Context Acute liver failure (ALF) is a life-threatening condition that occurs on the background of a healthy liver. The most common cause of acute liver failure in the UK is paracetamol overdose. Acute liver failure results from liver damage and activation of the body's inflammatory defences with subsequent damage to other organs including kidneys, lungs and heart. This often requires life support in an intensive care unit before liver transplantation (LT), the only currently available and effective rescue treatment for acute liver failure.

Challenge Patient factors and organ availability limit who can benefit from liver transplant. At present there are no effective alternative therapies for patients who do not get a liver transplant, and survival rates in these situations are poor. The underlying mechanisms of inflammation are poorly understood, thus therapies are limited.

Aim The investigators research aims to understand the mechanisms that underpin the inflammation seen in acute liver failure by studying the inflammatory cells in the blood and examining their cellular programmes. This will allow the investigators to identify pathways that are activated and understand how the liver and blood interact to spread inflammation around the body. The investigators aim to identify targets for disease-modifying therapies to avert the need for liver transplant.

Importance Understanding how the body responds to acute liver failure, and whether there are different patterns of inflammatory response, will enable trials of immune-modulating drugs to prevent the need for liver transplantation or prolong the time a patient can wait for an organ. This has the potential to help improve organ availability for other patients and save lives in acute liver failure.

Inclusion Criteria:

• acute liver failure due to acetaminophen (paracetamol) overdose admitted to ICU
• all cause sepsis admitted to ICU

Exclusion Criteria:

• age <16y

Patients with acute liver failure due to acetaminophen overdose OR sepsis who are admitted to ICU