The study mainly aim at exploring the ascites risk factors among decompensated cirrhosis patients via constructing the prediction model of ascites incidence.

Here, we recruited 148 decompensated cirrhosis patients for analysis, their laboratory tests and complications recorded. T-test, chi-square test, single-factor logistic regression, multi-factor logistic regression, and nomogram model were used to investigate the ascites occurred factors in decompensated cirrhosis patients with ascites. To validate the data analysis results, we applied the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) to evaluate the discrimination, calibration, and clinical usefulness of the prediction model, respectively.

Serum creatinine levels were higher in the cirrhotic ascites group than in the non-ascites group. The ascites group had lower albumin and serum sodium levels, as well as a lower incidence of variceal bleeding and varicose veins compared to the non-ascites group.

Varicose veins, variceal bleeding, and serum sodium levels are significant factors contributing to ascites development in cirrhosis. Furthermore, decreased serum albumin and elevated creatinine levels are important indicators of poor prognosis. Nomograms can improve clinicians' informed decision-making for patients with decompensated cirrhosis, ultimately reducing ascites risk.

Malignant ascites is a common complication of advanced ovarian cancer (OC) and gastrointestinal cancer (GI), significantly impacting metastasis, quality of life, and survival. Increased intestinal permeability can lead to blood or lymphatic infiltration and microbial translocation from the gastrointestinal or uterine tract. This study aimed to identify microbiota-derived metabolites in ascites from OC (stages II-III and IV) and GI patients, assessing their roles in tumor progression.

Malignant ascites samples from 18 OC and GI patients were analyzed using a four-dimensional (4D) untargeted metabolomics approach combining reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) with trapped ion mobility spectrometry time-of-flight mass spectrometry (timsTOF-MS). Additonally, a targeted flow cytometry-based cytokine panel was used to screen for inflammatory markers. Non-endogenous, microbiota-derived metabolites were identified through the Human Microbial Metabolome Database (MiMeDB).

OC stage IV exhibited metabolic profiles similar to GI cancers, while OC stage II-III differed significantly. Stage IV OC patients exhibited higher levels of 11 typically microbiome-derived metabolites, including 1-methylhistidine, 3-hydroxyanthranilic acid, 4-pyridoxic acid, biliverdin, butyryl-L-carnitine, hydroxypropionic acid, indole, lysophosphatidylinositol 18:1 (LPI 18:1), mevalonic acid, N-acetyl-L-phenylalanine, and nudifloramide, and lower levels of 5 metabolites, including benzyl alcohol, naringenin, o-cresol, octadecanedioic acid, and phenol, compared to stage II-III. Correlation analysis revealed positive associations between IL-10 and metabolites such as glucosamine and LPCs, while MCP-1 positively correlated with benzyl alcohol and phenol.

4D metabolomics revealed distinct metabolic signatures in OC and GI ascites, highlighting microbiota-derived metabolites involved in lipid metabolism and inflammation. Metabolites like 3-hydroxyanthranilic acid, indole, and naringenin may serve as markers of disease progression and underscore the microbiota's role in shaping malignant ascites and tumor biology.

Chronic pancreatitis (CP) is a known risk factor for pancreatic cancer; however its association to extra pancreatic (EP) cancers remains inadequately explored. The aim of this systematic review is to investigate the evidence for CP as a risk factor for developing EP cancers.

Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to January 27, 2024 to identify patients with CP who developed EP cancers. Prevalence and incidence of each cancer were calculated where possible from the reported numbers. A random effects meta-analysis was used to pool prevalence, incidence and hazard ratios (HR) of each EP cancer. Heterogeneity was assessed using I2. PROSPERO registration: CRD42024543050.

Sixteen (16) studies consisting of 117,163 CP patients met the eligibility criteria. 4015 (3.4%) patients developed 4019 EP cancers. The overall annual prevalence and incidence of EP cancers were 7962 (95% CI 5044-10880) per 100,000 CP patients and 1039 (95% CI 649-1663) per 100,000 person years. Lung cancer had the highest annual prevalence - (1540 (95% CI 667-2413) per 100,000 CP patients) and incidence (260 (95% CI 120-390) per 100,000 person years). The pooled HR were 1.31 (95% CI 1.03-1.66) and 1.58 (95% CI 1.27-1.98) for adjusted lung cancer and crude liver cancer in patients with CP compared to patients without CP, respectively.

Patients with CP have an increased risk of developing EP cancers compared to patients without CP, in particular lung and liver cancer which had the highest relative risk. Shared risk factor modifications, such as smoking cessation and alcohol reduction, could lower the risk of common EP cancers. Further, implementing non-invasive screening measures may aid in early diagnosis in this high-risk group.

Limited data exist on the role of systemic inflammation and gut barrier dysfunction in acute variceal bleed (AVB). We studied inflammatory markers and changes in the intestinal barrier in patients with AVB and assessed if these can be used to identify a higher risk subgroup with regard to outcomes.

In this prospective observational study, patients with cirrhosis and AVB presenting at a tertiary care center were stratified by whether or not they developed acute decompensation (AD) over 6 weeks follow-up. Utility of systemic inflammatory markers (interleukin-6 [IL-6], C-reactive protein), endotoxinemia (serum IgM/IgG anti-endotoxin antibodies), and duodenal epithelial tight junction proteins (TJPs) by immunohistochemistry (IHC) for tight-junction proteins (claudin-2,-4, zonula occludens-1(ZO-1), junctional adhesion molecule (JAM)) was assessed to predict the outcomes. These parameters were compared with a pre-existing cohort of patients with cirrhosis and no recent variceal bleed and with those without cirrhosis (dyspepsia with no endoscopic pathology). A nomogram was developed from multivariate model to predict 6-wk AD in patients with AVB.

Patients with AVB(n = 66) (age:46.4 ± 11.7 years; etiology: alcohol/NASH/HBV/HCV [48.5%/12.1%/12.1%/7.6%]) were included. Twenty-four (36.3%) patients developed 6-wk AD. Patients with 6-wk AD had higher serum IL-6 (median: 156.14 pg/ml [IQR: 136.12-170.52] vs 58.28 pg/ml [31.70-110.67]; P < 0.001) and Child score (median: 9 [6.75-10.25] vs 7 [6-9]; P = 0.042) at baseline. Serum endotoxinemia and duodenal epithelial TJP were similar. A nomogram combining CTP and IL-6 was generated that predicted 6-wk AD with optimism-corrected c-statistic of 0.87. Comparison with non-bleeder cirrhosis (n = 52) (7.57 [5.48-9.87]) and dyspepsia controls (n = 53) (5.72 [4.40-6.45]; P < 0.001) also identified significant elevation of serum IL-6, not entirely explainable by derangements in TJP and bacterial translocation markers.

6-wk AD rates in patients with cirrhosis and AVB can be predicted using combination of Child score and serum IL-6.

Alcohol use disorder is a prevalent and major but preventable cause of morbidity and mortality worldwide, causing several important health consequences, including chronic liver disease. Despite its substantial effects, most clinicians do not adequately assess alcohol intake in clinical practice, and there are several barriers to providing integrated management to patients with alcohol use disorder. Standardised questionnaires, such as the Alcohol Use Identification Test (AUDIT), can facilitate the identification of individuals at risk of alcohol use disorder, and alcohol biomarkers such as phosphatidylethanol aid in quantifying levels of alcohol consumption. Non-pharmacological interventions-including brief interventions, twelve-step facilitation, motivational enhancement therapy, contingency management, and cognitive behavioural therapy-are effective for patients with alcohol use disorder, regardless of the presence of advanced liver disease. Pharmacological treatments should be considered according to the severity of liver disease and other comorbidities, safety profile, and local availability. The management of patients with alcohol use disorder and associated liver disease should ideally be performed in the setting of integrated multidisciplinary teams.

In Ethiopia, cirrhosis is the 6th leading cause of death and is responsible for high hospitalization and mortality rates. However, until now, factors affecting in-hospital mortality of patients with liver cirrhosis are poorly understood. This study assessed the predictors of in-hospital mortality among cirrhotic patients in Ethiopia.

A retrospective cross-sectional study using data collected from the electronic medical records of patients who were admitted for complications of liver cirrhosis between January 1, 2023, and March 31, 2024, in the medical wards of Adera Medical Center, St. Paul's Hospital Millennium Medical College, and Tikur Anbessa Specialized Hospital. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression.

Of the 299 patients included in the final analysis, the majority (79.6%) were males, and the median age of the study participants was 45 (IQR, 36-56) years. Hepatitis B virus (32.1%) was the most common etiology, followed by alcohol (30.1%) and hepatitis C virus (13.4%). Ascites (69.2%), upper gastrointestinal bleeding (50.5%), and hepatic encephalopathy (44.8%) were the most common forms of presentation. The in-hospital mortality rate was 25.4%. West Haven grade III or IV hepatic encephalopathy (AOR: 12.0; 95% CI 2.33-61.63; P < 0.01), hepatocellular carcinoma (AOR: 9.05; 95% CI 2.18-37.14; P: 0.01), history of previous admission within one year period (AOR: 6.80; 95% CI 2.18-21.18; P < 0.01), acute kidney injury (AOR: 6.47; 95% CI 1.77-23.64; P < 0.01), and model for end-stage liver disease - sodium score (AOR: 1.17; 95% CI 1.05-1.30; P: 0.02), were found to be predictors of in-hospital mortality.

In-hospital mortality of cirrhotic patients is high in Ethiopia. West Haven grade III or IV hepatic encephalopathy is the leading cause of mortality. Hence, prompt identification and management of hepatic encephalopathy and its precipitant at an earlier stage is crucial for better treatment outcomes and survival.

Acute kidney injury (AKI) is a critical and often fatal complication in decompensated cirrhosis, significantly affecting inpatient survival rates. Hepatorenal syndrome (HRS), a distinct subtype of AKI, develops in individuals with advanced cirrhosis and portal hypertension. It is marked by progressive kidney dysfunction, poor prognosis, and frequently causes death before liver transplantation. The pathogenesis of HRS involves vasodilation of the splanchnic vessels, leading to overactivation of the endogenous vasoactive systems, circulatory dysfunction, and reduced renal perfusion, which ultimately impairs glomerular filtration. Recent studies have highlighted the role of systemic inflammation in exacerbating renal damage. Despite these changes, renal histology in HRS usually shows no significant abnormalities, and there is typically no hematuria, proteinuria, or abnormal findings on ultrasound. Common risk factors for HRS include spontaneous bacterial peritonitis, infections, and large-volume paracentesis without albumin infusion. Diagnosing HRS is challenging, particularly in distinguishing it from acute tubular necrosis, due to the absence of specific biomarkers. Treatment primarily involves vasoconstrictors such as terlipressin and albumin, with liver transplantation being the definitive therapeutic option. This review provides an updated understanding of HRS, addressing its pathophysiology, diagnosis, management, and future challenges, based on recent expert consensus.

Liver cirrhosis (LC) affect millions of people worldwide. The pathogenesis of cirrhosis involves complex interactions between immune responses and gut microbiota. Recent studies have highlighted the role of the interleukin-36 (IL-36) subfamily in inflammation and immune regulation. However, the relationship between serum IL-36 subfamily levels and gut microbiota in cirrhosis patients remains unclear. This study aimed to explore the clinical significance of serum IL-36 subfamily levels and their association with gut microbiota in cirrhosis patients.

To explore the clinical significance of serum IL-36 subfamily levels and their relationship with gut microbiota among cirrhosis patients.

Sixty-one cirrhosis patients were enrolled from Lihuili Hospital of Ningbo University from May 2022 to November 2023 as the LC group and 29 healthy volunteers as the healthy control (HC) group. The serum expressions of IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 were measured through ELISA, while 16S rRNA gene sequencing was employed to rate microbial community in human fecal samples.

The serum levels of IL-36α, IL-36γ, IL-36Ra, and IL-38 in the LC group remarkably exceeded those in the HC group (P < 0.05). IL-36α, IL-36γ, and IL-38 were related positively to the Child-Pugh score (P < 0.05) and prominently exceeded those in the Child-Pugh C group (P < 0.05). The absolute abundance of harmful bacteria (Bacteroides, Bifidobacterium, Faecalibacterium) remarkably rose, while the beneficial bacteria (Firmicutes, Bacteroides, Escherichia-Shigella) notably decreased in the LC group (P < 0.05). IL-36α, IL-36γ, and IL-38 related positively to Lactobacillus (P < 0.05), while IL-38 negatively related to Fusicatenibacter (P < 0.05).

IL-36γ and IL-38 show promise as potential biomarkers for LC progression, but further validation is required.

Patients with cirrhosis with hepatopulmonary syndrome (HPS) have a poorer prognosis. The disease has a subtle onset, symptoms are easily masked, clinical attention is insufficient, and misdiagnosis rates are high.

To compare the clinical characteristics of patients with cirrhosis, cirrhosis combined with intrapulmonary vascular dilatation (IPVD), and HPS, and to establish predictive models for IPVD and HPS.

Patients with cirrhosis were prospectively screened at a liver-specialized university teaching hospital. Clinical information and blood samples were collected, and biomarker levels in blood samples were measured. Patients with cirrhosis were divided into three groups: Those with pure cirrhosis, those with combined IPVD, and those with HPS based on contrast-enhanced transthoracic echocardiography results and the pulmonary alveolar-arterial oxygen gradient values. Univariate logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression methods were utilized to identify risk factors for IPVD and HPS, and nomograms were constructed to predict IPVD and HPS.

A total of 320 patients were analyzed, with 101 diagnosed with IPVD, of whom 54 were diagnosed with HPS. There were statistically significant differences in clinical parameters among these three groups of patients. Among the tested biomarkers, sphingosine 1 phosphate, angiopoietin-2, and platelet-derived growth factor BB were significantly associated with IPVD and HPS in patients with cirrhosis. Following LASSO logistic regression screening, prediction models for IPVD and HPS were established. The area under the receiver operating characteristic curve for IPVD prediction was 0.792 (95% confidence interval [CI]: 0.737-0.847), and for HPS prediction was 0.891 (95%CI: 0.848-0.934).

This study systematically compared the clinical characteristics of patients with cirrhosis, IPVD, and HPS, and constructed predictive models for IPVD and HPS based on clinical parameters and laboratory indicators. These models showed good predictive value for IPVD and HPS in patients with cirrhosis. They can assist clinicians in the early prognosis assessment of patients with cirrhosis, ultimately benefiting the patients.

Excessive alcohol consumption drives the development of alcohol-associated liver disease (ALD), including steatohepatitis, cirrhosis, and hepatocellular carcinoma, and its associated complications, such as hepatorenal syndrome. Hepatocyte death, inflammation, and impaired liver regeneration are key processes implicated in the pathogenesis and progression of ALD. Despite extensive research, therapeutic options for ALD remain limited. IL-22 has emerged as a promising therapeutic target because of its hepatoprotective properties mediated through the activation of the STAT3 signaling pathway. IL-22 enhances hepatocyte survival by mitigating apoptosis, oxidative stress, and inflammation while simultaneously promoting liver regeneration through the proliferation of hepatocytes and hepatic progenitor cells and the up-regulation of growth factors. Additionally, IL-22 exerts protective effects on epithelial cells in various organs affected by ALD and its associated complications. Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration. However, the heterogeneity and multifactorial nature of ALD present ongoing challenges. Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits, and limitations.

Liver hepatocellular carcinoma (LIHC) is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment (TME) and immune evasion. Regulatory T cells (Tregs) play a critical role in tumor progression. Suppressor of cytokine signaling 2 (SOCS2), a key immune regulator, may modulate Treg activity and impact LIHC growth and metastasis.

To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.

LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis, Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data, and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration. Key prognostic genes were identified using Weighted Gene Co-expression Network Analysis and machine learning. In vitro, co-culture experiments, migration assays, apoptosis detection, and enzyme-linked immunosorbent assay were conducted. In vivo, tumor growth, metastasis, and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining, Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling, and immunohistochemistry analyses.

SOCS2 overexpression inhibited Treg cell activity, reducing LIHC cell migration and invasion while increasing apoptosis. In vivo, SOCS2 suppressed tumor growth and metastasis, confirming its therapeutic potential.

SOCS2 modulates CD4+ T function in the TME, contributing to LIHC progression. Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.

Effective interventions for metabolic liver disease include optimized nutritional intake. It is increasingly clear, however, that many patients with metabolic liver disease lack the resources to execute nutritional advice. Data on the trends of food insecurity are needed to prioritize public health strategies to address the burden of liver disease.

Cross-sectional analysis of six waves of data from 24,847 adults aged > 20 years from the 2017-2018 National Health and Nutrition Examination Survey. Food security was measured using the US Department of Agriculture's Core Food Security Module. Liver disease was defined as elevated liver enzymes and a risk factor: elevated BMI, diabetes, and/or excess alcohol consumption. Advanced liver disease was estimated using FIB-4 > 2.67.Additional covariates included age, sex, race/ethnicity, education, marital status, poverty-income ratio, alcohol intake, body mass index, diabetes, and participation in the Supplemental Nutrition Assistance Program (SNAP).

The overall prevalence of liver disease was 24.6%, ranging from 21.1% (2017-2018) to 28.3% (2015-2016) (P-trend = 0.85). 3.4% of participants had possible advanced liver disease, ranging from 1.9% (2007-2008) to 4.2% (2015-2016)(P-trend = 0.07). Among those with liver disease, the prevalence of food insecurity was 13.6% in 2007-2008, which rose steadily to 21.6% in 2015-2016, before declining to 18.0% in 2017-2018 (P-trend = 0.0004). Food insecurity rose more sharply for adults aged < 50 years (2007-2008: 17.6%, 2015-2016: 28.0%, P-trend = 0.004) compared to adults aged ≥ 50 years (2007-2008: 9.5%, 2015-2016: 16.5%, P-trend < 0.0001). Similarly among those with liver disease, significant predictors of food insecurity included Hispanic ethnicity, low educational attainment, and participating in SNAP.

Food insecurity is increasingly common among those with liver disease.

Hepatic decompensation carries profound implications for patient quality of life and risk of mortality. We lack comparative data on how noninvasive tools perform in risk stratification for those with compensated cirrhosis. We performed a systematic review to assess the performance of laboratory and transient elastography-based models for predicting hepatic decompensation in patients with compensated cirrhosis.

The following databases were searched by an informationist to identify relevant studies, including adult patients with compensated cirrhosis from inception to August 2023: Medline, Embase, Scopus, Web of Science, and ClinicalTrials.gov. Title and abstract screening followed by full-text review were performed by 2 independent reviewers, and data abstraction was completed using standardized forms. Studies of patients with decompensation at baseline (defined by ascites, variceal bleeding, and HE) or any primary hepatic malignancy were excluded. The primary outcome was hepatic decompensation, as defined above. Pooled HRs were calculated using the common-effect inverse-variance model.

Forty-four full-text studies met the inclusion criteria. Across 52,589 patients, the cumulative incidence of any decompensation was 17.9% over a follow-up time of 111,401 patient years. Pooled risk estimates for all-cause decompensation demonstrated that MELD (HR: 1.08; 95% CI: 1.06-1.10), albumin-bilirubin (HR: 2.13, 95% CI: 1.92-2.36), fibrosis-4 (HR: 1.04, 95% CI: 1.03-1.06), albumin-bilirubin-fibrosis-4 (HR: 1.25, 95% CI: 1.18-1.33), and liver stiffness by transient elastography (HR: 1.04; 95% CI: 1.04-1.05) predict decompensation.

Available blood and imaging-based biomarkers can risk-stratify patients for hepatic decompensation. Changes in albumin-bilirubin appear to have the highest discrimination in predicting decompensation events.

Driven by genetic and environmental factors, aging is a physiological process responsible for age-related degenerative changes in the body, cognitive decline, and impaired overall wellbeing. Notably, premature aging as well as the emergence of progeroid syndromes have posed concerns regarding chronic health conditions and comorbidities in the aging population. Accelerated telomere attrition is also implicated in metabolic dysfunction and the development of metabolic disorders. Impaired metabolic homeostasis arises secondary to age-related increases in the synthesis of free radicals, decreased oxidative capacity, impaired antioxidant defense, and disrupted energy metabolism. In particular, several cellular and molecular mechanisms of aging have been identified to decipher the influence of premature aging on metabolic diseases. These include defective DNA repair, telomere attrition, epigenetic alterations, and dysregulation of nutrient-sensing pathways. The role of telomere attrition premature aging in the pathogenesis of metabolic diseases has been largely attributed to pro-inflammatory states that promote telomere shortening, genetic mutations in the telomerase reverse transcriptase, epigenetic alteration, oxidative stress, and mitochondrial dysfunctions. Nonetheless, the therapeutic interventions focus on restoring the length of telomeres and may include treatment approaches to restore telomerase enzyme activity, promote alternative lengthening of telomeres, counter oxidative stress, and decrease the concentration of pro-inflammatory cytokines. Given the significance and robust potential of delaying telomere attrition in age-related metabolic diseases, this review aimed to explore the molecular and cellular mechanisms of aging underlying premature telomere attrition and metabolic diseases, assimilating evidence from both human and animal studies.

To explore the value of preoperative Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) in predicting short-term prognosis of children with biliary atresia (BA) undergoing Kasai portoenterostomy (KPE).

Clinical data from children who underwent KPE were analyzed. Patients were divided into two groups based on their 2-year native liver survival after KPE. General information and laboratory findings were collected before KPE. The difference in liver fibrosis between the two groups was analyzed. The predictive efficacy of each index for short-term prognosis of children with BA was evaluated using the receiver operating characteristic curve.

The APRI and FIB-4 in the good prognosis group were lower than those in the poor prognosis group (p=0.008 and 0.023, respectively), and postoperative jaundice clearance rate was higher (p=0.002). In the poor prognosis group, gamma-glutamyl transpeptidase levels in the F3+F4 fibrosis subgroup were significantly higher than those in the F1 subgroup (p=0.038). The area under the curve (AUC) for preoperative APRI in predicting short-term prognosis was the highest at 0.667, with a cut-off value of 1.190. The AUC for preoperative FIB-4 was predicted to be 0.642. The combination of preoperative APRI and alanine aminotransferase showed a higher AUC for prognosis prediction compared with either marker alone.

Preoperative APRI and FIB-4 may havepredictive values for short-term prognosis. The predictive value of APRI and FIB-4 combined with liver function indicators for the short-term prognosis of children is superior to that of a single indicator, but the results are not satisfactory.

Many men with cirrhosis have low testosterone levels. This is associated with sarcopenia, anemia, and poor quality of life. Data are lacking, however, regarding the clinical impact of testosterone replacement.

We conducted an emulated clinical trial evaluating the impact of testosterone replacement among men who were diagnosed with hypogonadism at the same time as their diagnosis of cirrhosis (new user design). We used nationally representative Medicare data (2008-2020) to examine the risk of death, decompensation events, and fractures in patients who did or did not receive testosterone. We balanced treated and untreated with inverse probability of treatment weighting and evaluated outcomes using an intention-to-treat design.

A total of 282 patients (7.4%) with testicular hypofunction and cirrhosis received testosterone replacement after diagnosis. Patients started on testosterone spent 28.6% of patient-days on therapy, and patients not started would spend 0.5% of patient-days on therapy (P < .0001). Testosterone use was associated with lower mortality (subdistribution hazard ratio [sHR], 0.92; 95% confidence interval [CI], 0.85-0.99). Testosterone also led to a lower risk of new decompensation events (sHR, 0.92; 95% CI, 0.86-0.99) and especially for ascites requiring paracentesis (sHR, 0.82; 95% CI, 0.76-0.89) and variceal hemorrhage (sHR, 0.67; 95% CI, 0.54-0.85) with less effect on hepatic encephalopathy requiring hospitalization (sHR, 0.92; 95% CI, 0.84-1.01) and fractures (sHR, 0.99; 95% CI, 0.91-1.08) and without increased risk of hepatocellular carcinoma (sHR, 1.09; 95% CI, 0.91-1.3). There was substantial heterogeneity of treatment effect across baseline subgroups.

In our target trial emulation of a nationally representative cohort of older patients with cirrhosis and hypogonadism, testosterone use improved clinical outcomes.

Liver cirrhosis is a critical stage in the progression of various chronic liver diseases, often leading to severe complications such as ascites, hepatic encephalopathy, and a high mortality rate, and it thus poses a serious threat to patient life. The activation of hepatic stellate cells is a central driver of disease progression. Cellular autophagy, a lysosome-mediated degradation process, plays a key role in maintaining cellular function and dynamic homeostasis. Research has shown that autophagy is closely associated with proteins like LC3, Beclin-1, P62, and mTOR, and is regulated through signaling pathways such as PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and AMPK/mTOR. Additionally, the relationship between autophagy and apoptosis, as well as between autophagy and exosomes, has been further demonstrated. While modern medicine has made progress in treating cirrhosis, it still faces significant limitations. By contrast, numerous studies have demonstrated the efficacy of traditional Chinese medicine in preventing and treating liver cirrhosis by regulating autophagy, with fewer adverse effects. Chinese herbal monomers and formulations can modulate various autophagy-related signaling pathways, including PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and AMPK/mTOR, and influence key autophagy proteins such as LC3 and Beclin-1. This modulation inhibits hepatic stellate cell activation, reduces extracellular matrix deposition, and exerts anticirrhotic effects. Moreover, Chinese medicine appears to reduce adverse reactions in cirrhosis treatment and lower the risk of disease recurrence. This review explores the mechanisms of autophagy in the prevention and treatment of liver cirrhosis through Chinese medicine, offering new insights for the development of Chinese medicinal therapies for cirrhosis and their rational clinical application.

Ethics consultations may reflect the nature and frequency of conflicts in clinical care. Data regarding consultations for patients with cirrhosis, however, are limited.

To understand the reasons and context for ethics consultations and identify areas for improvement.

We evaluated inpatient ethics consultations from 06/2015 to 08/2023. Consults for people with severe liver, heart, and lung diseases were examined for the reasons and contextual factors for consultation. These were coded according to a qualitative conceptual content analysis by two independent reviewers. The rate of consultations was derived from the denominator of hospitalized patients with each condition over the same time.

During the study period, there were 38 ethics consults from 17,460 patients with liver disease (incidence 0.2%) and 96 among 48,394 patients with heart/lung disease (incidence 0.2%). The primary ethical issue was surrogate decision-making related to the lack of an identified durable power of attorney or when surrogate decision-making went against care team recommendations. These conflicts were twice as likely for patients with cirrhosis. The second most common primary ethical issues were code status and futility. Medical error, symptom management, and withdrawal of life supports were not associated with ethics consults. Legal issues were more common in patients without cirrhosis. Communication disputes with the team, intra-family disputes, and quality of life concerns were the most common contextual factors.

Ethics consultations for patients with cirrhosis occur for 0.2% of hospitalizations and are linked to deficits in advanced care planning, poor communication, and poor patient quality of life.

Recent epidemiological evidence indicates a significant rise in cirrhosis burden over the past 2 decades in all parts of the world, with cirrhosis incidence rates and related deaths escalating quickly. Women face unique risk factors and susceptibility to chronic liver diseases compared with men, underscoring the need for a sex-specific approach in early identification, reversal of causative factors, and complication prevention. This review aims to explore epidemiological trends and sex-specific factors contributing to the global epidemiology of cirrhosis among female patients today. While cirrhosis prevalence remains higher in male patients globally, the incidence rate from 2010 to 2019 grew faster among female patients. The female-to-male incidence ratio of metabolic dysfunction-associated steatotic liver disease-related cirrhosis globally in 2019 was 1.3, indicating a shifting trend toward new diagnoses among women now surpassing that of men. Alcohol-associated cirrhosis epidemiology is also changing, with trends toward an equal incidence of alcohol-associated cirrhosis between both sexes, particularly in industrialized nations with increased alcohol accessibility. Cirrhosis from viral hepatitis remains the main etiology among female patients in endemic regions. Sex differences in epidemiology are likely multifactorial, influenced by varying risk factors, susceptibility, and behaviors between sexes. Further research is necessary to better understand these disparities and to tailor sex-specific interventions toward improved management and treatment strategies, ultimately enhancing outcomes for women with cirrhosis and providing better patient-centered care.

Background Liver cirrhosis (LC) is characterized by the development of fibrosis and nodules within the liver, leading to progressive liver dysfunction. The mortality rate associated with LC has consistently remained high over the years. Prognostic tools such as the Child-Turcotte-Pugh (CTP) score and the Model for End-Stage Liver Disease (MELD) score are commonly used to predict mortality and assess the severity of LC. Both scoring systems rely on laboratory parameters, including serum albumin, total bilirubin, and international normalized ratio (INR) levels. However, the CTP score interpretation can be variable, and INR testing is not routinely performed in many clinical settings, which may limit its utility. This study aims to assess the MELD and CTP scores, along with a new predictive tool, in estimating 30-day mortality for patients with LC. Methodology This retrospective cohort study focuses on patients diagnosed with LC at Ngoerah Central General Hospital. Physical examination data and laboratory ratios, including neutrophil-to-lymphocyte ratio (NLR), aspartate transaminase (AST) to alanine transaminase (ALT) ratio (de Ritis), neutrophil-to-lymphocyte-to-albumin (NLA) ratio, albumin bilirubin index (ALBI), and blood urea nitrogen-to-albumin ratio (BAR), were collected from medical records. Optimal cutoff values were established using receiver operating characteristic (ROC) curves. Survival analysis was performed using the Kaplan-Meier method, and multivariate Cox regression was employed to determine the hazard ratio (HR) for each variable that was statistically significant as a predictor of 30-day mortality. Results In this study, a total of 140 samples were analyzed. Kaplan-Meier analysis revealed that hepatic encephalopathy (HE) met the criteria, while interaction analysis testing was required for other variables. Results from the multivariate Cox regression interaction model showed that ALBI-HE (HR = 1.743, 95% confidence interval [CI] 1.102-2.759, P = 0.018), BAR-HE (HR = 0.577, 95% CI 0.367-0.905, P = 0.017), and NLA-HE (HR = 0.332, 95% CI 0.195-0.563, P < 0.001) were significant independent predictors of 30-day mortality in LC. CTP, MELD, NLR, and de Ritis did not demonstrate statistical significance. ALBI-HE emerged as the strongest predictor based on its HR. Conclusions ALBI-HE, BAR-HE, and NLA-HE have emerged as novel predictors for assessing 30-day mortality in LC. ALBI-HE is the strongest predictor of 30-day mortality in LC.

Falls are a major threat to the well-being of patients with cirrhosis. We are performing a clinical trial to determine whether lactulose, TeleTai-Chi, or their combination will reduce falls in HE and improve health-related quality of life (HRQOL) among patients with cirrhosis.

Patients with cirrhosis and portal hypertension without HE will be enrolled in 3 US states and followed participants for 24 weeks. In stage 1 (12 wk), participants will be randomized to receive either lactulose therapy or enhanced usual care. In stage 2 (12 wk), participants will be randomized to either TeleTai-Chi or usual care. The primary outcome is a hierarchical composite: Injurious falls, noninjurious falls, incident HE, and death/transplantation. Secondary outcomes include cognitive function, days-alive and out-of-hospital, and HRQOL. After completion of the interventions, participants will be followed for 48 weeks for health and financial outcomes.

Our study has a central institutional review board with individual site IRB review. Dissemination includes the publication of study findings and patient-focused educational webinars.

One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis.

The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee.

The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified.

The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion.

NCT05740358.

This study aimed to investigate the characteristics and prognosis of recompensation in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

A total of 136 patients with HBV-related ACLF were followed up until the end of the study. Patients were categorized into recompensation and non-recompensation groups based on whether recompensation occurred in the first year. The survival rate and incidence of recompensation were calculated using the Kaplan-Meier method.

According to the BAVENO VII consensus criteria, 56 (41.18%) of these patients with ACLF regained recompensation in the 1-year follow-up. The recompensated group had less severe liver damage, higher alpha-fetoprotein, lower age, and lower model for end-stage liver disease score. Specifically, in terms of complications, the recompensated group showed a lower incidence compared with the non-recompensated group ( P  < 0.05). The 3-, 6-, 12-, 36-, and 60-month cumulative survival rates of ACLF were 44.9, 43.4, 43.4, 40.4, and 40.4% respectively. Among the patients who survived beyond 90 days, 57/61 (93.44%) patients showed recompensation of ACLF (with one patient recovering to recompensation after more than 1 year of follow-up), the 3-, 6-, 12-, and 24-month cumulative recompensation rates were 56.5, 90.9, 94.6, and 97.3%, respectively. Among the 57 patients with recompensation of ACLF, 87.7% maintained a stable condition, and 10.5% were diagnosed with hepatocellular carcinoma (HCC).

Milder necrosis, less inflammation, and more vigorous hepatic regeneration are conducive to recompensation and a better long-term prognosis in ACLF. However, the occurrence of HCC cannot be avoided and regular monitoring is necessary in the recompensation of ACLF.

Chronic hepatitis B (CHB) infection represents a significant global public health issue, often leading to hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) with poor prognoses. Early identification of HBV-LC risk is essential for timely intervention. This study develops and compares nine machine learning (ML) models to predict HBV-LC risk in CHB patients using routine clinical and laboratory data. A retrospective analysis was conducted involving 777 CHB patients, with 50.45% (392/777) progressing to HBV-LC. Admission data consisted of 52 clinical and laboratory variables, with missing values addressed using multiple imputation. Feature selection utilized Least Absolute Shrinkage and Selection Operator (LASSO) regression and the Boruta algorithm, identifying 24 key variables. The evaluated ML models included XGBoost, logistic regression (LR), LightGBM, random forest (RF), AdaBoost, Gaussian naive Bayes (GNB), multilayer perceptron (MLP), support vector machine (SVM), and k-nearest neighbors (KNN). The data set was partitioned into an 80% training set (n = 621) and a 20% independent testing set (n = 156). Cross-validation (CV) facilitated hyperparameter tuning and internal validation of the optimal model. Performance metrics included the area under the receiver operating characteristic curve (AUC), Brier score, accuracy, sensitivity, specificity, and F1 score. The RF model demonstrated superior performance, with AUCs of 0.992 (training) and 0.907 (validation), while the reconstructed model achieved AUCs of 0.944 (training) and 0.945 (validation), maintaining an AUC of 0.863 in the testing set. Calibration curves confirmed a strong alignment between observed and predicted probabilities. Decision curve analysis indicated that the RF model provided the highest net benefit across threshold probabilities. The SHAP algorithm identified RPR, PLT, HBV DNA, ALT, and TBA as critical predictors. This interpretable ML model enhances early HBV-LC prediction and supports clinical decision-making in resource-limited settings.

Novel therapies are needed to treat HE, and microbiome modulation is a promising target. VE303 is a defined consortium of 8 purified, clonal bacterial strains, known to produce metabolites that may be beneficial in HE. We evaluated the safety and efficacy of VE303 to treat HE.

We performed a single-center, randomized, placebo-controlled trial of VE303 in adult patients with a history of overt HE (NCT04899115). Eligible patients were taking lactulose and rifaximin, had no recent systemic antibiotics, and had MELD ≤20. All patients received 5 days of oral vancomycin followed by randomization to 14 days of VE303 or placebo (2:1). The primary endpoints were incidence of serious adverse events and change in psychometric HE score (PHES) from baseline to 4 weeks after treatment. Stool samples underwent metagenomic sequencing and metabolite quantification.

Eighteen patients completed the trial, 56% men, with a mean age of 59 years and a mean MELD of 11. Patients who received VE303 had a mean change in PHES of +1.5 versus -1.0 in those who received a placebo (p=0.20). Two of the 12 patients who received VE303 had at least 1 serious adverse event (all overt HE hospitalizations), compared with 0/6 patients who received a placebo. In the patients who received VE303, 2 of 8 strains engrafted in >50% of patients. Both VE303 strain engraftment and increased stool butyrate production had a trend toward improved PHES.

VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES.

A target heart rate of 55-60 beats per minute is a goal for propranolol in both primary and secondary prophylaxis of variceal hemorrhage (VH). However, dose adjustments are often needed based on baseline heart rates. This study analyzed the effect of heart rate reduction from baseline with propranolol therapy on VH in patients with cirrhosis. A retrospective study was conducted on cirrhotic patients receiving propranolol for primary and secondary prophylaxis, 2008-2023. Patients were categorized as responders or non-responders based on the achievement of a heart rate reduction of ≥ 25% from baseline. The primary outcome was the incidence of VH. A survival analysis with propensity score-inverse probability treatment weighting was performed to associate heart rate reduction and the outcome. Among the 215 patients treated with propranolol for primary prophylaxis, 72 (33.5%) were responders and 143 (66.5%) non-responders. In secondary prophylaxis, 157 patients were included, with 52 (33.1%) classified as responders and 105 (66.9%) as non-responders. The median Child-Pugh score was 6 (range 5-12) for primary and 7 (range 5-12) for secondary prophylaxis. Responders and non-responders showed a similar incidence of VH in both primary (adjusted hazard ratio (HR) 1.70, 95% CI: 0.82-3.49) and secondary prophylaxis (adjusted HR 1.00, 95% CI: 0.34-2.90). Our analysis did not support achieving a heart rate reduction of ≥ 25% from baseline as a response to propranolol for the primary and secondary prophylaxis of VH in cirrhosis.

Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms.

Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line.

Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.

NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.

Ascites is the most common complication from cirrhosis related to portal hypertension and depicts the onset of hepatic decompensation. Ranging from uncomplicated to refractory ascites, the progression carries prognostic value by reflecting the deterioration of underlying cirrhosis and portal hypertension. Diuretics have been the mainstay of treatment to control ascites, but the side effects heighten when the dosage is escalated. Non-selective beta-blockers (NSBBs) are widely used nowadays to prevent hepatic decompensation and variceal hemorrhage. However, with worsening systemic vasodilation and inflammation when ascites progresses, patients on NSBBs are at risk of hemodynamic collapse leading to renal hypoperfusion and thus hepatorenal syndrome. Long-term albumin infusion was studied to prevent the progression of ascites. However, the results were conflicting. Sodium-glucose cotransporter-2 inhibitors are under investigation to control refractory ascites. With that, patients with refractory ascites may require regular large-volume paracentesis. With an aging population, more patients are put on anti-thrombotic agents and their risks in decompensated cirrhosis and invasive procedures have to be considered. In general, decompensated cirrhosis with ascites poses multiple issues to pharmacological treatment. In the present review, we discuss the challenges and controversies in the pharmacological treatment of ascites.

Orthotopic liver transplant (OLT) medicine is a constantly evolving field, especially with the demographics of individuals with advanced liver disease drastically changing. OLT candidates are now older, and there is an increase of nonalcoholic steatohepatitis cirrhosis due to the epidemic of obesity, which has also resulted in an increase in cardiac comorbidities in this population. The pathophysiology of liver cirrhosis creates many complexities during the pre- and postoperative management of OLT. We discuss the role of screening for common co-existent cardiovascular comorbidities, including coronary artery disease, congestive heart failure, arrhythmias, and portopulmonary hypertension, as well as challenges in the standardization of pre-liver transplant cardiovascular care.

This review highlights the impact of weight loss on metabolic dysfunction associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease (NAFLD), and its progressive form of metabolic dysfunction associated steatohepatitis (MASH), formally known as nonalcoholic steatohepatitis (NASH). The effects of weight loss, as achieved through lifestyle modification, pharmacotherapy, bariatric surgery or endobariatric procedures on MASLD/MASH and hepatic fibrosis are discussed.

Although foundational in the treatment of MASLD/MASH, weight loss through life-style modification is challenging for most patients to achieve and sustain long-term. In patients with MASLD/MASH, a multidisciplinary approach may facilitate success with lifestyle modification, individualized consideration of pharmacotherapies and/or surgical approaches that have potential to lend an improvement in MASLD/MASH. Effective and sustained weight loss improves hepatic steatosis, steatohepatitis and potentially hepatic fibrosis. Improvement in hepatic fibrosis can improve patient-related outcomes associated with complications of advanced hepatic fibrosis or cirrhosis in patients with MASLD/MASH. Identifying risk factors that influence MASLD/MASH and early implementation of therapeutic weight loss strategies may improve chronic liver injury and decrease risk for adverse clinical outcomes related to progressive hepatic fibrosis attributable to MASLD/MASH.

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.

Background/Objectives: Rifaximin is a therapeutic agent for patients with hepatic encephalopathy (HE); however, there is little data on the effects of its long-term (>1 year) administration in Japanese patients with cirrhosis. The effects and safety of 3-year rifaximin treatment on HE was investigated in Japan. Methods: A total of 190 Japanese patients with cirrhosis who were continuously administered rifaximin for more than 1 year suffered overt or covert HE, which was diagnosed by a physician. Laboratory data were collected at baseline, 3, 6, 12, 18, 24, 30, and 36 months following rifaximin administration. We examined the cumulative overt HE incidences, overall survival rates, and hepatic functional reserves following rifaximin treatment. The occurrence of adverse events was also assessed. Results: The levels of ammonia improved significantly after 3 months of rifaximin administration, which continued for 3 years. Serum albumin and prothrombin activity also significantly improved 3 years after initiation of rifaximin treatment. Cumulative overt HE incidences were 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. The survival rates following rifaximin treatment were 100%, 88.9%, and 77.8% at 1, 2, and 3 years, respectively. In contrast, renal function and electrolytes did not change following rifaximin administration. Only three (1.6%) patients discontinued rifaximin therapy because of severe diarrhea after 1 year of rifaximin administration. No other serious adverse events were observed. Conclusions: Three years of continuous rifaximin (RFX) treatment was both effective and safe for patients with hepatic encephalopathy. Liver function improved and did not worsen during treatment.

Patients with liver cirrhosis face high infection risks due to immune dysfunction and hospital-related factors, increasing mortality rates when sepsis occurs. While various biomarkers predict outcomes in cirrhosis, few are accessible and reliable. This study addresses the gap by evaluating the prognostic potential of the lactate-to-albumin ratio (LAR).

We retrospectively analyzed data from patients with cirrhosis and sepsis who were admitted to the intensive care unit at Beth Israel Deaconess Medical Center between 2008 and 2022. LAR was calculated from the ratio obtained from the first measurement taken within 24 h of admission. The optimal LAR threshold was determined using R statistical software. Kaplan-Meier analysis was used to compare mortality risks between two patient groups, while multivariate Cox proportional hazards regression models were used to assess the association between LAR and mortality risk in patients with cirrhosis and concomitant sepsis. A restricted cubic spline (RCS) was used to explore potential dose-response relationships between LAR and mortality. Receiver operating characteristic (ROC) analyses were used to assess the predictive ability, sensitivity, and specificity of LAR for all-cause mortality in patients with cirrhosis and combined sepsis, and the area under the curve (AUC) was calculated. Finally, subgroup analyses were performed to assess the relationship between LAR and prognosis across different populations.

A total of 1731 patients were included in the study. The optimal LAR threshold was identified as 1.0 using R statistical software. Kaplan-Meier analysis indicated that patients with higher LAR levels had a higher risk of 14-day, 28-day, and 90-day all-cause mortality (all log-rank P < 0.001). Multivariate Cox proportional hazards models indicated independent associations between higher LAR levels and all-cause mortality at 14-day, 28-day, and 90-day before and after adjusting for confounders. RCS analysis revealed a nonlinear association between LAR and short- and long-term all-cause mortality in patients with cirrhosis and sepsis. ROC curve analysis showed that although the predictive value of LAR for the prognosis of patients with cirrhosis combined with sepsis was slightly inferior to that of the Model for End-Stage Liver Disease score, it was significantly better than that of lactate, albumin, and the Sequential Organ Failure Assessment. Subgroup analyses showed no significant interactions between LAR and any specific subgroup.

LAR has good predictive value for the prognosis of patients with cirrhosis and sepsis.

As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.

There is a well-established relationship between liver conditions and cardiovascular diseases. However, uncertainty persists regarding the contribution of liver fibrosis to major stroke types including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage at the population level.

In this large prospective cohort study, participants without previous stroke or coronary heart disease at baseline from the UK Biobank were included. We identified participants at high probability of advanced liver fibrosis using the Fibrosis-4 index >2.67 or aspartate aminotransferase to platelet ratio index ≥1.0. Multivariable Cox proportional hazard regression analyses were conducted to estimate hazard ratios (HRs) for liver fibrosis with the incidence of major stroke types, stroke-related death, and all-cause death.

Among 379 953 participants (mean age, 56.2 [SD, 8.1] years; 44.6% men), 7396 (1.9%) had a Fibrosis-4 index >2.67 at baseline. During a median follow-up of 12.75 (interquartile range, 12.03-13.48) years, 7143 (1.9%) incident stroke cases were documented. Advanced liver fibrosis assessed by the Fibrosis-4 index was associated with an increased risk of ischemic stroke (HR, 1.94 [95% CI, 1.70-2.22]), intracerebral hemorrhage (HR, 2.14 [95% CI, 1.63-2.81]), subarachnoid hemorrhage (HR, 1.90 [95% CI, 1.27-2.84), stroke-related death (HR, 2.20 [95% CI, 1.73-2.80]), and all-cause death (HR, 2.59 [95% CI, 2.46-2.73]). Using the aspartate aminotransferase to platelet ratio index as an alternative score, liver fibrosis was correlated with magnified risk of intracerebral hemorrhage (HR, 3.76 [95% CI, 2.38-5.93]) and subarachnoid hemorrhage (HR, 3.05 [95% CI, 1.51-6.13]) compared with ischemic stroke (HR, 1.58 [95% CI, 1.17-2.14]). Restricted cubic spline analysis showed nonlinear associations of the Fibrosis-4 index and aspartate aminotransferase to platelet ratio index with stroke incidence and all-cause death.

Liver fibrosis is associated with increased risk of incident stroke and death among people without previous stroke or cardiovascular events, with particularly greater risk of intracerebral hemorrhage and subarachnoid hemorrhage. Noninvasive indices of liver fibrosis may serve as an easily accessible marker to detect individuals facing elevated risk of stroke and death in the primary prevention settings.

Patients with cirrhosis are at risk of developing hepatic encephalopathy (HE), which can present with a wide range of symptoms, including confusion, lethargy, inappropriate behavior, and altered sleep patterns. In addition to HE, patients with cirrhosis are at risk of developing mild cognitive impairment, dementia, and delirium, which have features closely resembling HE. Given the similar presentation of these conditions, misdiagnosis can and does occur. Mild cognitive impairment is common in individuals aged 50 years and older and can progress to dementia in those affected. Dementia and HE are both characterized by sleep disturbance and cognitive dysfunction, thus differentiating these conditions can be difficult. Furthermore, delirium can disrupt sleep patterns, and liver disease is recognized as a risk factor for its development. As HE is a cirrhosis-related complication, determining if a patient has undiagnosed cirrhosis is critical, particularly given the large number of patients with asymptomatic, compensated cirrhosis. Separately, underdiagnosis of minimal HE can occur even in patients with diagnosed liver disease, related, in part, to lack of testing. Given the availability of effective therapies for managing symptoms and preventing future episodes, accurate diagnosis of HE is essential.

Ectopic Variceal Bleeding is a rare complication of portal hypertension, often difficult to manage and potentially life-threatening. However, established guidelines directing treatment are lacking. This report presents a 51-year-old female with hepatitis B-related cirrhosis, who experienced rare small intestinal bleeding due to varicose veins in the superior mesenteric vein and left ovarian vein. The bleeding was successfully resolved by Balloon-occluded Retrograde Transvenous Obliteration. This report discusses the feasibility of BRTO compared to Transjugular Intrahepatic Portosystemic Shunt for certain patients with EctVB.