Patients with acute decompensated (AD) liver cirrhosis or acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. Existing research, mostly from specialized liver transplant centers, largely addresses short-term outcomes. Our aim was to evaluate in-hospital mortality and 1-year transplant-free survival after hospital discharge in the Netherlands. We conducted a nationwide observational cohort study, including patients with an history of cirrhosis or first complications of cirrhotic portal hypertension admitted to ICUs in the Netherlands between 2012 and 2020. The influence of ACLF grade at ICU admission on 1-year transplant-free survival after hospital discharge among hospital survivors was evaluated using unadjusted Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazard model. Out of the 3,035 patients, 1,819 (59.9%) had ACLF grade 3. 1420 patients (46.8%) survived hospitalization after ICU admission. The overall probability of 1-year transplant-free survival after hospital discharge was 0.61 (95% CI 0.59-0.64). This rate varied with ACLF grade at ICU admission, being highest in patients without ACLF (0.71 [95% CI 0.66-0.76]) and lowest in those with ACLF-3 (0.53 [95% CI 0.49-0.58]) (Logrank P < 0.0001). However, after adjusting for age, malignancy status and MELD-score, ACLF grade at ICU admission was not associated with an increased risk of liver transplantation or death within one year after hospital discharge. In this nationwide cohort study, ACLF grade at ICU admission did not independently affect 1-year transplant-free survival after hospital discharge. Instead, age, presence of malignancy and the severity of liver disease played a more prominent role in influencing transplant-free survival after hospital discharge. Patients with Acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. In these patients' short-term mortality is high, but long-term outcomes of survivors remain unknown. Using a large nationwide cohort of ICU patients, we discovered that the severity of ACLF at ICU admission does not influence one-year transplant-free survival after hospital discharge. Instead, age, malignancy status and overall severity of liver disease are more critical factors in determining their long-term survival.

Mesenchymal stromal cells (MSC) have been shown to mitigate IRI through their anti-inflammatory and immune-modulating capacities. This study aims to demonstrate the feasibility, safety, and effectiveness of hepatic administration of bone marrow-derived (BM)-MSCs in a large pig model relevant to human anatomy. After complete vascular exclusion for 45 min, 3 × 10⁶ human BM-MSCs/kg body weight were infused via the portal vein or hepatic artery. BM-MSC infusion did not cause obstruction of hepatic or pulmonary blood flow within 6 h after infusion. Cells were effectively retained in the liver, being undetectable in peripheral blood, lung, and spleen samples. Human B2M expression, as a marker for BM-MSC presence, was significantly higher for the left liver lobe in arterial infusion compared to portal infusion. In liver samples with high BM-MSC levels, we identified the prevention of up- or downregulation of some genes related to inflammation and energy metabolism that was present in non-treated control samples, indicating biological effects within 6 h of infusion. We conclude that hepatic BM-MSC infusion is feasible and safe, with the hepatic artery serving as the optimal administration route for homogenous distribution. These findings pave the way for clinical studies on MSC infusion in IRI, either in situ in liver conditions or ex situ during machine perfusion.