End stage liver disease (ESLD) represents a growing health concern characterized by elevated morbidity and mortality, particularly among individual ineligible for liver transplantation. The demand for palliative care (PC) is pronounced in patients grappling with ESLD and acute on chronic liver failure (ACLF). Unfortunately, the historical underutilization of PC in ESLD patients, despite their substantial needs and those of their family caregivers, underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.

To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.

A systematic search in the Medline (PubMed) database was performed using a predetermined search command, encompassing studies published in English without any restrictions on the publication date. Subsequently, the retrieved studies were manually examined. Simple descriptive analyses were employed to summarize the results.

The search strategies yielded 721 references. Following the final analysis, 32 full-length references met the inclusion criteria and were consequently incorporated into the study. Meticulous data extraction from these 32 studies was undertaken, leading to the execution of a comprehensive narrative systematic review. The review found that PC provides significant benefits, reducing symptom burden, depressive symptoms, readmission rates, and hospital stays. Yet, barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization. Integrating PC early, upon the diagnosis of ESLD and ACLF, regardless of transplant eligibility and availability, improves the quality of life for these patients.

Despite the substantial suffering and poor prognosis associated with ESLD and ACLF, where liver transplantation stands as the only curative treatment, albeit largely inaccessible, PC services have been overtly provided too late in the course of the illness. A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers, involving healthcare providers, patients, and caregivers.

Nationwide US data on readmission rates for patients with cirrhosis admitted with hepatorenal syndrome (HRS) is lacking. We reviewed 30-day readmission rates after HRS-related hospitalizations, the associated predictors of readmissions, and their impact on resource utilization and mortality in the United States.

We identified all adults admitted with HRS between 2016 and 2019 using the Nationwide Readmission database of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. The primary outcome was all-cause 30-day readmission rate. Secondary outcomes were inpatient mortality rate, predictors of readmission, and resource utilization.

We identified 245 850 hospitalizations of patients admitted for HRS in the United States from 2016 to 2019. Of these, 214 890 met the inclusion criteria. Mean age was 59.16 years, and 61.31% were males. Medicare was the most common primary payer (44.82%) followed by Medicaid (25.58%). The readmission rate was 24.6% within 30 days of discharge from index hospitalization. The most common cause of readmission was alcoholic cirrhosis with ascites (14.87%), followed by sepsis (9.32%) and unspecified hepatic failure (9%). The in-hospital mortality rate for index hospitalization was 29.52% and 14.35% among those readmitted within 30 days. The mean length of stay (12.33 days vs. 7.15 days, p < 0.01) and hospitalization costs ($44 903 vs. $22 353, p < 0.01) were higher for index hospitalizations than readmissions.

Our study demonstrated that all-cause 30-day readmission and in-hospital mortality rates after the development of HRS were strikingly high. This warrants health policies and interventions at the institutional level, including close post-hospital discharge follow-up, to decrease readmission rates, improve patient outcomes, and reduce cost burden.

Hepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs).

PubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: "hepatorenal syndrome", "terlipressin", "noradrenaline", and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events.

15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio [RR]:2.75, 95% confidence interval [CI]:1.96 to 3.84; I2 = 28%, p = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2 = 16%, p = 0.31; n = 7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2 = 0%, p = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2 = 4%, p = 0.39; n = 7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2 = 0%, p = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2 = 0%, p = 0.92; n = 5).

Terlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.

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.

Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models.

To assess the utility of ML models in prognostication for LT, comparing their per formance and reliability to established traditional scoring systems.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English stu dies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws.

Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capa bilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI.

This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Sepsis is a severe medical condition that occurs when the body's immune system overreacts to an infection, leading to life-threatening organ dysfunction. The "Third international consensus definitions for sepsis and septic shock (Sepsis-3)" defines sepsis as an increase in sequential organ failure assessment score of 2 points or more, with a mortality rate above 10%. Sepsis is a leading cause of intensive care unit (ICU) admissions, and patients with underlying conditions such as cirrhosis have a higher risk of poor outcomes. Therefore, it is critical to recognize and manage sepsis promptly by administering fluids, vasopressors, steroids, and antibiotics, and identifying and treating the source of infection.

To conduct a systematic review and meta-analysis of existing literature on the management of sepsis in cirrhotic patients admitted to the ICU and compare the management of sepsis between cirrhotic and non-cirrhotic patients in the ICU.

This study is a systematic literature review that followed the PRISMA statement's standardized search method. The search for relevant studies was conducted across multiple databases, including PubMed, Embase, Base, and Cochrane, using predefined search terms. One reviewer conducted the initial search, and the eligibility criteria were applied to the titles and abstracts of the retrieved articles. The selected articles were then evaluated based on the research objectives to ensure relevance to the study's aims.

The study findings indicate that cirrhotic patients are more susceptible to infections, resulting in higher mortality rates ranging from 18% to 60%. Early identification of the infection source followed by timely administration of antibiotics, vasopressors, and corticosteroids has been shown to improve patient outcomes. Procalcitonin is a useful biomarker for diagnosing infections in cirrhotic patients. Moreover, presepsin and resistin have been found to be reliable markers of bacterial infection in patients with decompensated liver cirrhosis, with similar diagnostic performance compared to procalcitonin.

This review highlights the importance of early detection and management of infections in cirrhosis patients to reduce mortality. Therefore, early detection of infection using procalcitonin test and other biomarker as presepsin and resistin, associated with early management with antibiotics, fluids, vasopressors and low dose corticosteroids might reduce the mortality associated with sepsis in cirrhotic patients.

Acute esophageal variceal hemorrhage (AEVH) is a common complication of cirrhosis and might precipitate multi-organ failure, causing acute-on-chronic liver failure (ACLF).

To analyze if the presence and grading of ACLF as defined by European Society for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) is able to predict mortality in cirrhotic patients presenting AEVH.

Retrospective cohort study executed in Hospital Geral de Caxias do Sul. Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database for patients who received terlipressin. Medical records were reviewed in order to determine the diagnosis of cirrhosis and AEVH, including 97 patients. Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis.

All- cause mortality for AEVH patients was 36%, 40.2% and 49.4% for 30-, 90- and 365-day, respectively. The prevalence of ACLF was 41.3%. Of these, 35% grade 1, 50% grade 2 and 15% grade 3. In multivariate analysis, the non-use of non-selective beta-blockers, presence and higher grading of ACLF and higher Model for End-Stage Liver Disease scores were independently associated with higher mortality for 30-day with the addition of higher Child-Pugh scores for 90-day period.

Presence and grading of ACLF according to the EASL-CLIF criteria was independently associated with higher 30- and 90-day mortality in cirrhotic patients admitted due to AEVH.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by decompensation in individuals with chronic liver disease, generally secondary to one or more extra-hepatic organ failures, implying an elevated mortality rate. Acute decompensation (AD) is the term used for one or more significant consequences of liver disease in a short time and is the most common reason for hospital admission in cirrhotic patients. The European Association for the Study of Liver-Chronic-Liver Failure (EASL-CLIF) Group modified the intensive care Sequential Organ Failure Assessment score into CLIF-SOFA, which detects the presence of ACLF in patients with or without AD, classifying it into three grades.

To investigate the role of the EASL-CLIF definition for ACLF and the ability of CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores for prognosticating ACLF or AD.

This study is a literature review using a standardized search method, conducted using the steps following the guidelines for reporting systematic reviews set out by the PRISMA statement. For specific keywords, relevant articles were found by searching PubMed, ScienceDirect, and BioMed Central-BMC. The databases were searched using the search terms by one reviewer, and a list of potentially eligible studies was generated based on the titles and abstracts screened. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/).

Most of the included studies used the EASL-CLIF definition for ACLF to identify cirrhotic patients with a significant risk of short-term mortality. The primary outcome in all reviewed studies was mortality. Most of the study findings were based on an area under the receiver operating characteristic curve (AUROC) analysis, which revealed that CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores were preferable to other models predicting 28-d mortality. Their AUROC scores were higher and able to predict all-cause mortality at 90, 180, and 365 d. A total of 50 articles were included in this study, which found that the CLIF-SOFA, CLIF-C ACLF and CLIF-C AD scores in more than half of the articles were able to predict short-term and long-term mortality in patients with either ACLF or AD.

CLIF-SOFA score surpasses other models in predicting mortality in ACLF patients, especially in the short-term. CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD are accurate short-term and long-term mortality prognosticating scores.

Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications.

Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences.

Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored.

The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.

Hepatorenal syndrome (HRS) is a form of acute kidney injury occurring in patients with advanced cirrhosis and is associated with significant morbidity and mortality. The pathophysiology underlying HRS begins with increasing portal pressures leading to the release of vasodilatory substances which result in pooling blood in the splanchnic system and a corresponding reduction in effective circulating volume. Compensatory activation of the sympathetic nervous system, renin-angiotensin-aldosterone system and release of arginine vasopressin serve to defend mean arterial pressure but at the cost of severe constriction of the renal vasculature, leading to a progressive, often fulminant form of AKI. While there are no approved treatments for HRS in the United States, multiple countries, including much of Europe, utilize terlipressin, a synthetic vasopressin analogue, as first-line therapy. The recently published CONFIRM trial, the third randomized trial based in North America evaluating terlipressin, met its primary endpoint, showing greater rates of HRS reversal in the terlipressin arm. However, due to concerns about apparent increased rates of respiratory adverse events and a lack of evidence for mortality benefit, terlipressin was not approved by the Food and Drug Administration (FDA). In this Perspective, we explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised and consider the future role of terlipressin in this critical clinical area of continued unmet need.