To compare the long-term clinical efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created with Fluency versus Viatorr stent-grafts for the treatment of refractory ascites in patients with cirrhosis.

A retrospective analysis was conducted on 118 cirrhotic patients with refractory ascites undergoing TIPS with Fluency stent-grafts (Fluency group, n=83) or Viatorr stent-grafts (Viatorr group, n=35) at two centers from January 2017 to December 2021. Competing risk analysis was used to compare the incidence of clinical outcomes between groups after adjusting for confounders.

During a median of 30.9 months follow-up, 31 patients (26.3%) developed portal hypertension complications (11 cases of recurrent ascites, 16 cases of variceal bleeding, and four cases of both ascites and variceal bleeding), 15 patients (12.7%) developed shunt dysfunction, 58 patients (49.15%) developed overt hepatic encephalopathy (OHE), and 74 patients (62.7%) died. After adjusting for confounding factors, the Viatorr stent was associated with a reduced OHE risk (38% vs 54% at 5 years, p=0.004) but a comparable incidence of portal hypertension complications (27% vs 27%, p=0.536), shunt dysfunction (14% vs 12%, p=0.401), and mortality (41% vs 37%; p=0.064) compared to the Fluency stents. These findings were consistent across most relevant subgroups.

In cirrhotic patients with refractory ascites undergoing TIPS, Viatorr stent-grafts were associated with lower risk of OHE while no significant differences in clinical efficacy compared to the Fluency stent-grafts.

Hepatorenal Syndrome is a potentially reversible syndrome of endstage cirrhosis. It is a severe complication of cirrhosis that involves a high mortality rate and a significant economic impact on the healthcare system. This study shows the costs of the resources used for disease management and complications to be Int$14,189. Quantifying this figure contributes to an understanding of the economic impact of Hepatorenal Syndrome on patient survival.

The purpose of this study was to describe the direct medical costs incurred in Brazil for the treatment of Hepatorenal Syndrome in intensive care and intermediate therapy care units, and to investigate the impact of this syndrome on patient survival.

This longitudinal observational retrospective study included patients with Hepatorenal Syndrome admitted to the intensive and intermediate therapy care units of a public tertiary hospital. The cost generated by each patient was the sum of the direct costs and overheads.

Forty-four patients with 49 episodes of suspected Hepatorenal Syndrome were analyzed, 73% male, with a mean age of 55 years (SD= 11). Diagnosis was presumed in 21 episodes (43%), because not all of the Ascites International Club's criteria were met. Alcoholic cirrhosis was the main etiology (43%); 59% of the patients were Child-Pugh Class C at admission, with a mean (SD) model for end-stage liver disease score of 24.6 (8). Seventy-seven percent of the patients died, 32% from multiple organ failure, 29% of septic shock and 27% of hypovolemic shock. The median (IQR) of the total treatment cost for each patient was Int$14,819 (8,732-23,854). The median (IQR) length of intensive care unit stay in intensive care was 11 days (7-19). Patients with a presumed diagnosis did not have a higher hospitalization cost (p=0.249) than those with true Hepatorenal Syndrome.

The treatment of Hepatorenal Syndrome represents a significant cost, and new resource allocation in strategic areas, such as the treatment and monitoring of patients with cirrhosis, is necessary to improve their outcomes.

■ The treatment of Hepatorenal Syndrome places a huge economic burden on healthcare systems.

■ Cost analysis studies of Hepatorenal Syndrome management can help to rationally allocate resources in healthcare.

■ Timely diagnosis and management of Hepatorenal Syndrome may reduce mortality, resource utilization and costs.

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.

Adult stem cell therapy holds great promise for treating decompensated liver cirrhosis on the basis of animal studies, despite uncertainty about its clinical therapeutic efficacy and unclear underlying mechanisms. Here, we investigated the role of follistatin-like 1 (FSTL1), a profibrotic and proinflammatory matricellular protein, in inflammation-related heterogeneity in stem cell therapy. Our results showed that a high level of circulating FSTL1 is significantly correlated with therapeutic response in patients with cirrhosis. FSTL1 facilitated MSC-mediated early recruitment of Ly6C+ inflammatory macrophages within 24 h postinfusion, which was essential for the empowerment of MSCs and subsequent Ly6C-CX3CR1+ macrophage remodelling at 48 h postinfusion. Fstl1 deficiency abrogated early macrophage recruitment and effective Ly6C-CX3CR1+ macrophage accumulation, resulting in the poor antifibrotic effect of MSCs in mice. Whereas, recombinant FSTL1 protein restored the therapeutic efficacy of MSCs in CCl4-injured Fstl1+/- mice. Mechanistically, host FSTL1 enhanced rapid recycling of CCR2 to the membrane via activation of the CD14/TLR4/NF-κB/ATP6V1G2 axis, leading to early recruitment of Ly6C+ monocytes /macrophages. Taken together, our findings revealed that FSTL1 is a critical regulator of the fibrotic immune microenvironment and facilitates subsequent stem cell therapy. These data suggest that FSTL1 could serve as a predictive biomarker of stem cell therapy response in patients with liver cirrhosis.

The heterogenous presentation patterns in decompensated cirrhosis confer variable outcomes. While acute decompensation (AD) is well-characterized, the presentation patterns and outcomes of non-acute decompensation (NAD) remain unclear. The aim of this study was to characterize clinical and pathophysiological features of NAD and identify predictors of progression in NAD.

In this prospective study, patients across the cirrhosis spectrum were enrolled from two centers in India between 2020-2023: compensated cirrhosis (CC; n = 29), NAD (n = 311), AD (n = 201), and healthy controls (n = 10). Clinical and laboratory parameters, cytokine levels (IL-6, TNF, IL-10, MCP-1) and cell death markers (M30, M65, Gasdermin-D, RIPK3, MLKL) were assessed at baseline. Twelve-month overall survival was assessed in all patients. The predictors of progression to AD and mortality were evaluated in patients with NAD.

Survival was lower in patients with NAD (81.7%) than in those with CC (100%), but higher than in those with AD (31.2%) (p <0.001). Despite no significant systemic inflammation, patients with NAD exhibited elevated levels of cell death markers, particularly Gasdermin-D and RIPK3, compared to healthy controls and patients with CC. Both inflammatory and cell death markers were most pronounced in AD. Over 12 months, the cumulative incidence of progression to AD among those with NAD was 55.1%, significantly reducing their survival (68.2% vs. 95.3%, p <0.001). Predictors of such progression to AD included severe ascites, lower IGF-1, albumin, BMI, and higher bilirubin, Gasdermin-D, and RIPK3 levels, as well as higher CTP and MELD scores.

NAD represents a clinically, prognostically and pathophysiologically distinct entity in cirrhosis. Patients with NAD express elevated cell death markers and remain at risk of progression to AD and mortality. Identifying such high-risk patients should prompt interventions to prevent progression. Modulation of cell death is a potentially disease-modifying target in cirrhosis.

This study highlights non-acute decompensation as a clinically, prognostically and pathophysiologically distinct subset of cirrhosis, underscoring the importance of understanding its progression dynamics. Identifying key predictors of acute decompensation, including ascites severity, low IGF-1 levels, and elevated cell death markers, such as Gasdermin-D and RIPK3, potentially uncovers new therapeutic avenues. These findings are crucial for helping hepatologists and researchers to risk stratify patients and optimize transplant candidacy. Interventions targeting necroptosis and pyroptosis pathways may improve outcomes, providing a significant shift towards precision medicine in cirrhosis care.

This study aimed to identify pathogenic microorganisms and resistance profiles, clinical outcomes, and mortality-related risk factors in patients with culture-confirmed peritonitis.

This single-center, retrospective study included patients aged ≥18 years who were followed up with a culture-confirmed diagnosis of peritonitis.

Of the 134 patients, 54.5% (n=73) were male, and the mean age was 57.9 ± 16.1 years. Forty-three patients (32.1%) had primary peritonitis and 91 (67.9%) had secondary peritonitis. A total of 157 pathogens were isolated from 134 cases. The most common microorganisms were Escherichia coli (19.1%, n=9/47), coagulase-negative staphylococci (CoNS) (12.7%, n=6/47), Pseudomonas spp.(12.7%, n=6/47), Enterococcus spp. (10.6%, n=5/47), and Staphylococcus aureus (10.6%, n=5/47) in primary peritonitis and E. coli (27.3%, n=30/110), Enterococcus spp. (15.4%, n=17/110), Klebsiella pneumoniae (13.6%, n=15/110), Pseudomonas spp.(10.9%, n=12/110), and Candida spp. (%10.0, n=11/110) in secondary peritonitis. Among E. coli species, extended-spectrum beta-lactamase (ESBL) rates were 33% (n=3/9) in primary peritonitis and 63% (n=19/30) in secondary peritonitis. The 30-day mortality rate was 36.5% (n=49/134). Male gender (69.4% vs. 45.9%, p=0.009) and secondary perforation (14.3% vs. 4.7%, p=0.049) were more common in deceased patients, while peritonitis associated with peritoneal dialysis (2.0% vs. 11.7%, p=0.048) and peritonitis due to CoNS (0.0% vs. 9.4%, p=0.027) were less common in deceased patients than survivors. In addition, advanced age (63.6 ± 16.6 vs. 54.7 ± 14.9, p=0.001) and high aspartate aminotransferase (AST) levels (147 ± 412 vs. 135 ± 501, p=0.010) were associated with mortality.

This study highlights the importance of demographic characteristics, clinical features, and laboratory parameters for clinical outcomes in patients with peritonitis. Patients with secondary perforation-related peritonitis require close monitoring for clinical changes. Gram-positive bacteria and sensitive enteric bacilli for primary peritonitis and ESBL-producing Gram-negative bacteria for secondary peritonitis should be included in empirical treatment selection. Additionally, we recommend considering antifungal agents for severely ill patients with secondary peritonitis.

IntroductionThis study aims to evaluate clinical outcomes among severely injured trauma patients presenting with isolated blunt abdominal solid organ injuries with a pre-diagnosis of liver cirrhosis (LC) undergoing emergency laparotomy vs nonoperative management (NOM).MethodsThis retrospective cohort study utilized the American College of Surgeons Trauma Quality Program Participant Use File (ACS-TQIP-PUF) dataset from 2017 to 2021. Adults (≥18 years) with a pre-existing diagnosis of LC who presented with severe blunt (ISS ≥ 16) isolated solid organ abdominal injuries and underwent laparotomy or NOM were included. Outcomes of interest included in-hospital mortality, intensive care unit length of stay (ICU-LOS), and in-hospital complications such as acute renal failure and deep vein thrombosis.Results929 patients were included in this analysis, with 355 undergoing laparotomy and 574 managed nonoperatively. Laparotomy patients suffered greater in-hospital mortality (n = 186, 52.3% vs n = 115, 20.0%; P < .01), required significantly more blood within 4 hours (8.9 units vs 4.3 units, P < .01), and had a significantly longer ICU-LOS (10.2 days vs 6.7 days, P < .01). In the 1:1 propensity score matched analysis of 556 matched patients, in-hospital mortality was greater for laparotomy patients (52.3% vs 20.0%, P < .01).ConclusionLaparotomy was associated with significantly higher in-hospital mortality in propensity-matched trauma patients, longer ICU-LOS, and more blood products given at 4 hours compared to NOM. These findings illustrate that NOM may be a safe approach in managing severely injured trauma patients with isolated blunt abdominal solid organ injuries and a pre-diagnosis of LC.

Hepatitis B-associated cirrhosis (HBC) is associated with severe complications and adverse clinical outcomes. This study aimed to develop and validate a predictive model for the occurrence of multiple complications (three or more) in patients with HBC and to explore the effects of multiple complications on HBC prognosis.

In this retrospective cohort study, data from 121 HBC patients treated at Nanjing Second Hospital from February 2009 to November 2019 were analysed. The maximum follow-up period was 10.75 years, with a median of 5.75 years. Eight machine learning techniques were employed to construct predictive models, including C5.0, linear discriminant analysis (LDA), least absolute shrinkage and selection operator (LASSO), k-nearest neighbour (KNN), gradient boosting decision tree (GBDT), support vector machine (SVM), generalised linear model (GLM) and naive Bayes (NB), utilising variables such as medical history, demographics, clinical signs, and laboratory test results. Model performance was evaluated via receiver operating characteristic (ROC) curve analysis, residual analysis, calibration curve analysis, and decision curve analysis (DCA). The influence of multiple complications on HBC survival time was assessed via Kaplan‒Meier curve analysis. Furthermore, LASSO and univariable and multivariable Cox regression analyses were conducted to identify independent prognostic factors for overall survival (OS) in patients with HBC, followed by ROC, C-index, calibration curve, and DCA curve analyses of the constructed prognostic nomogram model. This study utilized bootstrap resampling for internal validation and employed the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for external validation.

The GBDT model exhibited the highest area under the curve (AUC) and emerged as the optimal model for predicting the occurrence of multiple complications. The key predictive factors included posthospitalisation fever (PHF), body mass index (BMI), retinol binding protein (RBP), total bilirubin (TB) levels, and eosinophils (EOS). Kaplan-Meier analysis revealed that patients with multiple complications had significantly worse OS than those with fewer complications. Additionally, multivariable Cox regression analysis, informed by least absolute shrinkage and LASSO selection, identified hepatocellular carcinoma (HCC), multiple complications, and lactate dehydrogenase (LDH) levels as independent prognostic factors for OS. The prognostic model demonstrated 1-year, 3-year, and 5-year OS ROC AUCs of 0.802, 0.793, and 0.817, respectively. For the internal validation cohort, the corresponding AUC values were 0.797, 0.832, and 0.835. In contrast, the external validation cohort yielded a 1-year ROC AUC of 0.707. Calibration curves indicated good consistency of the model, and DCA demonstrated the model's clinical utility, showing high net benefits within certain threshold ranges. Compared with the univariable models, the multivariable ROC curves indicated higher AUC values for this prognostic model, and the model also possessed the best c-index.

The GBDT prediction model provides a reliable tool for the early identification of high-risk HBC patients prone to developing multiple complications. The concurrent occurrence of multiple complications is an independent prognostic factor for OS in patients with HBC. The constructed prognostic model demonstrated remarkable predictive performance and clinical applicability, indicating its crucial role in enhancing patient outcomes through timely and targeted interventions.

The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding.

Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models.

The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHCs.

PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy.

The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS.

ClinicalTrials.gov, ID: NCT03590288.

Background: Portal hypertension is a major complication of chronic liver diseases, leading to serious issues such as esophageal variceal bleeding. The increase in portal vein pressure is driven by both an organic component and a functional component, including tonic contraction of hepatic stellate cells. These processes result in a pathological rise in intrahepatic vascular resistance, stemming from partial impairment of hepatic microcirculation, which is further exacerbated by abnormalities in extrahepatic vessels, including increased portal blood flow. Objectives: This review aims to provide a comprehensive overview of the evolving pharmacological therapies for portal hypertension, with consideration and discussion of pathophysiological mechanisms, clinical complications, and pharmacogenetic considerations, highlighting potential directions for future research. Methods: A review of recent literature was performed to evaluate current knowledge and potential therapeutic strategies in portal hypertension. Results: For over 35 years, non-selective beta-blockers have been the cornerstone therapy for portal hypertension by reducing portal vein inflow as an extrahepatic target, effectively preventing decompensation and variceal hemorrhages. However, since not all patients exhibit an adequate response to non-selective beta-blockers (NSBBs), and some may not tolerate NSBBs, alternative or adjunctive therapies that enhance the effects of NSBBs on portal pressure are being investigated in preclinical and early clinical studies. Conclusions: A better understanding of pharmacogenetic factors and pathophysiological mechanisms could lead to more individualized and effective treatments for portal hypertension. These insights highlight potential directions for future research.

Hepatorenal syndrome (HRS) is a key contributor to poor prognosis in liver cirrhosis. This study aims to leverage the database to build a predictive model for early identification of high-risk patients. From two sizable public databases, we retrieved pertinent information about the cirrhosis patients' therapies, comorbidities, laboratory results, and demographics. Patients from the eICU database served as a test set for external validation, while patients from the MIMIC database were divided into training and validation groups. Variables were screened using LASSO regression, Extreme Gradient Boosting (XG Boost), and Random Forest (RF). Core risk factors were determined from the intersection of the three methods. A predictive model was constructed using multivariable logistic regression and visualized via a nomogram. Model performance was assessed using ROC curves, decision curve analysis (DCA), clinical impact curves (CIC), and calibration curves. Eight critical variables associated with HRS were identified using machine learning methods. The final predictive model, based on five key variables-spontaneous bacterial peritonitis, red blood cell count, creatinine, activated partial thromboplastin time, and total bilirubin-showed excellent discrimination, with AUCs of 0.832 (95% CI 0.8069-0.8563) in the training set and 0.8415 (95% CI 0.8042-0.8789) in the validation set. The AUC in the external test set was 0.8212 (95% CI 0.7784-0.864). By integrating the MIMIC-IV database and machine learning algorithms, we developed an effective predictive model for HRS in liver cirrhosis patients, providing a robust tool for early clinical intervention.

To evaluate the potential of interpretable machine learning (ML) models to predict ascites improvement in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites.

In this retrospective study, 218 patients with refractory ascites who underwent TIPS placement were analyzed. Data on 29 demographic, clinical, and procedural features were collected. Ascites improvement was defined as reduction in the need of paracentesis by 50% or more at the 1-month follow-up. Univariate statistical analysis was performed. Data were split into train and test sets. Feature selection was performed using a wrapper-based sequential feature selection algorithm. Two ML models were built using support vector machine (SVM) and CatBoost algorithms. Shapley additive explanations values were calculated to assess interpretability of ML models. Performance metrics were calculated using the test set.

Refractory ascites improved in 168 (77%) patients. Higher sodium (Na; 136 mEq/L vs 134 mEq/L; P = .001) and albumin (2.91 g/dL vs 2.68 g/dL; P = .03) levels, lower creatinine levels (1.01 mg/dL vs 1.17 mg/dL; P = .04), and lower Model for End-stage Liver Disease (MELD) (13 vs 15; P = .01) and MELD-Na (15 vs 17.5, P = .002) scores were associated with significant improvement, whereas main portal vein puncture was associated with a lower improvement rate (P = .02). SVM and CatBoost models had accuracy ratios of 83% and 87%, with area under the curve values of 0.83 and 0.87, respectively. No statistically significant difference was found between performances of the models in DeLong test (P = .3).

ML models may have potential in patient selection for TIPS placement by predicting the improvement in refractory ascites.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.

Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital, but adherence is suboptimal with unclear impact on clinical outcomes. The aim of this meta-analysis was to assess the outcomes of early vs delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites.

We searched multiple databases for studies comparing early vs delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites. The pooled odds ratio (OR) and mean difference with confidence intervals (CIs) for proportional and continuous variables were calculated using the random-effects model. Early diagnostic paracentesis was defined as receiving diagnostic paracentesis within 12-24 hours of admission. The primary outcome was in-hospital mortality. Secondary outcomes were length of hospital stay, acute kidney injury, and 30-day readmission.

Seven studies (n = 78,744) (n = 45,533 early vs n = 33,211 delayed diagnostic paracentesis) were included. Early diagnostic paracentesis was associated with lower in-hospital mortality (OR 0.61, 95% CI 0.46-0.82, P = 0.001), length of hospital stay (mean difference -4.85 days; 95% CI -6.45 to -3.20; P < 0.001), and acute kidney injury (OR 0.62, 95% CI 0.42-0.92, P = 0.02) compared with delayed diagnostic paracentesis, with similar 30-day readmission (OR 1.11, 95% CI 0.52-2.39, P = 0.79). Subgroup analysis revealed consistent results for in-hospital mortality whether early diagnostic paracentesis performed within 12 hours (OR 0.51, 95% CI 0.32-0.79, P = 0.003, I2 = 0%) or within 24 hours of admission (OR 0.67, 95% CI 0.45-0.98, P = 0.04, I2 = 82%). Notably, the mortality OR was numerically lower when diagnostic paracentesis was performed within 12 hours, and the results were precise and homogenous ( I2 = 0%).

Findings from this meta-analysis suggest that early diagnostic paracentesis is associated with better patient outcomes. Early diagnostic paracentesis within 12 hours of admission may be associated with the greatest mortality benefit. Data from large-scale randomized trials are needed to validate our findings, especially if there is a greater mortality benefit for early diagnostic paracentesis within 12 hours.

Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians.

We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the use versus no use of albumin.

A total of 1248 respondents participated, with a mean response rate of 37%, ranging from 18% to 75% across 21 countries. Respondents mainly worked in mixed ICUs and 92% were specialists in intensive care medicine. The reported use of albumin in general shock varied as 18% reported 'almost never', 22% 'rarely', 34% 'occasionally', 22% 'frequently' and 4% 'almost always' using albumin. In septic shock, 19% reported 'almost never', 22% 'rarely', 29% 'occasionally', 22% 'frequently' and 7% 'almost always' using albumin. Physicians' preferences were more consistent for haemorrhagic- and cardiogenic shock, with more than 45% reporting 'almost never' using albumin. While the reported use of albumin for other purposes than resuscitation was infrequent (40%-85% reported 'almost never' for five other indications), the most frequent other indications were low serum albumin levels and improvement of the efficacy of diuretics. Most respondents (93%) would randomise adult ICU patients with shock to a trial of albumin versus no albumin.

In this international survey, the reported preferences for the use of albumin in adult ICU patients with shock varied considerably among surveyed ICU physicians. The support for a future randomised trial was high.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p <0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p =0.12; D90: 78% vs. 68%, p =0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p <0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

Myokines are the muscle-derived hormones orchestrating muscle and systemic health. Their role in the progression of alcohol-associated liver disease (ALD) remains elusive.

Three-hundred-one patients across the spectrum of ALD including fatty liver (FL, N = 13), compensated cirrhosis (CC, N = 17), non-acute decompensation (NAD, N = 95), acute decompensation (AD, N = 51) and acute-on-chronic liver failure (ACLF, N = 125) were recruited between 2021 and 2023. Plasma myostatin, decorin levels, nutritional status, handgrip strength (HGS), systemic inflammation, infection, ammonia, disease course and 30-day mortality were recorded.

Patients aged 48 years (IQR: 38-52) and 97.7% of males were enrolled. Myostatin was elevated while decorin was reduced in cirrhosis compared to without cirrhosis, and further in DC compared to CC (p < 0.001). A step-wise increase in myostatin and reduction in decorin was observed transitioning from NAD to AD to ACLF (p < 0.001). Myostatin was further increased and decorin was reduced along with the grades and organ failures in AD and ACLF (p < 0.001, each). Baseline decorin (AUC: 0.797) and its combination with MELD (AUC: 0.814) predicted disease resolution in AD and ACLF. Although, both myostatin (aOR: 18.96) and decorin (aOR: 0.02) could predict mortality, decorin was independent (aOR: 0.04) and additive to MELD (AUC of MELD+logDecorin + logTLC + HE-grade:0.815); p < 0.05 each. Myostatin increased and decorin reduced with inflammation, hyperammonaemia, malnutrition and HGS in AD and ACLF (p < 0.05, each).

Myokines are linked with malnutrition, fibrosis, systemic inflammation, organ failures, disease course and mortality in ALD. Decorin enhances the risk estimation of mortality of MELD in AD and ACLF. Therapeutic modulation of myokines is a potentially disease-modifying target in ALD.

For cirrhotic refractory ascites, diuretics combined with albumin and vasoactive drugs are the first-line choice for ascites management. However, their therapeutic effects are limited, and most refractory ascites do not respond to medication treatment, necessitating consideration of drainage or surgical interventions. Consequently, numerous drainage methods for cirrhotic ascites have emerged, including large-volume paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, automated low-flow ascites pump, cell-free and concentrated ascites reinfusion therapy, and peritoneal catheter drainage. This review introduces the advantages and disadvantages of these methods in different aspects, as well as indications and contraindications for this disease.

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.

Hereditary haemorrhagic telangiectasia is a genetic condition of abnormal blood vessel formation resulting from an imbalance of pro- and anti-angiogenic products of the transforming growth factor β/bone morphogenetic protein signalling pathway which contributes to vascular remodelling and maintenance. Hepatic vascular malformations are common although less frequently symptomatic, but may result in high-output cardiac failure, portal hypertension and biliary ischaemia. Whilst the understanding of the genetic and cell signalling pathways that are the hallmark of hereditary haemorrhagic telangiectasia have been clarified, there remain challenges in therapy for these patients. Only patients with symptomatic hepatic vascular malformations require treatment, with most (63%) responding to first-line medical therapy. For non-responders, bevacizumab is effective in reducing cardiac output in those with heart failure secondary to hepatic vascular malformations as well as other manifestations of the disease. Although liver transplantation is the only curative option, optimal timing is critical. Novel anti-angiogenetic drugs and those that target aberrant cell signalling pathway are being explored.

Nosocomial infections (NIs) frequently occur and adversely impact prognosis for hospitalized patients with cirrhosis. This study aims to develop and validate two machine learning models for NIs and in-hospital mortality risk prediction.

The Prediction of Nosocomial Infection and Prognosis in Cirrhotic patients (PIPC) study included hospitalized patients with cirrhosis at the Qingchun Campus of the First Affiliated Hospital of Zhejiang University. We then assessed several machine learning algorithms to construct predictive models for NIs and prognosis. We validated the best-performing models with bootstrapping techniques and an external validation dataset. The accuracy of the predictions was evaluated through sensitivity, specificity, predictive values, and likelihood ratios, while predictive robustness was examined through subgroup analyses and comparisons between models.

We enrolled 1,297 patients into derivation cohort and 496 patients into external validation cohort. Among the six algorithms assessed, the Random Forest algorithm performed best. For NIs, the PIPC-NI model achieved an area under the curve (AUC) of 0.784 (95% confidence interval [CI] 0.741-0.826), a sensitivity of 0.712, and a specificity of 0.702. For in-hospital mortality, the PIPC- mortality model achieved an AUC of 0.793 (95% CI 0.749-0.836), a sensitivity of 0.769, and a specificity of 0.701. Moreover, our PIPC models demonstrated superior predictive performance compared to the existing MELD, MELD-Na, and Child-Pugh scores.

The PIPC models showed good predictive power and may facilitate healthcare providers in easily assessing the risk of NIs and prognosis among hospitalized patients with cirrhosis.

Decompensated-cirrhosis encompasses several stages with different prognosis, such as bleeding, ascites and bleeding-plus-ascites. Development of further-decompensation worsens survival, while non-selective β-blockers (NSBBs) can modify the risk. However, how this applies to each stage is uncertain. We aimed to investigate, in each stage of decompensated-cirrhosis, the influence of further-decompensation on mortality and whether changes in portal-pressure (HVPG) under NSBBs influence these outcomes.

Patients with variceal bleeding were consecutively included differentiating those with bleeding-alone from those who also had ascites. Patients with ascites and high-risk varices referred for primary-prophylaxis were also investigated. A baseline haemodynamic study was performed and was repeated after 1-3-months under NSBBs. Outcomes were investigated by competing-risk.

Totally 103 patients had bleeding-alone, 186 bleeding-plus-ascites and 187 ascites-alone. Mean follow-up was 32-months (IQR, 12-60). Patients with bleeding-plus-ascites had higher HVPG and were more hyperdynamic than patients with ascites-alone and these than those with bleeding-alone. At each stage, the mortality risk was more than twice in patients developing further-decompensation vs. those without (p < .001). In each stage, HVPG-decrease under NSBBs showed better discrimination to predict further-decompensation than the baseline MELD, Child-Pugh or HVPG, by time-dependent ROC-curves (c-statistic >70%). At each stage, patients without HVPG-decreases, either ≥10% or ≥20% from the baseline, had higher risk of further-decompensation (sHR from 2.43 to 6.73, p < .01) and worse survival.

In each stage of decompensated cirrhosis, mortality risk significantly and very markedly increase with further-decompensation. HVPG-non-response to NSBBs may adequately stratify the risk of further decompensation and death, in each stage. This suggests potential benefit with pre-emptive therapies in HVPG-non-responders at each-stage.

Patients with cirrhosis are more susceptible to coronavirus disease 2019 (COVID-19) due to immune dysfunction. In this retrospective study we aimed to investigate whether suppression of mild systemic inflammation with selective cyclooxygenase-2 inhibitor (COX-2-I) during chronic care of cirrhotic patients would reduce the occurrence of acute decompensated events and improve patient prognosis of COVID-19.

Medical records of cirrhotic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were sequentially reviewed. The patients were divided into the COX-2-I and control groups depending on whether they took oral selective COX-2-I for over 3 months or not. The primary outcomes included the occurrence of severe/critical COVID-19, acute decompensated events, and acute-on-chronic liver failure (ACLF).

After propensity score matching analysis, there were 314 cases in the control group and 118 cases in the COX-2-I group. Compared with the control group, the risk of severe/critical COVID-19 in the COX-2-I group was significantly decreased by 83.1% (p = 0.004). Acute decompensated events and ACLF occurred in 23 (7.32%) and nine (2.87%) cases in the control group, but none in the COX-2-I group (p = 0.003 and 0.122). The rate of hospitalization in the COX-2-I group was significantly lower than that of the control group (3.39% vs 13.06%, p = 0.003). No patient in the COX-2-I group required intensive care unit admission.

Long-term intermittent oral administration of selective COX-2-I in cirrhotic patients significantly reduces the occurrence of severe/critical COVID-19, acute decompensated events, and ACLF. It may also be used for systemic inflammation caused by other pathogens.

How to cite this article: Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, et al. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(S2):S104-S216.

Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy.

This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable.

The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences.

ChiCTR2300073864.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in those who respond to therapy. Arguments for the MELD lock include protecting waitlist priority for terlipressin responders or partial responders who may miss offers due to MELD reduction in the terlipressin treatment window. Arguments against MELD lock include the fact that terlipressin may produce a durable response and improve overall survival and that equitable access to terlipressin is not guaranteed due to cost and availability. We subsequently discuss the proposed next steps for studying terlipressin implementation in the United States. A successful approach will require the involvement of all major stakeholders and the mobilization of our transplant community to spearhead research in this area.

Though acute kidney injury (AKI) is a prevalent complication in critically ill patients, knowledge on the epidemiological differences and clinical characteristics of patients with AKI admitted to medical and surgical intensive care units (ICUs) remains limited.

Electronic medical records of patients in ICUs in Pusan National University Hospital and Pusan National University Hospital Yangsan, from January 2011 to December 2020, were retrospectively analyzed. Different characteristics of AKI between patients were analyzed. The contribution of AKI to the in-hospital mortality rate was assessed using a Cox proportional hazards model.

A total of 7,150 patients were included in this study. AKI was more frequent in medical (48.7%) than in surgical patients (19.7%), with the severity of AKI higher in medical patients. In surgical patients, hospital-acquired AKI was more frequent (51.0% vs. 49.0%), whereas community-acquired AKI was more common in medical patients (58.5% vs. 41.5%). 16.9% and 5.9% of medical and surgical patients died in the hospital, respectively. AKI affected patient groups to different degrees. In surgical patients, AKI patients had 4.778 folds higher risk of mortality (95% confidence interval [CI], 3.577-6.382; p < 0.001) than non-AKI patients; whereas in medical AKI patients, it was 1.239 (95% CI, 1.051-1.461; p = 0.01).

While the prevalence of AKI itself is higher in medical patients, the impact of AKI on mortality was stronger in surgical patients compared to medical patients. This suggests that more attention is needed for perioperative patients to prevent and manage AKI.

Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.

Spontaneous bacterial peritonitis is a life-threatening complication of cirrhosis that can increase healthcare utilization. The impact of albumin administration timing on hospital resource utilization and its optimal timing is unclear, despite its efficacy in improving survival for cirrhosis patients with spontaneous bacterial peritonitis. A retrospective study was conducted to evaluate the influence of the timing of albumin administration on the length of stay and total hospital cost for patients with cirrhosis and spontaneous bacterial peritonitis who require fluid resuscitation. The study utilized de-identified data from Cerner Health Facts® data. Adult inpatients with a diagnosis of cirrhosis and SBP receiving ≥1 antibiotic and fluid resuscitation between January 1, 2009, and April 30, 2018, were included and stratified by albumin administration timing: ≤24 hours from hospital admission ("timely albumin") or >24 hours of admission or no albumin ("non-timely albumin"). We used a Kaplan-Meier curve with log-rank test to evaluate the association between timing of albumin administration and time to hospital discharge and a generalized linear model to examine the association between albumin timing and total hospital costs. We identified 1,308 hospitalizations, of which 301 contained valid cost data. The timely albumin group had a median time to discharge of 6.95 days compared to 7.78 days in the non-timely group (p = 0.02). Cost model showed that receiving timely albumin incurred 16% lower costs (p = 0.027) than patients in the non-timely albumin group. Timely albumin administration with an antibiotic regimen may shorten the length of stay and lower costs, thereby reducing hospital resource utilization in patients with cirrhosis and spontaneous bacterial peritonitis requiring fluid resuscitation.