All disease begins in the gut.

HIPPOCRATES (460 - 370 BC)




About rare liver diseases

Rare liver diseases encompass acute conditions such as acute-on-chronic liver failure (ACLF), acute liver failure (ALF), and congenital metabolic disorders (e.g., urea cycle disorders). Three distinct diseases which have in common an alarming mortality rate (between 50 and 100%) because the current treatments are either preventive or unsafe

Acute-on-chronic liver failure

Is a syndrome in patients with chronic liver disease (e.g., cirrhosis) which is characterized by an acute deterioration resulting in liver failure and one or more extrahepatic organ failures (brain, kidneys, cardiovascular, and respiratory). The cascade of multiple organ failure and the development of a neuropsychiatric condition called hepatic encephalopathy represent major complications in patients with ACLF who can rapidly progress into coma and death. The precipitating events are half of the time unknown, or related to infections, alcoholism, and gastrointestinal bleeding. ACLF occurs in 100'000 patients yearly in the EU and USA and continues to increase dramatically due to the aging population, and a higher prevalence of diabetes, obesity, alcohol, and drug intoxications.

Acute liver failure

Is a severe liver injury in the absence of a pre-existing liver disease. It is associated with hepatic encephalopathy, a key symptom for the final prognostic, and occasionally with an impaired renal function. Liver transplant is the only treatment currently available for patients with ALF but the pre-transplant conditions are often complicated by a high incidence of multi-organ dysfunctions. Moreover, due to organ shortage, approximately half of the patients die while waiting for a liver graft. ALF affects 7’500 patients yearly in the EU and USA.

Urea cycle disorders (UCDs)

Are a family of rare genetic disorders characterized by a reduced activity of enzymes involved in the urea cycle which leads to high levels of neurotoxic ammonia in the blood (the so-called hyperammonemia). Currently, neonate screening fails to detect most UCDs and the majority of patients are first diagnosed at clinical presentation with symptoms such as lethargy and periodic vomiting. Hyperammonemia rapidly evolves to coma and death if not treated within the next couple of hours. UCDs affect 1’200 newborns yearly in the EU and USA.

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