This study investigates the relationship between Cyclin D1 (CCND1) gene and promoter methylation and liver fibrosis (LF)/liver cirrhosis (LC)induced by chronic hepatitis B (CHB). Peripheral blood mononuclear cells (PBMCs) are collected from patients diagnosed with chronic hepatitis B (CHB) and hepatitis B-related LF/LC, as well as from healthy individuals. The mRNA levels and promoter methylation of the CCND1 gene are measured. Single-cell analysis is performed to determine the cell types primarily expressing the CCND1 gene in LF/LC. The GSE84044 dataset is utilized to validate the experimental results. Single-gene GSEA and immune infiltration analyses are conducted to identify significant pathways and immune characteristics associated with the CCND1 gene. The mRNA level of CCND1 in PBMCs from patients with hepatitis B-related LF/LC is elevated compared to those with chronic hepatitis B (CHB) and healthy individuals, while the promoter methylation level of CCND1 is reduced. Single-cell analysis indicates high expression of CCND1 in M2 macrophages (M2) and T cells. The GSE84044 dataset confirms higher CCND1 mRNA levels in liver tissues from patients with CHB-related LF/LC compared to CHB patients. Single-gene GSEA analysis associates CCND1 expression with natural killer cell-mediated cytotoxicity, T cell receptor signaling, and B cell receptor signaling pathways. Increased expression of CCND1 enhances immune infiltration during the fibrosis/cirrhosis process of CHB. The CCND1 expression and promoter methylation may be involved in the process of LF/LC in CHB and may be related to the immune response in the course of the disease.

HCV genotype (GT) 3 is associated with rapid liver disease progression. However, the liver disease progression and its risk factors in patients with HCV GT 3 infection after sustained virological response (SVR) following direct-acting antivirals (DAAs) remain unclear. Therefore, we aimed to investigate the liver disease progression of patients with GT 3 after SVR.

This was a retrospective cohort study of patients with HCV infection who achieved SVR by DAAs. The clinical outcome was overall liver disease progression (OLDP), defined as newly diagnosed compensated liver cirrhosis, decompensated liver cirrhosis, or hepatocellular carcinoma. The incidence of OLDP was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the risk factors for OLDP.

A total of 409 patients (46.9% GT3) were followed for 43.7 (32.9, 58.7) months. The incidence of OLDP was higher in patients with GT 3 (4.63/100PY) than non-GT 3 (0.60/100PY; P < 0.001). According to Cox multivariate analysis, GT 3 was significantly associated with OLDP (HR 6.41, 95% CI 1.82 - 22.56; P=0.004). The predictors of OLDP in patients with GT 3 were HCV recurrence (HR 12.15, 95% CI 3.18 - 46.46; P < 0.001) and FIB-4 > 3.25 (HR 16.40, 95% CI 1.03 - 39.81; P = 0.046) at baseline.

HCV GT 3-infected patients remain at a higher risk of OLDP even after achieving SVR by DAAs, especially patients with advanced liver fibrosis and at high risk for reinfection or virological late relapse.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for managing complications of portal hypertension, particularly acute variceal bleeding (AVB). While effective in reducing portal pressure and preventing rebleeding, TIPS is associated with a considerable risk of overt hepatic encephalopathy (OHE), a complication that significantly elevates mortality rates.

To develop a machine learning (ML) model to predict OHE occurrence post-TIPS in patients with AVB using a 5-year dataset.

This retrospective single-center study included 218 patients with AVB who underwent TIPS. The dataset was divided into training (70%) and testing (30%) sets. Critical features were identified using embedded methods and recursive feature elimination. Three ML algorithms-random forest, extreme gradient boosting, and logistic regression-were validated via 10-fold cross-validation. SHapley Additive exPlanations analysis was employed to interpret the model's predictions. Survival analysis was conducted using Kaplan-Meier curves and stepwise Cox regression analysis to compare overall survival (OS) between patients with and without OHE.

The median OS of the study cohort was 47.83 ± 22.95 months. Among the models evaluated, logistic regression demonstrated the highest performance with an area under the curve (AUC) of 0.825. Key predictors identified were Child-Pugh score, age, and portal vein thrombosis. Kaplan-Meier analysis revealed that patients without OHE had a significantly longer OS (P = 0.005). The 5-year survival rate was 78.4%, with an OHE incidence of 15.1%. Both actual OHE status and predicted OHE value were significant predictors in each Cox model, with model-predicted OHE achieving an AUC of 88.1 in survival prediction.

The ML model accurately predicts post-TIPS OHE and outperforms traditional models, supporting its use in improving outcomes in patients with AVB.

Inflammatory reactions and dyslipidemia are associated with the pathogenesis and prognosis of hepatitis B virus-related cirrhosis. We aimed to assess the predictive ability of these parameters in patients with hepatitis B virus-related cirrhosis and overt hepatic encephalopathy (HBV-related OHE).

We conducted an analysis of 1,404 participants diagnosed with HBV-related OHE between January 2008 and July 2023. The prognostic significance of the neutrophil-to-high-density lipoprotein cholesterol (HDL-C) ratio (NHR), lymphocyte-to-HDL-C ratio (LHR), and monocyte-to-HDL-C ratio (MHR) was evaluated using the area under the receiver operating characteristic curve (AUC). Restrictive cubic splines (RCS) were employed to explore the relationship between NHR and 12-month transplant-free (TF) mortality. This study included a prospective test cohort of 328 patients.

NHR was identified as an independent risk factor for 12-month TF mortality. The AUC for NHR (0.776) was similar to that of the model end-stage liver disease (MELD) score (AUC: 0.777). In the test cohort, NHR demonstrated AUC values comparable to MELD, with significantly higher AUCs than LHR and MHR (both p < 0.05). Based on cutoff values for NHR and MELD, patients were classified into four risk subgroups: very-low (NHR < 10 and MELD <18), low (NHR ≥ 10 and MELD <18), moderate (NHR < 10 and MELD ≥18), and high (NHR ≥ 10 and MELD ≥18). The 12-month TF mortality rates in the training cohort were 7.2, 23.5, 30.8, and 51.4%, respectively, for these subgroups, while in the test cohort, the rates were 8.7, 20.5, 30.7, and 46.0%.

NHR is a valuable and accessible prognostic indicator for 12-month TF mortality in patients with HBV-related OHE. Patients with both NHR ≥ 10 and MELD ≥18 are at the highest risk of mortality.

Infiltrative hepatocellular carcinoma (HCC) remains a therapeutic challenge due to its aggressive course and poor prognosis. Hepatic arterial infusion chemotherapy (HAIC) plus immune checkpoint inhibitors (ICIs) and molecular targeted therapies (MTTs) has shown early promise for advanced HCC, but its role in advanced infiltrative HCC is unclear. This study aims to investigate the efficacy and safety of HAIC combined with ICIs and MTTs in the treatment of advanced infiltrative HCC.

Patients with infiltrative HCC initially treated with HAIC plus ICIs and MTTs were consecutively included at our institution from November 2021 to June 2023. The efficacy evaluation included tumor response, time to response (TTR), duration of response (DOR), progression-free survival (PFS) per RECIST 1.1, and patient survival. Adverse events (AEs) were recorded for safety evaluation.

A total of 27 patients were included and the median follow-up was 15.8 months (range, 4.3-25.9). The best objective response rate (ORR) and disease control rate (DCR) were 70.4% and 88.9%, respectively. The median TTR was 2.8 months (95% confidence interval [CI], 2.6-3.0) and the median DOR was 7.9 months (95% CI, 3.2-12.5). The median PFS was 7.5 months (95% CI, 4.2-10.7), and the median overall survival (OS) was 16.8 months (95% CI, 14.0-19.6), with a 1-year OS rate of 74.1%. No cases of grade 4 or 5 treatment-related adverse events (TRAEs) were observed in this study. Grade 3 TRAEs occurred in 17/27 (63.0%) patients, and the predominant grade 3 treatment-related adverse events were lymphocyte count decreased (18.5%) and neutrophil count decreased (14.8%).

The combination of HAIC plus ICIs and MTTs demonstrated encouraging outcomes and manageable safety concerns for infiltrative HCC.

Extrachromosomal circular DNA (eccDNA) regulates tumor occurrence and development. Relevant eccDNA profiles have been established for various types of cancer; however, the eccDNA expression profiles in the blood of patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC) remain unknown. The present study aimed to investigate the eccDNA expression profiles in the blood of patients with HCC and LC.

Circle-seq was used to detect eccDNAs in the blood samples. Full transcript sequencing was used to analyze the RNA in the samples. Geno Ontology enrichment and Kyoto Encyclopedia of Genes and Genome pathway analyses were performed on differentially expressed eccDNA-related genes. The identified eccDNA is combined with mRNA to screen target genes using bioinformatics analysis. EccDNAs were confirmed through polymerase chain reaction and Sanger sequencing.

Overall, 103,235 eccDNAs were identified in HCC, whereas 67,110 eccDNAs were detected in LC. In total, 7,095 upregulated eccDNAs and 1,284 downregulated eccDNAs were identified. Following analysis of differential genes using bioinformatics, six candidate genes were screened out based on gene expression and cancer relevance. Experiments have verified that LAMA4 [circle112550019-112550510] and KANK1 [circle674459-674907] are real and expressed target genes, and their source genes are closely related to the survival time of patients with liver cancer.

Our research results revealed the main characteristics of eccDNAs in the blood of patients with HBV-related HCC and LC. It was found that eccDNAs were mainly less than 1,000 bp in length. Difference analysis showed that some eccDNAs had consistent and overlapping expressions with mRNAs. We found that LAMA4 [circle112550019-112550510] and KANK1 [circle674459-674907] are target genes related to HCC, and both of them may become potential biomarkers for the diagnosis and prognosis of HCC.

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) stems from disrupted lipid metabolism in the liver, often linked to obesity, type 2 diabetes, and dyslipidemia. In Mexico, where obesity affects 36.9% of adults, MASLD prevalence has risen, especially with metabolic syndrome affecting 56.31% by 2018. MASLD can progress to Metabolic Dysfunction-Associated Steatohepatitis (MASH), affecting 5.27% globally, leading to severe complications like cirrhosis and hepatocellular carcinoma. Background: Visceral fat distribution varies by gender, impacting MASLD development due to hormonal influences. Insulin resistance plays a central role in MASLD pathogenesis, exacerbated by high-fat diets and specific fatty acids, leading to hepatic steatosis. Lipotoxicity from saturated fatty acids further damages hepatocytes, triggering inflammation and fibrosis progression in MASH. Diagnosing MASLD traditionally involves invasive liver biopsy, but non-invasive methods like ultrasound and transient elastography are preferred due to their safety and availability. These methods detect liver steatosis and fibrosis with reasonable accuracy, offering alternatives to biopsy despite varying sensitivity and specificity. Conclusions: MASLD as a metabolic disorder underscores its impact on public health, necessitating improved awareness and early management strategies to mitigate its progression to severe liver diseases.

Pegylated interferon-α (PEG-IFN-α) therapy could decrease hepatitis B surface antigen (HBsAg) and improve long-term prognosis of hepatitis B virus (HBV) infection. However, studies on safety and efficacy of PEG-IFN-α for patients with HBV-related cirrhosis are limited.

This was a single-center study. Fifty-four patients with HBV-related compensated cirrhosis were enrolled. All patients received subcutaneous injection of PEG-IFN-α-2b 180 μg per week for 48 weeks. The monotherapy of PEG-IFN-α-2b was used for treatment-naïve patients, while addition of PEG-IFN-α-2b to on-going nucleos(t)ide analogs (NAs) was used for NAs-experienced patients. Clinical symptoms, laboratory tests, examination indicators, and adverse events were collected at each observational time point.

Forty-two patients achieved undetectable serum HBV DNA at 48 weeks post-therapy. HBsAg level was significantly reduced at 48 weeks post-therapy (227.2 IU/mL vs. 1,668 IU/mL; p < 0.001), especially in NAs-experienced patients (161.0 IU/mL vs. 1,207 IU/mL; p = 0.005). Three patients achieved HBsAg loss, and two of them obtained HBsAg seroconversion. There were no significant differences in liver stiffness measurement, thickness and length of spleen, or diameter of portal vein between baseline and 48 weeks post-therapy (p > 0.05). The aminotransferase levels were increased, while white blood cells, neutrophils, and platelets counts were decreased during PEG-IFN-α-2b therapy (p < 0.05), especially in treatment-naïve patients. Three patients discontinued PEG-IFN-α-2b therapy due to severe adverse events. No patients suffered with virological breakthrough or progressed to end-stage liver diseases during observational period.

A finite course of PEG-IFN-α-2b therapy was well-tolerated, and reduced HBsAg level without accelerating disease progression in patients with HBV-related compensated cirrhosis.

This trial is a part of ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837).

The Systemic Inflammation Response Index (SIRI) has demonstrated predictive capabilities for clinical outcomes in various diseases. However, its prognostic utility in decompensated liver cirrhosis (DLC) remains underexplored. This study aimed to investigate the association between SIRI and the risk of short-term (3 and 6 months) all-cause mortality in DLC patients.

A total of 926 eligible patients with DLC from diverse etiologies was included in this study. In the initial cohort, the predictive accuracy of SIRI was evaluated using receiver operating characteristic (ROC) curve analysis. Patients were categorized into high- and low-SIRI groups based on the Youden index. Multivariable logistic regression analysis was employed to evaluate the independent association between SIRI and all-cause mortality. Restricted cubic spline (RCS) analysis was utilized to visualize the relationship between the continuous variable SIRI and mortality risk. These findings were validated in a validation cohort.

The initial cohort had mortality rates of 8.8% and 11.6% at 3 and 6 months, respectively. The SIRI level was significantly higher in the deceased group compared to the survival group. At both time points, SIRI was an independent indicator of all-cause mortality. RCS analysis demonstrated the risk of the risk of increased with an increase in SIRI value. The Validation cohort validated the independent association between higher SIRI levels and lower short-term all-cause mortality.

This study's findings underscore the prognostic value of SIRI in DLC patients, indicating that higher SIRI levels are significantly associated with short-term adverse outcomes.

Liver cirrhosis is one of the most prevalent chronic liver disorders with high mortality. We aimed to explore changed gut microbiome and urine metabolome in compensatory liver cirrhosis (CLC) patients, thus providing novel diagnostic biomarkers for CLC. Forty fecal samples from healthy volunteers (control: 19) and CLC patients (patient: 21) were undertaken 16S rDNA sequencing. Chromatography-mass spectrometry was performed on 40 urine samples (20 controls and 20 patients). Microbiome and metabolome data were separately analyzed using corresponding bioinformatics approaches. The diagnostic model was constructed using the least absolute shrinkage and selection operator regression. The optimal diagnostic model was determined by five-fold cross-validation. Pearson correlation analysis was applied to clarify the relations among the diagnostic markers. 16S rDNA sequencing analyses showed changed overall alpha diversity and beta diversity in patient samples compared with those of controls. Similarly, we identified 841 changed metabolites. Pathway analysis revealed that the differential metabolites were mainly associated with pathways, such as tryptophan metabolism, purine metabolism, and steroid hormone biosynthesis. A 9-maker diagnostic model for CLC was determined, including 7 microorganisms and 2 metabolites. In this model, there were multiple correlations between microorganisms and metabolites. Subdoligranulum, Agathobacter, norank_f_Eubacterium_coprostanoligenes_group, Butyricicoccus, Lachnospiraceae_UCG_004, and L-2,3-Dihydrodipicolinate were elevated in CLC patients, whereas Blautia, Monoglobus, and 5-Acetamidovalerate were reduced. A novel diagnostic model for CLC was constructed and verified to be reliable, which provides new strategies for the diagnosis and treatment of CLC.

The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels.

A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models.

Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 μmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model.

The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

Cirrhosis represents a significant global health challenge, characterized by high morbidity and mortality rates that severely impact human health. Timely and precise prognostic assessments of liver cirrhosis are crucial for improving patient outcomes and reducing mortality rates as they enable physicians to identify high-risk patients and implement early interventions. This paper features a thorough literature review on the prognostic assessment of liver cirrhosis, aiming to summarize and delineate the present status and constraints associated with the application of traditional prognostic tools in clinical settings. Among these tools, the Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems are predominantly utilized. However, their accuracy varies significantly. These systems are generally suitable for broad assessments but lack condition-specific applicability and fail to capture the risks associated with dynamic changes in patient conditions. Future research in this field is poised for deep exploration into the integration of artificial intelligence (AI) with routine clinical and multi-omics data in patients with cirrhosis. The goal is to transition from static, unimodal assessment models to dynamic, multimodal frameworks. Such advancements will not only improve the precision of prognostic tools but also facilitate personalized medicine approaches, potentially revolutionizing clinical outcomes.

Sarcopenia, a prevalent condition, significantly impacts the prognosis of patients with decompensated cirrhosis (DC). Serum fibroblast growth factor 21 (FGF21) levels are significantly higher in DC patients with sarcopenia. Satellite cells (SCs) play a role in aging- and cancer-induced sarcopenia. Here, we investigated the roles of FGF21 and SCs in DC-related sarcopenia as well as the underlying mechanisms.

We developed two DC mouse models and performed in vivo and in vitro experiments. Klotho beta (KLB) knockout mice in SCs were constructed to investigate the role of KLB downstream of FGF21. In addition, biological samples were collected from patients with DC and control patients to validate the results.

Muscle wasting and impaired SC myogenesis were observed in the DC mouse model and patients with DC. Elevated circulating levels of liver-derived FGF21 were observed, which were significantly negatively correlated with skeletal muscle mass/skeletal muscle index. Liver-secreted FGF21 induces SC dysfunction, contributing to sarcopenia. Mechanistically, FGF21 in the DC state exhibits enhanced interactions with KLB on SC surfaces, leading to downstream phosphatase and tensin homolog upregulation. This inhibits the protein kinase B (PI3K/Akt) pathway, hampering SC proliferation and differentiation, and blocking new myotube formation to repair atrophy. Neutralizing circulating FGF21 using neutralizing antibodies, knockdown of hepatic FGF21 by adeno-associated virus, or knockout of KLB in SCs effectively improved or reversed DC-related sarcopenia.

Hepatocyte-derived FGF21 mediates liver-muscle crosstalk, which impairs muscle regeneration via the inhibition of the PI3K/Akt pathway, thereby demonstrating a novel therapeutic strategy for DC-related sarcopenia.

Myeloid-derived suppressor cells (MDSCs) play a pivotal role in immunosuppression and tumor progression in hepatocellular carcinoma (HCC). While various treatments like surgical resection, ablation, and radiotherapy have been studied for their effects on circulating MDSC frequencies in HCC patients, the findings remain inconclusive. Transarterial Chemoembolization (TACE) stands as the standard care for unresectable HCC, with Microparticle TACE (mTACE) gaining prominence for its capacity to induce significant tumor necrosis. However, the immunological ramifications of such pathological outcomes are scarcely reported.

This study aims to elucidate the alterations in MDSC subtypes, specifically monocytic MDSCs (mMDSCs) and early-stage MDSCs (eMDSCs), post-mTACE and to investigate their clinical correlations in HCC patients. A cohort comprising 75 HCC patients, 16 liver cirrhosis patients, and 20 healthy controls (HC) was studied. Peripheral blood samples were collected and analyzed for MDSC subtypes. The study also explored the associations between MDSC frequencies and various clinical parameters in HCC patients. The frequency of mMDSCs was significantly elevated in the HCC group compared to liver cirrhosis and HC. Importantly, mMDSC levels were strongly correlated with aggressive clinical features of HCC, including tumor size, vascular invasion, and distant metastasis. Post-mTACE, a marked reduction in mMDSC frequencies was observed, while eMDSC levels remained stable.

Our findings underscore the critical role of mMDSCs in HCC pathogenesis and their potential as a therapeutic target. The study also highlights the efficacy of mTACE in modulating the immunosuppressive tumor microenvironment, thereby opening new avenues for combinatorial immunotherapeutic strategies in HCC management.

Chronic hepatitis B (CHB) virus infection remains a major public health concern. In this study, the diagnostic capability of C-X-C chemokine receptor type 4 promoter methylation in patients with CHB-associated liver fibrosis/cirrhosis was evaluated.

Two hundred participants were recruited, including 25 healthy controls (HCs), 60 patients with CHB and 115 patients with hepatitis B virus (HBV)-related liver fibrosis/LC. Researchers monitored the methylation and messenger ribonucleic acid (mRNA) levels of C-X-C chemokine receptor type 4 (CXCR4) in peripheral blood mononuclear cells (PBMCs). In addition, we utilized single cell sequencing to analyze the cell types highly expressing CXCR4 in HBV-related liver fibrosis/LC.

HBV-related fibrosis/cirrhosis patients exhibited a significant elevation in the expression level of CXCR4 mRNA in PBMCs compared to CHB ones. The CXCR4 promoter showed a significantly lower methylation level in patients with CHB-related fibrosis/cirrhosis than in patients with CHB. Additionally, the diagnostic area under the area under the curve (AUC) of methylation of the CXCR4 promoter for CHB -related liver fibrosis/LC exceeded liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4). Furthermore, single-cell analysis demonstrated that CXCR4 expression is closely associated with Natural Killer cells(NK cells), T lymphocytes (T cells), and monocytes.

The low methylation of the CXCR4 promoter holds promise as a non-invasive biomarker for detecting CHB-associated liver fibrosis/LC.

Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray's competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000-1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312-1.710, P < 0.001), and sarcopenia (HR 1.802, 95% CI 1.062-3.060, P = 0.029) were independently associated with increased 90-day mortality. Subgroup analysis of male patients with HBV-ACLF revealed that myosteatosis (HR 2.119, 95% CI 1.101-4.078, P = 0.025) was promising prognostic factors for 90-day mortality after being adjusted for ascites, acute kidney injury, AARC score, and sarcopenia. Myosteatosis is predictive of short-term outcomes in male patients with HBV-ACLF. Our results emphasise the importance of focusing on muscle fat infiltration in patients with HBV-ACLF. Further studies are warranted to investigate the underlying mechanisms and potential therapies for myosteatosis.

Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes' biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted.

The prognosis for hepatocellular carcinoma (HCC) in the presence of cirrhosis is unfavourable, primarily attributable to the high incidence of recurrence.

To develop a machine learning model for predicting early recurrence (ER) of post-hepatectomy HCC in patients with cirrhosis and to stratify patients' overall survival (OS) based on the predicted risk of recurrence.

In this retrospective study, 214 HCC patients with cirrhosis who underwent curative hepatectomy were examined. Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods. Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses. Five machine learning methods were used for model comparison, aiming to identify the optimal model. The model's performance was evaluated using the receiver operating characteristic curve [area under the curve (AUC)], calibration, and decision curve analysis. Additionally, the Kaplan-Meier (K-M) curve was used to evaluate the stratification effect of the model on patient OS.

Within this study, the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features. In the training cohort, this model attained an AUC of 0.844, while in the validation cohort, it achieved a value of 0.790. The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients' OS.

The combined model, integrating both radiomics and clinical-radiologic characteristics, exhibited excellent performance in HCC with cirrhosis. The K-M curves assessing OS revealed statistically significant differences.

Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation.

To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS.

The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT.

Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72.

This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

Hepatocellular carcinoma (HCC) is associated with higher mortality as a result of poor prognosis and unavailability of effective treatment options. This study retrospectively analyzed the clinical value of platelet-to-lymphocyte ratio (PLR) to aid in differentiating early hepatocellular carcinoma from liver cirrhosis patients. Three hundred and nine (309) patients including 155 patients with hepatocellular carcinoma (HCC) and 154 patients with liver cirrhosis were enrolled in this study. General clinical characteristics and blood parameters of each patient were collected, calculated, and retrospectively analyzed. Mann-Whitney U test was calculated to compare the two groups. Receiver operating characteristics (ROC) curve was performed to investigate the diagnostic potential of PLR in the prediction of HCC at a cut-off with high accuracy (area under the curve [AUC]) > 0.80. Hemoglobin (HB) concentration, red blood cell (RBC) count, neutrophil (NEU) count, platelet count, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the HCC patients than in the liver cirrhosis patients (p < 0.05). ROC curve analysis showed that the AUC, optimal cut-off value, sensitivity, and specificity of PLR to predict HCC patients were 0.912, 98.7, 81.2%, and 80.6% respectively. The results suggest that PLR is a potential biomarker that can be used to predict early HCC.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.

Recompensation between patients with ascites and bleeding was unknown in treatment-naïve HBV-related decompensated cirrhosis.

In this retrospective multi-center study, treatment-naïve HBV-related decompensated patients were enrolled at first decompensating event of ascites and/or variceal bleeding. Further complications and clinical characteristics were collected using standard case report form every 6 months to year-5 of antiviral treatment. Recompensation was defined as maintaining free of decompensation for one year and achieving liver function within Child-Pugh A and/or MELD < 10.

Totally, 170 (170/298, 57.0%) patients in ascites group of 298 (298/383, 77.8%) treatment-naïve decompensated patients and 33 (33/85, 38.8%) in bleeding group of 85 (85/383, 22.2%) patients, achieved recompensation. Ascites group had higher 5-year rate of recompensation than bleeding group (63.3% vs. 46.5%, p = 0.012), respectively. Patients achieving recompensation in ascites group maintained lower rate of second decompensation than these in bleeding group (at year-5: 26.7% vs. 43.3%, p = 0.032). Specifically, recompensated patients in ascites group had predominantly 5-year rate of further ascites (24.0%) and lower rate of further bleeding (6.0%), which differed from the pattern of these in bleeding group, with lower rate of further ascites (16.0%, p = 0.599) and significantly higher rate of further bleeding (33.9%, p < 0.001). Both patients had superior long-term prognosis (death/LT rate at year-5: 0.6% vs. 3.0%, p = 0.196).

Ascites patients could achieve higher rate of recompensation through antiviral therapy than bleeding patients. Recompensated patients in ascites group had better prognosis in terms of preventing further bleeding.

Metabolic risk factors in primary biliary cholangitis (PBC) have not been well described in China. Additionally, it is unclear whether these factors have an impact on the prognosis of PBC patients. Therefore, this study aimed to investigate the prevalence of main metabolic risk factors in PBC, and to evaluate their prognostic values for liver-related outcomes.

A cohort of 789 PBC patients was retrospectively studied between July 2008 and September 2019 by investigating the main metabolic risk factors and analyzing liver-related outcomes.

At presentation, 271 (34.3%) patients had concomitant hyperlipidemia, 126 (16.0%) had hypertension, 94 (11.9%) had type 2 diabetes mellitus (T2DM), and 17 (2.2%) had nonalcoholic fatty liver disease (NAFLD). Hyperlipidemia was found to be associated with the lower risk of liver-related death [P<0.0001, hazard ratio (HR): 0.397, 95% confidence interval (CI): 0.268-0.588] and adverse outcomes (P<0.0001, HR: 0.487, 95% CI:0.367-0.646), while hypertension was noted as a risk factor for liver-related death (P=0.001, HR: 1.788, 95% CI:1.268-2.521) and adverse outcomes (P=0.014, HR: 1.417, 95% CI:1.074-1.869). Moreover, age ≥ 55 years old (P=0.005) and cirrhosis (P<0.0001) had superimposition effects on hypertension as a risk factor for liver-related death, while only cirrhosis (P<0.0001) had an effect on hypertension as a risk factor for adverse outcomes. Additionally, anti-sp100 was associated with adverse outcomes (P=0.013) in PBC patients with hypertension in univariate Cox regression analysis.

Hyperlipidemia, hypertension, and T2DM were found as main metabolic risk factors in PBC in China. Hyperlipidemia indicated a benign clinical outcome of PBC, while hypertension indicated a poor outcome of PBC. Older age and cirrhosis had superimposition effects on hypertension for liver-related poor outcomes. Anti-sp100 might be associated with adverse outcomes, especially in PBC patients with hypertension.

Cirrhotic patients with sarcopenia have poor prognoses and higher mortality. The third lumbar vertebra (L3) skeletal muscle index (SMI) is widely used to assess sarcopenia. However, L3 is generally outside the scanning volume on standard liver MRI.

To investigate SMIs change between slices in cirrhotic patients and the relationships between SMI at the 12th thoracic vertebra (T12), the first lumbar vertebra (L1) and the second lumbar vertebra (L2) levels and L3-SMI and assess the accuracy of the estimated L3-SMIs in diagnosing sarcopenia.

Prospective.

A total of 155 cirrhotic patients (109 with sarcopenia, 67 male; 46 without sarcopenia, 18 male).

A 3.0 T, 3D dual-echo T1-weighted gradient echo sequence (T1WI).

Two observers analyzed T12 to L3 skeletal muscle area (SMA) in each patient based on T1W water images and calculated the SMI (SMA/height2 ). Reference standard was L3-SMI.

Intraclass correlation coefficient (ICC), Pearson correlation coefficients (r), and Bland-Altman plots. Models relating L3-SMI to the SMI at T12, L1, and L2 levels were constructed using 10-fold cross-validation. Accuracy, sensitivity, and specificity were calculated for the estimated L3-SMIs for diagnosing sarcopenia. P < 0.05 was considered statistically significant.

Intraobserver and interobserver ICCs were 0.998-0.999. The L3-SMA/L3-SMI were correlated with the T12 to L2 SMA/SMI (r = 0.852-0.977). T12-L2 models had mean-adjusted R2 values of 0.75-0.95. The estimated L3-SMI from T12 to L2 levels to diagnose sarcopenia had good accuracy (81.4%-95.3%), sensitivity (88.1%-97.0%), and specificity (71.4%-92.9%). The recommended L1-SMI threshold of 43.24 cm2 /m2 in males and 33.73 cm2 /m2 in females.

The estimated L3-SMI from T12, L1 and L2 levels had good diagnostic accuracy in assessing sarcopenia in cirrhotic patients. Although L2 was best associated with L3-SMI, L2 is generally not included in standard liver MRI. L3-SMI estimate from L1 may therefore be most clinically applicable.

1.

Stage 2.

The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome (VBDS) have yet to be elucidated. The study aims to investigate these features and identify factors associated with poor prognosis.

This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022. Clinical and pathological data at time of biopsy were reviewed. Clinical outcomes including cirrhosis, decompensation events, liver transplantation (LT), and liver-related death were recorded. Cox regression analysis was used to identify the risk factors associated with poor outcomes.

A total of 183 patients were included. The median age was 47 years, with 77.6% being women. During a median follow-up of 4.8 years, 88 patients developed compensated or decompensated cirrhosis, 27 died, and 15 received LT. Multivariate Cox regression analysis showed that hepatocellular cholestasis (HR 2.953, 95% CI: 1.437-6.069), foam cells (HR 2.349, 95% CI: 1.092-5.053), and advanced fibrosis (HR 2.524, 95% CI: 1.313-4.851) were independent predictors of LT or liver-related deaths. A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746 (95% CI: 0.706-0.785).

Nearly half of VBDS patients studied progressed to end-stage liver disease and 23% of them had LT or liver-related death within two years of diagnosis. Hepatocellular cholestasis, foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.

Antimitochondrial antibody (AMA) serves as a serological marker for diagnosing primary biliary cholangitis (PBC). However, the association between AMA and prognosis for PBC patients remains unclear. The objective of this study was to investigate the relationship between AMA and cirrhosis in PBC patients. This retrospective study enrolled 225 PBC patients, including 127 with liver cirrhosis and 98 without cirrhosis. AMA was tested by indirect immunofluorescence (IIF) with rat kidney as the substrate. AMA-M2 and M2-3E were detected by line immunoassay (LIA). The overall positivity rate for AMA detection in PBC patients was 80.9%. The positivity rates of IIF-AMA, AMA-M2, and M2-3E were significantly higher in patients with liver cirrhosis than in those without cirrhosis (73.2% vs. 52.0%, 74.0% vs. 51.0%, and 80.3% vs. 60.2%, respectively). In multivariate logistic regression, IIF-AMA (OR: 3.05, 95% CI: 1.59-5.87), AMA-M2 (OR: 3.11, 95% CI: 1.61-6.01), and M2-3E (OR: 3.29, 95% CI: 1.63-6.66) remained significantly associated with an increased incidence of liver cirrhosis. Moreover, in multinomial logistic regression, IIF-AMA (compensated cirrhosis, OR: 3.55, 95% CI: 1.49-8.44; decompensated cirrhosis, OR: 2.86, 95% CI: 1.32-6.18), AMA-M2 (compensated cirrhosis, OR: 4.74, 95% CI: 1.94-11.58; decompensated cirrhosis, OR: 2.51, 95% CI: 1.19-5.33), and M2-3E (compensated cirrhosis, OR: 4.92, 95% CI: 1.74-13.96; decompensated cirrhosis, OR: 2.91, 95% CI: 1.28-6.64) were all found to be associated with different stages of liver cirrhosis. AMA was found to be associated with the occurrence of liver cirrhosis in PBC patients. Additionally, AMA was also related to different stages of liver cirrhosis, including compensated and decompensated cirrhosis.

Currently, most primary hospitals cannot routinely perform liver stiffness measurements (LSMs) and spleen stiffness measurements (SSMs), which are recommended by guidelines to exclude high-risk varices (HRVs). We tried to find more convenient indicators for HRV screening. We enrolled 213 cirrhosis patients as the training cohort (TC) and 65 primary biliary cirrhosis patients as the validation cohort (VC). We included indicators such as SSM by two-dimensional shear wave elastography, LSM by transient elastography, and other imaging and laboratory tests. Variable analysis revealed SSM, platelets (PLT), and spleen thickness (ST) as independent risk indicators for HRV. In TC, ST+PLT (ST < 42.2 mm and PLT > 113.5 × 109/L) could avoid 35.7% of the esophagogastroduodenoscopies (EGDs), with a 2.4% missed HRV rate. Although the proportion of EGDs spared by ST+PLT was less than SSM+PLT (SSM < 29.89 kPa + PLT > 113.5 × 109/L) (35.7% vs. 44.1%), it was higher than that of the Baveno VI criteria (B6) (35.7% vs. 28.2%). We did not validate SSM+PLT in VC considering our aims. ST+PLT safely spared 24.6% of EGDs in VC, identical to B6. Conclusions: The ability of ST+PLT to exclude HRVs was superior to B6 but slightly inferior to SSM+PLT. When SSM cannot be routinely performed, ST+PLT provides an extra option for patients to exclude HRVs as a more convenient model.

AFP appears to be negative in about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP-negative HCC (AFPN-HCC).

The training set included 294 AFPN-HCC patients, 159 healthy objects, 63 patients with chronic hepatitis B(CHB), and 64 patients with liver cirrhosis (LC). And the validation set enrolled 137 healthy controls objects, 47 CHB patients and 45 patients with LC. LASSO, univariate, and multivariable logistic regression analysis were performed to construct the model and then transformed into a visualized nomogram. The receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were further used for validation.

Four variables including age, PIVKA-II, platelet (PLT) counts, and prothrombin time (PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95% CI 0.892-0.938) in training set and 0.942(95% CI 0.921-0.963) in validation set. We also found that the model had high diagnostic value for small-size HCC (tumor size < 5 cm) (AUC = 0.886) and HBV surface antigen-positive AFPN-HCC (AUC = 0.883).

Our model was effective for discrimination of AFPN-HCC from patients with benign liver diseases and healthy controls, and might be helpful for the diagnosis for AFPN-HCC.

The impact of spontaneous portosystemic shunt (SPSS) on decompensated events and mortality for patients with hepatitis B-related cirrhosis remains poorly investigated.

To evaluate the prevalence, clinical characteristics, and outcomes of SPSS among patients with hepatitis B-related cirrhosis.

Patients who were diagnosed with hepatitis B-related cirrhosis were retrospectively recruited. All eligible patients were classified into SPSS and non-SPSS groups and their clinical characteristics and outcomes were compared and analyzed.

Of the 1282 patients included in this study, SPSS was identified in 488 patients (38.1%). SPSS group had more severe liver function impairment, higher prevalence and severity of esophageal and gastric varices (EGV), and a higher prevalence of EGV bleeding (EGVB), portal vein thrombosis (PVT), hepatic encephalopathy (HE), ascites, and hepatocellular carcinoma (HCC, all P<0.05). During the follow-up period, SPSS group experienced a significantly higher incidence of EGVB, PVT, and HE (all P<0.05); however, there was no significant difference in the incidence of ascites, HCC, and mortality between the two groups (all P>0.05).

With hepatitis B-related cirrhosis, SPSS was common and characterized by severe liver damage and a high prevalence of decompensated events. Moreover, patients with SPSS had higher risks of EGVB, PVT, and HE.

Emerging researches have regarded serum chloride as a capable predictor of mortality in liver cirrhosis. We aim to investigate the clinical role of admission chloride in cirrhotic patients with esophagogastric varices receiving transjugular intrahepatic portosystemic shunt (TIPS), which is unclear.

We retrospectively analyzed data of cirrhotic patients with esophagogastric varices undergoing TIPS in Zhongnan Hospital of Wuhan University. Mortality outcome was obtained by following up for 1-year after TIPS. Univariate and multivariate Cox regression were used to identify independent predictors of 1-year mortality post-TIPS. The receiver operating characteristic (ROC) curves were adopted to assess the predictive ability of the predictors. In addition, log-rank test and Kaplan-Meier (KM) analyses were employed to evaluate the prognostic value of predictors in the survival probability.

A total of 182 patients were included ultimately. Age, fever symptom, platelet-to lymphocyte-ratio (PLR), lymphocyte-to-monocyte ratio (LMR), total bilirubin, serum sodium, chloride, and Child-Pugh score were related to 1-year follow-up mortality. In multivariate Cox regression analysis, serum chloride (HR = 0.823, 95%CI = 0.757-0.894, p < 0.001) and Child-Pugh score (HR = 1.401, 95%CI = 1.151-1.704, p = 0.001) were identified as independent predictors of 1-year mortality. Patients with serum chloride <107.35 mmol/L showed worse survival probability than those with serum chloride ≥107.35 mmol/L no matter with or without ascites (p < 0.05).

Admission hypochloremia and increasing Child-Pugh score are independent predictors of 1-year mortality in cirrhotic patients with esophagogastric varices receiving TIPS.

Liver cytosol antibody type 1 (anti-LC1) is reported to be a marker of type 2 autoimmune hepatitis (AIH), a type of autoimmune liver disease (AILD). However, anti-LC1 is not entirely disease-specific, and its clinical value in other hepatic diseases has not been well elucidated. Our study aimed to explore the associations between the diagnoses and outcome of decompensated cirrhosis or liver failure (DC/LF) in patients positive for anti-LC1. A total of 157 patients positive for anti-LC1 were included in our final analysis. DC/LF was defined as the outcome of patients positive for anti-LC1. The risk of DC/LF according to diagnosis was estimated using multivariable Cox proportional hazards models, while stratified Cox regression models were used in the subgroup analyses. The diagnoses of patients positive for anti-LC1 were found to be comprised of various liver disorders. Versus other diagnoses, viral hepatitis was associated with a 2.25-fold increased risk of DC/LF in these patients, independent of sex, age, disease course, treatment and drinking history. Additionally, the associations were more significant by subgroup analysis in male patients, younger patients, non-newly diagnosed patients, patients without treatment and patients without drinking history. Anti-LC1 is not a disease-specific antibody, as it was found in multiple types of hepatic disease. Furthermore, viral hepatitis rather than AILD was associated with an increased risk of DC/LF in patients positive for anti-LC1. These findings emphasize the important role of viral hepatitis in the progression of DC/LF in patients positive for anti-LC1.

For patients with cirrhosis, early diagnosis is the key to delaying the development of liver fibrosis and improving prognosis. This study aimed to investigate the clinical significance of TL1A, which is a susceptibility gene for hepatic fibrosis, and DR3 in the development of cirrhosis and fibrosis. We analyzed the expression of TL1A, DR3, and other inflammatory cytokines associated with liver fibrosis in serum and PBMCs in 200 patients.TL1A methylation level was lower in patients with HBV-associated LC than in the other groups. In addition, the mRNA level and serum of TL1A and DR3 expression levels were found to increase in the LC. Hypomethylation of the TL1A promoter is present in HBV-associated LC, and TL1A and DR3 are highly expressed in HBV-associated cirrhosis. These results indicate that TL1A and DR3 may play an important role in the pathogenesis of LC and TL1A methylation levels may serve as a noninvasive biomarker for early diagnosis and progression of LC.

Spontaneous portosystemic shunt (SPSS) other than esophago-gastric varices is one of the consequences of cirrhosis-induced portal hypertension (PHT), but its role is not fully understood. Therefore, we conducted a systematic review and meta-analysis to determine the prevalence and clinical characteristics of SPSS (excluding esophago-gastric varices) and its impact on mortality in patients with cirrhosis.

Eligible studies were identified from MedLine, PubMed, Embase, Web of Science, and Cochrane Library between Jan 1, 1980 and Sep 30, 2022. Outcome indicators were SPSS prevalence, liver function, decompensated events, and overall survival (OS).

Totally, 2015 studies were reviewed, of which 19 studies recruiting 6884 patients were included. On pooled analysis, the prevalence of SPSS was 34.2% (26.6%∼42.1%). SPSS patients had significantly higher Child-Pugh scores and grades and Model for End-stage Liver Disease scores (all P<0.05). Moreover, SPSS patients experienced a higher incidence of decompensated events, including hepatic encephalopathy, portal vein thrombosis, and hepatorenal syndrome (all P<0.05). Additionally, SPSS patients had significantly shorter OS than the non-SPSS group (P<0.05).

In patients with cirrhosis, SPSS outside the esophago-gastric region is common, characterized by severe impairment of liver function, high rates of decompensated events, including HE, PVT, and hepatorenal syndrome, as well as a high mortality rate.

Previous studies have found that the production of platelets could enhance the therapeutic effects of stem cells. Nevertheless, there are still no articles reporting on the relationship between platelets and the clinical efficacy of umbilical cord mesenchymal stem cells (UCMSCs) for HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC).

In this retrospective observational study, patients who met the criteria were included. Patients were divided into subgroups according to the aims of this study. In the first part, the platelet count changes of ACLF and patients with LC after UCMSC therapy were compared and analyzed. Subgroup analysis based on UCMSC infusion times and patient age was also performed. In the second part, patients in the ACLF group and LC group were further divided into subgroups according to their platelet levels. Their clinical characteristics, demographics, and biochemical factors were compared.

This study enrolled 64 patients with ACLF and 59 patients with LC. In both groups, platelet levels declined similarly. Compared with the short-course UCMSC treatment group (≤4 times), patients with ACLF and patients with LC with long-course UCMSC treatment (>4 times) showed an overall increasing trend. Younger patients with LC (<45 years) had significantly higher platelet levels than older patients with LC (≥45 years). However, this age difference was not present in the ACLF group. The median TBIL decrease and cumulative TBIL decrease were not significantly different between patients with high PLT and patients with low PLT after UCMSC transfusions. For patients with ACLF, the cumulative TBIL decrease and the median TBIL decrease were significantly greater than those of patients with LC at the same platelet level after UCMSC treatment. However, this difference was not observed at all time points.

Trend of the platelet levels for HBV-related patients with ACLF and LC after UCMSC treatment did not parallel and varied according to treatment times and patients' age. Platelet levels did not affect the efficacy of MSCs for patients with ACLF or LC.