Cell death biomarkers are associated with outcome in hepatorenal cirrhotic patients

Background and aim: Hepatorenal syndrome (HRS) is a severe complication of patients with liver cirrhosis and associated with high mortality rates if left untreated. Levels of cell death parameters are significantly elevated in patients with acute and chronic liver diseases. However, the role of these markers in patients with HRS is unknown. Aim of the study was to investigate if serum levels of M30 and M65 correlate with the risk of HRS development in cirrhotic patients and clinical outcome of HRS.

Methods: Between April 2013 and July 2015, clinical relevant parameters from from patients with liver cirrhosis with HRS (66) and liver cirrhosis without HRS (49) were prospectively assessed. Serum samples were collected and serum levels of M30 and M65 were measured by ELISA.

Results: Patients in the HRS group presented with more advanced stages of cirrhosis (Child-Pugh B: 17% C: 76%, p =< 0.0001). M30 and M65 significantly discriminated patients with HRS compared to non-HRS controls (631 U/l vs. 261 U/l, p < 0.0001; 1.097 U/l vs. 401 U/l, p < 0.0001). Within the group of HRS patients, higher levels of M30 and M65 were associated with higher MELD (M30: p = 0.002; M65: p = 0.002). Furthermore, higher levels of M30 and M65 were associated with poor response to terlipressin therapy (M30: p = 0.009; M65: p = 0.007). Overall survival was significantly shorter in the HRS subgroup with high levels of M30 and M65 (M30: p = 0.04; M65: p = 0.03).

Conclusions: Serum levels of M30 and M65 are elevated in patients with liver cirrhosis and HRS and are associated with severity of liver disease as well as response to terlipressin therapy and overall survival. Cell death parameters could have potential value as a diagnostic and prognostic tool in patients with liver cirrhosis and HRS.