Why the gut leaks in cirrhosis, and why anxiety in IBD is not just a reaction to having IBD

The edition in brief

In 276 adults with alcohol-associated liver disease compared against 177 with chronic hepatitis B and 20 healthy controls, serum IgA was substantially higher (median 323-412 versus 194 and 211 mg/dL) and correlated with hepatic IgA area and with interleukin-1 beta transcripts normalised to macrophage content; hepatic CD14-positive cells bound more IgA in alcohol-associated disease than in hepatitis B. In ethanol-fed mice, fingolimod reduced serum IgA, IgA-bound macrophages, interleukin-1 beta transcripts and transaminase rise. A second study dissects why bacteria cross the gut wall in cirrhosis: using a carbon tetrachloride mouse model and duodenal biopsies from patients with compensated and decompensated disease, it identifies failure at several checkpoints — epithelial cell death, vascular barrier damage, and dysfunction of the macrophages that line intestinal blood vessels. Depleting those macrophages alone caused bacterial translocation even without liver disease. A review of metabolic steatohepatitis frames ferroptosis, iron-dependent lipid peroxidation, as the initiating lytic event that drives myeloid activation and, reciprocally, Kupffer cell death, with PNPLA3, TM6SF2 and MBOAT7 polymorphisms priming the vulnerability. The practice-changer is a review of gut-brain axis mechanisms in inflammatory bowel disease, arguing that the anxiety, depression and neurological comorbidity seen in these patients are secondary to disrupted gut-brain signalling rather than simply the psychological consequence of chronic illness.