Understanding confounding factors allows for accurate interpretation of liver stiffness measurements by ElastQ, a novel 2D shear wave elastography technique.

PURPOSE: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) or two-dimensional shear wave elastography (2D-SWE) is recommended to assess the risk of liver fibrosis and advanced chronic liver disease. Even though both techniques measure liver stiffness, their numerical results often diverge. Confounders and reliability criteria for 2D-SWE have not been systematically investigated. MATERIALS AND METHODS: We prospectively recruited participants with paired LSM by VCTE and the novel 2D-SWE technique ElastQ (Philips) in three European tertiary centers. The following parameters were recorded: sex, age, body mass index (BMI), etiology, laboratory markers of liver damage and function, as well as cholestasis, LSM by VCTE and controlled attenuation parameter (CAP), interquartile range (IQR)/median for VCTE-LSM and ElastQ-LSM, and the skin-to-liver capsule distance. RESULTS: We included 840 participants: 447 (53.2%) males; median age 57.0 [IQR:19.0] years; median BMI 25.4 [6.0] kg/m2; median VCTE-LSM 7.25 [9.2] kPa; median ElastQ-LSM 6.7 [5.4] kPa. On uni- and multivariable modeling (adjusted for LSM), we found that the discrepancy increased with liver stiffness and markers of disease severity. Skin-to-liver capsule distance and BMI affected VCTE-LSM more compared to ElastQ-LSM and significantly increased the discordance between the two measurements. CONCLUSION: The discrepancy of ElastQ-LSM to VCTE-LSM increases with liver stiffness and disease severity. BMI and skin-to-liver capsule distance increase the discrepancy between VCTE- and ElastQ-LSM but affect ElastQ-LSM less. The quality criterion IQR/median ≤ 30% indicates reliable ElastQ-LSM.

High histamine levels are associated with acute-on-chronic liver failure and liver-related death in patients with advanced chronic liver disease.

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.

Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

BACKGROUND AND AIMS: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking. APPROACH AND RESULTS: We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10 kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes).During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate: 0.74%/y, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12 kPa and follow-up platelet count >150 g/L) or rule-in (FU-liver stiffness measurement ≥25 kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure. CONCLUSIONS: In patients with compensated advanced chronic liver disease, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long term (>3 y). One-time post-treatment risk stratification based on noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

Prevalence and prognostic value of zinc and selenium deficiency in advanced chronic liver disease.

BACKGROUND AND AIMS: Zinc and selenium are essential trace elements involved in important (patho)physiological processes. The prevalence and prognostic implications of zinc and selenium deficiency in patients with advanced chronic liver disease (ACLD) remain unknown. METHODS: We determined serum zinc and selenium concentrations in 309 patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement between 2019 and 2022. We evaluated the prevalence of zinc/selenium deficiency and assessed its association with severity of ACLD and liver-related events (LRE, i.e. first/further hepatic decompensation/liver-related death). RESULTS: Among 309 ACLD patients (median: age: 57 [IQR: 50-64], MELD: 11 [IQR: 9-16], HVPG: 17 [IQR: 11-20]), 73% (227) and 63% (195) were deficient in zinc and selenium, respectively. Decompensated (dACLD) patients showed significantly lower serum zinc (median: 48 [IQR: 38-59] vs. compensated, cACLD: 65 [IQR: 54-78], p < 0.001) and selenium levels (median: 4.9 [IQR 4.0-6.2] vs. cACLD: 6.1 [IQR 5.1-7.3], p < 0.001). Significant correlations of zinc/selenium levels were found with MELD (zinc: ρ = -0.498, p < 0.001; selenium: ρ = -0.295, p < 0.001), HVPG (zinc: ρ = -0.400, p < 0.001; selenium: ρ = -0.157, p = 0.006) and liver disease-driving mechanisms (IL6, bile-acid homeostasis). On multivariable analysis, low zinc/selenium levels, age and MELD remained independently associated with LRE. CONCLUSION: Zinc and selenium deficiencies are common in ACLD patients especially with higher MELD and HVPG. Low zinc and selenium levels independently predicted hepatic decompensation and liver-related death. The effect of zinc/selenium supplementation in ACLD should be investigated in future trials.

Evolution of liver function during immune checkpoint inhibitor treatment for hepatocellular carcinoma.

BACKGROUND AND AIMS: Deterioration of liver function is a leading cause of death in patients with advanced hepatocellular carcinoma (HCC). We evaluated the impact of immune checkpoint inhibitor (ICI)-treatment on liver function and outcomes. METHOD: HCC patients receiving ICIs or sorafenib between 04/2003 and 05/2024 were included. Liver function (assessed by Child-Pugh score [CPS]) was evaluated at the start of ICI-treatment (baseline, BL) and 3 and 6 months thereafter. A ≥1 point change in CPS was defined as deterioration (-) or improvement (+), while equal CPS points were defined as stable (=). RESULTS: Overall, 182 ICI-treated patients (66.8 ± 11.8 years; cirrhosis: n = 134, 74%) were included. At BL, median CPS was 5 (IQR: 5-6; CPS-A: 147, 81%). After 3 months, liver function improved/stabilized in 102 (56%) and deteriorated in 61 (34%) patients, while 19 (10%) patients deceased/had missing follow-up (d/noFU). Comparable results were observed at 6 months (+/=: n = 82, 45%; -: n = 55, 30%; d/noFU: n = 45, 25%). In contrast, 54 (34%) and 33 (21%) out of 160 sorafenib patients achieved improvement/stabilization at 3 and 6 months, respectively. Radiological response was linked to CPS improvement/stabilization at 6 months (responders vs. non-responders, 73% vs. 50%; p = 0.007). CPS improvement/stabilization at 6 months was associated with better overall survival following landmark analysis (6 months: +/=: 28.4 [95% CI: 18.7-38.1] versus -: 14.2 [95% CI: 10.3-18.2] months; p < 0.001). Of 35 ICI-patients with CPS-B at BL, improvement/stabilization occurred in 16 (46%) patients, while 19 (54%) patients deteriorated/d/noFU at 3 months. Comparable results were observed at 6 months (CPS +/=: 14, 40%, -: 8, 23%). Importantly, 6/35 (17%) and 9/35 (26%) patients improved from CPS-B to CPS-A at 3 and 6 months. CONCLUSION: Radiological response to ICI-treatment was associated with stabilization or improvement in liver function, which correlated with improved survival, even in patients with Child-Pugh class B at baseline.

Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder.

BACKGROUND AND AIMS: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension. APPROACH AND RESULTS: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value. CONCLUSIONS: This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared.

Rapid improvement of hepatic steatosis and liver stiffness after metabolic/bariatric surgery: a prospective study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and related steatohepatitis (MASH) are common among obese patients and may improve after metabolic/bariatric surgery (MBS). 93 Patients undergoing MBS in 2021-2022 were prospectively enrolled. Liver stiffness measurement (LSM; via vibration-controlled transient elastography [VCTE], point [pSWE] and 2D [2DSWE] shear wave elastography) and non-invasive steatosis assessment (via controlled attenuation parameter [CAP]) were performed before (baseline [BL]) and three months (M3) after surgery. 93 patients (median age 40.9 years, 68.8% female, median BL-BMI: 46.0 kg/m2) were included. BL-liver biopsy showed MASLD in 82.8% and MASH in 34.4% of patients. At M3 the median relative total weight loss (%TWL) was 20.1% and the median BMI was 36.1 kg/m2. LSM assessed by VCTE and 2DSWE, as well as median CAP all decreased significantly from BL to M3 both in the overall cohort and among patients with MASH. There was a decrease from BL to M3 in median levels of ALT (34.0 U/L to 31 U/L; p = 0.025), gamma glutamyl transferase (BL: 30.0 to 21.0 U/L; p < 0.001) and MASLD fibrosis score (BL: - 0.97 to - 1.74; p < 0.001). Decreasing LSM and CAP, as well as liver injury markers suggest an improvement of MASLD/MASH as early as 3 months after MBS.

A roadmap for clinical trials in MASH-related compensated cirrhosis.

Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d'Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis.

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD). METHODS: This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Von Willebrand Factor Antigen Improves Risk Stratification for Patients with a Diagnosis of Resectable Hepatocellular Carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS). METHODS: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection. RESULTS: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated. CONCLUSION: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.

Inflammasomes in chronic liver disease: hepatic injury, fibrosis progression and systemic inflammation.

Chronic liver disease (CLD) leads to hepatocellular injury that triggers a pro-inflammatory state in several parenchymal and non-parenchymal hepatic cell types ultimately resulting in liver fibrosis, cirrhosis, portal hypertension (PH) and liver failure. Thus, an improved understanding of the inflammasomes - as key molecular drivers of liver injury - supports the development of novel diagnostic or prognostic biomarkers and effective therapeutics. In liver disease, innate immune cells respond to hepatic noxes by activating cell-intrinsic inflammasomes via toll-like receptors (TLRs) and nuclear factor kappa-B (NF-κB) and release of pro-inflammatory cytokines (such as IL-1ß, IL-18, TNF-α and IL-6). Subsequently, cells of the adaptive immune system are recruited to fuel hepatic inflammation, and liver parenchymal cells may undergo programmed cell-death mediated by gasdermin D, termed pyroptosis. With liver disease progression, there is a shift towards a type 2 inflammatory response, which promotes tissue repair but also fibrogenesis. Inflammasome activation may also occur at extrahepatic sites, such as the white adipose tissue in metabolic dysfunction-associated steatohepatitis (MASH). In end-stage liver disease, flares of inflammation (e.g., in severe alcohol-related hepatitis) that spark on a dysfunctional immune system, contribute to inflammasome-mediated liver injury and potentially result in organ dysfunctions/failures, as seen in acute-on-chronic liver failure (ACLF). This review provides an overview on current concepts regarding inflammasome activation in liver disease progression and related biomarkers and therapeutic approaches that are being developed for patients with liver disease.

Statins, metformin, and RAS inhibitors did not reduce variceal bleeding risk and mortality in a large, real-life cohort of patients with cirrhosis.

BACKGROUND: Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated. METHODS: Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications. RESULTS: A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118). CONCLUSION: In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.

EASL position paper on clinical follow-up after HCV cure.

Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.

Portal hypertension and its prognostic implications in patients with Wilson's disease.

BACKGROUND AND AIMS: Wilson's disease may progress to cirrhosis and clinically significant portal hypertension (CSPH). We aimed to assess the prevalence and prognostic impact of CSPH-related features on hepatic decompensation and transplant-free survival in patients with Wilson's disease. METHODS AND RESULTS: About 137 patients with Wilson's disease (Leipzig score ≥4), followed for a median observation period of 9.0 (3.9-17.7) years at the Vienna General Hospital, were included in this retrospective study. Overall, 49 (35.8%) developed features of CSPH: 14 (10.2%) varices, 40 (29.2%) splenomegaly, 20 (14.6%) ascites, 18 (13.1%) hepatic encephalopathy and 3 (2.2%) experienced acute variceal bleeding. Overall, 8 (5.8%) patients died, including three deaths caused by CSPH-related complications. Within 10 years, compensated patients with features of CSPH developed more decompensation events (8.3% vs. 1.5% in patients without CSPH, p = 0.3) and had worse transplant-free-survival (91.7% vs. 98.6%), which further declined in patients with hepatic decompensation (26.7%, log-rank: p < 0.0001). Patients with liver stiffness <15 kPa and normal platelets (≥150 G/L) were less likely to decompensate within 10 years (2.6% vs. 8.4%, p = 0.002) and had a better 10-year transplant-free-survival (97.7% vs. 83.9%, p = 0.006). CONCLUSIONS: Patients with Wilson's disease developing features of CSPH are at an increased risk for hepatic decompensation and liver-related mortality, warranting for regular screening and timely initiation of effective CSPH-directed treatments.

Use of the CytoSorb adsorber in patients with acute-on-chronic liver failure.

CytoSorb is a hemoadsorptive column used to remove high concentrations of proinflammatory cytokines in septic shock. Data on CytoSorb application in acute-on-chronic liver failure (ACLF) is lacking. This retrospective observational study analyzed 21 ACLF patients admitted to ICUs at the Vienna General Hospital who received CytoSorb adsorber therapy between 2017 and 2023. Median ICU length of stay was 8 days (IQR: 3-13), the ICU survival rate was 23.8% (n = 5). Significant decreases in bilirubin (median peak: 20.7 mg/dL to median post-treatment: 10.8 mg/dL; - 47.8%; p < 0.001), procalcitonin (1.34 to 0.74 pg/mL; - 44.6%; p < 0.001), interleukin-6 (385 to 131 ng/mL; - 66.0%; p = 0.0182)-but also of platelets (72 to 31 G/L; - 56.9%; p = 0.0014) and fibrinogen (230 to 154 mg/dL; - 33.0%; p = 0.0297) were detected. ICU survivors had a trend towards a stronger relative decrease in bilirubin (- 76.1% vs. - 48.2%), procalcitonin (- 90.6% vs. - 23.5%), and IL-6 (- 54.6% vs. - 17.8%) upon CytoSorb treatment. Moreover, no serious CytoSorb-attributed complications were detected. In conclusion, use of CytoSorb adsorber in ACLF patients results in a significant decrease in bilirubin and proinflammatory cytokines, while platelets and fibrinogen were also lowered. Prospective trials are warranted to investigate the impact of CytoSorb on clinical outcomes of ACLF patients with high proinflammatory cytokine levels.