Affiliation:
1. Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna Vienna Austria
2. Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna Vienna Austria
3. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria
4. Christian‐Doppler Laboratory for Portal Hypertension and Liver Fibrosis Medical University of Vienna Vienna Austria
Abstract
AbstractBackground and AimsThe role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value.MethodsWe included patients with evidence of ACLD, defined by portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mmHg) and/or a liver stiffness measurement by transient elastography ≥10 kPa, who underwent HVPG measurement between 2017 and 2020. Acute‐on‐chronic liver failure (ACLF) and/or liver‐related death were defined as composite endpoint.ResultsOf 251 patients, 82.5% had clinically significant portal hypertension (median HVPG: 17 mmHg [interquartile range (IQR) 12–21]) and 135 patients (53.8%) were decompensated at baseline.Median plasma histamine was 8.5 nmol/L (IQR: 6.4–11.5), 37.1% of patients showed elevated values (>9.9 nmol/L). Histamine levels did not differ significantly across Child‐Turcotte‐Pugh (CTP) stages nor strata of model for end‐stage liver disease (MELD) or HVPG. Histamine levels correlated with markers of circulatory dysfunction (i.e. sodium, renin and aldosterone).During a median follow‐up of 29.2 months, 68 patients developed ACLF or liver‐related death. In univariate as well as in multivariate analysis (adjusting for age, sex, HVPG as well as either MELD, clinical stage, and serum albumin or CTP and serum sodium), elevated histamine levels remained associated with the composite endpoint. CTP‐based multivariate model adjusted sub‐distribution hazard ratio (asHR): 1.010 (95% CI: 1.004–1.021), p < .001; MELD‐based multivariate model asHR: 1.030 (95% CI: 1.017–1.040), p < .001.ConclusionHigh levels of histamine were linked to circulatory dysfunction in ACLD patients and independently associated with increased risks of ACLF or liver‐related death. Further mechanistic studies on the link between histamine signalling and development of hyperdynamic circulation and ACLF are warranted.