Amsterdam, The Netherlands, Thursday 25 April 2013: New data from clinical studies presented for the first time at the International Liver Congress™ 2013 provide new rationale for an old and established treatment option for portal hypertension. Additionally, spleen stiffness predicts the occurrence of clinical complications, which is of paramount importance in clinical practice.
In patients with cirrhosis, increasing blood pressure in the abdominal circulatory system (known as portal hypertension) leads to potentially lethal complications which might be prevented with simple medical treatment. Patients with cirrhosis and portal hypertension have increased gastrointestinal permeability which allows the movement of bacteria or bacterial components through the lining of the gut into the blood stream in a process known as bacterial translocation. Bacterial components such as lipopolysaccharide can be involved in the genesis of complications of cirrhosis.
The first study evaluated the effects of a non-selective beta-blocker (NSBB) on gastrointestinal permeability and bacterial translocation in patients with cirrhosis with high levels of portal hypertension.1 Patients with severe portal hypertension (HVPG* ≥20mmHg) had increased markers of gastrointestinal permeability and bacterial translocation compared to patients with lower levels of portal hypertension (HVPG<20mmHg). Treatment with NSBB significantly reduced HVPG, improved gastrointestinal permeability and decreased bacterial translocation (LPS-binding protein (LBP) -16% p=0.018; IL-6 -41% p< 0.0001) levels.
Patients who were found to have the highest levels of gastrointestinal permeability were also found to be at most risk of bleeding from oesophageal varices; a complication of cirrhosis which carries a high risk of mortality.
These findings provide a new rationale for the use of non-selective beta-blockers in patients with cirrhosis. EASL’s Treasurer Prof. Mauro Bernardi commented on the data: “The movement of bacteria from the gut and into the bloodstream is extremely serious and potentially fatal in patients with cirrhosis often leading to complications or death. Beta-blockers have been successfully used in a number of conditions and as a standard treatment to control blood pressure in other disease areas. In cirrhosis, they have been used for decades for primary and secondary prophylaxis of bleeding from oesophageal varices. The results of this study show that besides improving portal hypertension, as it was thought up to now, their beneficial effects are also due to their ability to reduce bacterial translocation which may widen the indications for the use of these drugs in this setting.”
In the diagnostic landscape, promising data to support the validity of non-invasive techniques were also presented at the congress. HVPG, an invasive measurement technique currently considered as the best predictor to identify progression to severe scarring of the liver and disrupted essential body functions (clinical decompensation), was compared to techniques such as the evaluation of spleen stiffness (SS) combined with the MELD** score.2
Cirrhosis is an abnormal liver condition in which there is irreversible scarring of the liver. The main causes are sustained excessive alcohol consumption, viral hepatitis B and C, and fatty liver disease - however, there are many possible causes.
People with cirrhosis may develop jaundice (yellowing of the skin, eyes and tongue), itching and extreme tiredness.
For cirrhosis to develop long-term, continuous damage to the liver needs to occur. When healthy liver tissue is destroyed and replaced by scar tissue the condition becomes serious, as it can start blocking the flow of blood through the liver.
Cirrhosis is a progressive disease, developing slowly over many years, until eventually it can stop liver function (liver failure).
The liver carries out several essential functions, including the detoxification of harmful substances in the body. It also purifies the blood and manufactures vital nutrients.
If cirrhosis is mild the liver can make repairs and continue functioning properly. If the cirrhosis is advanced and more and more scar tissue forms in the liver, the damage is irreparable. The liver tissue is replaced by fibrous scar tissue as well as regenerative nodules (lumps that appear as a consequence of a process in which damaged tissue is regenerated).
The study showed that in compensated (early) patients with cirrhosis both the SS (p<0.0001) and the MELD (p=0.016) score provided an accurate prediction of clinical decompensation, and their combination in a new score had a predicting power even superior to that of HVPG.
Prof. Mauro Bernardi added, "HVPG is an invasive technique, which can often be discomforting for patients, is only performed in specialised centres and needs experienced operators to be fully reliable. While further studies will be required, if non-invasive techniques continue to present accurate predictions, they would be welcomed in the overall management of compensated patients with cirrhosis."
Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2013.
Why does cirrhosis cause problems?
The liver is an important organ in the body. It performs many critical functions, two of which are producing substances required by the body, for example, clotting proteins that are necessary in order for blood to clot, and removing toxic substances that can be harmful to the body, for example, drugs. The liver also has an important role in regulating the supply to the body of glucose (sugar) and lipids (fat) that the body uses as fuel. In order to perform these critical functions, the liver cells must be working normally, and they must have an intimate relationship with the blood since the substances that are added or removed by the liver are transported to and from the liver by the blood.
The relationship of the liver to the blood is unique. Unlike most organs in the body, only a small amount of blood is supplied to the liver by arteries. Most of the liver’s supply of blood comes from the intestinal veins as the blood returns to the heart. The main vein that returns blood from the intestines is called the portal vein. As the portal vein passes through the liver, it breaks up into increasingly smaller and smaller veins. The tiniest veins (called sinusoids because of their unique structure) are in close contact with the liver cells. In fact, the liver cells line up along the length of the sinusoids. This close relationship between the liver cells and blood from the portal vein allows the liver cells to remove and add substances to the blood. Once the blood has passed through the sinusoids, it is collected in increasingly larger and larger veins that ultimately form a single vein, the hepatic vein that returns the blood to the heart.
In cirrhosis, the relationship between blood and liver cells is destroyed. Even though the liver cells that survive or are newly-formed may be able to produce and remove substances from the blood, they do not have the normal, intimate relationship with the blood, and this interferes with the liver cells’ ability to add or remove substances from the blood. In addition, the scarring within the cirrhotic liver obstructs the flow of blood through the liver and to the liver cells. As a result of the obstruction to the flow of blood through the liver, blood “backs-up” in the portal vein, and the pressure in the portal vein increases, a condition called portal hypertension. Because of the obstruction to flow and high pressures in the portal vein, blood in the portal vein seeks other veins in which to return to the heart, veins with lower pressures that bypass the liver. Unfortunately, the liver is unable to add or remove substances from blood that bypasses it. It is a combination of reduced numbers of liver cells, loss of the normal contact between blood passing through the liver and the liver cells, and blood bypassing the liver that leads to many of the manifestations of cirrhosis.
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Notes to Editors
*HVPG or hepatic venous pressure gradient is the most widely used parameter for assessing portal hypertension
**MELD is a scoring system for assessing the severity of chronic liver disease
Compensated cirrhosis, where the body still functions fairly well despite scarring of the liver, is strongly associated with the development of portal hypertension.
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy. EASL’s main focus on education and research is delivered through numerous events and initiatives, including:
The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
Journal of Hepatology published monthly
Participation in a number of policy initiatives at European level
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European Association for the Study of the Liver
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