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19th ISAD

The International Liver Support Meeting Rostock

Acute on chronic liver failure in cirrhosis as an indication for liver support - who should be transferred, where and when?

Acute on Chronic Liver Failure (ACLF) is a recently characterized syndrome defined by acute decompensation of cirrhosis (i.e. ascites, encephalopathy and/or bacterial infections, the later in patients with prior history of acute decompensation) associated with organ failure and high 28-day mortality rate (33%). It occurs in the setting of an acute burst of the systemic inflammation already present in patients with decompensated cirrhosis triggered by infections, acute liver injury or major surgery among others. In 40-50% of cases in whom there is no apparent trigger, ACLF may be related to an acute increase in the process of the chronic translocation of bacterial products from the intestinal lumen to the systemic circulation.

ACLF is a rapidly evolving heterogeneous condition which may resolve, improve, follow a steady course or worsen under standard medical therapy (management of specific complications) within few days following diagnosis. Early clinical course of ACLF, the most sensitive determinant of short-term survival, is poorly predicted by the standard scores (MELD, Child-Pugh). The combination of the number of organ failures (as estimated by the CLIF-OF score) and the grade of systemic inflammation (as estimated by the WBC count) at diagnosis, the main components of the ACLF score, is significantly more accurate. Recent data indicate that prediction of survival of the ACLF score could be further improved by adding sensitive markers of systemic inflammation.

Although three large RCT failed to show any improvement in prognosis in patients with decompensated cirrhosis and severe liver failure treated by artificial liver support systems, a recent meta-analysis in individual cases from three RCT and a retrospective comparative study in a large cohort of patients treated with MARS® strongly suggest that liver support may improve short-term survival if given at appropriated dosages in patients with the most severe grades of ACLF (ACLF-2 and ACLF-3). Stratification of patients and treatment dosage should, therefore, be carefully considered in the design of future trials with artificial liver support systems. 

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