Albumin to prevent infection in Acute-on-Chronic Liver Failure (Acronym: ATTIRE Albumin To prevenT Infection in liveR failurE)

Liver cirrhosis is the 5th leading cause of death in the UK with patients having an increased predisposition to and mortality from infection. Health-care acquired infection carries a high mortality and substantial costs with ICU admission frequent. We have established that elevated (cyclooxygenase-derived) Prostaglandin E2 underlies immune dysfunction in cirrhosis and that its effects are antagonised by albumin, with a cut-off serum albumin value of 30 g/l predicting immune dysfunction in these patients i.e. patients with an albumin level below 30g/l are highly likely to have immune dysfunction and restoring albumin to >30g/l reverses this. We will investigate whether albumin can be repurposed as an immune restorative drug. No such treatment currently exists despite cirrhosis-induced immune dysfunction being identified >30 years ago. We shall perform a Phase II feasibility study to validate our immune restorative albumin regimen (to keep serum albumin >30g/l with 20% human albumin solution infusions) followed by a Phase III single-blind randomised clinical trial to determine whether albumin prevents or reduces incidence of health-care acquired infection in decompensated cirrhosis patients (ATTIRE 1/2). Albumin is safe, cheap and simple to administer. There is no risk of development of antibiotic resistance or Clostridium difficile infection, unlike prophylactic antibiotics.