cirrhosis patients with higher levels of ALT and aspartate transaminase. A nonsignificant trend toward lower memory domain scores was also observed with increasing ammonia levels and increasing severity of liver disease (higher Child–Pugh scores). Finally, suboptimal performance on the screening test was correlated with the severity of liver disease as assessed by the Model for End‐Stage Liver Disease Sodium (MELD‐Na), but not at the statistically significant level. Conclusions: The prevalence of CI, especially in patients with alcohol‐related liver cirrhosis, is high and can be a significant clinical problem, negatively affecting the transplantation process. Routine screening tests in this group would contribute to the implementation of appropriate management, such as rehabilitation program or psychosocial treatments and facilitate the provision of specialized health care. [ABSTRACT FROM AUTHOR]

Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome–acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic liver disease is a significant global neglected public health problem. End-stage liver disease is associated with substantial symptom complexity, disability, and care needs that require assistance from informal family care partners. Research on these care partners' caregiver burden or strain, symptoms, and quality of life is sparse and has not focused on these variables as co-occurring or in the context of the quality of the relationship care partners have with the patients. Objectives: The purpose of this study was to provide a collective presentation of patterns and determinants of well-being as measured by caregiver strain, depression, sleep, and quality of life in a cohort of informal family care partners for adult outpatients with end-stage liver disease. Methods: Care partners (aged >18 years) were recruited from two liver clinics within two tertiary healthcare systems and invited to complete a cross-sectional survey. They completed the Multidimensional Caregiver Strain Index, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Short Form Health Survey, and Mutuality Scale. Descriptive statistics and latent class mixture modeling were used to analyze these data. Results: The sample was predominantly female and White. The well-being of care partners was diminished. Three distinct classes of well-being were identified: mildly diminished (53.2%), moderately diminished (39.0%), and severely diminished (7. 8%). Those at a greater risk of worse well-being were younger and spouses and had poorer relationship quality with the patients. Discussion: To improve the well-being of care partners inmoderately and severely diminished classes, assessing and addressing caregiver strain and co-occurring symptoms is essential. Addressing the strain and symptoms has the potential to maintain or optimize care partners' ability to provide care to patients. Future researchers should include longitudinal and dyadic studies to examine how patients' disease progression and symptoms may affect family care partners' well-being and vice versa. [ABSTRACT FROM AUTHOR]

Background: Although Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of endstage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates. Methods: Referrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018-12/2019) and after (7/2021-6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras. Results: A greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, p = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%). Conclusions: A targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community. [ABSTRACT FROM AUTHOR]

Background: Palliative care is often suboptimal for patients with end-stage liver disease (ESLD). Ascites remains the most common complication in ESLD. Though long-term abdominal drains (LTAD) are commonly used in refractory malignant ascites, the standard care for ESLD is hospital drainage (large volume paracentesis (LVP)). There is an ongoing National Institute for Health and Care Research (NIHR) funded trial (REDUCe 2 Study) (ISRCTN269936824) comparing palliative LTAD to LVP in ESLD. This 35-site trial is being conducted in England, Scotland and Wales. Aim: To understand the views and experience of healthcare professionals (HCP) on the use of palliative LTAD in ESLD. Methods: An electronic survey comprised of seven questions with fixed quantitative options and three exploratory questions was used between August--December 2019. The survey was distributed electronically via the British Association for Study of Liver newsletter and to relevant hospital departments in Southeast England and Northeast London. An email reminder was sent at 4 and 8 weeks after the initial invitation to the survey. Results: There were 211 respondents (hepatologists (36.5%), specialist nurses (24.6%), gastroenterologists (16.6%), trainees (17%) and others (5.2%)). All respondents had access to LVP, 86% to a transjugular intrahepatic portosystemic shunt procedure for patients, 67% to LTADs and 10% to other options, such as the automated low-flow ascites (ALFA) pump. The majority of respondents to the survey (68%) reported their experience of using LTAD. Almost all respondents (91%) were willing to consider LTAD in ESLD. However, the main deterrents of this were the perceived risk of infection (90%), followed by LTAD management in community (57%). Some 51% of those with prior experience of using LTAD reported clinical complications for patients (including bleeding, infection and renal impairment), 41% reported technical issues and 35% inadequate community support. Conclusions: Almost all HCPs are willing to consider palliative LTAD in refractory ascites due to ESLD, but the main deterrents are the perceived infection risk and lack of published data to guide community management. The REDUCe 2 trial will clarify if these concerns are real and provide conclusive evidence on role, if any, of palliative LTADs in this vulnerable and under researched cohort with ESLD. [ABSTRACT FROM AUTHOR]

This review describes the assessment and listing of the patient for liver transplantation and some of the perioperative challenges specific to this group of patients. The principles of the postoperative management in the intensive care unit are discussed as well as some of the signs of early graft dysfunction. Increasingly complex patients with advanced liver disease are receiving grafts from more marginal donors and this can present significant challenges to the transplant team. The anaesthetist and intensivist play a vital role in determining outcome in the perioperative period and must work collaboratively with surgeons and hepatologists to achieve the best patient outcomes. [ABSTRACT FROM AUTHOR]

Sarcopenia, characterized by the loss of skeletal muscle mass and function, is a significant complication in patients with cirrhosis. This condition not only exacerbates the overall morbidity and mortality associated with liver disease but also complicates patient management, increasing the risk of hospitalization, infections, and hepatic encephalopathy. Despite its clinical significance, sarcopenia in cirrhotic patients remains underdiagnosed and undertreated. This review aims to summarize current knowledge on the pathophysiology of sarcopenia in cirrhosis, including mechanisms such as altered metabolism, hormonal imbalances, and inflammation. Additionally, we explore diagnostic challenges and discuss emerging therapeutic strategies, including nutritional support, exercise, and pharmacological interventions. By highlighting the gaps in existing research and proposing directions for future studies, this review seeks to improve the management and outcomes of cirrhotic patients affected by sarcopenia.

Background: Liver transplantation is the definitive management for patients with end-stage liver disease. Preoperative computed tomography (CT) is used in living donor liver transplant (LDLT) for donor and graft selection as well as predicting graft weight. Objectives: The aim of this study is to establish the relationship between estimated graft volume (EGV) and actual graft weight (AGW) and ascertain a correlation coefficient that will improve the accuracy of EGV in a South African population. Method: The study included 117 LDLT between March 2013 and August 2022. Of these, 86 were left lateral (LL), 15 right lobe (R), 10 left lobe with caudate (LC), five left lobe (L) and one segment two (monosegment) grafts. Estimated graft volume and actual graft weight were compared using the Pearson coefficient and the relationship was illustrated with scatter plots. Results: Estimated graft volume and AGW had a strong positive correlation with a Pearson correlation (R) of 0.95 (p 0.001). The relationship was significantly linear with a correlation coefficient of 0.71. The mean EGV was significantly higher than that of AGW (388 mL ± 249 mL vs. 353 g ± 184 g) with overestimation in 61% of cases. Left lateral and R grafts were the most prevalent LDLT graft type, both having a strong linear correlation between EGV and AGW. Conclusion: Applying a correlation coefficient of 0.71 will improve the accuracy of CT volumetry graft weight predictions. Contribution: A unique correlation coefficient will improve EGV accuracy, aiding in preoperative planning and mitigating post-operative complications in both donors and recipients.

Abstract Background Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China. Methods We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications. Results The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12–39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications. Conclusions Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD. Trial registration Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999–2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999–2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999–2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39–4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999–2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality. [ABSTRACT FROM AUTHOR]

To designed a new model using pre-transplant data to predict post-transplant mortality for Chinese population and compared its performance to that of existing models. In this multicenter study, 544 recipients of liver transplants for non-tumor indications were enrolled in the training group and 276 patients in the validation group. The new Simplified Mortality Prediction Scores (SMOPS) model was compared to the MELD and four existing models using the C-statistic. SMOPS model used 6 independent pre-transplantation risk factors screened from the training group (chronic liver failure/organ failure scores, fever > 37.6 ℃, ABO blood-type compatibility, arterial lactate level, leukocyte count and re-transplantation). The SMOPS accurately predicted patients' 30-day, 90-day and 365-day mortality following liver transplantation, and its' scores were more accurate than those of the other models. The SMOPS generated four levels of risk: low risk (<10 points), moderate risk (11–20 points), high risk (21–25 points) and futile risk (≥26 points). The survival within all risk levels was not different between MELD=40 and MELD<40. The survival within moderate-, high- or extreme-risk ALF was not different between ALF and non-ALF. The SMOPS model uses pre-transplant risk factors to stratify post-transplant survival and is superior to current models for Chinese population, and has the potential to contribute to improvements in organ-allocation policies. [ABSTRACT FROM AUTHOR]

Introduction: Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this regard, extracorporeal albumin dialysis devices such as single-pass albumin dialysis (SPAD), Prometheus, and molecular adsorbent recycling system (MARS) have been valuable in supplementing standard medical therapy (SMT). However, the efficacy and safety of these devices is often questioned. Aim: We performed a systematic review to summarize the efficacy and safety of MARS, SPAD, and Prometheus as supportive treatments for liver dysfunction. Material and methods: PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar electronic databases were extensively searched for all randomized trials published in English. In addition, meta-analytic analyses were performed with Review Manager software, and Cochrane's risk of bias tool embedded in this software was used for bias assessment. Results: Twelve trials including a total of 653 patients were eligible for inclusion. Subgroup analyses of data from these trials revealed that MARS and Prometheus were associated with significant removal of bilirubin (MD = -5.14 mg/dl; 95% CI: -7.26 - -3.02; p < 0.00001 and MD = -8.11 mg/dl; 95% CI: -12.40 - -3.82; p = 0.0002, respectively) but not bile acids and ammonia when compared to SMT. Furthermore, MARS was as effective as Prometheus and SPAD in the reduction of bilirubin (MD = 2.98 mg/dl; 95% CI: -4.26 - 10.22; p = 0.42 and MD = 0.67 mg/dl; 95% CI: -2.22 - 3.56; p = 0.65), bile acids (MD = -17.06 µmol/l; 95% CI: -64.33 - 30.20; p = 0.48 and MD = 16.21 µmol/l; 95% CI: -17.26 - 49.68; p = 0.34), and ammonia (MD = 26 µmol/l; 95% CI: -12.44 - 64.44; p = 0.18). In addition, MARS had a considerable effect in improving hepatic encephalopathy (HE) (RR = 1.54; 95% CI: 1.15-2.05; p = 0.004). However, neither MARS nor Prometheus had a mortality benefit compared to SMTRR (0.86; 95% CI: 0.71-1.03; p = 0.11 and RR = 0.87; 95% CI: 0.66-1.14; p = 0.31, respectively). Conclusions: MARS, SPAD, and Prometheus, as liver support therapies, are equally effective in reducing albumin-bound and water-soluble substances. Moreover, MARS is associated with HE improvement. However, none of the therapies was associated with a significant reduction in mortality or adverse events. [ABSTRACT FROM AUTHOR]

Background and aim: Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. Methods: This retrospective case–control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. Results: Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367–17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). Conclusions: Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA. [ABSTRACT FROM AUTHOR]

Abstract Introduction Cognitive impairment (CI) is common in both end‐stage kidney disease (ESKD) and alcohol‐related liver cirrhosis. The aim of this study was to assess the prevalence and patterns of CI in patients awaiting kidney and liver transplantation, and to identify its determinants. Methods In this cross‐sectional, prospective study, 31 consecutive patients with ESKD and 31 consecutive patients with alcohol‐related liver cirrhosis, all currently on transplant waiting lists, were screened for cognitive decline using the Addenbrooke's Cognitive Examination. Medical history, demographics, and laboratory test results were also collected. Results The prevalence of CI among patients with ESKD and alcohol‐related liver cirrhosis was 26% and 90%, respectively. In both groups, memory was the most affected cognitive domain, along with verbal fluency in patients with ESKD, and visuospatial abilities in patients with alcoholic cirrhosis. The most statistically significant increase in the prevalence of CI was found in patients with lower educational attainment, in both alcohol‐related liver cirrhosis and ESKD populations as well as in older patients with alcoholic cirrhosis. Furthermore, better cognitive functioning in ESKD patients was associated with higher levels of total lymphocyte count and alanine transaminase (ALT), and in alcohol‐related liver cirrhosis patients with higher levels of ALT and aspartate transaminase. A nonsignificant trend toward lower memory domain scores was also observed with increasing ammonia levels and increasing severity of liver disease (higher Child–Pugh scores). Finally, suboptimal performance on the screening test was correlated with the severity of liver disease as assessed by the Model for End‐Stage Liver Disease Sodium (MELD‐Na), but not at the statistically significant level. Conclusions The prevalence of CI, especially in patients with alcohol‐related liver cirrhosis, is high and can be a significant clinical problem, negatively affecting the transplantation process. Routine screening tests in this group would contribute to the implementation of appropriate management, such as rehabilitation program or psychosocial treatments and facilitate the provision of specialized health care.

IntroductionLoneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT).MethodsWe surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables.ResultsOf 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness.ConclusionLoneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population. Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290.

Aim To create a predictive score based on functional parameters of the liver and determine its prognostic value in survival of patients with decompensated cirrhosis. Methods Retrospective observational study included 91 consecutive patients with decompensated cirrhosis. Functional parameters (bilirubin, AST – aspartate aminotransferase, ALT – alanine aminotransferase, ALP – alkaline phosphatase, GGT – gamma-glutamyltranferase, albumin, prothrombin time, platelet count, haematocrit and creatinine), Child-Pugh (CP) and Model of End-Stage Liver Disease (MELD) scores have been measured at first hospitalization and at every exacerbation episode over follow-up period of 24 months. Results Using Cox regression analysis, we found that age (OR=1.206; p=0.03; 95% CI=1.019-1.428), serum bilirubin (OR=1.017; p=0.003; 95% CI=1.006-1.029), INR (International normalized ratio) (OR=6.262; p=0.002; 95% CI=1.924-20.378) and serum creatinine (OR=1.019; p=0.005; 95% CI=1.006-1.032) had statistically strong association with the incidence of a six-month mortality. Age (OR=1.120; p=0.006; 95% CI=1.033-1.214), serum bilirubin (OR=1.021; p=0.0001; 95% CI=1.010-1.032), GGT (OR=1.007; p=0.023; 95% CI=1.001-1.014), INR (OR=9.571; p=0.001; 95% CI=2.610-35.098), haematocrit (OR=0.695; p=0.001; 95% CI=0.559-0.864) and serum creatinine (OR=1.023; p=0.0001; 95% CI=1.011-1.035) showed an increased the risk for a 24-month lethal outcome. Predictive score derived from liver functional parameters, CP and MELD scores, each independently has shown a high degree of death prediction after 6 or 24 months in patients with end-stage liver disease. Conclusion Predictive score derived from liver functional parameters had a better prognostic value for short-term and long-term mortality comparing to MELD and Child-Pugh score.

Madelyn J Blake,1 Clifford J Steer2 1Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA; 2Departments of Medicine, and Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN, USACorrespondence: Madelyn J Blake, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street SE, MMC 195, Minneapolis, MN, 55455, USA, Email blake561@umn.edu Clifford J Steer, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street SE, MMC 36, Minneapolis, MN, 55455, USA, Email steer001@umn.eduAbstract: Orthotopic liver transplantation (OLT) currently serves as the sole definitive treatment for thousands of patients suffering from end-stage liver disease; and the existing supply of donor livers for OLT is drastically outpaced by the increasing demand. To alleviate this significant gap in treatment, several experimental approaches have been devised with the aim of either offering interim support to patients waiting on the transplant list or bioengineering complete livers for OLT by infusing them with fresh hepatic cells. Recently, interspecies blastocyst complementation has emerged as a promising method for generating complete organs in utero over a short timeframe. When coupled with gene editing technology, it has brought about a potentially revolutionary transformation in regenerative medicine. Blastocyst complementation harbors notable potential for generating complete human livers in large animals, which could be used for xenotransplantation in humans, addressing the scarcity of livers for OLT. Nevertheless, substantial experimental and ethical challenges still need to be overcome to produce human livers in larger domestic animals like pigs. This review compiles the current understanding of interspecies blastocyst complementation and outlines future possibilities for liver xenotransplantation in humans.Keywords: end-stage liver disease, interspecies blastocyst complementation, blastocyst complementation, chimeras, xenotransplantation

Background and Aims: Chronic liver injury that results in cirrhosis and end-stage liver disease (ESLD) causes more than 1 million deaths annually worldwide. Although the impact of genetic factors on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) has been previously studied, their contribution to the development of ESLD remains largely unexplored. Methods: We genotyped 6 MASLD-associated polymorphisms in healthy (n = 123), metabolic dysfunction-associated steatohepatitis (MASH) (n = 145), MASLD-associated ESLD (n = 72), and ALD-associated ESLD (n = 57) cohorts and performed multinomial logistic regression to determine the combined contribution of genetic, demographic, and clinical factors to the progression of ESLD. Results: Distinct sets of factors are associated with the progression to ESLD. The PNPLA3 rs738409:G and TM6SF2 rs58542926:T alleles, body mass index (BMI), age, and female sex were positively associated with progression from a healthy state to MASH. The PNPLA3 rs738409:G allele, age, male sex, and having type 2 diabetes mellitus were positively associated, while BMI was negatively associated with progression from MASH to MASLD-associated ESLD. The PNPLA3 rs738409:G and GCKR rs780094:T alleles, age, and male sex were positively associated, while BMI was negatively associated with progression from a healthy state to ALD-associated ESLD. The findings indicate that the PNPLA3 rs738409:G allele increases susceptibility to ESLD regardless of etiology, the TM6SF2 rs58542926:T allele increases susceptibility to MASH, and the GCKR rs780094:T allele increases susceptibility to ALD-associated ESLD. Conclusion: The PNPLA3, TM6SF2, and GCKR minor alleles influence the progression of MASLD-associated or ALD-associated ESLD. Genotyping for these variants in MASLD and ALD patients can enhance risk assessment, prompting early interventions to prevent ESLD.

Over the past decade, the field of solid organ transplantation has undergone significant changes, with some of the most notable advancements occurring in liver transplantation. Recent years have seen substantial progress in preoperative patient optimization protocols, anesthesia monitoring, coagulation management, and fluid management, among other areas. These improvements have led to excellent perioperative outcomes for all surgical patients, including those undergoing liver transplantation. In the last few decades, there have been numerous publications in the field of liver transplantation, but controversies related to perioperative management of liver transplant recipients persist. In this review article, we address the unresolved issues surrounding the anesthetic management of patients scheduled for liver transplantation.

Abstract Background This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD). Methods We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars. Results During a median of 10.5 (IQR: 10.2–11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14–2.39) for free sugars, 0.51 (0.35–0.74) for non-free sugars, and 0.55 (0.36–0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04–1.39) for free sugars, 0.79 (0.68–0.92) for non-free sugars, and 0.79 (0.67–0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality. Conclusions A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Aim To create a predictive score based on functional parameters of the liver and determine its prognostic value in survival of patients with decompensated cirrhosis. Methods Retrospective observational study included 91 consecutive patients with decompensated cirrhosis. Functional parameters (bilirubin, AST -- aspartate aminotransferase, ALT -- alanine aminotransferase, ALP -- alkaline phosphatase, GGT -- gammaglutamyltranferase, albumin, prothrombin time, platelet count, haematocrit and creatinine), Child-Pugh (CP) and Model of End- Stage Liver Disease (MELD) scores have been measured at first hospitalization and at every exacerbation episode over follow-up period of 24 months. Results Using Cox regression analysis, we found that age (OR=1.206; p=0.03; 95% CI=1.019-1.428), serum bilirubin (OR=1.017; p=0.003; 95% CI=1.006-1.029), INR (International normalized ratio) (OR=6.262; p=0.002; 95% CI=1.924-20.378) and serum creatinine (OR=1.019; p=0.005; 95% CI=1.006- 1.032) had statistically strong association with the incidence of a six-month mortality. Age (OR=1.120; p=0.006; 95% CI=1.033- 1.214), serum bilirubin (OR=1.021; p=0.0001; 95% CI=1.010- 1.032), GGT (OR=1.007; p=0.023; 95% CI=1.001-1.014), INR (OR=9.571; p=0.001; 95% CI=2.610-35.098), haematocrit (OR=0.695; p=0.001; 95% CI=0.559-0.864) and serum creatinine (OR=1.023; p=0.0001; 95% CI=1.011-1.035) showed an increased the risk for a 24-month lethal outcome. Predictive score derived from liver functional parameters, CP and MELD scores, each independently has shown a high degree of death prediction after 6 or 24 months in patients with end-stage liver disease. Conclusion Predictive score derived from liver functional parameters had a better prognostic value for short-term and long-term mortality comparing to MELD and Child-Pugh score. [ABSTRACT FROM AUTHOR]

Third‐spacing of fluid is a common complication in hospitalized patients with decompensated cirrhosis. In addition to ascites, patients with advanced cirrhosis may develop significant peripheral edema, which may limit mobility and exacerbate debility and muscle wasting. Concomitant kidney failure and cardiac dysfunction may lead to worsening hypervolemia, which may ultimately result in pulmonary edema and respiratory compromise. Diuretic use in such patients may be limited by kidney dysfunction and electrolyte abnormalities, including hyponatremia and hypokalemia. A slow, continuous form of ultrafiltration known as aquapheresis is a method of extracorporeal fluid removal whereby a pump generates a transmembrane pressure that forces an isotonic ultrafiltrate across a semipermeable membrane. This leads to removal of an ultrafiltrate that is isotonic to blood without the need for dialysate or replacement fluid as is necessary in other forms of continuous kidney replacement therapy. This technique has been utilized in other conditions including acute decompensated heart failure, with trials showing mixed, but generally favorable results. Herein, we present a series of our own experience using aquapheresis among patients with cirrhosis, review the literature regarding its use in other hypervolemic states, and discuss how we may apply lessons learned from use of aquapheresis in heart failure to patients with end‐stage liver disease. [ABSTRACT FROM AUTHOR]

Background and aim: Limited data are available regarding pre‐liver transplantation (LT) bacteremia in adults with end‐stage liver disease. In this study, we investigated the risk factors independently associated with pre‐LT bacteremia and their effects on clinical outcomes of LT. Methods: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre‐LT bacteremia and those without pre‐LT infection. Pre‐LT bacteremia was defined as bacteremia detected within 90 days before LT. Results: Among 1287 LT recipients, 92 (7.1%) developed pre‐LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram‐negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048–2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074–1.257) were independent risk factors for pre‐LT bacteremia in patients with end‐stage liver disease. Intensive care unit and in‐hospital stay were significantly longer, and in‐hospital mortality was significantly higher among LT recipients with pre‐LT bacteremia than among those without pre‐LT infection. Conclusions: This study highlights predictors of pre‐LT bacteremia in patients with end‐stage liver disease. Pre‐LT bacteremia increases the post‐transplantation mortality risk. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD). Methods: We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars. Results: During a median of 10.5 (IQR: 10.2–11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14–2.39) for free sugars, 0.51 (0.35–0.74) for non-free sugars, and 0.55 (0.36–0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04–1.39) for free sugars, 0.79 (0.68–0.92) for non-free sugars, and 0.79 (0.67–0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality. Conclusions: A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients. [ABSTRACT FROM AUTHOR]

Background: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV‐GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV‐GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). Methods: One hundred and thirty‐five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D‐STE) were performed, and dual X‐ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. Results: LV‐GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV‐GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV‐GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3, p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. Conclusion: In our study, absolute LV‐GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end‐stage liver disease. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether stress echocardiography and coronary computed tomography angiography (CCTA) could detect CAD in end-stage liver disease (ESLD) patients without previous evidence of heart disease. LT candidates ≥30 years underwent a cardiovascular (CV) assessment through stress echocardiography. CCTA was performed in patients ≥50 years with two or more CV risk factors (e.g. diabetes, CAD family history, dyslipidaemia). Coronary angiography (CAG) was scheduled when stress echocardiography and/or CCTA were positive. Sensibility, specificity, positive and negative predictive values of stress echocardiography and CCTA were assessed by numbers of coronary revascularization (true positives) and lack of acute coronary events over a mean follow-up of 3 years (true negatives). Stress echocardiography was performed in 273 patients, CCTA in 34 and CAG in 41. Eight patients had critical coronary lesions, and 19 not-critical lesions. Sensitivity, specificity, positive and negative predictive values were 50.0%, 90.2%, 13.3% and 98.4% for stress echocardiography and 100%, 76.7%, 36.4% and 100% for CCTA. Among 163 patients who underwent LT (57.6%), 16 died and 5 had major adverse CV events over a mean follow-up of 3 years. A very low prevalence of CAD in a selected population of ESLD at intermediate to high CV risk was found. A screening based on stress echocardiography and CCTA resulted in low incidence of post-LT acute coronary events in ELSD patients. CAD has no impact on mid-term survival. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis. Methods: A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48 hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population. Results: The mean FCAL (µg/g) level in healthy control (n = 5), stable cirrhotics (n = 10), ESLD (n = 10) and ACLF (n = 10) patients was 109.2 (95% CI: − 53.39 to 271.79), 143.3 (95% CI: 50.5–236.45), 176.9 (95% CI: 122.93–230.87) and 543.5 (95% CI: 207.09–879.91) (p = 0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p = 0.005) and FCAL ≥ 200 µg/g (OR = 10.8, p = 0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) μg/g,p = 0.005. Conclusions: FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of ≥ 200 µg/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality. [ABSTRACT FROM AUTHOR]

Abstract Liver diseases lead to 1.3 million deaths per year around the world, the majority of which are secondary to cirrhosis. In the management of liver diseases in chronic and acute conditions, liver transplant (LT) plays a major role in improving the survival and quality of life of patients. LT programmes require the technical capabilities in performing the pre‐transplant evaluation, transplant surgery and post‐transplant care supported by adequate infrastructure and a set of trained teams. Globally, there were 28,000 deceased donor LTs, and 14,000 living donor LTs were performed in 2021. In the South Asia region, India, Pakistan and Sri Lanka conducted 2998 LTs in 2021. Many countries report sociocultural, religious and legislative barriers to acquiring adequate donor livers. We describe the challenges in LT programmes in low‐ and middle‐income countries and experiences from Sri Lanka. Sri Lanka carried out its first LT in 2010, and the service is provided free of charge in the state health sector. In Sri Lanka, the common indications for LT in adults are non‐alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and alcoholic liver disease. In children, the indications are biliary atresia, hepatocellular carcinoma and Wilson disease. The common challenges include a lack of an adequate number of doctors and post‐transplant team members, a low number of organ donors and a long waiting list, all of which can be disadvantageous for transplant programmes. To continue providing LT services, there is a need to adopt multimodal strategies in the areas of providing additional skills training to the operating team and promoting organ donation culture in the background of supportive organ donation legislation. With the adoption of the national strategic plan for organ, tissue and cell transplantation, the country hopes to strengthen its capacity of providing transplant services to its people.

Objective To investigate the value of the combined score of Model for End-Stage Liver Disease (MELD) and alpha-fetoprotein (AFP) in predicting the prognosis of patients with acute-on-chronic liver failure (ACLF) and the influencing factors for the prognosis of patients with ACLF. Methods A retrospective analysis was performed for the clinical data of the patients with ACLF who were admitted to The Affiliated Hospital of Qingdao University and The Qingdao Sixth People’s Hospital from September 2015 to September 2021, and according to the prognosis on day 90 after diagnosis, they were divided into survival group and death group. The influencing factors for the prognosis of ACLF patients were analyzed, as well as the performance of serum AFP level, MELD score, and MELD-AFP combined score in predicting the short-term prognosis of patients. Results A total of 159 patients with ACLF were enrolled; 129 patients survived and 30 patients died on day 28 after diagnosis, while 111 patients survived and 48 patients died on day 90 after diagnosis. Serum AFP level, lactate dehydrogenase level, red blood cell count, hemoglobin level, alanine aminotransferase/aspartate aminotransferase ratio, urea nitrogen/creatinine ratio, and MELD score were independent influencing factors for the prognosis of ACLF patients on day 90 after diagnosis. Compared with MELD score, MELD-AFP combined score had better performance in predicting the prognosis of ACLF patients on day 90 after diagnosis, with an area under the ROC curve of 0.81. Conclusion Increases in serum lactate dehydrogenase level, urea nitrogen/creatinine ratio, alanine aminotransferase/aspartate aminotransferase ratio, red blood cell count, serum AFP level, and serum hemoglobin level are closely associated with the prognosis of ACLF patients on day 90 after diagnosis. MELD-AFP combined score significantly optimizes the performance of traditional MELD score in predicting the short-term prognosis of ACLF patients.

Background and Aims: End-stage liver disease (ESLD) is an important cause of morbidity and mortality, comparable to a large extent to other organ insufficiencies. The need for palliative care (PC) in patients with ESLD is high. In Portugal, in the only identified study, more than 80% of patients hospitalized with ESLD had criteria for PC. No results specified which needs they identified or their transplantation prospect status. Methods: Prospective observational study including 54 ESLD patients who presented to a university hospital and transplantation center, between November 2019 and September 2020. Assessment of their PC needs through the application of NECPAL CCOMS-ICO© and IPOS, considering their transplantation perspective status. Results: Of the 54 patients, 5 (9.3%) were on active waiting list for transplantation and 8 (14.8%) under evaluation. NECPAL CCOMS-ICO© identified 23 patients (n = 42.6%) that would benefit from PC. Assessment of PC needs by clinicians, functional markers and significant comorbidities were the most frequent criteria (47.8%, n = 11). IPOS also revealed a different sort of needs: on average, each patient identified about 9 needs (8.9 ±2.8). Among the symptoms identified, weakness (77.8%), reduced mobility (70.3%), and pain (48.1%) stood out, as well as the psychoemotional symptoms of depression (66.7%) and anxiety (77.8%). There were no significant differences between the subgroups of patients analyzed. Only 4 patients (7.4%) were followed by the PC team. Conclusion: All the ESLD patients included, independently of the group they belonged to, presented with PC needs. No significant differences between the subgroups of patients were identified, confirming that even patients with a transplantation prospect have important needs for PC.