Circulating acute phase cytokines and cytokine inhibitors in fluminant hepatic failure: Associations with mortality and haemodynamics

Objective: To determine if mortality, multi-organ failure and haemodynamic instability in fulminant hepatic failure are related to levels of circulating acute phase cytokines. Design: A prospective study of patients admitted with fulminant hepatic failure. Setting: A UK national referral centre for the management of acute liver failure based in the specialist liver intensive care unit of a large teaching hospital. Patients: Patients with acute liver failure were studied in two cohorts (n = 57 and n = 63). Interventions: Blood sampling, detailed haemodynamic studies. Measurements: Plasma interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor alpha (TNF), endotoxin, p55 and p75 soluble tumour necrosis factor receptors. Clinical and haemodynamic parameters. Main results: In the initial cohort (n = 57) circulating levels of interleukin 6 and 8 but no other parameters were associated with mortality. IL-6 and to a lesser extent IL-8 were significantly associated with haemodynamic instability as assessed by systolic hypotension. In a further cohort comprising 63 patients who underwent detailed haemodyamic assessment IL-6 levels were significantly associated with acidosis, systemic vascular resistance, oxygen consumption and low mean arterial pressure. Conclusions: Mortality in acute liver failure is associated with high levels of the circulating acute phase cytokines IL-6 and IL-8, independently of endotoxaemia. Levels of IL-6 in particular are closely associated with the severity of haemodynamic instability, similar to the pattern seen in septic shock. The underlying mechanism of circulatory derrangement in acute liver failure remains unknown, but patterns of proinflammatory cytokine mediator are very similar to those found in sepsis, and are not related to endotoxaemia.