Liver transplantation (LT) is recognized as an effective approach that offers survival benefits for patients with acute-on-chronic liver failure (ACLF). However, controversies remain regarding the LT selection criteria, and meta-analyses reporting overall survival outcomes across different ACLF severity grades are lacking.

To depict a comprehensive postoperative picture of patients with ACLF of varying severity and contribute to updating LT selection.

Systematic searches in Web of Science, EMBASE, PubMed, and Cochrane databases were performed, from inception to December 26, 2023, for studies exploring post-transplant outcomes among ACLF patients, stratified by severity grades as identified by the European Association for the Study of the Liver-Chronic Liver Failure criteria. The primary outcome of interest was the survival rate within one year, with post-transplant complications as secondary outcomes. Additionally, the subgroup analysis examined region-specific one-year survival rates.

A total of 17 studies involving 28025 participants were included. Patients with ACLF-1 and ACLF-2 have favorable survival within one year, with survival rates reaching 87% [95% confidence interval (CI): 84%-91%] and 86% (95%CI: 81%-91%), respectively. Despite the relatively lower survival (73%, 95%CI: 66%-80%) and higher incidence of infection (48%, 95%CI: 29%-67%) observed in ACLF-3 patients, their survival exceeds that of those who do not undergo LT. Moreover, post-transplant survival was highest in North America across all ACLF grades.

LT can provide survival advantages for ACLF patients. To optimize the utilization of scarce donor organs and improve prognosis, comprehensive preoperative health evaluations are essential, especially for ACLF-3 patients.

Acute-on-chronic liver failure (ACLF) occurs in the context of advanced liver disease and is associated with hepatic and extrahepatic organ failure, eventually leading to a major risk of short-term mortality. To date, there are very few effective therapeutic options for ACLF. In many cases, liver transplantation is the only life-saving treatment that has acceptable outcomes in carefully selected recipients. This Review addresses key aspects of the use of liver transplantation for patients with ACLF, providing an in-depth discussion of existing evidence regarding candidate selection, the optimal window for transplantation, potential prioritisation of liver grafts for this indication, and the global management of ACLF to bridge patients to liver transplantation.

Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis. Although primary prevention drugs, including non-selective β-blockers, have effectively reduced the incidence of bleeding, their efficacy is limited due to side effects and related contraindications. With recent advances in precision medicine, precise drug treatment provides better treatment efficacy.

Literature search was conducted in PubMed, MEDLINE and Web of Science for relevant articles published up to May 2022. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/.

The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs. According to the site of action, these drugs could be classified into four classes: intrahepatic, extrahepatic, both intrahepatic and extrahepatic targets and others. All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

This review classified and summarized the promising drugs, which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension, demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

Acute-on-chronic liver failure (ACLF) is an acute decompensated syndrome based on chronic liver disease, while neutrophil recruitment is the most critical early step. C-X-C motif chemokine ligand 1 (CXCL1), a cytokine that recruits neutrophils, was significantly upregulated in both ACLF mice and patients with ACLF. This present study aims to explore the role of CXCL1 in the pathogenesis of ACLF.

We established an ACLF mouse model induced by carbon tetrachloride, lipopolysaccharide, and D-galactosamine, and used adeno-associated virus to achieve overexpression and knockdown of Cxcl1. We employed mass cytometry, flow cytometry, multiplex cytokine and chemokine analysis, Western blot, and reactive oxygen species (ROS) detection in mice blood and liver. ACLF patients (n = 10) and healthy controls (n = 5) were included, and their liver samples were stained using multiplex immunohistochemistry techniques.

CXCL1 was significantly elevated in both ACLF mice and patients. CXCL1 recruits neutrophils by binding to the C-X-C motif chemokine receptor 2 on the surface of neutrophils, affects ACLF prognosis by generating ROS and mitochondrial depolarization and modulating caspase3-related apoptotic pathways. We found that the knockdown of CXCL1 attenuated the infiltration of neutrophils in the mouse liver, reduced the expression of inflammatory cytokines, and also significantly downregulated ROS production and caspase3-related hepatocyte apoptosis, thereby ameliorating the liver injury of ACLF.

CXCL1 is a core player in the mobilization of neutrophils in ACLF, and the knockdown of Cxcl1 improves neutrophil infiltration, reduces ROS levels, and reduces hepatocyte apoptosis, thereby attenuating inflammation and liver injury in ACLF. Our results revealed a previously unknown link between CXCL1-induced neutrophil recruitment and ACLF, providing evidencing for potential therapies targeting ACLF.