The liver is a vital organ in the human body, being central to many crucial processes.
Not only does it filter the blood from the digestive tract before it enters the rest of the body, it is also responsible for the production, storage and control of many key compounds, including sugar, hormones, digestive enzymes, blood clotting factors, etc. Therefore, any failure of any of the liver’s normal activities, or even of the entire liver itself can cause many diseases in the body leading to death in the advanced forms of liver ailment if no organ replacement is available.
Drug metabolism and synthesis of proteins, fat and carbohydrates
Blood filtration and purification
Storage of glycogen and vitamins
Production and excretion of bile for cholesterol metabolism and bilirubin elimination
PROGRESSION OF LIVER DISEASE
Liver disease can either be inherited (genetic) or be due to a variety of environmental and lifestyle factors such as viral infection, obesity or alcohol abuse.
If diagnosed and treated during the early stages, the liver can usually heal itself over time since it has a remarkable regenerative capacity. Unfortunately, these initial stages generally produce few or no symptoms, with diagnosis often being due to a routine blood test or checkup. Therefore, your best defense against liver disease is to maintain a healthy lifestyle and to get regular checkups, particularly if you are in an at-risk group (obese, alcoholic, infected with Hepatitis B or C).
Normal compensated inflammation. Liver fights infection or heals injury
Prolonged inflammation causes scar tissue formation, replacing healthy tissue and reducing the liver’s effectiveness
Widespread fibrosis leads to cirrhosis
Scarring from cirrhosis eventually prevents proper liver function
End stage liver disease begins to affect other vital organs
Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly significant global liver-health problem. It is caused when lifestyle factors, such as an unhealthy diet, a lack of exercise or diabetes, disrupt the normal sugar and fat processing functions of liver cells, resulting in a buildup of fat within the liver cells known as steatosis. This can lead to a ballooning of hepatocyte cells in the liver and inflammation.
Non-Alcoholic SteatoHepatitis (NASH) occurs when additional factors, such as insulin resistance, obesity or type II diabetes, cause NAFLD to progress. This results in localized inflammation and fibrosis that carry the risk of cirrhosis or liver cancer, as well as increasing the risk of heart disease.
The prevalence of NAFLD is increasing with the worldwide obesity epidemic. Various studies estimate a prevalence of between 6% – 40% of the population2, around 15% – 20% of whom have NASH, resulting in an estimated two million plus adults in the US having NASH-related advanced liver disease3.
NASH is a very slow developing disease, and often remains undiagnosed. Nonetheless, it is predicted to become the leading reason for liver transplants by 2020. It is therefore in urgent need of a new, effective treatment, since growing waiting lists for transplants mean an increasing number of patients will die while waiting for a suitable donor liver to become available.
Acute-on-Chronic Liver Failure (ACLF) is a recently recognized syndrome whereby ongoing chronic liver disease suddenly creates an abrupt loss of function, associated with organ failures and poor survival. The most commonly identified triggers of ACLF are bacterial or viral infection and excessive alcohol consumption, but more than 40% of cases have no identifiable trigger, although it seems likely that a systemic inflammatory response plays a crucial role4.
Liver cirrhosis is a condition in which the liver does not function properly due to chronic damage and is characterized by the replacement of normal liver parenchyma by scar tissue. This condition is becoming more prevalent
5 and the natural progression is from compensated to decompensated form with its associated clinical complications and poor prognosis. Around one-third of patients admitted to hospital due to acute decompensation of cirrhosis either have ACLF at admission or develop the syndrome during their stay. The result is that there are around 70,000 ACLF patients per year in Europe, the US and Japan combined.
There is no specific effective treatment available currently for ACLF. Therefore, once any known trigger is treated, ACLF is managed by providing organ support and treating any complications. Transplantation is currently the best treatment option, however, the rapid progression of the disease can make this difficult. To be successful, a donor organ must be available at a time when the patient is not too sick to undergo the surgery
- Michalopoulos GK. Principles of liver regeneration and growth homeostasis. Comprehensive Physiology. 2013;3:485-513.
- Miyajima A, Tanaka M, Itoh T. Stem/Progenitor Cells in Liver Development, Homeostasis, Regeneration, and Reprogramming. Cell Stem Cell. 2014;14(5): 561-574.
- HEPAMAP. A roadmap for hepatology research in Europe: An overview for policy makers. 2016.
- Hermaez R, Solà E, Moreau R, Ginès P. Acute-on-chronic liver failure: an update. Gut. 2017;66(3):541-553.
- Murray CJ et al. GBD 2010: a multi-investigator collaboration for global comparative descriptive epidemiology. Lancet. 2012;380(9859);2055-2058.