Advanced chronic liver disease (ACLD) is associated with high morbidity, mortality and healthcare costs, primarily from complications of decompensated cirrhosis, including ascites and variceal bleeding. In 2019, a quarter of global cirrhosis deaths were associated with alcohol, with worsening trends driven by comorbidities like metabolic syndrome.1 Alcohol-related liver disease (ALD) is increasingly understood as a disorder driven by innate immunity as much as by hepatocyte injury. In particular, neutrophils accumulate in ALD and amplify liver damage.2 3 Neutrophils are highly plastic cells whose phenotype is shaped by local environments.4 However, the location where pathogenic neutrophil priming occurs in advanced liver disease remains unclear. Reinartz Groba and colleagues place that event in the portal circulation and identify local tryptophan depletion as a key metabolic regulator of the process.5
The authors analysed paired portal vein and superior vena cava (SVC) blood obtained during…
