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
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.
*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.
1 Reiberger, T et al, IMPROVEMENT OF INTESTINAL PERMEABILITY AND REDUCING BACTERIAL TRANSLOCATION BY BETABLOCKER TREATMENT IS ASSOCIATED WITH A LOWER RISK OF VARICEAL BLEEDING. Abstract presented at the International Liver CongressTM 2013
2 Colecchia, A et al, SPLEEN AND LIVER STIFFNESS MEASUREMENT CAN PREDICT CLINICAL COMPLICATIONS IN COMPENSATED CIRRHOTIC PATIENTS: A PROSPECTIVE STUDY Abstract presented at the International Liver CongressTM 2013