Test Predicts Death in Patients with Serious Liver Disease

Acute-on-chronic liver failure (ACLF) is a sudden deterioration of the liver function in a patient with liver cirrhosis accompanied by failure of one or more organ systems and this liver disease has a serious prognosis and the four-week mortality rate is 20% to 30%.

This condition is often triggered by an infection, bleeding or other stressful events and due to the severity of the disease it is important to develop a test to identify patients with the highest risk of developing this condition and thus the highest risk of a fatal outcome.

Scientists at Aarhus University (Denmark) screened patients at liver units in 29 university hospitals with a diagnosis of cirrhosis based on previous liver biopsy findings or a composite of clinical signs and findings provided by laboratory test results, endoscopy, and radiologic imaging. Eighty-six cirrhosis patients had no ascites and no ACLF, 580 had ascites but no ACLF; 100, 66, and 19 had ACLF-grade-I (ACLF-I), ACLF-II, and ACLF-III, respectively.

The scientists measured the circulating macrophage activation markers soluble sCD163 and mannose receptor (sMR) and related them to the short-(one to three months) and long-term (6 months) mortality in the cirrhosis patients. The plasma concentration of sCD163 was determined in duplicate in samples that had been frozen at -80 °C by an in-house sandwich enzyme-linked immunosorbent assay (ELISA) using a BEP-2000 ELISA-analyzer (Dade Behring, Deerfield, IL, USA). The team measured sMR by a newly developed in-house ELISA assay.

The investigators found a stepwise increase in median sCD163: 5.68; 8.26; 9.50; 15.68; 20.18 mg/L, and sMR: 0.60; 0.81; 1.17; 1.41mg/L with increasing grades of ACLF. Both sCD163 and sMR were independently associated with short and long-term mortality and showed equal or higher predictive accuracy than MELD, CLIF-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy. In ACLF patients sCD163 improved prediction of short-term mortality and in patients without ACLF sMR improved prediction of long-term mortality.

The authors concluded that the severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. The study was published in the April 2016 issue of the Journal of Hepatology.

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