Refractory esophageal varices that are difficult to control or unresponsive to endoscopic treatment remain a major clinical challenge in the management of portal hypertension. This review provides a comprehensive overview of treatment strategies for these cases, along with a comparative analysis of the American Association for the Study of Liver Diseases, Baveno VII, and Japanese clinical practice guidelines. Treatment approaches are classified into four domains: endoscopic therapy, interventional radiology (IVR), surgical procedures, and internal medicine-based strategies. In recent years, clinical practice has shifted from traditional surgical interventions and transjugular intrahepatic portosystemic shunt (TIPS) to minimally invasive IVR techniques, such as partial splenic embolization, percutaneous transhepatic obliteration, and transileocolic vein obliteration, often combined with endoscopic methods. In Japan, where TIPS is not routinely performed due to limited availability and lack of insurance coverage, these alternative IVR procedures are more commonly utilized. Differences among regional guidelines highlight the need for adaptable treatment strategies based on local resources and institutional expertise. Effective management of refractory cases requires multidisciplinary collaboration among gastroenterologists, interventional radiologists, and surgeons. This review emphasizes the importance of integrating international evidence with local clinical practice to develop a tailored, team-based approach that improves outcomes in patients with complex variceal disease.

Our objective was to identify distinct clinical subtypes among critically ill patients with cirrhosis and analyze the clinical features and prognosis of each subtype.

We extracted routine clinical data within 24 h of ICU admission from the MIMIC-IV database. To determine the number of clinical subtypes, we employed the "elbow method," "cumulative distribution function (CDF) plot," and "consensus matrix." Consensus k-means, k-means, and SOM methods were used to identify different clinical subtypes of critically ill cirrhosis. We validated our findings using patients from the eICU database. The SHapley Additive exPlanations (SHAP) method was used to explore the features of each clinical subtype, and 28-day Kaplan-Meier curves were generated. Survival differences among the clinical subtypes were assessed using the log-rank test.

Our study included 2,586 patients from the MIMIC-IV database and 1,670 patients from the eICU database. Based on the clinical routine variables, we identified three clinical subtypes among patients in the MIMIC-IV database. Subtype A (N = 1424, 55.07 %) was labeled the "common subtype" and exhibited the lowest mortality. Subtype B (N = 703, 27.18 %) was classified as the "hyperinflammatory response subtype" and had a relatively high mortality. Subtype C (N = 459, 17.75 %) was identified as the "liver dysfunction subtype" and had the highest mortality. These findings were consistent with the results obtained from both the internal validation set (MIMIC-IV database) and the external validation set (eICU database).

Our study presents a novel and clinically applicable approach for subtyping critically ill cirrhosis.

IntroductionEpidemiological models benefit from incorporating detailed time-to-event data to understand how disease risk evolves. For example, decompensation risk in liver cirrhosis depends on sojourn time spent with cirrhosis. Semi-Markov and related models capture these details by modeling time-to-event distributions based on published survival data. However, implementations of semi-Markov processes rely on Monte Carlo sampling methods, which increase computational requirements and introduce stochastic variability. Explicitly calculating the evolving transition likelihood can avoid these issues and provide fast, reliable estimates.MethodsWe present the sojourn time density framework for computing semi-Markov and related models by calculating the evolving sojourn time probability density as a system of partial differential equations. The framework is parametrized by commonly used hazard and models the distribution of current disease state and sojourn time. We describe the mathematical background, a numerical method for computation, and an example model of liver disease.ResultsModels developed with the sojourn time density framework can directly incorporate time-to-event data and serial events in a deterministic system. This increases the level of potential model detail over Markov-type models, improves parameter identifiability, and reduces computational burden and stochastic uncertainty compared with Monte Carlo methods. The example model of liver disease was able to accurately reproduce targets without extensive calibration or fitting and required minimal computational burden.ConclusionsExplicitly modeling sojourn time distribution allows us to represent semi-Markov systems using detailed survival data from epidemiological studies without requiring sampling, avoiding the need for calibration, reducing computational time, and allowing for more robust probabilistic sensitivity analyses.HighlightsTime-inhomogeneous semi-Markov models and other time-to-event-based modeling approaches can capture risks that evolve over time spent with a disease.We describe an approach to computing these models that represents them as partial differential equations representing the evolution of the sojourn time probability density.This sojourn time density framework incorporates complex data sources on competing risks and serial events while minimizing computational complexity.

Point-of-care ultrasound (POCUS) is changing the practice of nearly all specialties and is increasingly being incorporated as a bedside tool by more gastroenterologists and hepatologists. POCUS is most often used to answer focused diagnostic questions, supplement the traditional physical examination, and guide performance of invasive bedside procedures. This review describes several common POCUS applications used in gastroenterology and hepatology, as well as some novel applications that warrant further investigation.

To compare the performance of updated model for end-stage liver disease (MELD) systems with that of the original MELD score for predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation.

In this single-center retrospective study, 6 MELD variations were quantified in 553 patients (n = 332; 60% male; mean age, 55 years) who underwent TIPS creation between 1998 and 2023. Scoring systems included original MELD, MELD-sodium (MELD-Na), MELD 3.0, MELD-lactate, MELD-glomerular filtration rate assessment in patients with liver disease-sodium (MELD-GRAIL-Na), and MELD-plus. Association of MELD schemes with 30-day, 6-week, and 90-day mortality was assessed using DeLong test, and the predictive capacity of MELD systems was evaluated by comparing area under receiver operating characteristic (AUROC) curves.

TIPS were created for ascites (n = 263, 47%), variceal hemorrhage (n = 247, 45%), or other indications (n = 43, 8%). All MELD systems statistically associated with mortality at each time point (P < .001). Based on 30-day, 6-week, and 90-day AUROC curves, none of the updated MELD systems showed superior predictive capacity for early mortality compared with original MELD-MELD: 0.847, 0.841, and 0.818; MELD-Na : 0.847, 0.846, and 0.829; MELD 3.0: 0.848, 0.850, and 0.842; MELD-lactate: 0.915, 0.881, and 0.866; MELD-GRAIL-Na: 0.851, 0.847, and 0.831; and MELD-Plus: 0.843-0.898, 0.853-0.910, and 0.814-0.829, respectively (P > .05). Findings were principally confirmed on subset analyses stratified by sex, TIPS indication, TIPS urgency, stent type, and TIPS date.

Updated MELD systems have prognostic value for early mortality after TIPS creation. However, in this study, these newer schemes did not offer additional predictive power beyond the original MELD, which still effectively estimates early post-TIPS survival.

Carvedilol has limited research on decompensated cirrhosis. This study compared the effects of carvedilol, traditional nonselective beta blockers (NSBBs), including propranolol and nadolol, and other interventions in patients using carvedilol or traditional NSBBs for secondary prophylaxis of variceal hemorrhage (VH) and portal hypertension (PH)-related complications.

A systematic search of databases, including PubMed, Embase, Cochrane Library, and Scopus, was conducted through October 2023. Randomized controlled trials (RCTs) evaluating carvedilol or traditional NSBBs for secondary prophylaxis of VH were included. The outcomes were the occurrence of VH and portal PH-related complications, including new or worsening ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. A network meta-analysis was performed using a random-effects model.

A total of 60 RCTs involving 5,600 patients with a median Child Pugh score of 8.0 (range 6.8-10) were included. The risk of carvedilol plus variceal band ligation (VBL) on VH was lower than placebo (relative risk (RR) 0.24; 95% confidence interval (CI): 0.10-0.57), and the risk of carvedilol on new or worsening ascites was lower than placebo (RR = 0.10, 95%CI; 0.01-0.93). Traditional NSBBs plus VBL also had preventive effects on VH compared to placebo (RR = 0.31, 95%CI; 0.18-0.54). However, there were no differences between carvedilol and traditional NSBBs in other outcomes.

Carvedilol can prevent PH-related complications, including VH and new or worsening ascites, in cirrhosis patients with a history of VH. No significant differences were observed between the effects of carvedilol and traditional NSBBs, both combined with VBL.

Alpha-1 antitrypsin deficiency (A1ATD) is an inherited metabolic disorder caused by a mutation (ZZ) in the SERPINA1 gene. Carriers are predisposed to liver and lung pathology. The severity of A1ATD-associated liver disease is highly variable, necessitating further characterisation. This study aims to investigate the risk and extent of liver disease and the prevalence of liver transplantation in ZZ A1ATD patients. Several established databases, including Ovid, EBSCO, PubMed, and Cochrane Library, were searched from inception to May 12, 2024. Data were pooled using a random effects model, and study weight was calculated using the inverse variance method. Crude odds ratios (cOR) were calculated using participants with the MM genotype as the comparator. The study was registered in PROSPERO (CRD42022335666). Of the 4420 studies identified, 45 studies and 8638 A1ATD patients (38.8% female) were included. ZZ A1ATD patients demonstrate an increased risk of liver diseases compared to controls, including steatosis (crude odds ratio (cOR): 1.52 [95% CI: 1.21, 1.91]), fibrosis (cOR: 9.85 [95% CI: 5.70, 17.03]), cirrhosis (cOR: 10.43 [95% CI: 5.51, 19.73]), and liver cancers (cOR: 14.12 [95% CI: 6.50, 30.66]). The prevalence of liver transplantation is considerable, with rates reaching 5% [95% CI: 0.00, 12.34]. Our findings confirm the substantial burden of liver disease in ZZ A1ATD patients, including subclinical manifestations such as steatosis and fibrosis that may remain undetected. Given the lack of approved treatments for A1ATD-associated liver disease, prioritising the development of novel therapies to stop or reverse liver disease is essential.

While mortality rates from advanced chronic liver disease (ACLD) are rapidly increasing, patients with an advanced disease stage have a comparable or even higher symptom burden than those with other life-limiting diseases. Although evidence is limited there is increasing recognition of the need to improve care for patients with ACLD; however, there are many limiting factors to providing good palliative care for these patients, including unpredictable disease progression, the misconception of palliative care and end of life care as being equivalent, a lack of confidence in prescribing medication and a lack of time and resources. Health professionals working with these patients need to develop the skills to ensure effective palliative care, while referral to specialized palliative care centers should be reserved for patients with complex needs. Basic palliative care, along with active disease management, is best delivered by the treating hepatologists. This includes discussions about disease progression and advance care planning, alongside the active management of disease complications. Liver disease is closely associated with significant social, psychological, and financial burdens for patients and their caregivers. Strategies to engage the discussion in multidisciplinary teams early in disease progression help to ensure addressing these issues proactively. This review summarizes the evidence on palliative care for patients with ACLD, provides examples of current best practice and offers suggestions on how disease-modifying and palliative care can coexist, to ensure that patients do not miss opportunities for quality of life improving interventions.

Background: The burden of liver cirrhosis correlated with diabetes mellitus (DM) poses a significant public health challenge in the United States. Both conditions independently contribute to high morbidity and mortality rates. While extensive individual analyses have been conducted, US trends in comorbid liver cirrhosis-DM-related mortality remain unexplored. This study seeks to investigate mortality trends associated with the simultaneous occurrence of liver cirrhosis and DM among U.S. adults over the period from 1999 to 2020. Methods: We conducted a descriptive analysis using publicly available mortality data from the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated using the 2000 U.S. standard population. Trends were stratified by year, age, sex, race/ethnicity, urbanization, region, and state. Joinpoint regression analysis was employed to determine annual percentage changes (APCs) and assess statistical significance (p < 0.05). Results: A total of 90,418 deaths were recorded among adults with both cirrhosis and DM between 1999 and 2020. The overall AAMR increased from 1.02/100,000 in 1999 to 1.78/100,000 in 2020, reflecting a significant upward trend in mortality. The highest mortality rates were observed in non-metropolitan regions, in the South, and among males, older adults (65+), and NH American Indian or Alaska Native and Hispanic populations. All demographic groups exhibited a pronounced mortality surge between 2018 and 2020. A state-level analysis revealed notable disparities, with Oklahoma and Texas presenting the highest AAMRs. Conclusions: Liver cirrhosis and diabetes-related mortality have been steadily increasing over the past two decades, with notable disparities in demographics and regions. These findings underscore the urgent necessity for targeted prevention, early intervention, and policy-level strategies specifically designed for high-risk populations to reduce future mortality rates in the US and ultimately, globally.

This study aimed to estimate the lifetime cost of alcohol consumption per individual drinker in Thailand to support policy formulation. Using an incidence-based cost-of-illness (COI) approach, a hybrid model combining a decision tree and a Markov model, incorporating six major alcohol-related diseases and conditions (i.e., hypertension, hemorrhagic stroke, liver cirrhosis, liver cancer, alcohol use disorders, and road injuries), was employed to analyze both direct costs (i.e., direct medical, direct nonmedical, property damage) and indirect costs (i.e., absenteeism, premature mortality). All costs were reported in Thai baht 2022 (35.06 THB = 1US$). From a societal perspective, the lifetime costs for individual male and female drinker were estimated at 721,344 THB (95% CI: 687,910-754,779) and 263,812 THB (95% CI: 249,250-278,374), respectively. Quitting earlier reduced costs significantly, with average quitting ages resulting in the cost of 568,932 THB for males and 115,167 THB for females. On average, each Thai drinker incurs a cost of 498,196 THB. These findings highlight the substantial economic burden of alcohol consumption in Thailand, underscoring the critical need for effective interventions and policies, along with more rigorous enforcement of current regulations aimed at encouraging early cessation and preventing the initiation of drinking, such as through advertising bans, sales restrictions, improving access to counseling and treatment.

This meta-analysis aims to evaluate the effect of prophylactic anticoagulation on incidence of venous thromboembolism (VTE), bleeding events, and mortality in hospitalized cirrhotic patients.

We utilized the following databases (EMBASE, PubMed, MedRxiv and google-scholar) to search for studies that satisfied the reviewers pre-specified inclusion criteria. The incidence of VTE, bleeding risks, and mortality were assessed using a quality effect meta-analytic model.

From screening of 539 studies, a total of 9 studies (n = 6275 patients) satisfied inclusion criteria. Our results suggested no significant difference in the primary outcome of VTE events in both groups of cirrhotic patients who received and did not receive anticoagulation for VTE prophylaxis, (OR:0.9, 95 % CI:0.50-1.62). Similarly, there was a non-significant reduced risk of bleeding events in hospitalized cirrhotic amongst patient cohorts receiving VTE prophylaxis compared to those who did not (OR:0.51, 95 % CI:0.22-1.14). Analysis of three studies showed no significant difference in mortality in both groups (OR 1.02, 95 % CI:0.8-1.31).

In a pooled examination of studies evaluating outcomes in patients exposed to VTE prophylactic anticoagulation, we found no significant difference in the burden of VTE or mortality between treated and untreated patients with chronic liver disease (CLD). The retrospective design of a plurality of studies enrolled in the review meant further prospective studies are needed to objectively ascertain the efficacy and safety of VTE prophylaxis amongst patient cohorts with CLD.

Esophageal variceal bleeding is affected by various risk factors. We hypothesized that increased exposure to gastric acid in patients with abnormal gastroesophageal flap valve (GEFV) might increase esophageal variceal bleeding. The aim of this study is to investigate the relationship between GEFV and esophageal variceal bleeding episodes.

In this cross-sectional study, 300 consecutive patients with esophageal varices and a documented GEFV during esophagogastroduodenoscopy were included. Patients were divided into two groups according to: the Hill's grade of flap valve (grade 1,2- normal and grade 3,4- abnormal), size of varices - large (>5 mm) and small (<5 mm) and the number of bleeding episodes into: Group A with ≤ 1 and Group B with ≥ 2 bleeding episodes. We compared GEFV and various other factors to the number of variceal bleeding episodes.

224 patients (74.60 %) had a normal and 76 (25.40 %) had an abnormal GEFV. Clinical variables were statistically significant in the abnormal GEFV group (P < 0.0.5). Propensity score matching was done to reduce the significant differences in the clinical background at baseline between the 2 groups. 152 patients (76 in each group) were analysed after propensity score matching. A significant difference between the two groups disappeared except for number of bleeding episodes. Binary logistic Cox regression analysis was applied using the clinical variables to assess their role in predicting recurrent variceal bleeding. On univariate analysis, abnormal GEFV and large varices were significantly associated with recurrent esophageal variceal bleed (P = 0.001). On Multivariate analysis, abnormal GEFV (OR 7.25, 95 % CI 3.27- 16.08, P = 0.001), History of EVL (OR 6.21, 95 % CI 1.98- 12.22, P = 0.03) and large varices (OR 5.70, 95 % CI 2.45- 13.20, P = 0.001) were independent predictors for recurrent esophageal variceal bleeding.

Abnormal GEFV, History of EVL and large varices are independent risk factors for recurrent esophageal variceal haemorrhage.

The exact pathophysiology of portal vein thrombosis (PVT), a common complication of cirrhosis, remains largely unknown. We previously found that cirrhotic PVT consists of fibrotic intimal thickening of the portal vein wall rather than of true fibrin-rich thrombus. We hypothesized that this intimal thickening of portal vein is secondary to portal hypertension and/or to local inflammatory responses.

To investigate the portal vein intimal thickness in cirrhotic patients, and its relationship with clinical and laboratory parameters associated with portal hypertension and inflammation.

The intimal thickness of right and left portal branches was measured in hilar liver samples from 232 cirrhotic patients without PVT who underwent liver transplantation. The relation between intimal thickness and pretransplant clinical variables was studied with linear regression. Computed tomography scans of 25 patients prior to liver transplantation were reanalyzed for portal vein and portal hypertension related characteristics.

Median right intimal thickness was 129 (1-300 [IQR]) μm; median left intimal thickness was 112 (1-230) μm, and there was a correlation between the intimal thickness of the right and left branches in individual patients (r = 0.30, P < .001). Intimal thickness of the portal vein was associated with a history of variceal bleeding, hepatic encephalopathy or ascites, etiology of disease, and statin use. Other factors, including duration of liver disease, presence of infection, or radiological characteristics were not significantly associated with intimal thickness.

Intrahepatic portal vein intimal thickness is highly variable in patients with cirrhosis, but relatively consistent between right and left portal branches. The association between intimal thickness and history of variceal bleeding suggests that portal hypertension may contribute to initiation of intimal thickening, and consequently to the development of PVT.

Accurate prediction of disease severity and prognosis are challenging in patients with cirrhosis. We evaluated whether the deep learning-based AI-Cirrhosis-ECG (ACE) score could detect hepatic decompensation and predict clinical outcomes in cirrhosis.

We analyzed 2,166 ECGs from 472 patients in a retrospective Mayo Clinic cohort, 420 patients in a prospective Mayo transplant cohort, and 341 patients in an external validation cohort from Hospital Clínic de Barcelona. The ACE score's performance was assessed using receiver-operating characteristic analysis for decompensation detection and competing risks Cox regression for outcome prediction.

The ACE score showed high accuracy in detecting hepatic decompensation (area under the curve 0.933, 95% CI: 0.923-0.942) with 88.0% sensitivity and 84.3% specificity at an optimal threshold of 0.25. In multivariable analysis, each 0.1-point increase in ACE score was independently associated with increased risk of liver-related death (hazard ratio [HR] 1.44, 95% CI 1.32-1.58, p <0.001). Adding ACE to model for end-stage liver disease-sodium significantly improved prediction of adverse outcomes across all cohorts (c-statistics: retrospective cohort 0.903 vs. 0.844; prospective cohort 0.779 vs. 0.735; external validation 0.744 vs. 0.732; all p <0.001).

The ACE score accurately identifies hepatic decompensation and independently predicts liver-related outcomes in cirrhosis. This non-invasive tool enhances current prognostic models and may improve risk stratification in cirrhosis management.

This study demonstrates the potential of artificial intelligence to enhance prognostication in liver disease, addressing the critical need for improved risk stratification in cirrhosis management. The AI-Cirrhosis-ECG (ACE) score, derived from widely available ECGs, shows promise as a non-invasive tool for detecting hepatic decompensation and predicting liver-related outcomes, which could significantly impact clinical decision-making and resource allocation in hepatology. These findings are particularly important for hepatologists, transplant surgeons, and patients with cirrhosis, as they offer a novel approach to complement existing prognostic models such as model for end-stage liver disease-sodium. In practical terms, the ACE score could be integrated into routine clinical assessments to provide more accurate risk predictions, potentially improving the timing of interventions, optimizing transplant listing decisions, and ultimately enhancing patient outcomes. However, further validation in diverse populations and integration with other established predictors is necessary before widespread clinical implementation.

Systemic inflammation drives the progression of portal hypertension in patients with liver cirrhosis. Interleukin-6 is a key mediator of the cytokine network in acute inflammation that stimulates the production of many acute phase reactants. In this study, we investigated the association between serum interleukin-6 and acute phase reactant levels and the disease stage and prognosis of patients with liver cirrhosis.

A single-center retrospective cohort of 359 patients with liver cirrhosis was staged according to the symptomatic decompensation. Baseline serum C-reactive protein , interleukin-6, procalcitonin, and serum amyloid A protein levels were measured. The outcomes of further decompensation, hepatocellular carcinoma development, and mortality were identified during a 3.3-year median follow-up period.

Serum C-reactive protein , interleukin-6, and procalcitonin levels were significantly different across the stages. The multivariate Cox proportional hazards model identified serum interleukin-6 as an independent predictor of further decompensation in patients with compensated and the first single decompensated cirrhosis. Kaplan-Meier analyses showed that the probability of further decompensation was stratified by serum interleukin-6 level in a dose-dependent manner. In the entire cohort, serum interleukin-6 level also showed a significant association with liver-related and all-cause mortalities, but not with hepatocellular carcinoma development, independent of stage and liver disease severity indices.

Elevated levels of serum markers of systemic inflammation were associated with symptomatic decompensation, and serum interleukin-6 level is a predictor of further decompensation and mortality in patients with liver cirrhosis.

Background: Patients with end-stage liver disease (ESLD) have complex needs and may benefit from palliative care (PC), which is often underutilized or delayed. Objectives: To characterize patients with ESLD who received inpatient PC consultation and to explore differences in characteristics between those who received PC consultation before (pre-Pall) or after (post-Pall) PC participation at weekly liver transplant (LT) Patient Selection Committee (PSC) meetings. Design: Single-center retrospective cohort study. Setting/Subjects: Hospitalized patients with ESLD who received inpatient PC consultation between February 2017 and February 2019 at an academic LT center in the United States. Measurements: PC referral reasons and timing, code status, hospice referrals, discharge location, and mortality. Results: Two hundred five patients were included. The primary reason for PC was goals of care (88.8%; n = 182). Most (86.8%; n = 178) were Full Code at hospital admission, while 81% (n = 166) were do-not-resuscitate at discharge. Nearly one quarter (22.9%; n = 47) sought life-prolonging care at discharge, while 41.5% (n = 85) were discharged with hospice, and 34.1% (n = 70) died before discharge. By the end of the study, 85.9% (n = 176) were confirmed as deceased. Median time from PC to hospice referral was 12 days [95% confidence interval [CI]: 8-23]. Median time from PC consult to death was 13 days [95% CI: 9-17] and from hospice referral to death was 7 days [95% CI: 4-13]. There were no statistically significant differences between the pre- and post-Pall groups related to PC referral patterns or outcomes. Conclusions: Most PC contacts occurred near end of life, and many led to comfort-focused care. Late referrals may be due to reliance on inpatient consults during acute illness. PC presence at PSC meetings represents an important step in collaboration with LT teams but did not lead to direct impact on PC referral patterns or outcomes.

The hepatic blood supply and its several homeostatic and pathologic processes have always been a matter of great interest. Many views commonly held today are derived from an earlier era, but major reorientations have occurred recently in almost all aspects of knowledge of the role and regulation of hepatic blood flow. Moreover, with the advent of liver transplantation (LT), especially living donor LT, there has been a resurgence of interest in attempting to comprehend this deceptively simple topic. It is nonetheless important to concede that even though our knowledge of the practical modulation of hepatic hemodynamics has expanded enormously, there still remains the need to explore the depths of our remaining ignorance to further improve outcomes in living donor LT. This review focuses on the current view, controversies, and gaps in knowledge of the hepatic vascular bed, with an emphasis on the importance of portal hemodynamics in liver disease and its impact on liver regeneration and LT.

Background: Chronic liver disease (CLD) is a major global health concern, contributing significantly to morbidity and mortality. Cirrhosis and liver cancer are the leading causes of liver-related deaths, with various etiological factors, such as metabolic disorders and alcohol-related and viral hepatitis, driving its global prevalence. Non-invasive biomarkers and scoring systems have emerged as key tools for assessing liver disease severity and differentiating CLD from cirrhosis. This study evaluates biomarkers and non-invasive scores and their utility in distinguishing CLD from cirrhosis. Methods: This retrospective observational study included 250 adult patients hospitalized between January 2021 and December 2023 at Cluj County Emergency Clinical Hospital, Romania. Patients were diagnosed with either cirrhosis or CLD of viral, autoimmune, or primary biliary cholangitis (PBC) etiology. Non-invasive biomarkers, scores, and various hemogram-derived ratios were evaluated. Statistical analysis involved descriptive statistics, comparative tests, and receiver operating characteristic (ROC) curve analysis. Results: Among the 250 patients, 137 had liver cirrhosis (54.8%) and 113 had CLD without cirrhosis (45.2%). Significant differences were observed in laboratory parameters, with cirrhosis patients showing lower hemoglobin, platelet count, and albumin levels alongside higher liver enzymes and INR values. Non-invasive scores such as APRI, FIB-4, and NFS demonstrated higher values in the cirrhosis group, indicating more advanced liver damage. Hemogram-derived ratios, particularly the neutrophil-to-lymphocyte ratio (NLR), were higher in cirrhosis patients. ROC analysis revealed that the Lok index had the highest discriminatory power (AUC 0.89), followed by the King score (AUC 0.864) and the Fibrosis index (AUC 0.856), which effectively distinguished cirrhosis from CLD. Conclusions: This study underscores the utility of non-invasive biomarkers and scoring systems in differentiating CLD from cirrhosis. The Lok index, King score, and Fibrosis index demonstrated excellent diagnostic accuracy, while hemogram-derived ratios, such as NLR, offer insights into systemic inflammation associated with liver disease progression. These findings support the integration of non-invasive markers into clinical practice for improved risk stratification and management of liver diseases.

Frailty is a well-established risk factor for adverse outcomes, particularly in liver transplant candidates. This study investigates the impact of age and frailty on key clinical outcomes-hospitalizations, waitlist survival, and post-transplant mortality-in cirrhotic patients evaluated for liver transplantation.

This study included older adults with chronic liver disease under consideration for transplantation. Data collected encompassed medical history, Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores, Mini-Mental State Examination (MMSE), Mini Nutritional Assessment (MNA), and frailty status, assessed using both the Liver Frailty Index (LFI) and the Survey of Health, Ageing, and Retirement in Europe Frailty Index (SHARE-FI). Clinical outcomes, including mortality and hospitalizations, were tracked over a 24-month period.

Among 100 patients (67% male), those under 70 exhibited higher MNA, MMSE, and SHARE-FI scores. Based on frailty classification, 25 patients were frail, 28 pre-frail, and 47 robust. Younger patients experienced more hospitalizations during follow-up (p = 0.03) and had a higher probability of hospitalization within 24 months (p = 0.002). Although transplant-free survival did not differ significantly across groups, frail patients had a significantly higher mortality rate (p = 0.04). Overall, 24 patients underwent transplantation, while 26 died, including six post-transplant deaths. MELD and CTP scores were strong predictors of mortality, while among frailty measures, only SHARE-FI demonstrated significant predictive value. In multivariate Cox models, MELD [HR = 1.17, p = 0.001; HR = 1.11, p = 0.002], CTP [HR = 1.43, p = 0.003; HR = 1.41, p = 0.006], and LFI (HR = 1.69, p = 0.04) were significantly associated with mortality.

Frailty, rather than age, emerges as a key predictor of mortality in liver transplant candidates. Further research is needed to validate these findings and enhance frailty assessment, ultimately improving candidate selection for transplantation.

This scoping review aimed to delineate the detailed components of exercise therapy and the evaluation methods used for patients with liver cirrhosis.

The methodology involved searching the original PubMed, Web of Science, and Scopus for studies published between January 1975 and March 2025. The search was completed on 13 March 2025. Studies describing exercise therapy for liver cirrhosis patients were selected. Relevant information matching the study objectives, such as intervention duration, content, intensity setting, evaluation criteria, and outcomes, was extracted and documented.

Of the 2314 articles identified, 18 fit the inclusion and exclusion criteria, with a total of 950 participants. The most prevalent form of exercise therapy was a combined aerobic exercise and strength training program (55.6%). Commonly used assessment criteria included the 6-minute walking distance for endurance evaluation (44.4%) and the Chronic Liver Disease Questionnaire for quality of life assessment (33.3%). Intervention durations ranged from 30 to 60 min per day, 2 to 7 days per week, and 8 to 12 weeks. Concerning intensity setting, subjective fatigue levels and heart rate were frequently used (38.9%), though detailed descriptions were limited.

For the establishment of effective exercise therapy for patients with liver cirrhosis, future research should concentrate on tailoring intensity settings according to individual patient needs. Additionally, standardized reporting of intervention details and assessment methods is crucial for improving the quality and comparability of studies in this field.

The development of portal hypertension (PH) is a key prognostic factor in patients with compensated advanced chronic liver disease (cACLD). The gold standard for assessing PH is the hepatic venous pressure gradient measurement. However, noninvasive tools have gained significant importance in recent years, mainly liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE). Spleen stiffness measurement (SSM) by VCTE using a dedicated 100-Hz module has emerged as a promising non-invasive diagnostic tool, although data on its prognostic value remain limited. This study aimed to evaluate the accuracy of SSM, as measured by transient elastography, in predicting the risk of liver decompensation.

A prospective study was conducted including patients with cACLD followed at a tertiary center from January 2020 to April 2024. All patients underwent liver and spleen VCTE (utilizing the 100-Hz module) performed by the same blinded operator. Patients were subsequently monitored at the same institution for the development of PH complications.

The study included 242 patients with cACLD, with a mean age of 63.0 ± 10.5 years and who were 78.5% male. The most common etiology was alcoholic liver disease (62.0%). The median LSM value was 21.9 kPa (interquartile range [IQR], 15.0-34.0 kPa), and the median SSM value was 38.9 kPa (IQR, 28.0-58.0 kPa). The median follow-up period was 501.5 days (IQR, 343.0-725.3 days). During this time, 28 patients (11.6%) developed liver decompensations, with 20 requiring hospital admission. SSM demonstrated good predictive capacity for the risk of liver decompensation (area under the curve, 0.823; 95% confidence interval, 0.742-0.904). Alongside LSM, SSM was an effective predictor of liver decompensation, with a cutoff of 50.0 kPa indicating a significantly increased risk of hepatic decompensation.

Noninvasive assessment using SSM may serve as an excellent tool for predicting the risk of liver-related complications and risk-stratifying patients with cACLD, thereby improving their management.

The Baveno VII group recently proposed criteria to define recompensation in patients with decompensated cirrhosis achieving etiological cure. However, the incidence, predictors and clinical significance of recompensation are poorly understood. The aim of this study was to evaluate the incidence and prognostic impact of recompensation in patients with decompensated cirrhosis.

Outpatients with cirrhosis and curable etiologies (alcohol, HCV, HBV) were consecutively included and followed up. Recompensation was defined according to Baveno VII criteria. Additionally, expanded recompensation criteria were evaluated for patients on low-dose diuretics and/or lactulose/rifaximin for ≥12 months. In 160 patients, inflammatory cytokines (IL-6, IL-1β, IL-10) were measured in serum samples. An external cohort was used to validate study findings.

Out of 525 outpatients with decompensated cirrhosis, 298 received effective etiological treatment and 21 (7%) achieved recompensation (Baveno VII criteria), while 112 patients achieved expanded recompensation criteria (37.6%). MELD score (subdistribution hazard ratio [sHR] 0.89; p <0.001), BMI (sHR 0.93; p = 0.020), hemoglobin (sHR 1.14; p = 0.010) and further decompensation (sHR 0.50; p = 0.001) were independent predictors of recompensation. In multivariable analysis, mortality risk was not significantly different between patients achieving recompensation and compensated patients (HR 0.97; p = 0.947), while decompensated patients had the highest mortality risk (HR 4.96; p <0.001). Mortality risk was not significantly different between patients meeting expanded recompensation criteria and Baveno VII criteria (HR 0.97; p = 0.938). Serum IL-6, IL-1β and IL-10 were significantly higher in decompensated patients than in compensated and recompensated patients.

Baveno VII criteria identify patients with cirrhosis and a good prognosis, but fewer than 10% of decompensated patients achieve recompensation. Expanding these criteria to include patients receiving minimal decompensation treatment identifies those with similarly low mortality risk.

In recent years, growing evidence has shown that achieving an etiological cure can significantly improve the prognosis of patients with decompensated cirrhosis, leading to the concept of recompensation. The Baveno VII group recently proposed criteria to define recompensation; however, data on the clinical impact of this state remain limited. In this study we evaluated Baveno VII criteria and developed and validated expanded Baveno VII criteria for recompensation. Our findings demonstrate that recompensation is associated with improved survival, reduced hyperdynamic circulation and decreased systemic inflammation in outpatients with decompensated cirrhosis. These results are valuable for hepatologists and researchers aiming to refine patient management strategies and risk stratification in cirrhosis care.

Higher immature granulocyte levels have a predictive role in several clinical conditions, although data concerning cirrhosis are scarce. Reduced muscle mass is a known factor affecting the outcome of these patients. The aim of the study was to evaluate the association of immature granulocytes with muscle mass and their role in predicting the outcome (survival, death or liver transplantation) in patients with stable decompensated cirrhosis.

We prospectively studied 210 patients with decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded, including complete blood count with immature granulocyte count and immature granulocyte percentage. The severity of liver disease was evaluated by estimating the Child-Turcotte-Pugh and MELD-sodium scores. Dual energy X-ray absorptiometry was used to quantify the total and regional lean mass, while mid-arm muscle circumference was used for the evaluation of upper limb muscle mass.

Immature granulocyte percentage was proved to be the only factor independently associated with transplant-free survival (Hazard Ratio: 1.98, 95% confidence interval [1.03-3.81], p = .04). Stratification of our cohort based on the best discriminative cut-off values of immature granulocyte count and percentage revealed significant differences in the outcome based on Kaplan-Meier curves, while immature granulocyte count and percentage were significantly associated with parameters of body composition.

Higher immature granulocyte count and percentage have a significant prognostic role and are associated with worse outcome in patients with stable decompensated cirrhosis.

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) prevent fibrosis progression in a preclinical model of steatotic liver disease. Our objective was to assess the impact of ACEi/ARB use on clinical outcomes in patients with metabolic dysfunction-associated steatotic liver diseases.

Using TriNetX, a nationwide database, we identified all patients with metabolic dysfunction-associated steatotic liver diseases from January 1, 2011, to December 31, 2019. Using a target trial emulation framework, ACEi/ARB users were matched with calcium channel blocker (CCB) users using propensity score matching (PSM). Patients were followed up to 10 years after the index date. Cox proportional hazards regression was used to determine the risk of mortality, major adverse liver outcomes, major adverse cardiac events, and incident cancers. Of the 35,988 eligible patients, 28,423 were ACEi/ARB users, and 7565 were CCB users. After PSM, 7238 pairs were well-balanced. ACEi/ARB use was associated with a significantly decreased mortality risk (HR: 0.59, 95% CI: 0.51-0.68). ACEi/ARB was associated with a significantly reduced risk of developing major adverse liver outcomes (HR: 0.70, 95% CI: 0.61-0.80), including ascites (HR: 0.78, 95% CI: 0.63-0.98) and HE (HR: 0.67, 95% CI: 0.57-0.78). ACEi/ARB use was also associated with a lower risk of major adverse cardiac events (HR: 0.82, 95% CI: 0.76-0.90) but not incident cancer (HR: 0.97, 95% CI: 0.86-1.10) compared with CCB.

ACEi/ARB use in patients with metabolic dysfunction-associated steatotic liver diseases was associated with a reduced risk of mortality, major adverse liver outcomes, and major adverse cardiac events compared with CCB use. A large prospective study is needed for external validation.

Continuous infusion of terlipressin may result in a more sustained reduction in portal pressure with fewer adverse effects than administered as a bolus. This study aimed to compare the hepatic and cardiopulmonary hemodynamic effects and safety profiles of bolus vs. terlipressin continuous infusion.

This is a single-center, single-blinded, double-dummy, parallel-group, clinical trial in which 38 patients with cirrhosis and portal hypertension were randomized to receive the following: 1 mg bolus of terlipressin + continuous infusion of placebo (TERLBOL, n = 12), a bolus of placebo + continuous infusion of terlipressin (2 or 4 mg/day if <10% reduction in hepatic venous pressure gradient [HVPG] at 30 min of infusion) (TERLINF, n = 14), or a bolus of octreotide (50 μg) + continuous infusion of octreotide (50 μg/h) (OCTR, n = 12) as an additional control group. HVPG, cardiopulmonary pressures, and cardiac output were measured at baseline and after 30, 60, and 120 min.

Sixty-eight percent of patients were male, with a median age of 59 years. There were no significant differences in baseline characteristics. In the TERLBOL group, there was a nonsignificant reduction in HVPG (at 120 min, -4.9%; p = 0.14). However, cardiopulmonary and mean arterial pressures significantly increased, whereas cardiac output and heart rate significantly decreased. In the TERLINF group, there were nonsignificant changes in cardiopulmonary hemodynamics or HVPG (NS) despite doubling the infusion dose after 30 min in 13/14 patients. In the OCTR group, there was a nonsignificant reduction in HVPG (at 120 min, -4.9%; p = 0.08), and pulmonary capillary pressure significantly decreased. All treatments were well tolerated, and no adverse events were observed.

There were nonsignificant reductions in HVPG with the three therapeutic strategies. Further investigations are warranted to determine the optimal dosing strategy for continuous infusion of terlipressin in patients with cirrhosis and portal hypertension.

The results of our study do not show a significant reduction in portal pressure, at least in the first 2 h after the selected dose. Although the study was not performed in the setting of acute variceal bleeding and terlipressin was used as a standard therapy, these results do not support the treatment strategy of terlipressin infusion alone at the doses studied for the management of acute variceal bleeding, where a quick reduction in portal pressure is thought to play a major role controlling variceal bleeding. It is important to highlight that the continuously infused terlipressin regimen is better tolerated and appears to have a better cardiopulmonary safety profile. Other treatment strategies of continuous terlipressin infusion, such as initial bolus administration or higher infusion doses, should be evaluated to support its use in managing variceal bleeding.

EudraCT No. 2019-004328-39.

The management of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) presents a significant clinical challenge, with a focus on preventing progression to liver and renal complications.

To evaluate the liver and renal outcomes among new users of sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP4i) and other anti-diabetic medications in patients with MASLD and T2DM.

Retrospective cohort study.

Electronic health records.

A total number of 88 306 patients with MASLD and T2DM were included in a propensity score-matched analysis comparing the effects of anti-diabetic drugs.

Patients were categorized into groups based on their initiation of anti-diabetic medications.

The primary outcomes were the incidence of cirrhosis, hepatic decompensations, and hepatocellular carcinoma. Secondary outcomes were a progression of chronic kidney disease (CKD), severity of CKD stages, and the need for hemodialysis.

In the SGLT2i versus DPP4i, a reduced risk of cirrhosis was observed in the SGLT2i (HR: 0.97), along with fewer hepatic decompensations (HR: 0.84) and a lower incidence of HCC (HR: 0.50). CKD progression, particularly to stages 4-5, was significantly lower in the SGLT2i (HR: 0.53), as was hemodialysis (HR: 0.38). However, SGLT2i exhibited a slightly lower risk of CKD progression (HR: 0.77) and a reduced need for hemodialysis (HR: 0.71) compared to the GLP-1RA, while there was no difference in hepatic outcomes between the GLP-1RA and SGLT2i.

SGLT2 inhibitors in patients with MASLD and T2DM demonstrated reduced risks of liver complications and a favorable impact on renal outcomes. These findings support the preferential consideration of SGLT2i in managing this patient population, particularly for mitigating the progression of liver and kidney diseases.

Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complications (ascites, variceal bleeding and hepatic encephalopathy) and associated with high mortality. Preventing the progression to dACLD might dramatically improve prognosis and reduce the burden of care associated with ACLD. Portal hypertension is a major driver of the transition from cACLD to dACLD, and a portal pressure of ≥10 mmHg defines clinically significant portal hypertension (CSPH) as the threshold from which decompensating events may occur. In recent years, innovative studies have provided evidence supporting new strategies to prevent decompensation in cACLD. These studies have yielded major advances, including the development of noninvasive tests (NITs) to identify patients with CSPH with reasonable confidence, the demonstration that aetiological therapies can prevent disease progression and even achieve regression of cirrhosis, and the finding that non-selective β-blockers can effectively prevent decompensation in patients with cACLD and CSPH, mainly by reducing the risk of ascites, the most frequent decompensating event. Here, we review the evidence supporting new strategies to manage cACLD to prevent decompensation and the caveats for their implementation, from patient selection using NITs to ancillary therapies.

Despite nearly 250 million people worldwide estimated to have chronic HBV infection, health-related quality of life (HRQOL) in HBV-related disease has not been well characterised. Here, we summarise existing data on HBV-related HRQOL and quantify summary utility values by stage of disease.

Embase, Global Health, PubMed, and Web of Science were searched for articles investigating HBV HRQOL. Meta-analyses for utility scores were pooled by stage of disease and utility instrument; meta-regression was further adjusted for the effect of current health expenditure as a percentage of gross domestic product (CHE/GDP), as a proxy of the importance of healthcare perceived by different countries.

Twenty-two articles from 19 studies, comprising 10,311 patients, were included. Of these studies, 74% were performed in the Western Pacific Region, and 47% used the EuroQoL-5D-3L instrument. HRQOL was found to decrease with advancing stages of HBV-related disease. Meta-regression showed the following predicted mean utility scores for the different stages of chronic HBV infection: non-cirrhotic, 0.842; compensated cirrhosis, 0.820 (p = 0.474 compared with non-cirrhotic); decompensated cirrhosis, 0.722 (p = 0.001); and hepatocellular carcinoma, 0.749 (p = 0.008). The type of tool affected HRQOL and populations with a higher CHE/GDP were associated with higher predicted utility values.

Chronic HBV infection impairs the HRQOL of patients, even when there is no evidence of cirrhosis. HRQOL is particularly impaired in the advanced stages of decompensated cirrhosis and hepatocellular carcinoma. These results have important implications for global hepatitis elimination efforts and are useful for economic analyses. However, further research is needed, particularly in high-burden, low-income settings where data are lacking.

This study, based on 22 articles and 10,311 patients, provides a comprehensive synthesis of data on the impact of chronic hepatitis B virus (HBV) infection on patients' health-related quality of life (HRQOL) worldwide. These findings, of how HRQOL is affected in people living with HBV, highlight the importance of patient-centred care and holistic approaches to management, even at the early stages of disease. These results are useful for cost-effectiveness analyses and may help inform decision-making in improving public health policy towards the elimination of viral hepatitis. The study also underscores the need for further data from low-to middle-income settings, and on the effects of treatment on HRQOL.

Chronic liver disease (CLD) is a leading cause of death worldwide. End-stage liver disease (ESLD) causes a rapid and progressive decline in health and quality of life (QOL) and creates significant suffering and burdens for patients, families, and health systems alike. These patients have significant physical, psychological, and complex social needs that benefit from the support of an interdisciplinary palliative care (PC) team.

This review of the English literature analyzes general palliative care principles for the CLD and ESLD populations including factors affecting QOL and review of symptom management per AASLD and AGA Guidelines. We have also reviewed the impacts of palliative support on QOL, caregiver burden, and healthcare-related outcomes.

ESLD causes significant suffering and burdens for patients, families, and healthcare systems. PC is an essential component of ESLD care; it improves QOL, reduces caregiver burdens, and shows benefits of reduced healthcare costs and aggressive care at end of life. Provider and community misunderstanding or inexperience of PC is often a barrier to PC involvement. There is a clear lack of standardization in medical training and lack of clear guidelines on when to involve PC in the ESLD population that must be addressed.

Objective: The prevalence and mortality of chronic liver disease has risen significantly. In end-stage liver disease (ESLD), the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden, integration of palliative care in ESLD is reduced, and the majority of patients continue to die in inpatient care. We aim to assess predictors and outcomes of home palliative care, as well as factors associated with death at home in patients with ESLD. Methods: Retrospective cohort study of patients with ESLD, followed by a palliative care team between 2017 and 2022. Information regarding patient demographics, ESLD etiology, decompensations, and interventions was collected. Two-sided tests were used to identify factors associated with home palliative care. Results: We analyzed 75 patients: 44% had home palliative care and 33% died at home. ESLD patients with home palliative care were older (72.52 vs 64.45; p = 0.002), had a longer palliative care intervention time (149.97 ± 196.23 vs 43.69 ± 100.60 days; p = 0.007), higher rates of ascites or hepatic encephalopathy (χ2 = 11.024; p = 0.029), and hepatocarcinoma (90.9% vs 64.3%; p = 0.007). Patients with home palliative care had a reduction in-hospital admissions (2.61 vs 1.06; p = 0.000) and a greater probability of death at home (66.7% vs 33.3%; p = 0.000). Patients who died at home (33.3%) were older (72.20 vs 64.40; p = 0.000) and had longer palliative care intervention time (178.80 ± 211.78 vs 46.28 ± 99.67 days; p = 0.006). Conclusion: Home palliative care in ESLD differs based on demographics and disease complications, with a positive impact of homecare translated into a reduction in hospital admissions and an increased probability of death at home.

It is unclear if the risk of hepatic decompensation or hepatocellular carcinoma (HCC) differs between patients with compensated alcohol-related liver disease (ALD)- and metabolic dysfunction-associated steatotic liver disease (MASLD)-cirrhosis. We investigated the risk to develop hepatic decompensation or HCC based on ALD or MASLD as the underlying etiology of cirrhosis.

All patients with a new diagnosis in hospital-based outpatient care of ALD- or MASLD-cirrhosis in Sweden between 2002 and 2020 were identified using national registers. Hepatic decompensation was analyzed as a composite outcome with HCC. Cox regression was employed to compare rates of hepatic decompensation or HCC, and subsequent death.

1660 patients with ALD-cirrhosis and 943 patients with MASLD-cirrhosis were identified. The median ages were 64 years (IQR 57-70) and 69 years (IQR 62-75) in patients with ALD- and MASLD-cirrhosis, respectively. Patients with ALD-cirrhosis consisted of 69.4 % males, compared to 47.6 % males in the MASLD-cirrhosis group. 581 (35 %) patients with ALD-cirrhosis and 284 (30 %) patients with MASLD-cirrhosis developed hepatic decompensation or HCC (median follow-up time: 25 months), resulting in an adjusted hazard ratio of 1.12 (ALD- vs. MASLD-cirrhosis, 95 %-confidence interval=0.88-1.41). The adjusted risk of mortality afterwards was lower in patients with ALD-cirrhosis compared to patients with MASLD-cirrhosis (adjusted hazard ratio 0.62, 95 %-confidence interval=0.39-0.97).

The risk of hepatic decompensation or HCC is comparable in patients with ALD- and MASLD-cirrhosis, but the risk of mortality after a decompensation event or HCC tends to be higher in patients with MASLD-cirrhosis.

Portal hypertension is the main pathophysiological driver of decompensation in patients with liver cirrhosis. Epithelial cell death markers, m30 and m65, correlate with hepatic injury and predict outcomes across various stages of liver disease. We aim (i) to evaluate whether portal hypertension itself contributes to liver outcome-relevant epithelial injury, and (ii) to analyse the capacity of m30/m65 to predict outcome in patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites.

Sixty-six patients undergoing TIPS placement for refractory ascites and 20 patients with compensated cirrhosis as controls were prospectively enrolled in this monocentric cohort study. Epithelial cell death markers were analysed pre-TIPS, as well as 1-3 and 6-9 months post-TIPS. The capacity of baseline levels of m30/m65 in predicting six-month transplant-free survival rates was analysed by multivariable Cox proportional hazards regression.

Levels of m30 and m65 were higher in patients with decompensated cirrhosis (pre-TIPS) compared with compensated cirrhosis (controls). Following correction of portal hypertension by TIPS and recompensation, both markers decreased over time, reaching levels comparable to patients with compensated cirrhosis. On multivariable analysis, pre-TIPS baseline levels of m30 and m65 were not predictive for six-month survival.

Correction of portal hypertension via TIPS reduces levels of epithelial cell death markers, indicating that portal hypertension is a driver of outcome-relevant, hepatic cell death in patients with decompensated cirrhosis. Baseline m30/m65 values do not affect six-month survival rates, which suggests that TIPS placement overcomes the unfavourable spontaneous prognosis otherwise indicated by elevated baseline m30/65 levels.

Large hepatocellular carcinoma (HCC) is difficult to resect and accompanied by poor outcome. The aim was to evaluate the short-term and long-term outcomes of patients who underwent liver resection for large HCC, eventually drawing prediction models for short-term and long-term outcomes.

1710 large HCC patients were recruited and randomly divided into the training (n = 1140) and validation (n = 570) cohorts in a 2:1 ratio. Independent risk factors were identified by regression model and used to establish three nomograms for surgical risk, overall survival (OS), and recurrence-free survival (RFS) in the training cohort. Model performances were assessed by discrimination and calibration. The three models were also compared with six other staging systems.

Platelet (PLT), gamma-glutamyl transpeptidase (GGT), albumin-bilirubin (ALBI) grade, blood transfusion and loss, resection margin, tumor size, and tumor number were established in a nomogram to evaluate surgical risk ( https://largehcc.shinyapps.io/largehcc-morbidity/ ). The model had a good prediction capability with a C-index of 0.764 and 0.773 in the training and validation cohorts. Alpha-fetoprotein (AFP), resection margin, tumor size, tumor number, microvascular invasion, Edmondson-Steiner grade, tumor capsular, and satellite nodules were considered to construct a prognostic nomogram to predict the 1-, 3- and 5-year OS ( https://largehcc.shinyapps.io/largehcc-os/ ). The C-index of the model was 0.709 and 0.702 for the training and validation cohorts. Liver cirrhosis, albumin (ALB), total bilirubin (TBIL), AFP, tumor size, tumor number, microvascular invasion, and tumor capsular were used to draw a prognostic nomogram to predict the 1-, 3- and 5-year RFS ( https://largehcc.shinyapps.io/largehcc-rfs/ ). The C-index of the model was 0.695 and 0.675 in the training and validation cohorts. The discrimination showed that the models had significantly better predictive performances than six other staging systems.

Three novel nomograms were developed to predict short-term and long-term outcomes in patients with large HCC who underwent curative resection with adequate performance. These predictive models could help to design therapeutic interventions and surveillance for patients with large HCC.

Transjugular intrahepatic portosystemic shunt (TIPS) effectively treats complications of cirrhosis. Systemic inflammation (SI) is linked to acute-on-chronic liver failure (ACLF) and liver-related death. We aimed to assess the trajectory and clinical impact of SI parameters after TIPS implantation.

Consecutive patients undergoing elective implantation of covered TIPS for recurrent/refractory ascites or portal-hypertensive bleeding at the Medical University Vienna (NCT03409263; n = 58) and at the Hannover Medical School (NCT04801290, n = 51) were included. IL-6 was assessed at baseline (BL), 3 months (M3) and up to 6 (M6; Hannover cohort) or 9 months (M9; Vienna cohort) of follow-up; C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were assessed in the Vienna cohort only.

In 109 patients (66.1% male, median age 57 years) receiving TIPS mainly (72.4%) by indication ascites the median BL IL-6 levels were 10.5 pg/ml; and 41.3% (n = 45/109) patients exhibiting IL-6 ≥14 pg/ml. From BL to M3, IL-6 decreased in 63.8% (n = 37/58; Vienna cohort) and in 68.6% (n = 35/51; Hannover cohort) of patients, respectively. Similar rates of decreases were observed also for CRP (in 62.1%) and for LBP (in 77.4%). A considerable IL-6 reduction (≥50% of baseline) was noted in 41 (37.6%) patients during follow-up. Competing risk regression in the combined cohort adjusted for age, albumin, and model for end-stage liver disease revealed that IL-6 decrease at M3 was an independently protective factor for the development of ACLF (adjusted subdistribution hazard ratio [asHR]: 0.26; 95% CI: 0.09-0.77; p = 0.016) and liver-related death (asHR: 0.26; 95% CI: 0.07-0.95; p = 0.042).

TIPS leads to a sustained reduction of SI and bacterial translocation in patients with decompensated cirrhosis. Decreasing IL-6 levels three months after TIPS implantation indicate a lower risk of ACLF and liver-related death in patients with cirrhosis.

Systemic inflammation is a major driver of disease progression in patients with decompensated advanced chronic liver disease (dACLD). This study demonstrates that systemic inflammation (i.e. interleukin-6 [IL-6]) effectively and sustainedly decreases after transjugular intrahepatic portosystemic shunt (TIPS) implantation. A decrease of IL-6 3 months after TIPS implantation is a protective factor for acute-on-chronic liver failure and liver-related death. Thus, our results suggest that TIPS reduces systemic inflammation in a clinically meaningful way.

To evaluate how well liver fibrosis markers (fibrosis-4 index, aspartate aminotransferase to platelet ratio index, and model for end-stage liver disease excluding international normalized ratio score) can predict early detection of Fontan-associated liver disease and to identify risk factors for Fontan-associated liver disease development.

This retrospective multicentre study included patients who underwent the Fontan procedure between 2004 and 2020 with at least 3 years of follow-up. Blood tests and imaging were conducted to diagnose Fontan-associated liver disease. The predictive value of these markers was assessed using receiver operating characteristic curve analysis. Risk factors for Fontan-associated liver disease development were identified using Fine-Gray subdistribution hazard analysis.

This study included 137 patients. The fibrosis-4 index, measured at 2 years post-Fontan, was a strong predictor for Fontan-associated liver disease development 10 years later (area under the curve: 0.81, optimal cutoff value: 0.17, 83.1% sensitivity, and 73.0% specificity). Fine-Gray subdistribution hazard analysis shows that a fibrosis-4 index level was a key risk factor for Fontan-associated liver disease. Patients with a fibrosis-4 index >0.17 after 2 years had a higher incidence of Fontan-associated liver disease after 10 years (45.6%) than patients with fibrosis-4 index ≤0.17 (3.9%, P = 0.002). These patients also had higher pulmonary artery pressure 5 years later.

The fibrosis-4 may be a useful marker for early detection of Fontan-associated liver disease, which, in this study, was identified as a risk factor for the disease's development.

Kitasato University, No. B23-130; 7 February 2024.

The prevalence and incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) are significantly increasing globally, but the index of non-invasive disease is limited. Platelet-albumin ratio(PAR) is a non-invasive biomarker of inflammation, the aim of this study was to evaluate the relationship between PAR and MASLD. This population-based cross-sectional retrospective study analyzed data extracted from the National Health and Nutrition Survey (NHANES) database from 2017 to 2018. Multivariate logistic regression analysis was used to evaluate the correlation between PAR and MASLD in different models. Model I was unadjusted, model II adjusted for race, sex and age, and model III was adjusted based on model II plus smoking status, hypertension, and diabetes. Further subgroup analysis was carried out according to sex, age, hypertension and diabetes status. The study involved 3287 participants, of whom 873 (26.5%) were diagnosed with MASLD. The PAR level in MASLD group was significantly higher than non-MASLD group (P < 0.05). Multivariate logistic regression revealed that high PAR level was an independent risk factor for MASLD (OR = 2.58, 95%CI: 1.26-5.27, P = 0.03), which adjusted for sex, age, race, smoking status, hypertension, and diabetes.The same results were observed in multiple subgroups of further subgroup analysis, and it can effectively predict the risk of MASLD (AUC = 0.842, 95% CI: 0.826-0.859). In conclusion, the new biomarker PAR shows a positive correlation with the risk of MASLD in the population, and can be used as a biomarker of MASLD to help clinicians identify people at high risk of MASLD.