Some adipose-related parameters exhibit distinct prognostic value in patients with cirrhosis. However, the magnitude and direction of the association between individual adipose parameter and mortality in patients with cirrhosis are unclear.

This study aimed to evaluate the association between individual adipose parameter and mortality in patients with cirrhosis using the meta-analysis method.

The PubMed, Embase, Web of Science, China Biological Medicine, WanFang, and China National Knowledge Infrastructure databases were searched from inception through December 15, 2023, to identify eligible studies. The impact of each adipose parameter on mortality was assessed by the pooled unadjusted or adjusted hazard ratio (HR) with 95% confidence intervals (CIs) using the random effects model.

A total of 33 studies involving 9626 patients were included in our analysis, with 11 adipose parameters evaluated. The pooled prevalence of sarcopenic obesity (SO) and myosteatosis in patients with cirrhosis was 15.5% and 34.4%, respectively. In adjusted analysis, each unit increase in subcutaneous adipose tissue index (SATI) (HR: 0.99, 95% CI: 0.98-1.00) or muscle attenuation (MA) (HR: 0.94, 95% CI: 0.90-0.98) and each unit decrease in visceral-to-subcutaneous adipose tissue ratio (VSR) (HR: 1.92, 95% CI: 1.45-2.54) showed an independent association with a decreased risk of mortality. However, concurrent myosteatosis (HR: 1.88, 95% CI: 1.48-2.40) or SO (HR: 2.77, 95% CI: 1.95-3.93) significantly increased the risk of mortality in patients with cirrhosis.

Decreased SATI or MA, increased VSR, and concurrent myosteatosis or SO were independently associated with a higher risk of mortality in patients with cirrhosis.

Hepatitis B virus (HBV) infection represents a major public health challenge due to its potential progression to liver cirrhosis and hepatocellular carcinoma, underscoring the importance of early diagnosis for effective management. This study aimed to identify plasma biomarkers for the non-invasive diagnosis of hepatitis B cirrhosis (HBC). We employed quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry on plasma samples from 27 individuals, including 13 patients with HBC and 14 with chronic hepatitis B (CHB). Bioinformatics analysis of 963 identified proteins revealed 234 differential expressed proteins, comprising 115 upregulated and 119 downregulated proteins. Four candidate biomarkers-CHI3L1, IGFBP1, SHBG, and TIMP2-were subsequently selected and validated using ELISA in a cohort of 158 patients, all demonstrating elevated levels in HBC patients. The four-biomarker panel (4MP) demonstrated superior diagnostic performance, achieving an area under the curve (AUC) of 0.902 for distinguishing HBC from CHB. For differentiating decompensated HBC from CHB, the 4MP achieved an AUC of 0.993, with a sensitivity of 93.75 % and specificity of 98.73 %. Mostly, the 4MP also performed well in identifying severe HBC from non-severe HBC, achieving an AUC of 0.911, with a sensitivity of 81.25% and specificity of 93.65%. In conclusion, this study identifies four novel plasma biomarkers for HBC, highlighting their potential to enhance non-invasive diagnostic strategies for monitoring HBC progression.

With the increasing prevalence of large language models (LLMs) in the medical field, patients are increasingly turning to advanced online resources for information related to liver cirrhosis due to its long-term management processes. Therefore, a comprehensive evaluation of real-world performance of LLMs in these specialized medical areas is necessary.

This study evaluates the performance of four mainstream LLMs (ChatGPT-4o, Claude-3.5 Sonnet, Gemini-1.5 Pro, and Llama-3.1) in answering 39 questions related to liver cirrhosis. The information quality, readability and accuracy were assessed using Ensuring Quality Information for Patients tool, Flesch-Kincaid metrics and consensus scoring. The simplification and their self-correction ability of LLMs were also assessed.

Significant performance differences were observed among the models. Gemini scored highest in providing high-quality information. While the readability of all four LLMs was generally low, requiring a college-level reading comprehension ability, they exhibited strong capabilities in simplifying complex information. ChatGPT performed best in terms of accuracy, with a "Good" rating of 80%, higher than Claude (72%), Gemini (49%), and Llama (64%). All models received high scores for comprehensiveness. Each of the four LLMs demonstrated some degree of self-correction ability, improving the accuracy of initial answers with simple prompts. ChatGPT's and Llama's accuracy improved by 100%, Claude's by 50% and Gemini's by 67%.

LLMs demonstrate excellent performance in generating health information related to liver cirrhosis, yet they exhibit differences in answer quality, readability and accuracy. Future research should enhance their value in healthcare, ultimately achieving reliable, accessible and patient-centered medical information dissemination.

Chronic liver diseases pose a significant global health concern, ranking as the 11th leading cause of death worldwide. It often progresses to organ fibrosis and severe complications such as portal hypertension and cirrhosis. Liver transplantation is the most effective treatment for such diseases, however, the persistent shortage of donors highlights the need for alternatives. Radiofrequency ablation (RFA) is a promising alternative since it is a minimally invasive procedure. RFA uses heat to destroy abnormal tissues. Its benefits include reduced recovery time compared to surgery, precise targeting of affected areas, and long-lasting symptom relief in many cases. However, RFA has challenges, such as potential risks of nerve damage, infection, or incomplete ablation, requiring repeat treatments. Although significant progress in RFA techniques, effective monitoring remains challenging due to the limited ability to accurately characterize the dynamic thermal diffusion and complex tissue responses.

To address this challenge, hyperspectral imaging (HSI) shows promise in monitoring tissue necrosis post-ablation. Our study evaluated HSI's efficacy in monitoring RFA on ex vivo human fibrotic liver tissue samples.

Statistical analysis revealed correlations between spectral patterns and tissue conditions, which helped identify the optimal spectral bands of 543 nm and 579 nm for accurately distinguishing different tissue states. Analyzing the hemoglobin absorption profile indicated significant reductions in absorption of the green light band, showing approximately 40 % reduction in fibrotic tissue and around 20 % reduction in ablated tissue when compared to normal liver tissue. Additionally, a threshold was established for predicting the ablated area of liver samples, ensuring a condition of 90 % specificity.

Consequently, HSI proved to be a valuable tool for monitoring ablation and a step for improving treatment outcomes for liver fibrosis.

Limited data exist regarding the estimate of the prevalence of advanced liver fibrosis and cirrhosis in the general population. Therefore, we conducted a systematic review and meta-analysis to evaluate the global prevalence and risk factors of advanced fibrosis and cirrhosis.

We searched Embase, PubMed, Scopus, and Web of Science from inception to April 30 2024, with no language restriction. We included cross-sectional studies reporting the prevalence of advanced liver fibrosis and/or cirrhosis in a sample of at least 100 individuals aged ≥18 years from the general population. Subjects with cirrhosis were included in the advanced fibrosis group. The pooled prevalence proportions utilizing a random-effects model and 95% confidence intervals (CIs) were estimated using global data.

A total of 46 studies fulfilled the eligibility criteria, comprising approximately 8 million participants from 21 countries. The pooled prevalence rates of advanced liver fibrosis and cirrhosis in the general population were 3.3% (95% CI, 2.4%-4.2%) and 1.3% (95% CI, 0.9%-1.7%) worldwide, respectively. A trend was observed for an increase in the prevalence of advanced fibrosis (P = .004) and cirrhosis (P = .034) after 2016. There were significant geographic variations in the advanced fibrosis and cirrhosis prevalence at continental and national levels (P < .0001). Potential risk factors for cirrhosis were viral hepatitis, diabetes, excessive alcohol intake, obesity, and male sex.

The prevalence of advanced fibrosis and cirrhosis is considerable and increasing worldwide with significant geographic variation. Further research is needed to better understand the risk factors and how to mitigate them worldwide to address the growing global burden of cirrhosis.

Cirrhosis is associated with a procoagulant state that may worsen disease evolution. Anticoagulation could be of particular interest in these patients. However, evidence on the use of direct oral anticoagulants (DOAC) in patients with cirrhosis is limited.

Our aim was to explore the in vitro effect of DOAC on thrombin generation (TG) in plasma from patients with cirrhosis compared to plasma from healthy controls.

Platelet-poor-plasma was obtained from patients with cirrhosis (n = 87; Child-Turcotte-Pugh class: A, n = 68; B, n = 14; C, n = 5) and controls (n = 17). TG was assessed with ST-Genesia analyzer. Plasma from patients with cirrhosis and thrombomodulin-mediated inhibition of endogenous thrombin potential <20% (ThromboScreen) were defined as "highly procoagulant" (n = 36), ≥20% to 50% as "procoagulant" (n = 31), and >50% as "nonprocoagulant" (n = 20). Plasma samples were spiked with apixaban, edoxaban, rivaroxaban, or dabigatran at final concentrations of 50 and 150 ng/mL. TG was measured (DrugScreen) in plasma samples without and with DOAC.

Apixaban, edoxaban, and rivaroxaban demonstrated significantly reduced inhibition of in vitro TG parameters in highly procoagulant plasma from patients with cirrhosis compared to plasma from controls, whereas possibly artifactual results were observed with dabigatran.

The anticoagulant potency of DOAC differs according to the individual procoagulant potential. Highly procoagulant plasma from patients with cirrhosis is less sensitive to the anticoagulant action of apixaban, edoxaban, and rivaroxaban than control plasma. These results, if confirmed in vivo, would support the concept of personalizing anticoagulant treatment in patients with a highly procoagulant state.

Globally, the aetiology and epidemiology of chronic liver disease (CLD) are undergoing significant changes. We aimed to investigate the updated global burden of CLD, evaluate the cross-country inequalities, and provide 2050 predictions.

Using the Global Burden of Disease Study (GBD) 2021 data resources, we analysed and forecasted CLD prevalence, incidence, and related death from 1990-2021 to 2050, respectively. We calculated average annual percent change (AAPC) by joinpoint regression model and quantified inequalities according to World Health Organisation-recommended health equity standards.

In 2021, the number of prevalent, incident CLD and related deaths globally were 1.7 billion (95% uncertainty interval (UI): 1.6-1.8), 58.4 million (95% UI: 54.2-62.8) and 1.4 million (95% UI: 1.3-1.5), respectively. During 1990-2021, the age-standardised incidence rate (ASIR) increased, especially in those aged 15-49 (AAPC: 0.49%; 95% confidence interval [CI]: 0.45%-0.53%), in Europe (AAPC: 0.41%; 95% CI: 0.41%-0.42%) and the Americas (AAPC: 0.41%; 95% CI: 0.39%-0.42%), whereas the age-standardised death rate (ASDR) decreased globally (AAPC: -1.26%; 95% CI: -1.35% [-1.17%]) and across subgroups. During 1990-2021, the ASIR of metabolic dysfunction-associated steatotic liver disease (MASLD) increased the most in those aged 15-49 (AAPC: 0.72%; 95% CI: 0.67%-0.77%) and in the Western Pacific region (AAPC: 0.73%; 95% CI: 0.59%-0.86%). Socio-demographic index (SDI)-related inequalities decreased for the age-standardised prevalence rate (ASPR) and ASIR of CLD but increased for ASDR, placing a disproportionately heavier burden on low-SDI countries. From 2022 to 2050, the ASIR of CLD is projected to increase (AAPC: 0.20%; 95% CI: 0.19%-0.20%), but the ASDR is projected to decline (AAPC: -1.91%; 95% CI: -1.96% [-1.85%]).

This study's findings highlight targeted interventions for CLD disparities, focusing on MASLD management, the younger population (15-49 years), and socio-demographic inequalities.

Advanced liver fibrosis (ALF) predicts an adverse prognosis in chronic liver disease. In addition to etiological treatment, a new approach to stop or reverse residual fibrosis is desirable.

To assess the efficacy and safety of prolonged-release pirfenidone (PR-PFD) versus placebo in compensated cirrhosis.

180 patients with ALF (F4) were randomly assigned to: placebo, 1200 mg/d, and 1800 mg/d PR-PFD, plus standardised care, for 24mo. Frequency of lab tests: (3mo), liver stiffness measurement (LSM), FibroTest, ultrasound (US) (6mo), and endoscopy (annually).

Fibrosis evolution estimated from LSM was significantly lower only in the 1200 compared to placebo and 1800 groups (24.2 ± 2.4 vs. 15.4 ± 2.4; 27.6 ± 2.4 vs. 24.6 ± 2.4; 24.4 ± 2.3 vs. 23.3 ± 2.3 kPa, respectively, p < 0.001), in intergroup analysis, meeting the primary endpoint. Fibrotest was significantly lower only in the 1200 mg/d group, compared to baseline values (0.86 ± 0.02 vs. 0.83 ± 0.02 units, p < 0.001). Liver function test (LFT's) also improved as well as Model for End-Stage Liver Disease (MELD) score and quality of life (QoL). Decompensations occurred in 19 patients: 12 ascites (more frequent in placebo, p = 0.003), 5 variceal bleeding, 4 encephalopathies, 4 hepatocarcinomas. Adverse events were mainly mild gastrointestinal (n = 35, 48 and 46, p = 0.010) and cutaneous (n = 12, 15, and 22, p = 0.0001) in placebo, 1200 and 1800 mg/day, respectively.

PR-PFD at a dose of 1200 mg significantly decreased non-invasive liver fibrosis markers at 24 months and induced improvement in LFT's, MELD, and QoL in compensated cirrhosis, without safety concerns.

ClinicalTrials.gov identifier: NCT01046474.

Liver cirrhosis represents the end stage of chronic liver disease, characterized by extensive fibrosis and nodular regeneration that significantly increases mortality risk. While magnetic resonance imaging (MRI) offers a non-invasive assessment, accurately segmenting cirrhotic livers presents substantial challenges due to morphological alterations and heterogeneous signal characteristics. Deep learning approaches show promise for automating these tasks, but progress has been limited by the absence of large-scale, annotated datasets. Here, we present CirrMRI600+, the first comprehensive dataset comprising 628 high-resolution abdominal MRI scans (310 T1-weighted and 318 T2-weighted sequences, totaling nearly 40,000 annotated slices) with expert-validated segmentation labels for cirrhotic livers. The dataset includes demographic information, clinical parameters, and histopathological validation where available. Additionally, we provide benchmark results from 11 state-of-the-art deep learning experiments to establish performance standards. CirrMRI600+ enables the development and validation of advanced computational methods for cirrhotic liver analysis, potentially accelerating progress toward automated Cirrhosis visual staging and personalized treatment planning.

Biejia Ruangan Tablet (BJRG) is a patented traditional Chinese medicine formula with demonstrated efficacy against liver fibrosis. However, its underlying molecular mechanisms remain unclear.

This study aimed to investigate the anti-fibrotic effects of BJRG and elucidate its molecular mechanisms.

Liver fibrosis was induced in murine models using carbon tetrachloride (CCl4) or bile duct ligation (BDL) to evaluate the efficacy of BJRG. Network pharmacology was employed to predict the mechanisms of BJRG. The expression of PDGF-AA was assessed in both murine and human samples. The interaction between BJRG and PDGF-AA was investigated in vitro using primary mouse bone marrow-derived macrophages (BMDMs) and LX-2 cells. Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used to identify liver-entry active components of BJRG. Molecular docking was performed to predict their binding affinity with PDGF-AA.

BJRG significantly alleviated liver fibrosis in both CCl4- and BDL-induced murine models. Network pharmacology suggested that BJRG targeted the PDGF/PI3K/AKT signaling pathway. Then we revealed that BJRG specifically downregulated PDGF-AA expression and PI3K/AKT signaling in M2-like macrophages, thereby attenuating hepatic stellate cell (HSC) activation. Clinical data demonstrated that PDGF-AA was associated with liver cirrhosis, and BJRG suppressed PDGF-AA levels in patients with lower Ishak inflammation scores. Molecular docking indicated that the liver-entry components of BJRG exhibited strong binding affinity with PDGF-AA.

BJRG ameliorated liver fibrosis by disrupting the crosstalk between M2-like macrophages and HSCs through downregulation of the PDGF-AA/PI3K/AKT pathway.

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.

Relative changes in the prevalence of gastrointestinal (GI) diseases have been reported worldwide over the past decades. However, data on changing trends of upper GI diseases remain scarce in sub-Saharan Africa. This study examines the shifting patterns of upper GI endoscopic findings over 35 years in Ethiopia.

To analyze trends in upper GI endoscopic findings over two distinct time periods, 35 years apart, in Ethiopia.

We extracted findings from 8412 upper GI endoscopies performed between 2016 and 2024 at a tertiary referral center in Addis Ababa, Ethiopia. Patient characteristics, indications, and endoscopic findings were analyzed using descriptive statistics and presented in tables, map and graphs. These findings were compared to 10000 procedures conducted between 1979 and 1994. Key endoscopic findings were identified, and percentage changes in disease prevalence were calculated.

Between the two study periods, the male-to-female ratio of patients undergoing upper GI endoscopy shifted from 2:1 to 1.4:1, while the median patient age increased from 36 to 40 years. The proportion of patients older than 50 years doubled (14.6% to 30.2%), and referrals from outside Addis Ababa increased from 33% to 57%. The prevalence of peptic ulcer disease and its complications decreased from 46.2% to 9.5%. Conversely, gastroesophageal varices increased from 9.5% to 21.8%, and upper GI malignancies rose from 3.6% to 18.8%.

This study sheds light on critical epidemiological shifts in upper GI diseases in Ethiopia, with a decline in peptic ulcer disease and a rise in portal hypertensive lesions and malignancies which have important public health implications. These findings underscore the need for increased awareness, improved clinical practices, enhanced resource allocation, and expanded access to early diagnosis and treatment of prevailing conditions. Preventive strategies targeting immunization and treatment of viral hepatitis, schistosomiasis, and Helicobacter pylori infection are urgently needed.

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are widely used for type 2 diabetes mellitus (T2DM), conferring cardiovascular and renal benefits with evidence supporting their role in metabolic-associated steatotic liver disease (MASLD), the fastest rising etiology for liver cirrhosis. Our study collects and synthesizes all available data on SGLT2I use in liver cirrhosis to summarize their potential benefits and risks. We systematically reviewed the literature on SGLT2I use in adults with cirrhosis, focusing on 6 outcome domains, including ascites reduction, disease progression, hemodynamics, acute kidney injury (AKI), electrolyte abnormalities, and infection risk. We identified 16 studies: compensated (n = 5), decompensated (n = 3), and refractory ascites (n = 8). All studies of decompensated cirrhosis (n = 11) reported ascites reduction. Most studies (7 of 9) indicated SGLT2Is slowed disease progression by reducing clinical decompensation (n = 4) or improving laboratory markers (n = 3). A minority of studies revealed safety concerns with 2 of 9 studies showing evidence of hemodynamic instability and acute kidney injury (AKI), 2 out of 13 for electrolyte abnormalities, and 2 out of 5 for infection risk. Current evidence strongly supports SGLT2Is for refractory ascites management and suggests potential benefits in slowing progression across cirrhosis severities. Longer-term prospective trials in patients with non-refractory decompensated cirrhosis and real-world safety data are essential to clarify and potentially expand the role of SGLT2Is in cirrhosis management.

: Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear.

: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis.

: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer.

: In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

ACLF is a severe stage of liver cirrhosis, characterized by multiple organ failure, systemic inflammation, and high short-term mortality. The intestinal microbiota (IM) influences its pathophysiology; however, there are currently no studies in Latin American populations. Therefore, we analyzed IM and its relationships with sepsis, organ failure, and mortality. In parallel, we quantified serum lipopolysaccharides as a marker of bacterial translocation. Fecal samples from 33 patients and 20 healthy controls (HCs) were obtained. The IMs were characterized by 16S-rRNA amplicon sequencing, the metagenomic functional predictive profiles were analyzed by PICRUSt2, and LPS quantification was performed by ELISA. Patients with ACLF showed significant alterations in alpha and beta diversity compared to the HCs. A strong dominance index accurately predicted 28-day and 90-day mortalities. The IMs showed a polarization toward Proteobacteria associated with increased LPS. The LPS correlated with clinical severity, organ dysfunction, and higher pathogenic taxa. The Klebsiella/Faecalibacterium ratio showed good performance in identifying sepsis (AUROC = 0.83). Furthermore, Morganella, Proteus, and Klebsiella were enriched in patients with multiorgan failure. Lactobacillus, Escherichia/Shigella, Veillonella, and Ruminococcus gnavus exhibited potential in predicting 28- and 90-day mortalities. The IM alterations in ACLF may be useful as clinical biomarkers of poor prognosis, primarily for mortality and sepsis. These findings are representative of western Mexico.

Liver cirrhosis continues to be a major global health issue, contributing to high morbidity and mortality due to its progressive nature and associated complications. This review explores recent advancements in the diagnosis and treatment of liver cirrhosis and its related syndromes. Non-invasive diagnostic tools, such as elastography and serum biomarkers, have significantly improved early detection, reducing the need for liver biopsies. Advanced imaging techniques, including MRI and CT, further enhance diagnostic accuracy. In parallel, molecular and genomic research is providing new insights into the pathogenesis of the disease, paving the way for precision medicine. On the treatment front, pharmacological innovations, such as antifibrotic agents and targeted therapies, show promise in slowing disease progression. Endoscopic interventions like variceal banding are improving the management of complications, while advancements in liver transplantation and artificial liver support systems offer life-saving alternatives. Regenerative medicine, particularly stem cell therapy and tissue engineering, is emerging as a promising strategy for liver repair. Managing cirrhosis-related syndromes, including portal hypertension, ascites, hepatic encephalopathy, and hepatorenal syndrome, now involves evolving therapeutic approaches such as transjugular intrahepatic portosystemic shunt (TIPS) and novel pharmacotherapies. Prognostic scoring systems like the MELD and Child-Pugh are being refined with new biomarkers for better risk stratification. The future of cirrhosis care will likely involve the integration of artificial intelligence and machine learning for early diagnosis and personalized treatments, alongside emerging therapies currently under investigation. Despite these advancements, challenges such as costs, accessibility, and healthcare disparities remain barriers to widespread adoption. This review highlights the importance of incorporating innovative diagnostic and therapeutic strategies into clinical practice to improve the outcomes for patients with liver cirrhosis and its complications.

Cirrhosis, characterized by liver fibrosis and structural remodeling, is a leading cause of liver cancer. The Fuzheng Huayu formula (FZHY) has been approved for treating liver fibrosis in China since 2002, but its effects and mechanisms on cirrhosis remain largely unknown. This study employed network pharmacology, molecular docking, and in vitro experiments to elucidate the specific mechanisms of FZHY against liver cirrhosis. First, intersecting genes between FZHY and cirrhosis were obtained from the Chinese Medicine System Pharmacology Database, the Swiss Target Prediction online platform, UniProt, GeneCards, DisGeNET, and OMIM. The STRING database was used to construct a protein-protein interaction network. Subsequently, Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, followed by molecular docking analysis to verify binding affinities between active ingredients and candidate targets. These analyses provided a theoretical basis for subsequent experimental research. Finally, we identified 117 FZHY target genes associated with cirrhosis and constructed a drug-component-target-cirrhosis-pathway network. Enrichment analysis revealed the AGE-RAGE signaling pathway in diabetic complications as a key pathway. Molecular docking showed that Isotanshinone II had the highest affinity for CHUK, IKBKB, and MAPK14. In vitro experiments demonstrated that Isotanshinone II dose-dependently reduced the mRNA expression of COL1A1 and α-SMA, as well as the protein levels of MAPK p38, IKKβ, and NF-κB p65 in LX-2 cells. These results revealed the underlying mechanism by which Isotanshinone II in FZHY inhibited LX-2 cell activation and collagen production through suppression of the MAPK/NF-κB signaling pathway. These findings support Isotanshinone II as a promising compound for cirrhosis targeting the MAPK/NF-κB pathway. Further research is warranted to explore the bioavailability of Isotanshinone II and to optimize its structure for clinical applications.

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.

Background: Liver cirrhosis is often accompanied by metabolic dysfunction. Circulating β-hydroxybutyrate (BHB), the most abundant ketone body, is an emerging metabolic biomarker of mitochondrial dysfunction. Methods: In this prospective observational study, we evaluated plasma BHB concentrations in patients with cirrhosis compared to the general population and investigated their association with all-cause mortality in cirrhosis. Plasma BHB, measured by nuclear magnetic resonance spectroscopy, was compared between 125 patients with cirrhosis on the waiting list for liver transplantation (TransplantLines cohort study; NCT03272841) with 125 propensity-score-matched participants from the population-dwelling PREVEND cohort. Associations of BHB with all-cause mortality were established by tertile-based log-rank tests and Cox regression analyses. A generalized additive model was fitted to assess a potential non-linear association between BHB and mortality. Results: Patients with cirrhosis had lower plasma BHB concentrations than matched PREVEND participants (111.5 µmol/L vs. 138.4 µmol/L, p = 0.02). During 133 (interquartile range 42-375) days of follow up, 27 patients died. All-cause mortality was lowest in the middle BHB tertile and highest in the upper BHB tertile (p < 0.001 by log-rank test). A non-linear, J-shaped association between BHB levels and mortality risk was found with a higher risk of death with the highest and lowest BHB levels. In Cox regression analyses, adjusted for age, sex, MELD score, diabetes, and HDL cholesterol, mortality was highest in the highest BHB tertile (T3 vs. T2 HR: 7.6, 95% CI: 2.3-25.6, p < 0.001). Mortality also tended to be higher in the lowest vs. the middle (T1 vs. T2 HR: 3.5, 95% CI: 0.9-11.7, p = 0.06). Sensitivity analyses, excluding diabetic patients and those with metabolic dysfunction-associated steatotic liver disease, confirmed the robustness of these findings. Conclusion: BHB levels exhibit a J-shaped association with the risk of death in patients with liver cirrhosis. The highest circulating BHB levels are independently associated with increased mortality risk, potentially reflecting underlying metabolic dysregulation. Future studies are necessary to validate the utility of BHB as a prognostic target in cirrhosis.

Limited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in MASLD.

This cross-sectional study included prospectively recruited adults with MASLD aged 18-70 who underwent magnetic resonance elastography (MRE) and genotyping for PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13. A genetic risk score (GRS) was calculated as the sum of established risk alleles in PNPLA3 minus protective variants in HSD17B13 (0=low risk, 1=high risk). We also estimated the polygenic risk score-hepatic fat content (PRS-HFC) and the adjusted version (PRS-5). The primary endpoint was the age-related change in liver stiffness measurement (LSM) on MRE by GRS. Findings were validated using an external cohort from Latin America.

Among 570 participants, the median age was 57 [49-64] years, 56.8% were women, and 34.2% were Hispanic. Median MRE was 2.4 [2.1-3.0] kPa, and 51% had high GRS. High GRS was independently associated with increased LSM (β=0.28 kPa, 95%CI:0.12-0.44, p=0.001) per 10-year age increase, while the low GRS group showed no significant difference. Similar findings were observed using PRS-HFC and PRS-5. PNPLA3 genotype alone also predicted higher LSM (C/G: β=0.32 kPa, 95%CI:0.02-0.61, p=0.034; G/G: β=0.87 kPa, 95%CI:0.52-1.22, p<0.0001) and G/G genotype was associated with significantly higher LSM by age 44, which was consistent in the validation population.

GRS, PRS-HFC, PRS-5, and PNPLA3 genotypes alone are associated with greater fibrosis per decade, resulting in divergent disease trajectories starting in midlife. Assessing genetic risk in MASLD will identify high-risk patients who require more frequent monitoring.

This study provides granular evidence that genetic predisposition, particularly the PNPLA3 G/G genotype, significantly influences the trajectory of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), with a more pronounced impact emerging after the fourth decade of life. These findings highlight the importance of incorporating genetic risk assessment into MASLD management, as it allows for the early identification of high-risk individuals who may benefit from more frequent monitoring and targeted interventions. Given the rising global burden of MASLD, clinicians, researchers, and policymakers should consider integrating genetic stratification into existing risk assessment frameworks to refine screening and surveillance strategies. By optimizing patient selection for non-invasive fibrosis assessment and potential therapeutic interventions, this approach could enhance precision medicine efforts and may improve long-term outcomes.

Background and Aim: Dental diseases are common in patients with cirrhosis. In these patients, reduced mastication might interfere with protein intake and contribute to malnutrition. We addressed the relationship between reduced mastication and dynapenia in patients with cirrhosis. Methods: This cross-sectional study involved patients with cirrhosis treated in a Brazilian center. Trained dentists performed oral examinations and tested the patients for nutritional parameters such as handgrip strength (HGS) and gait speed test (GST). Reduced mastication was presumed when a patient had molar edentulism (≥ 3 teeth), bad dental occlusion, or ill-fitting denture. Associations between mastication status and malnutrition were evaluated using multivariate linear regression analysis for continuous measures and adjusted prevalence ratio (PR (95% confidence interval)) for binary measures. Results: We included 149 patients with cirrhosis (60 ± 13 years old, 76% men, 64% Child A, 60% due to alcoholism only). Reduced mastication affected 107 patients (72%), low muscle strength (decreased HGS) occurred in 45 (30%), and decreased GST was observed in 58 (41%, among 143 patients able to walk). Thirty-one out of 143 (22%) presented decreased HGS and GST, characterizing dynapenia. Reduced mastication was associated either with decreased HGS [PR = 2.28 (1.08-4.81), p = 0.030; reduced mastication decreases the HGS mean by 12.5 kg for men (p < 0.001) and 8.1 kg for women (p = 0.065)] or with decreased GST [PR 1.97 (1.09-3.55), p = 0.024; reduced mastication increased the time of GST by 1.1 s on average (p = 0.005)], adjusting for age, alcoholic etiology, and Child-Pugh classification. Conclusions: Reduced mastication is associated with dynapenia markers in patients with cirrhosis. Further studies are needed to assess whether oral rehabilitation can change the curse of malnutrition in this population.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition with a steadily increasing prevalence. Evidence indicates that both smoking and obesity are significant risk factors for NAFLD, yet the extent to which smoking influences NAFLD through weight gain remains unclear. This study aimed to dissect the intricate relationship between smoking, body mass index (BMI), and NAFLD using Mendelian randomization (MR) analysis. We leveraged data from 30 genome-wide association studies involving over 1.2 million individuals, from which 123 single nucleotide polymorphisms were selected as instrumental variables for smoking. BMI data were sourced from the Genetic Investigation of Anthropometric Traits (GIANT) consortium, encompassing more than 700,000 individuals, with 521 single nucleotide polymorphisms serving as instrumental variables. NAFLD data were obtained from multiple databases, including the eMERGE Network, UK Biobank, Estonian Biobank, and FinnGen, comprising 8434 cases and 770,180 controls. All participants in this study were of European ancestry. We first applied univariate MR analysis to assess the causal relationship between smoking, NAFLD, and BMI. Subsequently, multivariate MR was used to assess the effect of smoking on NAFLD after adjusting for BMI. The coefficient product method was used to calculate the mediating effect of BMI. Results found that both smoking and high BMI were able to increase the risk of NAFLD, with odds ratios of 1.83 (95% confidence interval [CI]: 1.31-2.55) and 1.58 (95% CI: 1.42-1.77), respectively. BMI mediated 73.3% (95% CI: 62.3%-80.5%) of the effect of smoking on NAFLD. The findings support weight control and the encouragement of smoking cessation, especially in obese populations, as strategies to reduce the risk of NAFLD.

Studies have shown a change in the etiological profile of liver cancer globally. We aimed to analyze the burden and changes in etiology of liver cancer in the Asia-Oceania region.

The burden of liver cancer in Asia-Oceania was estimated using data from the 2021 Global Burden of Disease (GBD) Study. The analysis included age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALY) per 100 000 population.

The Asia-Oceania region contributed 68.6%, 68.8%, and 67.3% of the global incidence, prevalence, and mortality of liver cancer in 2021. In 2021, Mongolia, Tonga, and South Korea had the highest ASIR, ASPR, and ASMR, whereas Australia, New Zealand, and Guam had the greatest increase in incidence and mortality rates. Viral hepatitis remained the most common etiology of liver cancer, with 47.7% and 26.1% of cases being related to hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. Around 14.5% and 7.1% of cases were related to alcohol and nonalcoholic steatohepatitis (NASH), respectively; however, the annual change in the ASIR was the highest for NASH. Alcohol, drug abuse, tobacco use, and metabolic syndrome, contributed to 15.2%, 11.7%, 11.5%, and 9.0% of liver cancer mortality in 2021; however, the change in death from 1990 to 2021 was the highest for metabolic syndrome.

Viral hepatitis remains the most common cause of liver cancer, with NASH having the highest annual rate of change in ASIR and liver cancer deaths in Asia-Oceania.

Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using healthcare claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated healthcare resource utilization among commercially and Medicare-insured adults in the United States.

Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020). Annual prevalence of cirrhosis, HE, overt HE (OHE) hospitalizations, and rifaximin ± lactulose use, and costs per hospitalization per year were calculated. Average year-over-year changes in prevalence of cirrhosis, and HE were estimated. Trends were extrapolated to 2030 using ordinary least-squares regression.

From 2007 to 2020, the prevalence of cirrhosis increased by an average of 4.6% year-over-year in the Commercial population and 8.1% in the Medicare population; the prevalence of HE increased by 4.3% and 2.5%, respectively. Rates of OHE hospitalizations decreased from 27.5% to 5.5% (Commercial) and from 26.2% to 9.5% (Medicare), and rates of liver transplantation increased. Average payer costs (Commercial) and provider charges (Medicare) per OHE hospitalization increased (from $40,881 to $77,699 and from $45,913 to $74,894, respectively). Use of rifaximin ± lactulose showed an increasing trend during the observation period, whereas lactulose use declined steadily.

The healthcare burden of cirrhosis and HE in the United States is increasing. Trends are projected to continue unless action is taken, such as improving medication access and developing policies addressing the contributing factors.

Background: Cirrhosis is associated with significant healthcare utilization, yet data about in-hospital decompensations remain sparse. Additionally, the impact of liver transplant candidacy status on resuscitation and outcomes is largely unknown. Aims:We aimed to evaluate the characteristics of resuscitation events for patients with cirrhosis with acute decompensation, analyzing liver transplant candidacy and intensive care unit (ICU) transfer parameters. Methods: Retrospective single-center review of adult patients with liver cirrhosis who had a rapid response team (RRT) activation during hospitalization and no prior liver transplantation. Results: Patients with cirrhosis who were liver transplant candidates were more likely to be younger (p = .003), have a higher serum total bilirubin (p = .015), higher INR (p < .001), and higher MELD 3.0 (p = .006). There was no significant difference in ICU transfer (p = .170) after RRT activation. Liver transplant candidates had a lower 30- and 60-day mortality (p = .008, p = .014) and were less likely to have a code status discussion after decompensation (p = .001). Lower serum albumin was associated with ICU transfer (p = .001). Patients who transferred to the ICU were more likely to have a code status discussion within 24 h after RRT (p = .011) without significant difference in 30- or 60-day mortality (p = .059, p = .277). Conclusions: Liver transplant candidacy in patients with cirrhosis with acute decompensation is not clearly correlated with ICU transfer. Liver transplant candidates are more likely to be younger, have higher MELD 3.0 scores, less likely to have code status discussed after RRT, and have lower 30- and 60-day mortality rates. Patients who transfer to the ICU are more likely to have a code status discussion without any significant difference in 30- or 60-day mortality.

Objective To evaluate the effect of pemafibrate (PEM) on metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We retrospectively evaluated 43 patients with hyperlipidemia and MASLD to determine changes in clinical factors between the start of PEM treatment and 0.5 years later. Using FibroScan, 39 of 43 patients were evaluated for liver stiffness (LS; kPa) and controlled attenuation parameter (CAP; dB/m). None of the patients had decompensated cirrhosis. Results Thirty patients were women, the median age was 66 years old, the median fibrosis-4 (FIB-4) score was 2.52, the median LS was 8.05 kPa, and the median CAP was 280.5 dB/m at the start of PEM treatment. AST, ALT, ALP, γGTP, and triglyceride levels decreased 0.5 years after starting PEM treatment, but FIB-4, LS, and CAP values did not decrease. However, LS decreased in patients with a FIB-4 index ≥1.3 at the start of PEM treatment, whereas it did not change in patients with a FIB-4 index <1.3. Similarly, LS decreased in patients with a value ≥8 kPa at the start of treatment and did not change in those with <8 kPa. The decreased LS group had higher baseline ALT and LS levels and lower ALT levels during 0.5 years of follow-up than the increased LS group. Conclusion At the initiation of PEM treatment, the LS decreased in patients with MASLD complicated by hyperlipidemia and moderate LS (FIB-4>1.3 or LS >8 kPa). Although there is currently no approved treatment for MASLD, PEM may be a viable treatment option for MASLD with mild LS.

Despite global vaccination efforts, hepatitis B virus (HBV) infection remains a major health threat, causing over a million deaths annually. Hepatitis B e-antigen (HBeAg) is an indicator of HBV replication and high infectivity. HBeAg is an essential serological marker for monitoring response to treatment and/or determining the stage of chronic HBV infection. Here, we produced a panel of mouse hybridomas secreting monoclonal antibodies (MAbs) to HBeAg by fusing a mouse myeloma cell line with splenocytes from mice immunized with recombinant HBeAg. Anti-HBe MAbs were then characterized by competition ELISA and Western blotting. We designed and optimized an in-house sandwich ELISA using HBeAg-specific rabbit polyclonal and mouse monoclonal antibodies. The diagnostic performance of the assay was then compared to a commercial HBeAg detection ELISA kit using 176 HBeAg[-] and 44 HBeAg[+] serum samples, showing a significant positive correlation (r = 0.8250; P < 0.0001). The in-house ELISA showed reasonable sensitivity (97.56 %) and specificity (99.40 %), with a cut-off value and area under the curve of 0.193 and 0.9884, respectively. Additionally, the assay showed high repeatability, with intra- and inter-assay coefficients of variation of 2.46 % and 11.38 %, respectively. Our designed HBeAg-detecting sandwich ELISA has the potential for use in clinical diagnosis.

During chronic liver diseases, LSECs undergo a dedifferentiation process contributing to the development of hepatic microvascular dysfunction. Although microRNAs (miRNAs) have been associated with chronic liver disease, their role as modulators of liver endothelial phenotype is mostly unknown. Therefore, the aim of this study was to analyze miRNAs as regulators of hepatic sinusoidal endothelial dysfunction in chronic liver disease to suggest novel and translatable therapeutic options for cirrhosis.

Global expression of miRNAs was determined in primary LSECs from healthy and cirrhotic patients (alcohol abuse) and rats (CCl4 inhalation). LSECs were transfected with the mimetic or inhibitor of dysregulated miRNAs or with quantum dot nano-complexes containing miR-27b-3p or negative control, and endothelial phenotype was analyzed by RNA sequencing, quantitative PCR, and western blot. Endothelial or mesenchymal phenotypes were analyzed in LSEC by RNA sequencing, followed by pathway analyses and gene deconvolution.

In all, 30 and 69 dysregulated miRNAs were identified in human and rat cirrhosis, respectively, of which 6 miRNAs were commonly dysregulated. Specific exogenous downregulation of miR-27b-3p was associated with the upregulation of target genes, suggesting a correlation between loss of miR-27b-3p and LSEC dedifferentiation. Finally, the expression of miR-27b-3p was efficiently and physiologically re-established in cirrhotic LSECs using nano-miR-27b-3p, leading to modulation of 1055 genes compared with the negative control, ultimately leading to inhibition of the endothelial-to-mesenchymal transition process observed in cirrhosis.

Loss of miR-27b-3p expression contributes to LSECs dedifferentiation in cirrhosis. The use of nano-miR-27b-3p represents a new therapeutic option for hepatic diseases coursing with endothelial dysfunction.

We aimed to recognize the burden of NAFLD and support public health policy development for its prevention and management.

A cross-sectional analysis of GBD 2021 results was conducted.

We collected incidence data on NAFLD from 1990 to 2021 using Global Burden of Disease Study in 2021. Estimated annual percentage changes (EAPCs) in NAFLD age standardized incidence rate (ASR) were calculated to quantify the temporal trends in NAFLD ASR. Bayesian age-period-cohort models were constructed to project NAFLD incidence rates and cases up to 2050. Additionally, we assessed the percentage of cirrhosis and liver cancer attributable to NAFLD.

Globally, the newly-occurred cases of NAFLD increased by 94.49 % from 24, 856, 159 in 1990 to 48, 353, 272 in 2021. The case number will further increase to 78,602,984 in 2050, and ASR will increase from 5.93 per 1000 in 2021 to 7.26 per 1000 in 2050. The most pronounced increases were observed in young people and men. In 2021, NAFLD accounted for 82.7 % of cirrhosis and other chronic liver diseases and 8.0 % of liver cancer cases.

From 1990 to 2021, the incidence of NAFLD has been continuously increasing and is expected to continue rising until 2050. The increases in young people and men highlight their priority in future schedules. The rising proportions of cirrhosis and liver cancer caused by NAFLD further underscore the serious health risks.

Prolonged therapy using nucleos(t)ide analogs (NUC) is inevitable in patients with chronic hepatitis B (CHB) infection, but its long-term impact on Parkinson's disease (PD) risk remains unclear. This study evaluated the association between NUC therapy and PD incidence in a nationwide CHB cohort. The study population comprised the National Health Insurance Service claims database from January 1, 2013, to December 31, 2013, only included treatment naïve CHB patients and those without previously diagnosed with PD. Participants were followed until PD diagnosis or study completion. The primary outcome was PD incidence, comparing patients who initiated NUC therapy at cohort entry with those who did not. Over the 7.9-year study period, the incidence rate of PD in NUC-treated patients was 1.48 per 1000 persons, compared to 1.95 per 1000 persons in the untreated group. In an adjusted competing risk model, the 3-year follow-up showed a statistically significant reduction in risk (hazard ratio [HR]: 0.61; 95% confidence interval [CI] 0.39-0.97). In the propensity score-matched cohort of 18,365 pairs, the cumulative incidence during 2-4 years of follow-up was significantly lower in the NUC-treated group compared to the untreated group. However, no statistically significant difference in cumulative PD incidence was observed between the groups at the early or late stages of the follow-up period. NUC therapy initially reduced PD incidence, but this protective effect diminished over time, indicating a time-varying effect. Regular PD screening may be needed for long-term NUC users.

Liver cirrhosis is posing a global public health concern despite improvements in early diagnosis and therapeutic innovations. The present work evaluates the acute toxicity and prophylactic effects of an O-methylated flavonoid (Ombuin) in thioacetamide (TAA)-induced liver injury in rats and its underlying mechanisms. Thirty Sprague-Dawley rats were aligned into five cages and treated for two months as follows: group A ingested orally 1% CMC + distilled water (i.p.); group B had 1% CMC + 200 mg/kg TAA i.p. (three times weekly); group C had 50 mg/kg silymarin + 200 mg/kg TAA; group D had 30 mg/kg Ombuin + TAA; group E had 60 mg/kg Ombuin + mg/kg TAA. The non-toxic effects of Ombuin were evidenced by the lack of any toxicity incidence in rats ingested with up to 500 mg/kg. The TAA inoculation provoked significant hepatic intoxication confirmed by histopathological indications, alteration of tissue architecture, cellular proliferation, endothelial injury, enlarged hepatic nucleus, cytoplasmic vacuolation, collagen deposition, and elevated necrotizing tissues. The oxidative stress and inflammation process was noticeably initiated following TAA delivery to rats evidenced by down-regulation of SOD, CAT, GPx, and IL- 10, while, up-regulating the MDA and TNF-α and IL- 6 cytokines. TAA injection stimulated cellular proliferation and apoptotic actions in injured liver tissues, indicated by increased proliferating cell nuclear antigen (PCNA) and elevated expression of Bcl- 2-associated X (Bax) proteins. Ombuin supplementation showed significant resistance against TAA-mediated hepatotoxicity, reversed those cellular alterations, and restored liver functions. These results demonstrate significant ameliorative effects of Ombuin in TAA hepatotoxic rats, which could be attributed to its anti-apoptotic, antioxidant, and anti-inflammatory potentials, making it a possible viable hepatoprotective agent for inflammatory-related hepatitis.

Background: LI-RADS CT/MRI Radiation Treatment Response Algorithm (TRA) version 2024 (v2024) addresses a pitfall of the earlier algorithm relating to expected persistent enhancement of hepatocellular carcinoma (HCC) responding to radiation. v2024 removes LR-TR Equivocal, introduces LR-TR Nonprogressing (stable or decreasing masslike enhancement), and more narrowly defines LR-TR Viable (new or increasing masslike enhancement). Objective: To evaluate in patients with HCC treated by Y-90 radioembolization the redistribution of categories in LI-RADS CT/MRI Radiation TRA v2024 versus LI-RADS CT/MRI TRA version 2018 (v2018) and to assess short-term outcomes of v2024 categories. Methods: This retrospective study included 242 patients (57 women, 185 men; median age, 65 years) with 319 HCCs treated by Y-90 radioembolization from February 2011 to March 2022 and evaluated by initial 3-month posttreatment CT or MRI. Two radiologists assigned v2018 and v2024 categories; a third radiologist resolved discrepancies. The radiologists also assessed available second posttreatment CT or MRI examinations using v2024. Overall survival (OS) was determined. Results: On initial follow-up, by v2018, 18 (5.6%) lesions were LR-TR Nonviable, 21 (6.6%) LR-TR Equivocal, and 280 (87.8%) LR-TR Viable; by v2024, 18 (5.6%) were LR-TR Nonviable, 182 (57.1%) LR-TR Nonprogressing, and 119 (37.3%) LR-TR Viable. All LR-TR Equivocal and 161 (57.5%) LR-TR Viable lesions by v2018 were recategorized as LRTR Nonprogressing by v2024. Of 96 LR-TR Nonprogressing lesions with second follow-up, 63 (65.6%) remained LRTR Nonprogressing, 19 (19.8%) transitioned to LR-TR Nonviable, and 14 (14.6%) transitioned to LR-TR Viable. Of 29 LR-TR Viable lesions by v2024 with second follow-up, 23 (79.3%) remained LR-TR Viable, and 6 (20.7%) transitioned to LR-TR Nonprogressing. By Kaplan-Meier analysis using initial categories, OS showed no significant difference between LR-TR Equivocal and LR-TR Viable for v2018 (p=.05) but was significantly worse for LR-TR Viable than LRTR Nonprogressing for v2024 (p<.001). Conclusion: For v2024, LR-TR Viable was substantially less frequent versus v2018, and the majority of lesions were assigned LR-TR Nonprogressing. Using v2024, most LR-TR Viable lesions and the majority of LR-TR Nonprogressing lesion on initial follow-up remained as such on later imaging. Initial v2024 categories were associated with OS. Clinical Impact: The findings support the revisions in v2024.