Liver disease: Understanding it will enable the provision of better treatment

(Press-News.org) In this prospective study, led by Dr Richard Moreau, INSERM Research Director (Mixed Research Unit 773 "Centre de Recherche biomédicale Bichat-Beaujon"; INSERM/Université Paris Diderot) who is also a practitioner attached to the Hepatology Department of the Beaujon Hospital (AP-HP), researchers studied a cohort of 1343 patients from 12 European countries. The results, published in the learned journal Gastroenterology, describe, for the first time, the specific profile of sufferers from this syndrome that is associated with cirrhosis. This also makes it possible to more clearly define the actual rules of attribution of the organs in those most severely affected, for whom there is a high risk of early death.

Cirrhosis is an irreversible liver disease. It is characterised by chronic inflammation that destroys the liver cells and produces anarchic regeneration in the form of nodules. The disease causes the liver to lose function and is accompanied by multiple complications. When these complications manifest (bleeding in the digestive tract, bacterial infection, accumulation of liquid in the abdomen, etc.), this is known as decompensated cirrhosis and the patients are hospitalised.

A certain number of these patients quickly develop a syndrome characterised by acute liver failure and/or failure of other vital organs1 (ACLF – acute-on-chronic liver failure). The syndrome is associated with a high risk of death at one month and no diagnostic criteria were clearly established hitherto that might make it possible to describe the condition.

Through a consortium , the researchers in Mixed Research Unit 773 "Centre de Recherche biomédicale Bichat-Beaujon" (INSERM/Université Paris Diderot), analysed data from 1343 patients hospitalised due to acute cirrhosis complications between February and September 2011 in 29 Hepatology Departments in 12

European countries . This enabled them to define robust diagnostic criteria for ACLF, indicating that one-third of the patients enrolled in the study had developed this syndrome.

The researchers noted that, compared to patients not suffering from ACLF, those who developed acute failure of an organ or organs were younger, were most frequently prey to alcoholism, suffered from a larger number of bacterial infections and had higher levels of white blood cells, as well as other markers of organ inflammation.

Quite unexpectedly, failure was most severe in patients without a previous history of cirrhosis complications. A high number of organ malfunctions (liver, kidneys, brain) were observed in these patients, including white blood cells in the blood and a mortality rate within one month of admission to hospital that was15 times greater than in patients who had a previous history.

"The identification of the criteria to define acute failure of an organ or organs enabled us to show that this is a separate syndrome from cirrhosis complications. In addition to organ failure and the high associated mortality, the development of the disease depends on the patient's age and medical history", explains Richard Moreau, INSERM Director of Research, and the Principal Investigator for the study. "We hope to be able to better identify those at risk of early death in order to improve their treatment. Furthermore, these results could lead to improving the current rules for assigning organs for grafting in the severest cases", he concludes.

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Liver and cirrhosis The liver is a vital organ whose main functions are the storage and production of glucose as well as the synthesis and breakdown of other substances (triglycerides, cholesterol, lipoproteins, coagulation factors).

There are about 700,000 cases of cirrhosis in France, of which 30% are at the severe stage, resulting in 10,000 to 15,000 deaths a year. Diagnosis is on average at the age of 50. Not everyone at risk of cirrhosis develops the disease. In fact, it only manifests in 10% to 20% of cases. The only current treatment for cirrhosis is a liver transplant. The first eligible patients are those whose life expectancy at three months is the lowest. Each year, around 1,000 patients receive liver transplants in France. Sources

Acute-on-Chronic Liver Failure is a Distinct Syndrome that Develops in Patients With Acute Decompensation of Cirrhosis Richard Moreau,* Rajiv Jalan,‡ Pere Gines,§ Marco Pavesi,║Paolo Angeli,¶ juan cordoba,# François Durand,* Thierry Gustot,** Faouzi Saliba,‡‡ Marco Domenicali,§§ Alexander Gerbes,║║ Julia Wendon,¶¶ Carlo Alessandria,## Wim Laleman,*** Stefan Zeuzem,‡‡‡ Jonel Trebicka, §§§ Mauro Bernardi,§§ Vicente Arroyo,§ for the canonic study investigators of the easl-clif consortium

* Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy; Inserm U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Clichy and Paris; and Université

Paris Diderot-Paris 7, Paris, France; ‡ Institute of Liver and Digestive Health, Liver Failure Group, Royal Free Hospital Campus, London, United Kingdom; § Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Spain; ║Data Management Centre, CLIF Consortium, Hospital Clinic, Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Spain; ¶ Department of Medicine, Unit of Hepatic Emergencies and Liver Transplantation, University of Padova, Padova, Italy; # Servicio de Hepatologia, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Spain; ** Department of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium; ‡‡ Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique- Hôpitaux de Paris, Villejuif, France; §§Semeiotica Medica, Policlinico S. Orsola-Malpighi, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; ║║ Liver Center Munich, Department of Medicine 2, Klinikum der LMU Munchen-Grosshadern, Munich, Germany; ¶¶Institute of Liver Studies and the Cellular Biology of Inflammation, King's College Hospital, London, United Kingdom; ## Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, University of Turin, Turin, Italy;

***Department of Liver and Biliopancreatic Diseases, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium; ‡‡‡ Department of Medicine I, JW Goethe University Hospital, Frankfurt, Germany; §§§Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany

Gastroenterology April 2013