Advanced Liver Disease
The liver is at the centre of everything we do.
Chronic liver disease represents a global public health problem, with about 100 million suffering from cirrhosis and the main causes relating to alcohol, fat and viral infection.4
Liver disease is a global challenge with social and individual causes
A major disease with a great need for new treatments
people suffering from chronic liver disease in the world1
deaths per year worldwide, a rising number1
biggest cause of death in the US in middle age2
Although there has been remarkable success in the development of certain drugs for the treatment of viral-induced chronic liver disease the options for patients with cirrhosis remain limited
One patient’s journey
One patient’s journey, which represents the many lives that could be saved today and where Yaqrit is focused on developing end-to-end solutions for patients with advanced liver disease
David, a 52-year old accountant, drinking 2 large glasses of wine per day is diagnosed with alcoholic cirrhosis during a routine health check.
No known liver disease previously.
Image not of actual patient.
David is admitted to hospital with pneumonia. On admission he has fever, raised inflammatory markers, jaundice and fluid accumulation in his abdomen.
David develops progressive jaundice and goes into a coma requiring admission into intensive care.
He dies 5 days later with progressive liver, renal, circulatory and cerebral failure
Acute-on-chronic liver failure (ACLF)
Treating liver disease
Chronic liver disease is a complex, multifactorial condition that evolves over time. Progression of chronic live disease leads to cirrhosis, which is the leading cause of liver-related death globally3 and the ultimate fate for patients. The primary cause of this progression is a combination of liver injury and inflammation. Yaqrit has harnessed its deep and new understanding of the underlying mechanisms of inflammation – an important cause of liver disease progression – to identify novel therapeutic targets.
The liver has an exceptional ability to regenerate. In the initial stages of cirrhosis the patient does not exhibit any features of liver disease. This state is referred to as compensated cirrhosis. The life expectancy of patients with compensated cirrhosis may be similar to that of a healthy adult unless they decompensate, which refers to a state where they start to exhibit signs and symptoms of liver disease.
Further deterioration in liver function can lead to decompensated cirrhosis. This occurs when the amount of functioning liver can no longer compensate for the requirements of the body. A patient with decompensated cirrhosis can suffer from a range of complications, including the collection of fluid in the abdominal cavity, bleeding, decline in brain function, infection and jaundice. Once decompensation occurs the one year mortality risk varies up to 80% depending upon its severity.5 Quality of life is also seriously affected with the need for frequent hospital admissions. There are no specific, approved treatments for decompensated cirrhosis that have been shown to reduce mortality. At present, liver transplantation is the only treatment known to improve the survival of these patients.
Acute-on-chronic liver failure
Acute-on-chronic liver failure (ACLF) occurs in about 30% of patients with cirrhosis who decompensate acutely.6 This syndrome is characterised by the failure of not only the liver but also other organs such as the kidneys and brain. Depending upon the number of organs failing, the 28-day mortality rate as high as 89%. At this stage, the patients require support for their failing organs in the intensive care unit.5 Three major features characterise ACLF: it occurs in the context of intense systemic inflammation, is frequently related to pro-inflammatory precipitating events and is associated with single or multiple-organ failure.5 It is remarkable that even at this stage, ACLF is potentially reversible but the chances of reversibility diminish with the severity of the ACLF.
Ntandja-Wandji, Line Carolle et al., (2020) Combined alcoholic and non-alcoholic steatohepatitis. JHEP Reports.
National Vital Statistics Reports, Deaths: Leading Causes for 2017.
Sepanlou S. et al. (2020). The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet Gastroenterology & Hepatology.
Arroyo V., Moreau R. and Jalan R. (2020). Acute-on Chronic Liver Failure. The New England Journal of Medicine.
Moreau R. et al. (2013). Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology.