Search

Background and Aims: The role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value. Methods: We 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. Results: Of 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. Conclusion: High 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. [ABSTRACT FROM AUTHOR]

Background: Anaemia is common in advanced chronic liver disease (ACLD) as a result of various risk factors. Aims & Methods: We evaluated the prevalence and severity of anaemia as well as the impact of anaemia on clinical outcomes in consecutive patients with ACLD and portal hypertension. Results: Among 494 patients, 324 (66%) patients had anaemia. Anaemic patients showed higher MELD (12 ± 4 vs 9 ± 3; P <.001), lower albumin (34 ± 6 vs 39 ± 5 g/dL; P <.001) and more often Child‐Pugh B/C stage (56% vs 17%; P <.001). The prevalence of moderate‐severe anaemia (haemoglobin <10 g/dL) increased with the degree of portal hypertension (HVPG: 6‐9 mm Hg: 22% vs HVPG: 10‐19 mm Hg: 24% vs HVPG ≥ 20 mm Hg: 36%; P =.031). The most common aetiologies of anaemia were gastrointestinal bleeding (25%) and iron deficiency (9%), while reason for anaemia remained unclear in 53% of cases. Male gender (odds ratio [OR]: 1.94 [95% CI: 1.09‐3.47]; P =.025), MELD (OR: 1.20 [95% CI: 1.09‐1.32]; P <.001), hepatic decompensation (OR: 4.40 [95% CI: 2.48‐7.82]; P <.001) and HVPG (OR per mm Hg: 1.07 [95% CI: 1.02‐1.13]; P =.004) were independent risk factors for anaemia. Anaemia was associated with hepatic decompensation (1 year: 25.1% vs 8.1%; 5 years: 60.3% vs 32.9%; P <.0001), hospitalization (73% vs 57%; P <.001) and a higher incidence rate of acute‐on‐chronic liver failure (0.05 [95% CI: 0.04‐0.07] vs 0.03 [95% CI: 0.01‐0.04]). Anaemic patients had worse overall survival (1 year: 87.1% vs 93.7%, 5 year survival: 50.5% vs 68.6%; P <.0001) and increased liver‐related mortality (1 year mortality: 9.7% vs 5.7%, 5 year mortality: 38.0% vs 26.9%; P =.003). Conclusion: Two‐thirds of patients with ACLD suffer from anaemia. The degree of hepatic dysfunction and of portal hypertension correlate with severity of anaemia. Anaemia is associated with decompensation, ACLF and increased mortality in patients with ACLD. [ABSTRACT FROM AUTHOR]

Background & Aims: Assessment of hepatic steatosis by transient elastography (TE)‐based controlled attenuation parameter (CAP) might predict hepatic decompensation. Therefore, we aimed to evaluate the prognostic value of CAP in patients with compensated advanced chronic liver disease (cACLD) and decompensated cirrhosis (DC). Methods: A total of 430 patients who underwent TE (liver stiffness ≥10 kPa) and CAP measurements were included in this retrospective analysis. Half of patients (n = 189) underwent simultaneous HVPG measurement. In cACLD patients, first hepatic decompensation was defined by new onset of ascites, hepatic encephalopathy or variceal bleeding. In patients with DC, the following events were considered as further hepatic decompensation: requirement of paracentesis, admission for/development of grade 3/4 hepatic encephalopathy, variceal (re‐)bleeding or liver‐related death. Results: First hepatic decompensation occurred in 25 of 292 (9%) cACLD patients, while 46 of 138 (33%) DC patients developed further hepatic decompensation during a median follow‐up of 22 and 12 months respectively. CAP was not predictive of first (cACLD; per 10 dB/m; hazard ratio [HR]: 0.97, 95% confidence interval [95% CI]: 0.91‐1.03, P = 0.321) or further hepatic decompensation (DC; HR: 0.99, 95% CI: 0.94‐1.03, P = 0.554) in adjusted analysis. Using the well‐established CAP cut‐off of ≥248 dB/m for hepatic steatosis, the incidence of first (cACLD; P = 0.065) and further hepatic decompensation (DC; P = 0.578) was similar in patients with hepatic steatosis or without. Serum albumin levels (per mg/dL; HR: 0.83, 95% CI: 0.77‐0.89, P < 0.001) and MELD‐Na (per point; HR: 1.15, 95% CI: 1.04‐1.28, P = 0.006) in cACLD and MELD‐Na (per point; HR: 1.12, 95% CI: 1.05‐1.19, P < 0.0001) in DC patients were the only parameters independently associated with first and further hepatic decompensation, respectively. Conclusion: Controlled attenuation parameter does not predict the development of first (cACLD)/further (DC) hepatic decompensation, while serum albumin levels and MELD‐Na are of prognostic value. [ABSTRACT FROM AUTHOR]