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UEG Presentation

HIGH HISTAMINE LEVELS ASSOCIATE WITH ACUTE-ON-CHRONIC LIVER FAILURE AND LIVER-RELATED DEATH IN PATIENTS WITH ADVANCED CHRONIC LIVER DISEASE

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Introduction

Mast cells play an important role in the human innate immune system, however, their role in liver disease is not fully understood. Histamine is a key component of mast cells granules and plasma histamine levels have been found to be increased in patients undergoing liver transplantation. However, their relationship with circulatory function and outcome have yet to be evaluated.

Aims & Methods

Two hundred fifty-one patients (pts) who underwent hepatic venous pressure gradient (HVPG) measurement (= baseline, BL) from 04/2017 until 03/2020 as part of the prospective Vienna Cirrhosis Study (VICIS) and had ACLD (as defined by the presence of portal hypertension (HVPG ≥6mmHg) and/or a liver stiffness measurement ≥10kPa, as assessed by vibration-controlled transient elastography) were included.

Results

Alcohol-related liver disease (102 pts, 40.6%) and viral hepatitis (51 pts, 20.3%) were the most common etiologies. Median HVPG was 17 mmHg (IQR 12-21) and 207 (82.5%) pts had clinically significant portal hypertension, i.e., an HVPG ≥10mmHg. About half of the pts were decompensated at BL (135 pts, 53.8%). Regarding Child-Turcotte Pugh (CTP) stages, 142 pts (56.6%) were stage A, 84 pts (33.5%) stage B, and 25 pts (10.0%) stage C. Sixty-seven pts (26.7%) had a model for end-stage liver disease (MELD) score ≥15.
The median plasma histamine concentration was 8.5nmol/L (IQR 6.3-11.5) and histamine levels above the upper limits of normal limit (i.e., 9.9nmol/L) were found in 37.1% of pts. Histamine concentrations did not differ significantly across CTP, MELD, or HVPG strata, but showed weak positive correlations with markers of circulatory dysfunction (i.e., plasma renin and serum sodium).
During a median follow-up of 28.9 month, acute-on-chronic liver failure (ACLF) and liver-related death were observed in 69 and 52 pts, respectively. Interestingly, plasma histamine levels were predictive of ACLF or liver-related death (univariate Cox proportional hazards model; hazard ratio [HR]: 1.023 per nmol/L; 95% confidence interval [95%CI]: 1.007-1.039; p = 0.004 and overall mortality (HR: 1.021; 95%CI: 1.005-1.038; p = 0.010). When adjusting for age, sex, CRP, HVPG, as well as either for MELD, decompensation, and serum albumin or for CTP and serum sodium, histamine levels remained associated with ACLF or liver-related death: CTP-based model: HR: 1.033; 95%CI 1.014-1.053; p < 0.001; MELD-based model: HR: 1.030; 95%CI: 1.010-1.050, p = 0.003.

Patient characteristics	Univariate HR (95%CI)	p	MELD-based model HR (95%CI)	p	CTP-based model HR (95%CI)	p
age, per years sex, male vs. female (ref) CRP, per mg/dL	1.013 (0.994-1.034) 1.166 (0.698-1.948) 1.280 (1.089-1.504)	0.187 0.558 0.003	1.020 (0.998-1.041) 1.231 (0.710-2.137) 1.264 (1.052-1.518)	0.073 0.460 0.012	1.025 (1.001-1.047) 1.211 (0.704-2.085) 1.303 (1.087-1.563)	0.021 0.489 0.004
HVPG, per mmHg	1.069 (1.029-1.111)	<0.001	1.048 (0.999-1.100)	0.053	1.038 (0.991-1.088)	0.119
UNOS-MELD, per points	1.056 (1.010-1.104)	0.017	1.024 (0.965-1.086)	0.434	-	-
decompensation, yes vs. no	1.898 (1.155-3.117)	0.011	0.992 (0.547-1.832)	0.980	-	-
albumin, per g/L	0.923 (0.885-0.962)	<0.001	0.961 (0.910-1.014)	0.149	-	-
CTP A CTP B vs. A CTP C vs. A	1 2.325 (1.380-3.918) 3.933 (1.977-7.826)	reference 0.002 <0.001	-	-	1 1.788 (0.980-3.261) 3.787 (1.688-8.495)	reference 0.058 0.001
Sodium, per mmol/L	0.931 (0.886-0.979)	0.006	-	-	0.995 (0.945-1.060)	0.884
Creatinine, per mg/dL	0.997 (0.747-1.331)	0.985	-	-	1.032 (0.725-1.469)	0.862
Histamine, per nmol/L	1.023 (1.007-1.039)	0.004	1.030 (1.010-1.050)	0.003	1.033 (1.014-1.053)	<0.001

Conclusion

We found that high plasma levels of histamine correlated with markers of circulatory dysfunction and were associated with increased risks of ACLF and liver-related death. Further studies investigating the underlying mechanism (i.e., mast cell activation vs. decreased degradation) as well as the role of histamine and related therapeutic strategies in hyperdynamic circulation and ACLF development are warranted.

HIGH HISTAMINE LEVELS ASSOCIATE WITH ACUTE-ON-CHRONIC LIVER FAILURE AND LIVER-RELATED DEATH IN PATIENTS WITH ADVANCED CHRONIC LIVER DISEASE

Michael Schwarz 1, Benedikt Simbrunner 1, Mathias Jachs 1, Lukas Hartl 1, Bernhard Scheiner 1, Rafael Paternostro 1, David Bauer 1, Matthias Pinter 1, Albert Friedrich Stättermayer 1, Michael Trauner 2, Thomas Reiberger 1, Mattias Mandorfer 1

1 Medical University of Vienna, Vienna, Austria|||Medical University of Vienna, Vienna, Austria

2 Medical University of Vienna, Vienna, Austria

Event

UEG Week Copenhagen 2023

Topics

Hepatobiliary Paediatrics Stomach & H. Pylori Surgery

Submission format

Abstract

Session

Outcomes in liver disease

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023