Search Results (347)

Background: Hepatocellular carcinoma (HCC) shows a high rate of early recurrence after curative resection, indicating a critical contribution of tumor microenvironment-driven molecular mechanisms. Early recurrence of hepatocellular carcinoma is defined as recurrence within 6 months after curative resection, with a prevalence exceeding 30%. Hypoxia signaling and immune dysregulation have been implicated, yet their compartment-specific relevance remains unclear. Methods: This multicenter nested case–control study included 49 HCC patients to evaluate associations between hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), tumor-infiltrating lymphocytes (TILs), CD4⁺ T cells, CD8⁺ T cells, regulatory T cells (Tregs), programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) and early recurrence after resection. TIL density was assessed using hematoxylin and eosin staining, while immunohistochemistry was performed to quantify intratumoral and peritumoral expression of the studied markers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance. Recurrence-free survival (RFS) was analyzed using the Kaplan–Meier, and independent predictors were identified using multivariate Cox proportional hazards regression. Results: Early recurrence occurred in 11 of 49 patients (22.4%) of Child–Pugh A patients. Recurrent tumors were characterized by elevated VEGF expression despite absent HIF-1α, alongside significant depletion of intratumoral TILs (HR 5.02; 95% CI 1.09–23.26), CD4⁺ (HR 7.68; 95% CI 1.66–35.60) and CD8⁺ cells (HR 6.68; 95% CI 1.77–25.23) and reduced peritumoral CD8⁺ infiltration (HR 4.20; 95% CI 1.11–15.91). Multivariable analysis identified low intratumoral CD4⁺ (HR 7.98; 95% CI 1.63–39.07) and reduced peritumoral CD8⁺ expression (HR 4.98; 95% CI 1.14–21.70) as independent predictors, whereas HIF-1α, VEGF, Treg, PD-1, and PD-L1 were not significantly associated. Conclusions: Early HCC recurrence shows HIF-1α-independent angiogenesis alongside spatial immune depletion, supporting integrated immune profiling over single angiogenic markers. Full article

Background/Objectives: Regional adipose tissue has been studied as a prognostic factor in various extra-hepatic diseases, but data in the setting of cirrhosis is scarce. Our aim was to evaluate the association of regional adipose tissue indices with the severity of liver disease and its impact on the outcome of patients with cirrhosis. Methods: Three hundred and thirty-seven patients with cirrhosis were prospectively enrolled in the study. Clinical and laboratory data were recorded, and MELD-Na and Child-Turcotte-Pugh scores were calculated. Physical performance was evaluated with handgrip strength, the Short Physical Performance Battery test, and the Liver Frailty Index. Dual-energy X-ray absorptiometry was used for the evaluation of total and regional lean and fat mass. Results: A low trunk fat percentage was found to be independently associated with a MELD-Na score ≥ 15 (Odds Ratio: 0.92, p = 0.007). MELD-Na score and trunk fat percentage were the only factors independently associated with mortality [Hazard Ratio (HR): 1.078, p = 0.02 and HR: 0.95, p = 0.03, respectively], while a separate analysis based on gender confirmed this finding only in men. In the total cohort, patients with a trunk fat percentage < 27.5% had worse outcomes (log-rank 11.4; p < 0.001). Conclusions: This study marks the first effort to examine the association of indices related to regional adipose tissue distribution with the severity of liver disease and outcome. Trunk fat percentage was the only body composition parameter independently associated with advanced liver disease and prognosis in the total cohort specifically in men, but not in women. Further studies are needed to validate the predictive role of adipose tissue in patients with cirrhosis. Full article

Background and Objectives: Post-hepatectomy liver failure (PHLF) remains the leading cause of mortality following hepatic resection, with reported incidence rates ranging from 1.2% to 32%. Traditional scoring systems such as the Child–Pugh score, Model for End-Stage Liver Disease (MELD), and Albumin–Bilirubin (ALBI) grade have demonstrated limited predictive accuracy for PHLF. Machine learning (ML) algorithms have emerged as promising tools capable of integrating complex, multidimensional clinical data to improve predictive performance. This systematic review aims to evaluate the current evidence on ML-based prediction models for PHLF, assessing their predictive accuracy, methodological quality, clinical applicability, and the key variables utilized across models. Methods: A systematic literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library from inception to January 2026. Studies that developed or validated ML models for predicting PHLF after hepatic resection were included. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to evaluate the risk of bias. Data on model performance, algorithms employed, sample sizes, predictor variables, and validation strategies were extracted. The review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO. Results: Twelve PubMed-verified studies involving 6913 patients were retained in the final analysis. Publication years ranged from 2020 to 2025, with five studies published in 2025. Gradient boosting approaches (LightGBM/XGBoost or phase-specific boosting models) were the most frequent best-performing architectures, while ANN/deep learning, radiomics-integrated, and ensemble approaches also showed clinically relevant discrimination. Best reported non-training AUCs ranged from 0.7927 to 0.981 (median, 0.873). The strongest generalization signals came from studies with temporal, external, or prospective validation structures. Common predictor domains included bilirubin-based liver function measures, coagulation variables, platelet count, volumetry or extent of resection, imaging-derived radiomics features, and perioperative dynamic data. Conclusions: Machine learning models remain promising for PHLF prediction, but the evidence base is smaller and more heterogeneous than the original draft suggested. Performance is highest in studies that combine clinical liver-reserve markers with imaging or perioperative temporal data; however, widespread clinical adoption is still limited by retrospective design predominance, inconsistent outcome definitions, and incomplete external validation. Full article

Background: Acute kidney injury (AKI) is a common and serious complication in patients with liver cirrhosis and is associated with poor outcomes. However, whether the association between nephrotic-range proteinuria (NRP) and severe AKI varies by liver disease severity remains unclear. Methods: This retrospective cohort study included 408 adult patients with cirrhosis stratified by Child–Pugh class (A, B, and C). Severe AKI was defined as Kidney Disease: Improving Global Outcomes stage 2–3. Multivariable logistic regression analyses were performed in the overall cohort and within each class, with the additional evaluation of interaction effects. Results: The incidence of severe AKI increased from 18.4% in class A to 38.8% in class C. In the extended multivariable model incorporating hemodynamic and inflammatory variables, nephrotic-range proteinuria was not significantly associated with severe AKI. In stratified analyses, a significant association was observed only in Child–Pugh class A. Additional analyses suggested that this relationship was attenuated after accounting for sepsis and systemic severity. Conclusions: Although NRP prevalence was similar across Child–Pugh classes, the association between NRP and severe AKI appeared to vary by disease stage, particularly before adjustment for systemic severity. Full article

Background: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, had profound primary effects on global health and secondary effects through widespread disruption of healthcare systems, limiting access to elective medical services essential for the management of chronic diseases such as liver cirrhosis. Elective hospitalizations play a key role in disease monitoring, prevention of complications, and therapeutic optimization. This study aimed to evaluate the impact of the pandemic on the clinical profile, disease severity, and outcomes of patients electively admitted with liver cirrhosis across three periods: pre-pandemic, pandemic, and post-pandemic. Methods: This retrospective, single-center cohort study included 248 adult patients electively admitted with a primary diagnosis of liver cirrhosis between February 2018 and February 2024. Patients were stratified according to admission period. Data on demographics, clinical presentation, etiology, decompensation markers, severity scores (Child–Pugh, Baveno), procedures, and hospitalization outcomes were analyzed. Results: A total of 248 patients were included, with a significant reduction in elective admissions during the pandemic (23.0% vs. 46.4% pre-pandemic), followed by partial recovery post-pandemic (30.6%) (p = 0.031). A higher proportion of urban patients was observed during the pandemic (70.2%, p = 0.004). Disease severity increased during the pandemic, with a higher prevalence of Child–Pugh C (17.5%) and Baveno stage 6 (10.5%), whereas post-pandemic data showed improvement (Child–Pugh C: 6.57%; no Baveno stage 6; p = 0.004). Ascites (47.4%) and paracentesis (21.1%) peaked post-pandemic (p = 0.012; p = 0.003). Endoscopic activity decreased during the pandemic (22.8%, p = 0.017), while interventional procedures were more frequent (8.8%, p = 0.045). Transfusion requirements (17.5%, p = 0.001) and hospitalization costs (€467.08, p = 0.01) were highest during the pandemic, while no deaths were recorded post-pandemic. In-hospital mortality was observed in 1.7% of patients during the pre-pandemic period and increased to 3.5% during the pandemic period, while no deaths were recorded post-pandemic. Conclusions: The COVID-19 pandemic significantly altered elective cirrhosis care, leading to reduced admissions, increased disease severity, and higher resource utilization. Although partial recovery was observed post-pandemic, persistent evidence of delayed decompensation underscores the importance of maintaining continuity in elective hepatology services. Full article

Purpose: This retrospective study aimed to identify factors associated with postoperative cognitive dysfunction (POCD) in patients undergoing hepatectomy, with particular attention to liver disease-related characteristics and perioperative variables. A secondary aim was to develop a clinically applicable nomogram for individualized risk estimation in this population. Patients and Methods: A retrospective cohort study was conducted in 314 consecutive patients who underwent hepatectomy at Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School between January 2023 and December 2024. Patients were included if they had complete clinical data and underwent preoperative and postoperative cognitive assessment. Exclusion criteria included preoperative cognitive impairment (Montreal Cognitive Assessment [MoCA] score < 26), preexisting neurological or psychiatric disorders, and in-hospital death within 72 h after surgery. POCD was defined as a decline of ≥3 points in the MoCA score from baseline to postoperative day 5. Clinical, surgical, nutritional, and perioperative variables were analyzed, and a nomogram was constructed based on the final multivariable logistic regression model. Results: The overall incidence of POCD was 27.4% (86/314). The final multivariable model included sarcopenia, preoperative hemoglobin < 120 g/L, Child–Pugh classification, alcohol consumption, operative duration, and pain score on postoperative day 1. The nomogram incorporating these variables showed good discriminative ability, with an area under the curve of 0.87 (95% CI: 0.83–0.92). Conclusions: In this retrospective cohort of patients undergoing hepatectomy, several perioperative clinical factors were associated with POCD. The proposed nomogram may serve as a practical tool for perioperative risk estimation and support more individualized management in higher-risk patients. Full article

Background: Liver cirrhosis, particularly in its decompensated stages, is associated with high short-term mortality among hospitalized patients. Although the prognostic value of the Child–Pugh classification is well established, its independent impact on survival in real-world tertiary emergency settings requires further evaluation. This study aimed to assess the prognostic role of Child–Pugh stage and other clinical factors on short- and mid-term survival in hospitalized cirrhotic patients over a 10-year period. Methods: We conducted a retrospective cohort study including 2831 patients hospitalized for liver cirrhosis between 2015 and 2025. Among them, 631 patients with complete Child–Pugh staging were included in the survival analysis. Survival time was defined as the interval between the first hospitalization and the last recorded discharge or in-hospital death. Survival differences were assessed using Kaplan–Meier curves and log-rank tests, while independent predictors of mortality were identified using multivariate Cox proportional hazards regression. A complementary logistic regression model was used to evaluate predictors of mortality as a binary outcome. Results: Among the 631 staged patients, 13.5% were classified as Child–Pugh A, 31.9% as Child–Pugh B and 54.7% as Child–Pugh C. In-hospital mortality increased significantly across stages (1.2%, 9.0% and 46.7%, respectively; p < 0.001). One-year survival was 98.7% for Child–Pugh A, 83.6% for Child–Pugh B and 40.7% for Child–Pugh C (log-rank p < 0.001). In multivariate Coxregression analysis, the strongest predictor of mortality was mixed cirrhosis type (HR = 8.58, 95% CI: 4.81–15.32, p < 0.001). Child–Pugh C was also independently associated with a markedly increased mortality risk compared with Child–Pugh A (HR = 25.11, 95% CI: 3.44–183.29, p = 0.002). Alcohol-related etiology (HR = 1.81, 95% CI: 1.09–3.01, p = 0.023) and age (HR = 1.18 per SD increase, 95% CI: 1.00–1.39, p = 0.050) were additionalindependent predictors. The Cox model demonstrated good discrimination (C-statistic ≈ 0.80). In the logistic regression model, mixed cirrhosis type (OR = 13.28, p < 0.001) and Child–Pugh stage (OR = 8.66, p < 0.001) were the strongest predictors of mortality, while ascites showed an inverse association after adjustment (OR = 0.62, p = 0.036). The logistic model showed excellent discrimination (AUC = 0.865). Conclusions: Child–Pugh stage remains a strong and independent predictor of survival in hospitalized patients with decompensated cirrhosis. The marked survival gradient across stages, particularly the substantially reduced survival observed in Child–Pugh C patients, highlights thecontinued clinical utility of this simple classification for early risk stratification intertiary emergency hospital settings. Full article

Background/Objectives: Sarcopenia and impaired bone quality are increasingly recognized as important determinants of outcomes after liver transplantation (LT). However, longitudinal data describing early post-transplant musculoskeletal changes in patients with chronic hepatitis B virus (HBV) infection, particularly according to hepatocellular carcinoma (HCC) status, remain limited. Aim: To evaluate longitudinal changes in skeletal muscle mass and vertebral bone attenuation after LT in patients with chronic HBV infection and to assess the impact of concomitant HCC and clinical subgroups on these patterns. Methods: This retrospective, single-center study included 99 adult patients who underwent LT for chronic HBV infection (HBV alone, n = 59; HBV + HCC, n = 40) between January 2018 and December 2024. Contrast-enhanced abdominal computed tomography examinations obtained before transplantation and at approximately 6 (POD180) and 12 months (POD365) after transplantation were analyzed. Skeletal muscle was assessed using psoas muscle area (PMA) and psoas muscle index (PMI), while bone quality was evaluated using mean vertebral trabecular attenuation averaged across L1–4. Longitudinal changes were examined according to HCC status, sex, Child–Pugh class, and survival status. Results: Repeated-measures analyses of longitudinal changes demonstrated a significant decline in both PMA and PMI at POD180 and POD365 compared with pre-transplant values (PMA: p = 0.006; PMI: p = 0.009). These patterns were comparable between patients with HBV alone and those with HBV-related HCC, with no significant differences between groups (all p > 0.05). Male patients consistently exhibited higher PMA and PMI values than female patients across all assessed time points (both p < 0.001). In contrast, neither Child–Pugh class nor mortality status was associated with differences in PMA or PMI levels (all p > 0.05). L1–4 attenuation declined markedly by POD180 and remained below baseline at POD365 (p < 0.001). Although overall L1–4 values did not differ between disease groups (p = 0.109), the temporal pattern of L1–4 change differed according to survival status (p = 0.026), with a greater decline observed in non-survivors. Conclusions: In patients with chronic HBV undergoing LT, early post-transplant loss of skeletal muscle and vertebral bone attenuation is common and persists throughout the first year of follow-up. These changes occur similarly in patients with and without HCC. CT-based assessment of muscle and bone parameters, particularly L1–4 attenuation, may therefore support early post-transplant risk stratification. Full article

Background/Objectives: This study aimed to evaluate the differences between two blood product transfusion protocols [a standard coagulation (SC) group and a rotational thromboelastometry (ROTEM) group] in patients with decompensated liver cirrhosis (LC) undergoing high-bleeding-risk endoscopic procedures. Methods: Between December 2024 and March 2025, we conducted a prospective cohort study including adult decompensated cirrhotic patients who needed prophylactic blood product transfusion before high-bleeding-risk endoscopic procedures. The prophylactic blood product transfusion strategy in the SC group was based on conventional coagulation tests (INR, platelets, and fibrinogen), and in the ROTEM group on viscoelastic parameters. Results: A total of 72 patients were included in this study (36 patients in each group); most were male (63.9%), Child–Pugh B (54.2%), and had LC with a predominance of alcoholic etiology (51.4%). There were no clinically significant differences regarding the baseline characteristics between the study groups. The most frequent endoscopic procedure was polypectomy (76.4%). Postinterventional bleeding occurred after eight procedures in the SC group and after four procedures in the ROTEM group (p = 0.206). Endoscopic hemostasis was effective. Patients from the ROTEM group received fewer FFP transfusions than the SC group (5.6% vs. 69.4%; p < 0.0001). Blood product transfusion was needed less in patients evaluated using ROTEM compared with the SC group (41.2% vs. 100%; p < 0.0001). There were no differences in the length of hospital stay (p = 0.618) or 30-day mortality (p = 0.643) between the two study groups. Conclusions: ROTEM-guided transfusion management was associated with a significant reduction in blood product use compared with standard coagulation test-based management. However, this difference should be interpreted in the context of the distinct transfusion thresholds applied in the two groups, as the standard coagulation arm followed predefined laboratory-based criteria that may have increased the likelihood of prophylactic transfusion. No statistically significant differences were observed in bleeding complications, length of hospital stay, or 30-day mortality. Therefore, these findings reflect differences in transfusion strategies rather than demonstrating clinical superiority of ROTEM-based management and should be considered preliminary. Full article

Background and Objectives: Acute kidney injury (AKI) is a frequent and life-threatening complication in patients with liver cirrhosis (LC). Nephrotic-range proteinuria may reflect underlying structural renal vulnerability; however, its association with AKI severity in cirrhosis remains unclear. Materials and Methods: We conducted a retrospective cohort study of 408 adults with LC admitted to a tertiary referral hospital between January 2016 and December 2025. Nephrotic-range proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) ≥3.5 g/g measured within 7 days before or at admission. AKI was staged using serum creatinine-based Kidney Disease: Improving Global Outcomes criteria. Baseline creatinine was defined as the lowest value within 7 days before admission; if unavailable, the lowest stable value within the preceding 3 months was used. Severe AKI was defined as KDIGO stage 2–3. Multivariable logistic regression was performed to evaluate the association between nephrotic-range proteinuria and severe AKI after adjustment for age, sex, diabetes mellitus, hypertension, chronic kidney disease (CKD), sepsis, ICU admission, and Child–Pugh class. Results: Of the 408 patients, 56 (13.7%) had nephrotic-range proteinuria. Severe AKI occurred more frequently in patients with nephrotic-range proteinuria than in those without (39.3% vs. 21.9%), corresponding to an absolute risk difference of 17.4 percentage points (p = 0.008). In the adjusted model, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI (adjusted odds ratio [OR], 2.27; 95% confidence interval [CI], 1.17–4.41; p = 0.015). CKD (adjusted OR, 2.26; 95% CI, 1.33–3.81; p = 0.002), ICU admission (adjusted OR, 2.03; 95% CI, 1.22–3.39; p = 0.007), and Child–Pugh class C versus A (adjusted OR, 3.50; 95% CI, 1.37–8.93; p = 0.009) were also significantly associated with severe AKI. Conclusions: Among hospitalized patients with LC, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI. Quantitative proteinuria assessment may help identify patients at increased risk of advanced renal dysfunction, although causal inference is limited by the retrospective observational design. Full article

Background and aims: Hepatocellular carcinoma (HCC) patients frequently present with comorbidities that limit therapeutic options and increase mortality. This study evaluated the performance of the Charlson Comorbidity Index (CCI) and a modified CCI (mCCI) in stratifying patients with HCC to predict treatment allocation and survival. Methods: A retrospective single-center cohort study analyzed 401 patients with de novo HCC (74% male, median age 68 years, 80% Child–Pugh-Turcotte (CPT) A, 65% viral etiology, 70% Barcelona Clinic Liver Cancer stage (BCLC) 0/A). CCI and mCCI (with points related to HCC and chronic liver disease excluded), were calculated at diagnosis for each patient. The primary endpoint was overall survival (OS) estimated by Kaplan–Meier method and compared across mCCI classes; Cox uni/multivariable models were applied to identify predictors of mortality. The secondary aim was evaluating the association between mCCI and treatment allocation. Results: While CCI classified 94% of patients as “high-risk”, mCCI reclassified patients into “high-risk” (21%), “intermediate-risk” (48%), and “low-risk” (31%), demonstrating better stratification whilst maintaining a strong correlation with CCI (Kendall’s tau-b = 0.57, p < 0.001). BCLC B patients with “high-risk” mCCI exhibited significantly lower access to first-line curative treatment (14% vs. 47%, p = 0.03). Moreover, “high” or “intermediate-risk” patients according to mCCI experienced significantly shorter OS compared to “low-risk” (median OS 36 vs. 49 vs. 74 months, p < 0.001). “High-risk” and “intermediate-risk” mCCI classes were independent predictors of mortality, alongside alpha-fetoprotein, CPT and BCLC stage. Considering the items composing mCCI, age and cardiovascular diseases were independent predictors of mortality. Conclusions: mCCI provides a more accurate assessment of comorbidities than the standard CCI and is associated with survival, hence it can contribute to designing patient-tailored therapeutic strategies. Full article

Background/Objectives: The study aimed to determine the demographic and clinical characteristics of patients with acute variceal bleeding and identify predictive factors associated with treatment outcomes. Methods: The retrospective study included 91 adults hospitalised for oesophageal and/or gastric variceal bleeding at the Department of Gastroenterology, University Hospital of Split. Data were collected on patients’ demographics, clinical characteristics and laboratory findings, as well as treatment outcomes, including length of hospital stay, need for repeat endoscopy, rebleeding, infection incidence, and six-week mortality. Results: Of the 91 patients included, 85.7% were male, and the mean age was 61 ± 9 years. Liver cirrhosis was present in 94.5% of patients, with alcoholic aetiology in 76.7% of cases. The median MELD-Na score was 15 (IQR 11–21), and more than 40% of patients were classified as Child–Pugh B. The median length of hospital stay was 8 days (IQR 5–10.5). Diagnostic EGD was performed in 94.5% of patients, with 80.2% undergoing the procedure within 12 h of admission. Vasoactive therapy was administered to 65.9% of patients, while antibiotic prophylaxis was given in 82.4%. In-hospital mortality was 16.5%, and the cumulative six-week mortality was 25.3%. The severity of liver disease (expressed by MELD-Na and Child–Pugh scores) was associated with a higher risk of in-hospital mortality (p = 0.0045 and p = 0.009, respectively). Early endoscopic intervention did not result in a statistically significant reduction in in-hospital mortality (8.7% vs. 23.5%; p = 0.104). The use of antibiotic prophylaxis, vasoactive drugs, and endoscopic ligation was not associated with lower rates of infections, repeated endoscopies, or mortality. Conclusions: There was a positive correlation between the severity of decompensated liver cirrhosis and in-hospital mortality. Early endoscopic intervention (within 12 h of admission) was not statistically significant in reducing mortality. The use of antibiotic prophylaxis was not associated with reduced mortality or lower incidence of infections. Vasoactive therapy did not significantly reduce the need for repeat endoscopic intervention. Endoscopic ligation did not decrease the likelihood of rebleeding during hospitalisation, in-hospital mortality, or the length of hospital stay. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of mortality in patients with advanced chronic liver disease (ACLD), particularly in those with decompensated cirrhosis, where traditional biomarkers such as alpha-fetoprotein (AFP) often fail to reliably detect malignancy. Interleukin-37 (IL-37), an anti-inflammatory cytokine with reported tumour-suppressive properties, has emerged as a candidate biomarker in hepatocarcinogenesis. This prospective study investigated serum IL-37 concentrations in 221 patients with ACLD (54 with HCC and 167 without HCC). IL-37 was measured at the time of clinical assessment, and routine laboratory parameters, disease severity scores (MELD, Child–Pugh), and tumour staging (BCLC, LI-RADS) were recorded. IL-37 levels were not significantly different in patients with compensated ACLD (cACLD) with or without HCC. In contrast, in decompensated ACLD (dACLD), IL-37 concentrations were significantly lower in patients with HCC, particularly in those with advanced hepatic dysfunction. Stratified analyses revealed an inverse relationship between IL-37 and AFP in cACLD, whereas in dACLD, IL-37 appeared more informative, as AFP levels were affected by systemic inflammation. Patients with prevalent HCC exhibited numerically lower IL-37 compared with those who developed HCC during follow-up, suggesting that IL-37 decline may precede overt tumour manifestation. Kaplan–Meier survival analysis showed a trend toward improved overall survival in patients with higher IL-37 levels, although this did not reach statistical significance. These findings highlight IL-37 as a promising biomarker candidate that might reflect immune regulation and tumour biology in ACLD. In particular, IL-37 may complement AFP for HCC detection in decompensated cirrhosis, where conventional biomarkers often fail. Future studies with larger, longitudinal cohorts are warranted to validate IL-37 as a predictive and prognostic marker in high-risk populations. Full article

Background/Objectives: Cirrhosis is associated with increased mortality. In this study, we aimed to investigate the prognostic relevance of 6-min-walk-distance- and cardiopulmonary exercise testing (CPET)-derived peak oxygen uptake (VO₂) as estimates of exercise capacity in outpatients with cirrhosis. Methods: Patients underwent a comprehensive clinical characterization including cardiopulmonary exercise testing, six-minute-walking-test-derived distance, and echocardiography. We stratified the cohort using established prognostic thresholds for the six-minute-walking-test-derived distance (440 m) and peak VO₂ (65% predicted) and Child–Pugh class (A vs. B/C). Competing risk analyses were performed using cumulative incidence functions and subdistribution hazard models to assess the impact of baseline variables on mortality, accounting for liver transplantation (LT) as a competing event and for age and sex. The prognostic value of exercise performance was analyzed first, followed by the stepwise inclusion of additional variables; multicollinearity precluded a full multivariable model. Results: We enrolled 197 patients in Child–Pugh Class A, B, and C (N = 92, N = 80, N = 25 patients; male N = 146, age: 56 ± 9 years). During the observation time of 85 (25–105) months, 48 patients underwent a liver transplant, and 88 died. Both the six-minute-walking-test-derived distance ≤ 440 m (p = 0.002, sHR: 0.996 95% CI: 0.993–0.998) and peak VO₂ ≤ 65% predicted (p = 0.023, sHR: 0.987 95% CI: 0.976–0.998) were strong independent predictors of mortality. While the six-minute-walking-test-derived distance consistently remained significant across most models, the peak VO₂ retained significance only when adjusted for creatinine. Combining exercise capacity and the Child–Pugh classification identified patients at a particularly high mortality risk. Conclusions: In patients with liver cirrhosis outside the liver transplant setting, the impaired six-minute-walking-test-derived distance and peak VO₂ serve as predictors of mortality and may help to identify patients at a particularly high mortality risk. These results suggest that functional capacity provides complementary information to established liver disease severity scores and could be considered in a multidimensional risk assessment approach in patients with liver cirrhosis. Full article

Background: Elevated levels of the C-3 epimer (3-epi-25(OH)D) of 25-hydroxyvitamin D (25(OH)D) have been identified in premature infants as compared to most adults, and an immature liver has been suggested as a possible cause. We hypothesised that patients with cirrhosis might present with elevated C-3 epimerisation due to impaired liver function. The aim was to assess whether 3-epi-25(OH)D levels differ in patients with chronic liver disease with cirrhosis vs. those without cirrhosis. Methods: A total of 309 patients were included (254 patients with cirrhosis vs. 55 without cirrhosis). Serum 25(OH)D and 3-epi-25(OH)D levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Patients with cirrhosis had significantly higher median relative 3-epi-25(OH)D concentrations, as compared to patients without cirrhosis (7.4% (5.5–10.4) vs. 4.8% (2.4–5.7), respectively; p < 0.001). They also had similar absolute 3-epi-25(OH)D levels (despite having lower 25(OH)D serum concentrations) than patients without cirrhosis. A progressive increase in relative 3-epi-25(OH)D levels was observed with more advanced cirrhosis (p < 0.001). An analysis of the ROC area under the curve determined 6% as the optimal cut-off for relative 3-epi-25(OH)D. All patients with Child–Pugh stage C and 88.6% with stage B were above the 6% cut-off and had significantly higher absolute serum 3-epi-25(OH)D concentrations (0.9 ng/mL vs. 0.6 ng/mL; p < 0.05) and lower serum 25(OH)D levels (9.3 vs. 14.1 ng/mL; p < 0.001) than patients <6% cut-off. Conclusions: These results reflect the marked increases in relative 3-epi-25(OH)D levels that occur with cirrhosis. The specific hepatic metabolic alterations still need to be unravelled, including whether cirrhosis might lead to reduced epimer clearance. Full article