The main objective of this study is to investigate the effect of Prometheus liver support dialysis on intracranial pressure, cerebral metabolism and circulation in patients with acute liver failure.

Acute liver failure (ALF) is a highly mortal medical condition often complicated by multiorgan failure. Apart from severe coagulopathy ALF is characterized by onset of hepatic encephalopathy and in many cases intracranial hypertension (ICH) with the risk of cerebral incarceration. The pathogenesis behind ICH is incompletely understood and the therapeutic options are limited. Prometheus (R) liver support dialysis offers a system that apart from regular high-flux hemodialysis to a certain extent is able of removing albumin-bound substances from the patient - a feature that theoretically could benefit patients with ALF.

In this study we intend to investigate the effect of 6-8 hours of Prometheus (R) liver support dialysis on cerebral metabolism, ICH and cerebral bloodflow (CBF) in patients with ALF. The study is designed as a open, prospective and randomized study, where a control-group treated with 6-8 hours of continuously veno-venous hemodiafiltration (CVVHDF) and standard medical treatment (SMT) is compared to the intervention group treated with Prometheus (R) liver support dialysis and SMT. The study is designed as a cross-over study so that included patients will be treated in both groups in a randomized order.

The primary end-points are treatment effect on intracranial pressure, CBF and cerebral oxidative metabolism (lactate/pyruvate-ratio). We use a intracranial monitoring system from Integra/Camino (R) (United States) in combination with CMA microdialysis system and bedside analyzer (CMA-600) (Stockholm, Sweden).

Inclusion Criteria:

• acute liver failure
• and grade II-IV encephalopathy
• and persistent raised arterial ammonia-concentration above 150 micromol/L
• and informed consent from closest relative and general practitioner

Exclusion Criteria:

• withdrawal of informed consent
• severe untreated infection
• active bleeding within 48 hours
• suspicion of malignant liver disease
• severe heart insufficiency or middle artery pressure below 60 mmHg in spite of vasoactive therapy
• pregnant or lactating women
• disseminated intravascular coagulation
• clinical suspicion of cerebral damage