Abstract
BackgroundThe transition from compensated to decompensated liver cirrhosis is a hallmark of disease progression, however, reliable predictors to assess the risk of decompensation in individual patients from routine diagnostics are lacking. Here, we characterize serum levels of cell death-associated markers and routine biochemistry from patients with chronic liver disease with and without decompensation.MethodsA post-hoc analysis was based on prospectively collected clinical data from 160 patients with chronic liver disease, stably compensated or decompensated at baseline or during follow-up, over a median period of 721 days. Serum levels of damage-associated molecular patterns (DAMPs) and routine biochemistry are quantified at baseline (for all patients) and during follow-up (for patients with acute decompensation). The panel of DAMPs assessed in this study comprises high-mobility group-box protein 1 (HMGB1), cytochrome C (cyt C), soluble Fas-ligand (sFasL), interleukin 6 (IL-6), soluble cytokeratin-18 (CK18-M65) and its caspase‐cleaved fragment CK18-M30.ResultsIn this cohort study, 80 patients (50%) were diagnosed with alcoholic liver cirrhosis, 60 patients (37.5%) with hepatitis C virus- and 20 patients (13.5%) with hepatitis B virus-related liver cirrhosis. At baseline, 17 patients (10.6%) showed decompensated liver disease and another 28 patients (17.5%) developed acute decompensation during follow-up (within 24 months). One hundred fifteen patients showed stable liver disease (71.9%). We found DAMPs significantly elevated in patients with decompensated liver disease versus compensated liver disease. Patients with acute decompensation during follow-up showed higher baseline levels of IL-6, sFasL, CK18-M65 and–M30 (P<0.01) compared to patients with stably compensated liver disease. In multivariate analyses, we found an independent association of baseline serum levels of sFasL (P = 0.02; OR = 2.67) and gamma-glutamyl transferase (GGT) (P<0.001; OR = 2.1) with acute decompensation. Accuracy of the marker combination for predicting acute decompensation was high (AUC = 0.79). Elevated aminotransferase levels did not correlate with decompensated liver disease and acute decompensation.ConclusionsDAMPs are elevated in patients with decompensated liver disease and patients developing acute decompensation. The prognostic value of a marker combination with soluble Fas-ligand and GGT in patients with liver cirrhosis should be further evaluated.
Highlights
Accelerated cell death in chronic liver disease can lead to liver cirrhosis and its complications [1, 2] The most common causes underlying liver cirrhosis in Europe are alcohol abuse and chronic viral infections, i.e. hepatitis b and c virus infections [3, 4]
We found damage-associated molecular pattern (DAMP) significantly elevated in patients with decompensated liver disease versus compensated liver disease
DAMPs are elevated in patients with decompensated liver disease and patients developing acute decompensation
Summary
Accelerated cell death in chronic liver disease can lead to liver cirrhosis and its complications [1, 2] The most common causes underlying liver cirrhosis in Europe are alcohol abuse and chronic viral infections, i.e. hepatitis b and c virus infections [3, 4]. Liver cirrhosis is associated with high mortality and rank 14th among the most frequent causes of deaths around the world [6]. The natural history of liver cirrhosis is characterized by an asymptomatic (compensated) phase followed by a (rapidly) progressive phase marked by the development of complications [2]. Patients with decompensated liver disease show median overall survival of only two years and an almost 4-fold increased risk of death during the following year [8, 9]. The transition from compensated to decompensated liver cirrhosis is a hallmark of disease progression, reliable predictors to assess the risk of decompensation in individual patients from routine diagnostics are lacking. We characterize serum levels of cell death-associated markers and routine biochemistry from patients with chronic liver disease with and without decompensation
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