End-stage Liver Disease Research Articles

Deep Learning-Adjusted Monitoring of In-Hospital Mortality after Liver Transplantation.

Background: Surgeries represent a mainstay of medical care globally. Patterns of complications are frequently recognized late and place a considerable burden on health care systems. The aim was to develop and test the first deep learning-adjusted CUSUM program (DL-CUSUM) to predict and monitor in-hospital mortality in real time after liver transplantation. Methods: Data from 1066 individuals with 66,092 preoperatively available data point variables from 2004 to 2019 were included. DL-CUSUM is an application to predict in-hospital mortality. The area under the curve for risk adjustment with Model of End-stage Liver Disease (D-MELD), Balance of Risk (BAR) score, and deep learning (DL), as well as the ARL (average run length) and control limit (CL) for an in-control process over 5 years, were calculated. Results: D-MELD AUC was 0.618, BAR AUC was 0.648 and DL model AUC was 0.857. CL with BAR adjustment was 2.3 with an ARL of 326.31. D-MELD reached an ARL of 303.29 with a CL of 2.4. DL prediction resulted in a CL of 1.8 to reach an ARL of 332.67. Conclusions: This work introduces the first use of an automated DL-CUSUM system to monitor postoperative in-hospital mortality after liver transplantation. It allows for the real-time risk-adjusted monitoring of process quality.

Safety and Efficacy of Dapagliflozin in Recurrent Ascites: A Pilot Study.

In cirrhosis, activation of renin-angiotensin-aldosterone system leads to sodium and water retention causing ascites. Dapagliflozin, a sodium glucose linked transporter-2 inhibitor, induces natriuresis in patients with heart failure. A similar natriuretic effect may improve ascites in patients with cirrhosis. In this pilot study, we evaluated the safety and efficacy of dapagliflozin in patients with cirrhosis and recurrent ascites. Forty patients with recurrent ascites and cirrhosis were randomized to 1:1 in a double blinded fashion to receive either dapagliflozin (10mg/day) with standard medical therapy (Group A) or placebo with standard medical therapy (Group B). The primary outcome was control of ascites at 6 months. Secondary outcomes were urine output, 24-h urinary sodium, Child Turcotte Pugh (CTP), model for end-stage liver disease (MELD) scores, survival at 6 months, incidence of acute kidney injury (AKI) and infections. The 2 groups were comparable at baseline. Control of ascites at 6 months was significantly better in group A than that in Group B (p = 0.04). Change in urinary sodium was significantly higher in Group A (p < 0.001]. However, there was no difference in change in urine output, CTP or MELD scores and survival (65% vs 72.2%, p = 0.75) between the groups at 6 months. Incidence of AKI (50% vs 15%, p = 0.04) and infections (55% vs 20%, p = 0.04) were significantly higher in Group A. Significantly better control of ascites and higher natriuresis are observed with dapagliflozin. However, it does not improve disease severity scores or survival, and is associated with increased AKI and infections (NCT05014594).

Body composition and muscle composition phenotypes in patients on waitlist and shortly after liver transplant – results from a pilot study

BackgroundSarcopenia is common in end-stage liver disease and negatively impacts patients awaiting or undergoing liver transplantation (LT). Magnetic resonance imaging (MRI) may be used to measure body composition and sarcopenia. We aimed to evaluate the feasibility of MRI-based LT body composition profiling, describe waitlist body composition, and assess the natural rate of change in body composition while on the waitlist and post-LT.MethodsThis prospective pilot study recruited adults listed for LT at an urban, tertiary care facility. Eighteen participants were scanned at time of waitlisting and 15 had follow-up MRIs (waitlist and/or post-LT). An 8-min MRI was used to measure body composition (AMRA® Researcher) including thigh fat-free muscle volume (FFMV) and fat infiltration (MFI), visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissue volumes, and liver fat. A sex- and BMI invariant FFMV z-score (z-FFMV) was calculated, and muscle composition (MC) phenotypes were defined using the muscle assessment score (consisting of the FFMV z-score and sex-adjusted MFI). Rate of body composition change was calculated using mixed-effect modelling and is presented as rate per 30 days.ResultsAt time of waitlisting, 73% of the 18 participants had high MFI and 39% had the adverse MC (low FFMV z-score and high MFI) phenotype. Seven participants received an LT. Post-LT serial MRIs, at a median of 147 days apart within the first 200 days post-LT, demonstrated increased z-FFMV 0.22 SDs/(30 days) (p = 0.002), VAT 0.23 (p < 0.001), and ASAT 0.52 (p = 0.001) L/(30 days), but no change in MFI (p = 0.200) nor liver fat (p = 0.232).ConclusionMRI-based body composition profiling is feasible in LT patients and shortly after LT. This can be amended to routine clinical scans and may help in early identification of patients who may benefit from interventions to improve body composition. In addition, body composition changes significantly over time after LT.

Assessment of superior vena cava diameter and collapsibility index in liver transplantation: a prospective observational study

BackgroundSuperior Vena Cava (SVC) diameter and collapsibility index, dynamic measures of fluid responsiveness, have been successfully utilized as echocardiographic indices for fluid responsiveness in ventilated septic patients. Whether these measurements are correlated with Central Venous Pressure (CVP) measurements in liver transplant patients is unknown. We sought to assess the correlation of maximum and minimum SVC diameter and SVC collapsibility index measurements obtained intraoperatively by Transesophageal Echocardiography (TEE) with those of simultaneously recorded CVP measurements obtained through a right atrial port of a pulmonary artery catheter. The secondary aim of the study was to assess the correlation between SVC measurements and simultaneously obtained thermodilution cardiac index measurements. MethodsSingle center prospective observational trial of patients with end stage liver disease undergoing liver transplantation in an academic tertiary care center. ResultsThe minimum SVC exhibited a mild significant correlation with CVP as did the maximum SVC. The correlation between the SVC collapsibility index and CVP was not significantly different from zero. In our secondary analysis, the correlation between minimum SVC diameter and cardiac index was determined to be weak but non-zero as was the correlation between the maximum SVC diameter and cardiac index. The correlation between SVC collapsibility index and cardiac index was not different from zero. ConclusionWhile statistically significant, the weak clinical correlation of intraoperative SVC measurements obtained by TEE make them unsuitable as a replacement for central venous pressure or thermodilution cardiac index measurements in liver transplant recipients.

Liver cirrhosis is a risk-factor for Pneumocystis jirovecii associated mortality.

Pneumocystis jirovecci pneumonia (PCP) is a life threating disease in immunodeficient patients. Liver cirrhosis itself can lead to immunodefiency, however little is known if Pneumocystis jirovecci infection affects the outcome of patients with liver cirrhosis. We aimed to assess the predictors for Pneumocystis jirovecci-associated mortality in patients with Pneumocystis jirovecci infection treated at intensive care units. A total of 151 patients hospitalized between January 2013 and November 2019 with a PCR-confirmed Pneumocystis jirovecci infection were retrospectively included in this study and analysed for clinical predictors for PCJ associated mortality. The overall mortality in our patient cohort was 60%. Out of 151 patients included in the analysis, 67 (44%) patients suffered from liver cirrhosis. Patients with an advanced liver cirrhosis (Child-Pugh class C) showed the highest mortality rate of 84.7%. The presence of a liver cirrhosis was associated with a significant increased risk of mortality (OR: 4.809) ([95%-CI: 2.32-9.97]; p < 0.001). There was a significant correlation of Meld score and mortality (r = 0.612, p < 0.001). To our knowledge, this study represents the largest evaluation of Pneumocystis jirovecci infection in patients with advanced liver cirrhosis. Cirrhosis associated immune dysfunction (CAID) describes the spectrum of immunological disturbances in patients with cirrhosis, which is linked to a heightened vulnerability to bacterial infections. Our data indicate a heightened susceptibility to fungal infections. Understanding the phenotypic manifestations of CAID could lead to immune-targeted therapies aimed at reducing infection susceptibility and decreasing CAID-associated mortality in cirrhosis patients.

Kidney function after liver transplantation: the contrasting roles of inflammation and tubular repair.

Kidney injury is a significant complication in end-stage liver disease (ESLD), leading to increased morbidity and mortality. While liver transplant alone (LTA) can promote kidney recovery (KR), non-recovery associates with adverse outcomes, but the underlying pathophysiology is still unclear. We studied 10 LTA recipients with or without kidney failure (KF) and measured serum levels of OPN and TIMP-1 (previously identified predictors of KR), 92 proinflammatory proteins (Olink), and urinary cell populations. Our findings revealed elevated OPN and TIMP-1 levels in KF patients, strongly correlated with tubular epithelial cells in urine. Proteomic analysis showed distinct profiles in KF, non-KF, and healthy donors, indicating an ongoing proinflammatory signature in KF. Cytokines correlated with OPN and TIMP-1 levels. We propose that high pre-LTA OPN and TIMP-1 levels are crucial for tubular regeneration and normalize with kidney recovery. Insufficient pre-LTA OPN levels may lead to persistent kidney failure. Our present data also newly indicate that kidney failure post-LTA is an active condition, in which tubular cells are persistently shed in the urine. The strict association between systemic inflammation and tubular cell loss suggests a pathogenic link that could offer therapeutic opportunities to promote kidney recovery.

The Critical Role of Regulatory T Cells in Immune Tolerance and Rejection Following Liver Transplantation: Interactions With the Gut Microbiome.

Liver transplantation (LT) is the ultimate treatment for patients with end-stage liver disease or early hepatocellular carcinoma. In the context of LT, because of the unique immunological characteristics of human liver allograft, 5%-20% of selected LT recipients can achieve operational tolerance. Nonetheless, there remains a risk of rejection in LT patients. Maintaining immune homeostasis is thus crucial for improving clinical outcomes in these patients. In mechanism, several immune cells, including dendritic cells, Kupffer cells, myeloid-derived suppressor cells, hepatic stellate cells, regulatory B cells, and CD4+ regulatory T cells (Treg), contribute to achieving tolerance following LT. In terms of Treg, it plays a role in successfully minimizing immunosuppression or achieving tolerance post-LT while also reducing the risk of rejection. Furthermore, the gut microbiome modulates systemic immune functions along the gut-liver axis. Recent studies have explored changes in the microbiome and its metabolites under various conditions, including post-LT, acute rejection, and tolerance. Certain functional microbiomes and metabolites exhibit immunomodulatory functions, such as the augmentation of Treg, influencing immune homeostasis. Therefore, understanding the mechanisms of tolerance in LT, the role of Treg in tolerance and rejection, as well as their interactions with gut microbiome, is vital for the management of LT patients.

Prognosis of Acute HEV Infection in Patients With Liver Cirrhosis: A Retrospective Study of 628 Chinese Patients.

Acute hepatitis E virus infection is a serious global health problem, which a significant cause of morbidity and mortality. The aim of the present study was to characterise the clinical features and therapeutic response of patients with acute HEV infection and identify risk factors for poor prognosis. In a retrospective study from 01 January 2014 to 01 Januray 2022, we collected baseline data from all patients eligible for acute hepatitis E virus (HEV) infection and followed up with all patients via interviews and medical records. We explored the clinical feature of Chinese patients with acute HEV infection. The follow-up data of patients were used to identify risk factors for poor prognosis. In total, 628 acute hepatitis E (AHE) patients fulfilled the inclusion criteria and did not meet the exclusion criteria. Among them, 452 were males and 176 were females (M:F = 2.57:1). The median age at diagnosis was 57.0 years (interquartile range: 46-64 years). The median baseline serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were elevated in this cohort (642.3 U/L, 216.2 U/L, 104.1 μmol/L, respectively). The median hospitalisation duration was 16 days. Compared with patients without other liver diseases, patients with liver cirrhosis show lower baseline ALT and AST level, poorer coagulation indices and higher MELD scores. According to multivariate analysis, liver cirrhosis, high MELD score, low albumin concentration was found to be independent predictors of poor prognosis in patients with AHE. Our study used a lager sample size to validate that some demographic and serological features were quite different between patients with/without CLDs. Liver cirrhosis was a significant independent predictor of poor prognosis in acute HEV hepatitis.

Ultra-Small Copper-Based Multienzyme-Like Nanoparticles Protect Against Hepatic Ischemia-Reperfusion Injury Through Scavenging Reactive Oxygen Species in Mice.

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

Clinical Significance of Grade A Small-for-size Syndrome After Living Donor Liver Transplantation Utilizing the New Definition of Diagnostic Criteria: An International Multicenter Study.

New diagnostic criteria have recently been established to classify small-for-size syndrome (SFSS) after living donor liver transplantation into 3 groups based on severity. This study aimed to evaluate the clinical impact of grade A SFSS and identify the mortality risk. We collected data from 406 patients diagnosed with grade A SFSS after living donor liver transplantation. Grade A SFSS is characterized by total bilirubin >5 mg/dL on postoperative day (POD) 7 or total bilirubin >5 mg/dL or ascites >1 L/d on POD 14. After propensity score matching, 193 patients were categorized into the up-trend group, down-trend group, and ascites group, with 43 patients (22.3%) in the up-trend group (total bilirubin on POD 7 < POD 14), 107 patients (55.4%) in the down-trend group (total bilirubin on POD 7 > POD 14), and 43 patients (22.3%) in the ascites group (only satisfying ascites criteria). There was no significant difference in survival between patients with grade A SFSS and those without SFSS (P = 0.152). The up-trend group showed a higher 90-d mortality rate than the down-trend and ascites groups (P = 0.025). The 1-y survival rate differed significantly between the groups (87.6%, 91.9%, and 97.7%, respectively; P = 0.044). The independent risk factors for survival were up-trend of total bilirubin, recipient age (65 y and older), model for end-stage liver disease score (≥30), and ABO incompatibility. Patients with ≥2 risk factors had worse survival rates than those with none and only 1 risk factor (P < 0.001). Although the survival rate was comparable between the grade A SFSS and non-SFSS cohorts, the up-trend group showed worse survival. Aggressive interventions should be considered for up-trend patients with risk factors.

Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’

ObjectivesBeta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk...

Comparison of T1 Mapping on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging With Conventional Functional Liver Reserve Indices and Technetium-99m Galactosyl Serum Albumin Scintigraphy.

Background Gadoxetic acid (EOB)-enhanced magnetic resonance imaging (MRI) (EOB-MRI) can be used as a one-stop examination for detecting liver tumors and evaluating liver function. Purpose The study aimed to assess the functional liver reserve (FLR) using the T1 map from the hepatobiliary phase of EOB-MRI by conducting a comparison with the results of conventional FLR tests and the technetium-99m (99mTc)-galactosyl serum albumin (GSA) scintigraphy. Materials and methods The retrospective data from 43 patients were included in the study. The regions of interest covered the entire liver. The data acquired from each EOB-MRI slice were summed to derive voxel-by-voxel values. The average sum of the T1 values (pre- and post-enhancement), ∆T1, and ∆T1 ratios were calculated. The HH15, LHL15, and LU15 values were calculated from the GSA scintigraphy. The results of conventional FLR tests, such as the indocyanine green retention rate at 15 min (ICGR15), the Child-Pugh classification (CPC), and the albumin-bilirubin (ALBI) and albumin-indocyanine green evaluation (ALICE) scores, were obtained. Results The T1 pre- and post-sum values showed a weak correlation with the LHL15 (r=0.36 and 0.38, respectively). A strong correlation was observed between the liver volume and the T1 pre- and post-sum values (r=0.86 and 0.76, respectively). A moderate correlation was observed between the T1 mean and the ALBI and ALICE values (r=0.58 and 0.49, respectively) and between the ∆T1 ratio and the CPC, ALBI, and ALICE values (r=-0.40, 0.58, and -0.55, respectively). The T1 post-sum values showed a moderate correlation with the ALBI scores (r=0.47) and a weak correlation with the ALICE scores (r=0.38). Furthermore, the LU15 values showed a weak correlation with the ICGR15 and model for end-stage liver disease (MELD) scores (r=-0.32 and -0.34, respectively). Conclusions Representative indices, such as the T1 mean and ∆T1 ratio, demonstrated a better relationship with conventional FLR indices compared with volumetric radiological indices. Therefore, we propose that the T1 post-sum can be used as an FLR index.

Liver Dysfunction and Systemic Inflammation Drive Organ Failures in Acute Decompensation of Cirrhosis: A Multicentric Study.

Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF. In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation. Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm 3 ), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression ( P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression ( P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores ( P < 0.05). Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF.

Soluble TREM2 reflects liver fibrosis status and predicts postoperative liver dysfunction after liver surgery

Background & AimsChronic liver disease (CLD) represents a major risk for mortality and, while challenging, early detection is key to improve overall outcome. Triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophages and systemic levels of soluble TREM2 (sTREM2) appear critical in the development of CLD and seem relevant in its detection. The aim of this study was to examine sTREM2 as a marker for early CLD and its potential to predict posthepatectomy liver failure (PHLF) in patients undergoing partial hepatectomy. MethodsSTREM2 was assessed in plasma of 108 patients undergoing liver resection. Blood was drawn prior to surgery (preop) and on the first and fifth postoperative day. ResultsPreop sTREM2 levels were similar across different indications for resection (p=0.091). Higher preop sTREM2 levels were associated with advanced hepatic fibrosis (p=0.030) and PHLF (p=0.007). Fibrosis-4 index (FIB-4) (p=0.619) and Model for End Stage Liver Disease (MELD) (p=0.590) did not show a difference between patients grouped by their CLD. Comparing the area under the curve from receiver operating characteristic analysis, sTREM2 (AUC=0.708) outperformed FIB-4 (AUC=0.529), MELD (AUC=0.587), Child-Pugh grading (AUC=0.570) and liver maximum capacity test (LiMAx) (AUC=0.516) in predicting PHLF. Similarly, in uni- and multivariate analysis only sTREM2 proved predictive for PHLF (p=0.023). A high- (p=0.003) and low-risk cutoff (p=0.011) for systemic sTREM2 levels were able to identify patients at risk for adverse outcome after surgery. Finally, high sTREM2 was associated with decreased overall survival after liver surgery (p<0.001). ConclusionsCirculating sTREM2 shows sensitivity for early-stage, asymptomatic liver disease, irrespective of the underlying indication for liver surgery. Assessment of CLD via sTREM2 monitoring could improve early detection of CLD and improve outcome after liver surgery. Impact and ImplicationsSoluble TREM2 (sTREM2) has previously been established to correlate with the degree of chronic liver disease. We found that even in patients undergoing liver resection, who generally do not suffer from end stage liver disease, sTREM2 reflects liver fibrosis status and predicts postoperative development of liver dysfunction. This is especially relevant for liver surgeons and patients, as postoperative liver dysfunction is the main reason for postoperative mortality. Our findings are also important for hepatologists, as early detection of liver fiboris and cirrhosis is paramount for overall patient survival and we can show that even in a cohort with a median MELD of 6, sTREM2 is able to distuinguish patients based on their liver fibrosis status.

The LIVERAID (LIVER And Infectious Diseases)-ICU score predicts in-hospital mortality in liver cirrhosis patients with infections in the intensive care unit

ObjectivesThe admission of patients with liver cirrhosis to the intensive care unit (ICU) due to infections is a frequent occurrence, often leading to complications such as hepatic encephalopathy, renal failure...

Serum microRNA-181a Expression Level in Patients with Acute Liver Failure and Its Correlation with Prognosis.

This paper examined miR-181a expression in the serum of patients with acute liver failure (ALF) and investigated the impact of its expression in the prognosis of ALF patients. A total of 112 ALF patients (ALF group) and 100healthy controls during the same period (control group) were recruited as study subjects, and ALF patients were separated into the survival group and the death group. Serum ALT, AST, SCr, TBil, PTA, and International Normalized Ratio (INR) indices as well as serum miR-181a expression were assessed by using a fully automated biochemistry analyzer and RT-qPCR. Patients in the ALF group were evaluated using the Model for End-Stage Liver Disease (MELD) score. Correlation between serum miR-181a expression and MELD scores of ALF patients was processed by Pearson correlation analysis, and the diagnostic value of miR-181a level for the occurrence of ALF was estimated by ROC curve analysis. Multivariate logistic regression analysis was executed to assess the factors influencing the occurrence of death in ALF patients. ALF patients had higher levels of ALT, AST, TBiL, SCr, INR and miR-181a and lower PTA levels in comparison to healthy controls. Serum miR-181a expression level in ALF patients revealed a significant positive correlation with MELD score. Multivariate logistic regression analysis unveiled that TBil, INR, SCr, and miR-181a were the independent risk factors for the occurrence of death in ALF patients, and that PTA was an independent protective factor for the prognosis of ALF patients. miR-181a exhibited a favorable diagnostic value in ALF and its prognosis. miR-181a expression is upregulated in the serum of ALF patients, and it can be utilized as an indicator for ALF diagnostic and prognostic assessment.

Improving Clinical Decisions in IR: Interpretable Machine Learning Models for Predicting Ascites Improvement after Transjugular Intrahepatic Portosystemic Shunt Procedures

PurposeTo 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. Materials and MethodsIn 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. ResultsRefractory 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). ConclusionsAccording to this study, ML models may have potential in patient selection for TIPS placement by predicting the improvement in refractory ascites.

Clinical significance of surgical resection for hepatocellular carcinoma with portal vein invasion: a nationwide cohort study.

Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) is considered an advanced stage with a poor prognosis. Although current guidelines recommend systemic treatment for HCC with PVI, surgical resection could produce acceptable outcomes in selected patients. This study aimed to identify the clinical significance of surgical resection for HCC with PVI patients using a large-scale nationwide registry. This retrospective, multicenter, observational cohort analyzed data from the Korean Primary Liver Cancer Registry. A total of 16,781 patients who were newly diagnosed with HCC between 2008 and 2018 were enrolled in this study. Patients with worse Child-Turcotte-Pugh scores (≥7) or performance status (≥2) were excluded. Among them, 998 patients who received treatment for HCC with PVI were included in the analysis and were divided into two groups: resection group of 151 (15.1%) and palliative group of 847 (84.9%) who received transarterial and systemic therapy according to the treatment intent. After matching the number and size of the tumors and model for end-stage liver disease (MELD) score between the groups, the final study cohort for analysis comprised 151 (26.6%) patients in the resection group and 417 (73.4%) in the palliative group. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The number and maximum size of HCC did not differ between the resection and palliative groups after matching [1 (range, 1-5) vs. 1 (range, 1-6), P=0.11 and 5.5 (range, 1.2-20.6) vs. 6.0 (range, 1.0-20.5) cm, P=0.24, respectively]. Tumor markers, including alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), also did not differ between the groups (P=0.29 and P=0.36, respectively). The 5-year OS and CSS rates of the resection and palliative groups were 44.8% and 17.4% (P<0.001) and 47.7% and 18.6% (P<0.001), respectively. Multivariate analysis showed that palliative treatment intent was the most significant risk factor for OS and CSS [odds ratio (OR) =2.24; 95% confidence interval (CI): 1.66-3.02; P<0.001 and OR =2.29; 95% CI: 1.68-3.12; P<0.001, respectively]. Surgical resection could significantly improve OS and CSS in selected HCC with PVI patients who have preserved liver function and performance status.

Long-Term Outcomes of Patients with Liver Cirrhosis After Eradication of Chronic Hepatitis C with Direct-Acting Antiviral Drugs (DAAs).

This research was designed to determine the long-term outcomes in patients with liver cirrhosis who achieved sustained virological response (SVR) after direct-acting anti-viral drugs (DAAs) based regimens. This study involved 193 patients with HCV-related cirrhosis who had previously completed DAAs regimens and accomplished SVR. Clinical, laboratory, and radiological features at the first and 3rd-year follow-up after the end of treatment were analyzed. Overall survival (OS) and incidence of liver decompensation or hepatocellular carcinoma (HCC) were determined at the 5-year follow-up. About 68.4% of our patients with HCV-related cirrhosis were males and their mean age was 54.8 ± 7.7 years. Follow-up at the first and the 3rd-year showed significant improvements in albumin (P = 0.001), liver enzymes (P = 0.001), alpha-fetoprotein (AFP) (P < 0.001), platelet count (P = 0.001), the model for end-stage liver disease (MELD) score (P = 0.001 and 0.01), FIB4 and Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores (p < 0.001). The liver stiffness (LS) also significantly improved (p = 0.001). At the 5th year, the mean OS was 58.3 months, with 14.5% and 17.6% of patients developing de-novo HCC and decompensation, respectively. The mean OS at the 5th-year follow-up was shorter in patients who developed HCC and those with liver decompensation (p = 0.001). Alfa-fetoprotein and LS are predictive factors for HCC development. Despite achieving SVR, continuous surveillance for HCC and new-onset decompensation is mandatory in patients with liver cirrhosis.

Comparison of lactate/albumin ratio and established scoring systems for predicting mortality in critically ill cirrhotic patients.

critically ill cirrhotic patients may present a serious clinical condition defined as acute-on-chronic liver failure with high mortality. While established scoring systems like Child-Pugh and Model for End-stage Liver Disease (MELD) offer prognostic insights, their limitations warrant exploration of alternative markers. The lactate/albumin ratio (LAR) serves as a potential prognostic indicator in critical care settings, yet its utility in cirrhotic patients remains underexplored. one hundred and seventy-five critically ill cirrhotic patients were assessed in this retrospective cohort study. Clinical severity scores, including Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Chronic Liver Failure-Organ Failure Score (CLIF-OF) were compared with LAR along with traditional liver failure scoring systems. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to evaluate prognostic performance. Intensive Care Unit (ICU) nonsurvivors had significantly higher scores in all liver failure and clinical severity scores compared to survivors (p < 0.001). Median LAR was significantly higher in nonsurvivors (p < 0.001). ROC analysis revealed comparable prognostic accuracy between LAR, APACHE II, SOFA, and CLIF-OF scores in predicting ICU mortality. Logistic regression identified SOFA score at 48th hour, LAR, and requirement of mechanical ventilation as independent predictors of ICU mortality. LAR demonstrates promising prognostic utility in predicting ICU mortality among critically ill cirrhotic patients, complementing established scoring systems. Early reassessment using SOFA score at 48th hour may guide therapeutic interventions and improve patient outcomes. Further prospective studies are warranted to validate these findings and optimize clinical management strategies.