Summary: Background: The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life‐saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver‐centric intensive care protocols, to mitigate the high mortality in such patients.Aim: Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end‐of life care.Methods: We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta‐analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care.Results: Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource.Conclusions: Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end‐of‐life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi‐disciplinary approach towards critical care management is likely to yield better outcomes.

Insulin resistance is associated with increased risk of death and liver transplantation in the cirrhotic population, independent of disease aetiology. However, factors accounting for insulin resistance in the context of cirrhosis are incompletely understood. This study aimed to investigate the association between adiponectin and leptin with insulin resistance in cirrhotic patients and to assess the influence of disease severity on insulin resistance and metabolic status. This cross-sectional study included 126 non-diabetic cirrhotic transplant candidates. The homeostasis model assessment 2 model was used to determine the insulin resistance index, and fasting adiponectin, leptin, insulin, c-peptide, glucose, HbA1c, and lipid profiles were analysed. Insulin resistance was detected in 83% of subjects and associated with increased leptin, fasting plasma glucose and body mass index, and lower triglyceride levels. Logistic regression analysis identified leptin and triglycerides as independent predictors of insulin resistance (OR 1.247, 95% CI 1.076–1.447, p = 0.003; OR 0.357, 95% CI 0.137–0.917, p = 0.032.). Leptin levels remained unchanged, whereas adiponectin levels increased (p < 0.001) with disease progression, and inversely correlated with HbA1c (ρ = −0.349, p < 0.001). Our results indicate that leptin resistance, as indicated by elevated leptin levels, can be regarded as a contributing factor to insulin resistance in cirrhotic patients, whereas triglycerides elicited a weak protective effect. Progressively increasing adiponectin levels elicited a positive effect on glucose homeostasis, but not insulin sensitivity across disease stages.

BACKGROUND Colonization with multidrug-resistant organisms (MDROs) is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units (ICUs). However, whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear. Clarifying this relationship may help determine the prognostic significance of colonization in these patients. AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis. METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center (2018-2024). Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission. Outcomes analyzed included MDRO infection during ICU stay, concordance between colonizing and infecting strains, organ support requirements, and 28-day transplant free survival. Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality. RESULTS Nearly one-third (29.9%) of patients were colonized with MDROs on admission, more commonly in the acute-on-chronic liver failure phenotype than those with acute decompensation (34.5 vs 10.0%, P = 0.033). Although infections were established in the majority (85%) of cases, of which 17.6% due to MDROs, colonization alone did not independently predict these infections [odds ratio (OR) = 2.18, P = 0.383] nor influenced short-term mortality (OR = 1.14, P = 0.813). However, once MDRO infection occurred, an 82% concordance was observed between colonizing and infecting strains. MDRO infections, unlike colonization, significantly increased the need for organ-support interventions, including mechanical ventilation and vasopressor therapy and prolonged ICU stays. Only severity of organ dysfunction, quantified by the Sequential Organ Failure Assessment score, independently predicted 28-day mortality (OR = 1.38, P = 0.024). CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis, particularly those with acute-on-chronic liver failure. While colonization alone does not predict infection or early mortality, its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected. Ultimately, short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.

Background and Objectives: Sepsis still represents a syndrome with a high mortality. A timely sepsis diagnosis and an early intervention are crucial for the disease outcomes. Sepsis-associated acute kidney injury (SA-AKI) is highly prevalent but often diagnosed late. We aimed to investigate whether serum interleukin-6 (IL-6) and leukocyte cell population data (CPD) could be adequate biomarkers for the prediction of survival and SA-AKI development. Materials and Methods: We conducted a prospective observational study in a medical intensive care unit of a tertiary hospital centre in Zagreb, Croatia from June 2020 to October 2023. Adult patients with newly diagnosed sepsis were included and classified as immunocompetent or immunocompromised. Blood samples were collected upon admission. Results: A total of 150 patients were included in the study. Ninety-six (64%) patients were immunocompetent and fifty-four (36%) were immunocompromised. The median SOFA score was 8 (6–11). SA-AKI was diagnosed in 108 (72%) patients. ICU and hospital mortality was 27.3% and 37.3%, with no significant difference between groups. Significantly higher serum IL-6 levels were noted in the immunocompromised group, while neutrophil granularity intensity was higher in the immunocompetent group. According to logistic regression analyses, elevated IL-6 levels predicted a lethal ICU outcome, while elevated IL-6 levels and neutrophil reactivity intensity were predictors of SA-AKI development. A cluster analysis revealed two patient groups with different IL-6 concentrations, and further studies indicated that the group with higher IL-6 values had significantly higher SA-AKI occurrence and increased lethal outcomes. Conclusions: An early serum IL-6 measurement regardless of the patients’ immune status indicates disease severity. Its measurement in the early phase of disease presentation, potentially in the emergency department, might facilitate ICU admission. Further research is warranted in the field of leukocyte CDP application.

Background and objectives: Endothelial dysfunction has been proposed to be an underlying mechanism of the pronounced cardiovascular morbidity in end-stage liver disease (ESLD), but clinical evidence is still limited. In this study, we investigated the association of circulating levels of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) with estimated cardiovascular risk in patients with ESLD awaiting liver transplantation. Materials and Methods: ADMA and NO levels were measured in the sera of 160 adult ESLD patients. The severity of hepatic dysfunction was assessed by the model for end-stage liver disease (MELD) score. The cardiovascular risk was estimated with the European Society of Cardiology Systematic Coronary Risk Estimation (SCORE) index, which was used to dichotomize patients in the subgroups depicting higher and lower cardiovascular risk. Results: Severe hepatic dysfunction (MELD ≥ 18) was present in 38% of the patients, and a higher cardiovascular risk was present in almost half of the patients (N = 74). ADMA and NO both significantly increased with the progression of liver disease and were independently associated with higher cardiovascular risk. Fasting glucose also independently predicted a higher cardiovascular risk, while HDL cholesterol and the absence of concomitant hepatocellular carcinoma were protective factors. Conclusions: These results suggest a remarkable contribution of the deranged arginine/NO pathway to cardiovascular risk in patients with end-stage liver disease.