Background: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) represent non‐invasive surrogates of portal hypertension (PH) that both correlate with hepatic venous pressure gradient (HVPG). SSM may overcome limitations of HVPG and LSM in detecting presinusoidal PH components. We investigated the SSM/LSM ratio as a PH surrogate and its relationship to HVPG and spleen diameter across different liver disease aetiologies. Methods: 399 consecutive patients with compensated liver disease undergoing same‐day measurement of HVPG, LSM and SSM were prospectively included. Results: While patients with alcohol‐related liver disease (ALD; n = 200) showed higher LSM (median: 45.5 kPa) and HVPG (15.0 mmHg) than patients with metabolic dysfunction–associated steatohepatitis (MASH; n = 49; LSM: 20.9 kPa; HVPG: 12.0 mmHg), their SSM (median: 58.8 vs. 52.8 kPa; p = 0.868) was not significantly different. Consequently, the SSM/LSM ratio was higher in MASH (1.66) vs. ALD (1.28), but highest in patients with non‐cirrhotic PH (3.19). When adjusting for HVPG, SSM and spleen diameter remained significantly higher in MASH than in ALD at any given HVPG. Conclusions: This study demonstrates that SSM/LSM ratios vary across different liver disease aetiologies. Since MASH patients—after adjusting for liver disease severity—show higher SSM/LSM ratios and larger spleen diameters than ALD, our results support the concept of a presinusoidal component of PH in MASH patients.

Background: A more granular understanding of hepatic decompensation in cirrhosis has led to the classification of acute decompensation (AD) and non‐acute decompensation (NAD). In this study, we assessed differences in the clinical course of AD versus NAD in patients with ascites as the first decompensation event. Methods: 505 cirrhosis patients with ascites as first decompensation were included in this single‐center longitudinal cohort study and followed until further decompensation, orthotopic liver transplantation (OLT), or death. AD was defined as grade 3 ascites or ascites with spontaneous bacterial peritonitis (SBP) or acute‐kidney injury (AKI), while NAD was defined as grade 2 ascites. Hospitalisation was recorded. Results: Among 505 patients, 296 (58.6%) met the criteria for AD, with 216 (73.0%) requiring hospitalisation. NAD occurred in 209 (41.4%), with 107 (51.2%) requiring hospitalisation. During a median 4.4‐year follow‐up, further decompensation occurred in 65.1%, acute‐on‐chronic liver failure (ACLF) in 27.7%, 10.9% underwent OLT, and 51.1% died. Patients with AD had a higher incidence of further decompensation (at 12 months: 19% and 33%) and a higher risk of transplant‐free mortality (subdistribution hazard ratio [SHR]: 1.43 [95% CI: 1.12–1.82], p = 0.004) versus NAD. When stratified by hospitalisation, AD was associated with an increased risk of mortality only in cases requiring hospitalisation (SHR for hospitalised AD vs. non‐hospitalised NAD: 1.89, 95% CI: 1.35–2.65, p < 0.001). Inflammation (C‐reactive protein) predicted transplant‐free mortality in AD (SHR per log‐change: 1.20 [95% CI: 1.02–1.41], p = 0.032) but not NAD. Conclusions: Classifying patients as AD versus NAD identified subgroups with different risks for further decompensation and transplant‐free mortality.

Background: Indocyanine green (ICG) clearance, determined by venous sampling, has shown promising results in the diagnosis of clinically significant portal hypertension (CSPH) in compensated advanced chronic liver disease (cACLD) and prognostication in decompensated ACLD (decompensated cirrhosis). Data on ICG clearance measurement by pulse dye densitometry (PDD) via finger clip are comparatively scarce. Aims: To evaluate the diagnostic (CSPH) and prognostic utility of ICG clearance throughout ACLD stages. Methods: ACLD (liver stiffness ≥ 10 kPa) patients undergoing same‐day hepatic venous pressure gradient (HVPG) measurement and ICG clearance assessment via PDD in 2017–2022 were recruited from the prospective Vienna Cirrhosis Study (VICIS, NCT03267615). Results: Two hundred and sixty‐one ACLD patients (cACLD: n = 115, decompensated cirrhosis: n = 146) were included. Among cACLD patients (CSPH: 62.4%), ICG retention 15 min (ICG‐R15) correlated moderately with HVPG (Spearman's rho:0.458; p < 0.001) and yielded a suboptimal diagnostic accuracy for CSPH (AUROC: 0.687 [95% CI: 0.585–0.789]). ICG‐R15 showed a strong correlation with the model for end‐stage liver disease score (rho: 0.701; p < 0.001) and correlated with biomarkers of endothelial dysfunction (von Willebrand factor), systemic inflammation (C‐reactive protein, procalcitonin, interleukin 6) and extracellular matrix remodelling (enhanced liver fibrosis test). In decompensated cirrhosis, ICG‐R15 additionally correlated with mean arterial pressure, serum sodium and renin levels. ICG‐R15 predicted decompensation (subdistribution hazard ratio [SHR]: 1.042 [95% CI: 1.008–1.077] per %; p = 0.014) in cACLD and independently predicted ACLF/liver‐related mortality in decompensated cirrhosis (adjusted SHR: 1.062 [95% CI: 1.025–1.100] per %; p < 0.001). Conclusions: ICG‐R15 by PDD correlates with portal hypertension and systemic inflammation/circulatory dysfunction as key disease‐driving mechanisms in ACLD. While showing insufficient discrimination for CSPH, ICG‐R15 independently predicted ACLF/liver‐related mortality in decompensated cirrhosis.

Background &Aims: Growth differentiation factor‐15 (GDF‐15), a cell stress‐induced cytokine, is implicated in liver disease pathophysiology. We investigated GDF‐15 in cirrhosis, focusing on its association with disease‐driving pathomechanisms, platelet function, hepatic decompensation, and mortality. Methods: We included patients with cirrhosis undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital. Platelet surface P‐selectin and glycoprotein IIb/IIIa (GPIIb/IIIa) expression after agonist stimulation were assessed by flow cytometry as platelet activation markers. GDF‐15 serum levels were quantified by electrochemiluminescence immunoassay. Results: Among 106 patients (median age 55.1 years; 70.8% male), median GDF‐15 was 2880 (1850–4770) pg/mL. GDF‐15 correlated with hepatic dysfunction (MELD Spearman's ρ : 0.50; albumin ρ : −0.57), HVPG ( ρ : 0.47), systemic inflammation (C‐reactive protein ρ : 0.45; interleukin 6 [IL‐6] ρ : 0.55; procalcitonin ρ : 0.58), liver stiffness ( ρ : 0.67) and enhanced liver fibrosis test ( ρ : 0.64) (all p < 0.001). GDF‐15 was higher in patients with detectable bacterial DNA in blood (3520 vs. 2250 pg/mL; p < 0.001) and correlated with lipopolysaccharide ( ρ : 0.34; p = 0.010) and lipoteichoic acid ( ρ : 0.37; p = 0.004). Platelet activation was not linked to GDF‐15 after adjusting for liver disease severity, yet patients with undetectable GPIIb/IIIa activation after stimulation showed significantly higher GDF‐15. Over a median follow‐up of 51.5 (26.0–58.2) months, 38 patients decompensated and 21 died (61.9% liver‐related). GDF‐15 (aHR per 100 pg/mL: 1.015; 95% CI: 1.004–1.026; p = 0.007) predicted decompensation risk independently of HVPG, MELD, albumin and IL‐6. Similarly, GDF‐15 was associated with higher risk of all‐cause (HR: 1.019; 95% CI: 1.009–1.029; p < 0.001) and liver‐related mortality (HR: 1.019; 95% CI: 1.007–1.032; p = 0.002). Conclusions: GDF‐15 is a promising biomarker in cirrhosis that reflects disease‐driving pathomechanisms and independently predicts decompensation and mortality.

The transition from hospital-based palliative care to home care is a critical phase often marked by logistical, medical, and emotional challenges. Effective discharge planning is essential to ensure continuity of care, yet gaps in communication, interdisciplinary coordination, and access to resources frequently hinder this process. This qualitative study explored key barriers, related support needs, and strategies for optimising palliative care discharge through semi-structured interviews with 28 participants, including healthcare professionals, recently discharged palliative care patients, and primary caregivers. Reflexive thematic analysis revealed five main themes: (1) discharge planning and coordination; (2) symptom management and medication; (3) psychosocial support; (4) communication and information; (5) the role of assistive devices and home care services. Discharge processes were often late or unstructured. Poor interdisciplinary collaboration and a lack of caregiver preparation also contributed to hospital readmissions and emotional distress. By focusing on needs, our analysis identifies not only what was lacking but also what is required to overcome these barriers. Our findings suggest that standardised discharge protocols and checklists, earlier planning, structured communication tools, and improved integration of home care services could enhance patient outcomes and reduce caregiver burden. Addressing psychosocial needs and ensuring timely access to assistive devices are also crucial. Strengthening interdisciplinary collaboration and refining discharge practices can facilitate smoother transitions and improve the quality of palliative care at home.

Background and Aims: Smoking induces a proinflammatory state, yet its role in advanced chronic liver disease (ACLD) remains understudied. This study evaluated its impact on disease‐driving mechanisms and clinical outcomes in ACLD patients. Methods: ACLD patients undergoing hepatic venous pressure gradient measurements from 2017 to 2021 were included. The association of smoking with biomarkers of inflammation, fibrogenesis, angiogenesis and the incidence of hepatocellular carcinoma (HCC), extrahepatic malignancies and mortality was examined. Results: Among 339 ACLD patients (66.1% men, median age: 56.8 years, MELD: 11, HVPG: 17 mmHg), 62% ( n = 210) were ever‐smokers ( n = 78 former, n = 132 active). Compared to never/former smokers, active smokers exhibited significantly higher white blood cell counts (5.49 vs. former: 4.74 vs. never: 4.25 G/L; p < 0.001) and C‐reactive protein levels (CRP: 0.36 vs. former: 0.29 vs. 0.21 mg/dL; p = 0.035). Active smokers showed upregulated fibrogenic (TIMP‐1: 364 vs. former: 324 vs. never: 278 ng/mL, p < 0.001; P3NP: 20.9 vs. former: 15.6 vs. never: 17.2 μg/L, p = 0.008) and angiogenic (PLGF: 21.7 vs. former: 18.2 vs. never: 19.0 pg/mL, p = 0.004) activity markers. Over a median follow‐up of 30.4 months, ever‐smokers exhibited a higher incidence of extrahepatic malignancies (SHR: 11.30; p = 0.019) and numerically higher HCC incidence (SHR: 2.27 p = 0.150; mostly evident in Child‐Pugh A patients: SHR: 7.44, p = 0.053). All‐cause or liver‐related mortality risk did not differ significantly between ever‐smokers and never‐smokers. Conclusion: Smoking is linked to an upregulation of inflammatory, fibrogenic and angiogenic processes in ACLD and increases the risk of extrahepatic malignancies. These findings underscore the importance of strategies supporting smoking cessation in ACLD patients. Trial Registration: NCT03267615