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Background: This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC).Methods: Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression. Time-to-progression (TTP, primary endpoint), overall survival (OS) and progression-free survival (PFS) were determined.Results: Phase-I: no DLTs observed; nintedanib MTD in both groups was 200 mg bid. Phase-II: patients (N = 93) were randomised to nintedanib (n = 62) or sorafenib (n = 31); TTP was 5.5 vs. 4.6 months (HR = 1.44 [95% CI, 0.81-2.57]), OS was 11.9 vs. 11.4 months (HR = 0.88 [95% CI, 0.52-1.47]), PFS was 5.3 vs. 3.9 months (HR = 1.35 [95% CI, 0.78-2.34]), respectively (all medians). Dose intensity and tolerability favoured nintedanib. Fewer patients on nintedanib (87.1%) vs. sorafenib (96.8%) had drug-related adverse events (AEs) or grade ≥ 3 AEs (67.7% vs. 90.3%), but more patients on nintedanib (28 [45.2%]) had AEs leading to drug discontinuation than did those on sorafenib (7 [22.6%]).Conclusions: Nintedanib may have similar efficacy to sorafenib in aHCC. [ABSTRACT FROM AUTHOR]

Background: Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated. Methods: One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6 weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG ≤ 12 mmHg. Results: Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4 ± 16.5 vs. 70.3 ± 7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21 ± 5 vs. 26 ± 5 vs. 26 ± 4 mmHg). The correlation of LS and HVPG was stronger in controls with HVPG ≤ 12 mmHg ( R = 0.951; P < 0.0001) than in patients with HVPG > 12 mmHg ( R = 0.538; P = 0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS ( R = 0.930; P < 0.0001). Forty-three percent (53/122) of patients were hemodynamic responders to NSBB. The improvement in the correlation of LS and HVPG under NSBB was mainly noted in hemodynamic responders ( R = 0.864), but not in nonresponders ( R = 0.535), whereas changes in LS, heart rate, and MAP were similar in responders and nonresponders. Conclusions: Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HVPG > 12 mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the fifth leading cause of cancer death worldwide, is a tumour with dismal prognosis [1]. In recent years, significant advances have been made and survival of patients with HCC has been prolonged and even cure can be achieved in a sizeable number of patients. The biggest advances are viable through screening and surveillance programmes of the population at risk, which includes all patients with cirrhosis of the liver and patients chronically infected with hepatitis B virus. Through regular ultrasound screening at 6-month intervals, detection rates and through this treatment and survival have been improved dramatically [2]. Through these surveillance programmes, at least 80% of the patients with HCC in western countries will undergo treatment for HCC of any kind with proven efficacy on survival. Only about 20% of patients with endstage tumours at the time of diagnosis will have no other option left than supportive care [3]. [ABSTRACT FROM AUTHOR]

Our previous manuscript showed that thrombocytopenia predicts all-cause mortality in Chinese hemodialysis (HD) patients. Based on the role of platelets in coagulation, clot formation, and systemic inflammation, we speculate that high platelets increase risk of thrombo-embolic events, hence the mortality. However, research evidence is currently lacking. Therefore, we utilized data from a very large international cohort study to explore the association of platelet counts with mortality and cardiovascular (CV) death in hemodialysis (HD) patients. International data from 396 facilities enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012–2015) were analyzed. Participants were divided into 3 groups according to their platelet counts (low: <100, normal: 100–300, high: >300*109). Associations between platelet counts and all-cause and CV mortality were analyzed using Cox regression, adjusted for confounders. There were 13,631 patients with median age of 65 years old. Males accounted for 61.2%. Mean platelet count was 205*109/L overall and ranged from 173 *109/L in China to 227 *109/L in Sweden. Overall, 2,348 (17.2%) patients died and 1017 (7.5%) died from CV disease. Both low (HR:1.48, 95% CI 1.21–1.80, p < 0.001) and high (HR:1.17, 95% CI 1.00- 1.35, p = 0.044) platelet counts were associated with higher all-cause mortality after adjustment for covariates; results for CV death were consistent. Platelet count has a U-shaped association with all-cause and CV mortality in HD patients, and thus may be used as an outcome predictor that is readily available among HD patients. [ABSTRACT FROM AUTHOR]

Background: EphrinA5 belongs to a subclass of ephrin ligands. Abnormal signal transduction of EFNA5 shows a relationship to the development of various tumors. In this study, we explored the level of EFNA5 in hepatoma cells and the influence of up regulation of EFNA5 expression level on the proliferation, invasion, and migration of HepG2 and LM3 cells. Additionally, this work focused on examining its possible mechanism of action, and future impacts on clinical practice. Methods: Immunohistochemistry was utilized to explore the connection between EFNA5 and hepatoma. Real-time quantitative polymerase chain reaction was used for determining the expression levels of EFNA5 in several hepatoma cell lines and normal hepatocytes. Cells were transfected with a pCMV3-EFNA5-flag plasmid and an EFNA5 plasmid. The expression efficiency of EFNA5 was identified through qRT-PCR. For the purpose of further identifying cell proliferation, the Cell Counting Kit-8 assay was applied. To identify changes of cell migration and invasion ability, Transwell and Boyden tests were utilized. Western blot was employed to identify the expressions mof EFNA5 and possible downstream molecules. Results: Data acquired from The Cancer Genome Atlas demonstrated that the level of EFNA5 in hepatoma was significantly downregulated in relative to the normal hepatocytes (P < 0.05). Upregulation of EFNA5 expression in hepatoma cells hindered the proliferative, invasive, and migratory ability of cells (P < 0.05). Additionally, EFNA5 downregulated the level of epithelial–mesenchymal transition-related molecules and EGFR. Conclusions: The expression of EFNA5 was low in hepatoma cells. An increase in EFNA5 levels hinders the proliferation, invasion, and migration of hepatoma cells. These effects may occur through inhibition of hepatoma epithelial–mesenchymal transition by EFNA5. Moreover, the study on the mechanisms of proliferation, invasion and metastasis of hepatoma provides a novel theoretical basis, and may influence the clinical practice of tumor treatment in the future. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed. [ABSTRACT FROM AUTHOR]

Ascites remains a significant challenge in patients with cirrhosis, posing difficulties in management and affecting prognosis. This review examines the current understanding of ascites, including its underlying mechanisms, symptoms, and treatment options, with a specific focus on the innovative Alfa Pump device. The review begins by discussing traditional approaches to managing ascites while also addressing their limitations and potential complications. It then explores the emergence of the Alfa Pump system, a novel implantable device designed to tackle refractory ascites by continuously draining fluid from the abdomen while minimizing circulatory issues. Through a synthesis of current literature and clinical evidence, this narrative review underscores the importance of a multidisciplinary approach in the management of ascites, with a particular emphasis on the evolving role of the Alfa Pump in improving outcomes and quality of life for patients with refractory ascites. [ABSTRACT FROM AUTHOR]

Purpose of Review: Despite refractory ascites (RA) due to cirrhosis having a median transplant-free survival of 6–12 months, palliative care (PC) input remains uncertain. We aimed to review the existing literature on clinical outcomes in cirrhosis-related RA and report the findings of a single-centre retrospective cohort study with a special focus on linkage to PC in this cohort of patients. Recent Findings: Our study and subsequent literature review confirm the high mortality associated with cirrhosis-related RA (19–55% 1-year mortality) with only a minority of patients receiving curative options (3–23%). Despite this, in our study only a minority of patients (33%) were referred to PC. None of the studies identified in the scoping review makes any references to palliative care use. Summary: Our own data and a literature review confirm that, despite high mortality, only a minority with RA due to cirrhosis are referred for specialist PC input and often too late in their disease trajectory. Future research should focus on patient-centred outcomes in this cohort of patients where optimising quality-of-life and facilitating advanced care planning should be a priority. [ABSTRACT FROM AUTHOR]

Objectives: To develop a deep learning model combining CT scans and clinical information to predict overall survival in advanced hepatocellular carcinoma (HCC). Methods: This retrospective study included immunotherapy-treated advanced HCC patients from 52 multi-national in-house centers between 2018 and 2022. A multi-modal prognostic model using baseline and the first follow-up CT images and 7 clinical variables was proposed. A convolutional-recurrent neural network (CRNN) was developed to extract spatial-temporal information from automatically selected representative 2D CT slices to provide a radiological score, then fused with a Cox-based clinical score to provide the survival risk. The model's effectiveness was assessed using a time-dependent area under the receiver operating curve (AUC), and risk group stratification using the log-rank test. Prognostic performances of multi-modal inputs were compared to models of missing modality, and the size-based RECIST criteria. Results: Two-hundred seven patients (mean age, 61 years ± 12 [SD], 180 men) were included. The multi-modal CRNN model reached the AUC of 0.777 and 0.704 of 1-year overall survival predictions in the validation and test sets. The model achieved significant risk stratification in validation (hazard ratio [HR] = 3.330, p = 0.008), and test sets (HR = 2.024, p = 0.047) based on the median risk score of the training set. Models with missing modalities (the single-modal imaging-based model and the model incorporating only baseline scans) can still achieve favorable risk stratification performance (all p < 0.05, except for one, p = 0.053). Moreover, results proved the superiority of the deep learning-based model to the RECIST criteria. Conclusion: Deep learning analysis of CT scans and clinical data can offer significant prognostic insights for patients with advanced HCC. Critical relevance statement: The established model can help monitor patients' disease statuses and identify those with poor prognosis at the time of first follow-up, helping clinicians make informed treatment decisions, as well as early and timely interventions. Key Points: An AI-based prognostic model was developed for advanced HCC using multi-national patients. The model extracts spatial-temporal information from CT scans and integrates it with clinical variables to prognosticate. The model demonstrated superior prognostic ability compared to the conventional size-based RECIST method. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition globally and the leading cause of liver-related death and morbidity. The goal of this study was to collect current data in order to calculate the pooled prevalence of NAFLD in Pakistan. We conducted a comprehensive literature search on four electronic databases until March 2024 to find studies on the prevalence of NAFLD in Pakistan. Pooled prevalence estimates of NAFLD were obtained using random-effects meta-analytic models. The chi-square test was used to account for study heterogeneity, whereas the I2 statistic was used to assess inconsistency. The data were stratified by the general population (average risk) and individuals with metabolic diseases (high risk). Two reviewers thoroughly and independently screened, reviewed, and assessed all studies. In total, 468 studies were reviewed, and 34 were included. The pooled NAFLD prevalence in the general population was 29.82% (95% CI 21.39–39.01%; prediction interval: 2.98–68.92%) based on 13 studies. In individuals with metabolic disorders, the prevalence of NAFLD in patients with diabetes, hypertension, and obesity, was 58.47% (95% CI 54.23–62.64%; prediction interval: 38.16–77.40%), 74.08% (95% CI 60.50–85.70%), and 47.43% (95% CI 30.49–64.66%), respectively. There was no evidence of publication bias, although a statistically significant level of heterogeneity was seen among the studies (I2 ranged from 57.5 to 98.69%). The findings of this study indicate a substantial prevalence of NAFLD in the population of Pakistan. The Pakistani government must formulate a comprehensive approach and plan aimed at augmenting awareness, control, prevention, and treatment of fatty liver disease. Prospero Registration no: CRD42022356607. [ABSTRACT FROM AUTHOR]

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Background: Combined hepatocellular–cholangiocarcinoma (cHCC–CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC–CCA and to preliminarily explore the possible mechanism of TLS formation. Methods: The TLSs, with different spatial distributions and densities, of 137 cHCC–CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan–Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC–CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. Results: A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC–CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC–CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC–CCA patients. Our findings suggested that CXCL12 expression in cHCC–CCA tissue was significantly correlated with TLS presence. Conclusion: The spatial distribution and density of TLSs revealing the characteristics of the cHCC–CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC–CCA. [ABSTRACT FROM AUTHOR]

Preliminary work has shown that portal hypertension plays a key role for the prognosis in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Specifically, the presence of ascites appears to be a strong negative predictor for these patients. However, it remains unclear whether different ascites volumes influence prognosis. Therefore, the aim of this work was to investigate the influence of different ascites volumes on survival for patients with HCC undergoing TACE. A total of 327 treatment-naïve patients with HCC undergoing initial TACE at our tertiary care center between 2010 and 2020 were included. In patients with ascites, the fluid was segmented, and the volume quantified by slice-wise addition using contrast-enhanced CT imaging. Median overall survival (OS) was calculated and univariate and multivariate Cox regression analysis has been performed. Ascites was present in 102 (31.9%) patients. Ascites volume as continuous variable was significantly associated with an increased hazard ratio in univariate analysis (p < 0.001) and remained an independent predictor of impaired median OS in multivariate analysis (p < 0.001). Median OS without ascites was 17.1 months, and therefore significantly longer than in patients with ascites (6.4 months, p < 0.001). When subdivided into groups of low and high ascites volume in relation to the median ascites volume, patients with low ascites volume had a significantly longer median OS (8.6 vs 3.6 months, p < 0.001). Ascites in patients with HCC undergoing TACE is strongly associated with a poor prognosis. Our results show that not only the presence but also the amount of ascites is highly relevant. Therefore, true ascites volume as opportunistic quantitative biomarker is likely to impact clinical decision-making once automated solutions become available. [ABSTRACT FROM AUTHOR]

Background: Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. Methods: We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. Results: A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. Conclusions: This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans. [ABSTRACT FROM AUTHOR]

Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are emerging treatments for advanced hepatocellular carcinoma (HCC); however, evidence has shown they may induce hyperprogressive disease via unexplained mechanisms. Methods: In this study, we investigated the possible stimulative effect of ICIs on programmed cell death-ligand 1 (PD-L1)-harboring liver cancer cells under immunocompetent cell-free conditions. Results: The sarcomatous HAK-5 cell line displayed the highest expression of PD-L1 among 11 human liver cancer cell lines used in this study. HLF showed moderate expression, while HepG2, Hep3B, and HuH-7 did not show any. Moreover, sarcomatous HCC tissues expressed high levels of PD-L1. We observed approximately 20% increase in cell proliferation in HAK-5 cells treated with anti-PD-L1 antibodies, such as durvalumab and atezolizumab, for 48 h compared with that of those treated with the control IgG and the anti-PD-1 antibody pembrolizumab. No response to durvalumab or atezolizumab was shown in PD-L1-nonexpressing cells. Loss-of-function and gain-of-function experiments for PD-L1 in HAK-5 and HepG2 cells resulted in a significant decrease and increase in cell proliferation, respectively. Phosphorylated receptor tyrosine kinase array and immunoprecipitation revealed direct interactions between PD-L1 and AXL in tumor cells. This was stabilized by extrinsic anti-PD-L1 antibodies in a glycosylated PD-L1-dependent manner. Activation of AXL, triggering signal relay to the Akt and Erk pathways, boosted tumor cell proliferation both in vitro and in xenografted tumors in NOD/SCID mice. Conclusion: Collectively, this suggests that anti-PD-L1 antibodies stimulate cell proliferation via stabilization of the PD-L1–AXL complex in specific types of liver cancer, including in HCC with mesenchymal components. Significance: Therapeutic anti-PD-L1 antibodies promote cell proliferation by stabilizing the PD-L1–AXL complex in PD-L1-abundant neoplasms, including in HCC with mesenchymal components. Such a mechanism may contribute to the development of hyperprogressive disease. [ABSTRACT FROM AUTHOR]

Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability. This review explores the potential of phospholipid complex formulation technology to overcome these challenges. Phospholipids, as endogenous molecules, offer a viable solution, with drugs complexed with phospholipids demonstrating a similar absorption mechanism. The non-toxic and biodegradable nature of the phospholipid complex positions it as an ideal candidate for drug delivery. This article provides a comprehensive exploration of the mechanisms underlying phospholipid complexes. Special emphasis is placed on the solvent evaporation method, with meticulous scrutiny of formulation aspects such as the phospholipid ratio to the drug and solvent. Characterization techniques are employed to understand structural and functional attributes. Highlighting the adaptability of the phospholipid complex, the review discusses the loading of various nanoformulations and emulsion systems. These strategies aim to enhance drug delivery and efficacy in various malignancies, including breast, liver, lung, cervical, and pancreatic cancers. The broader application of the drug phospholipid complex is showcased, emphasizing its adaptability in diverse oncological settings. The review not only explores the mechanisms and formulation aspects of phospholipid complexes but also provides an overview of key clinical studies and patents. These insights contribute to the intellectual and translational advancements in drug phospholipid complexes. [ABSTRACT FROM AUTHOR]

Clinical symptoms of systemic lupus erythematosus (SLE), such as atherosclerosis and related cardiovascular diseases, are caused by inflammatory cytokines and endothelial cell damage. The serum sialic acid binding immunoglobulin-like lectin 1 (sSIGLEC-1) is thought to be an alternative biomarker of IFN signature and may have a role in the pathogenesis of atherosclerosis. The aim of the study was to measure the levels of sSIGLEC-1 in the serum of SLE patients in comparison to a control group and examine the associations between sSIGLEC-1, SLEDAI, lipid profile, oxidized low density lipoprotein (oxLDL), and carotid intima media thickness (CIMT) to investigate whether sSIGLEC-1 participates in the development of atherosclerosis. sSIGLEC-1 levels were tested in 53 patients and 20 volunteers using ELISA kit. Duplex measurements were performed on all subjects to measure CIMT. SLE patients had significantly higher values of sSIGLEC-1 (P < 0.0001), total cholesterol (P = 0.029), triglycerides (P = 0.001), low density lipoprotein (P = 0.032), oxLDL (P = 0.001), right CIMT (P = 0.0099) and a significantly lower value of high-density lipoprotein (P = 0.04) when compared to controls. sSIGLEC-1 had significant positive correlations with right CIMT (r = 0.5, P < 0.0002) and oxLDL (r = 0.67, P < 0.0001) in all SLE patients. When compared to non-dyslipidemic patients, the dyslipidemic group exhibited significantly higher levels of all previous parameters except HDL and left CIMT. Circulating form of SIGLEC-1 accelerates atherosclerosis and provides a simple way to predict the occurrence of atherosclerosis in SLE patients. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment. [ABSTRACT FROM AUTHOR]

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines. [ABSTRACT FROM AUTHOR]

Purpose of Review: We aim to succinctly summarize key clinical management principles in commonly encountered clinical scenarios with regard to prevention, diagnosis, and management of bacterial infections in patients with cirrhosis. Recent Findings: We review studies detailing the role for antibiotic prophylaxis in acute liver failure and in alcohol-related hepatitis. We also review growing concerns related to antibiotic resistance and emerging biomarkers for infection prediction in cirrhosis. Summary: We found that there is evidence of improved outcomes with administration of antibiotic prophylaxis to cirrhotic patients in specific clinical situations (such as acute gastrointestinal hemorrhage, low ascitic total fluid protein), while evidence of benefit is lacking in other circumstances (acute liver failure, alcoholic hepatitis). Additionally, there are several biomarkers that have shown promise in predicting infection in cirrhosis, which may help us tailor antibiotic exposure and mitigate growing antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and recurrence rate. The efficacy of the first-line drug sorafenib is impeded by drug resistance, which is closely related to activated hepatic stellate cells (HSCs). The natural product luteolin is good at alleviating the activation of HSC. However, its clinical application is limited to poor solubility, bioavailability and lacking of HSCs targeting effects. This study aims to construct luteolin-loaded biomimetic nanoparticles based on HepG2 exosomes for targeting HSCs and enhancing the therapeutic effects of sorafenib on HCC. Methods: The HepG2 exosomes extracted were identified by size distribution, Zeta potential and characteristic proteins. Luteolin-loaded polylactic acid-glycolic acid (PLGA) nanoparticles (Lut-NPs) were prepared and wrapped by HepG2 exosomes to form biomimetic nanoparticles (Exo-Lut-NPs). A HepG2 cell sorafenib-resistant model induced by LX2 cell conditioned medium (CM) was established to evaluate the effects of Exo-Lut-NPs on reversing sorafenib-resistant in vitro. And the combined therapeutic effects of Exo-Lut-NPs with sorafenib were evaluated on a HepG2/LX2 subcutaneous xenograft tumor model in vivo. Results: The particle size, drug loading capacity and encapsulation efficiency of Exo-Lut-NPs were 165 ± 10 nm, 2.6 ± 0.2% and 56.9 ± 4.3%, respectively. The in vitro HepG2 sorafenib-resistant model was induced by the CM of LX2 cells, and the results showed that Exo-Lut-NPs partially reversed the sorafenib resistance of HepG2 cells by affecting the CM of LX2 cells. The combined therapy of Exo-Lut-NPs with sorafenib markedly suppressed tumor growth in a HepG2/LX2 subcutaneous xenograft tumor model. Conclusions: This study suggests that the Exo-Lut-NP is a novel and promising biomimetic delivery system which can combine with sorafenib for HCC therapy. [ABSTRACT FROM AUTHOR]

Alcohol abuse is associated with several diseases, such as hepatocellular carcinoma, cirrhosis, and extrahepatic malignancies. Recently, we reported albumin platelet product (APP) and modified APP (mAPP) as novel indices of liver fibrosis staging and prognosis in patients without alcoholic liver diseases. This retrospective cohort study aimed to extend application of APP and mAPP in prognosis prediction of patients with alcoholic liver diseases. We enrolled 222 patients with alcoholic liver diseases based on their medical records. Cut-off values of APP = 4.349 and mAPP = 2.484 were adopted based on a past report. Hazard ratios of APP and mAPP were compared to those of albumin-bilirubin score and fibrosis-4 index. The primary and secondary endpoints were carcinogenesis and death, respectively. Thus, APP = 4.349 and mAPP = 2.484 significantly differentiated cancer-free survival and overall survival in univariate analysis. Hazard ratios of mAPP = 2.484 were greater than those of the albumin-bilirubin score of -2.270 and fibrosis-4 index of 3.25. Multivariate analysis revealed mAPP = 2.484 as an independent risk factor for carcinogenesis and overall death. In conclusion, mAPP is a simple index to stratify patient's risk for carcinogenesis and death. [ABSTRACT FROM AUTHOR]

Portal hypertension often precedes the development of advanced fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) and may accelerate disease progression to cirrhosis. We aimed to evaluate whether prioritization tools accurately predict survival in patients with MASLD and clinically significant portal hypertension (CSPH). We retrospectively identified patients diagnosed with esophageal or gastric varices (EGV). Laboratory results, endoscopy reports and outcomes of patients with MASLD were compared to patients with advanced stage chronic liver disease (CLD) of other etiologies. During the study period 326 patients were diagnosed with EGV. 88 (26.9%) had MASLD, 113 (34.6%) viral hepatitis (VH), 63 (19.3%) alcoholic liver disease (ALD) and 62 (19%) both VH and ALD (VHALD). EGV bleeding events were significantly more frequent in patients with MASLD (36.3%), compared to VH (28.3%), ALD (30.1%) and VHALD (25.8%), respectively (p < 0.01). Mean Model for End-Stage Liver Disease (MELD)-Na score surrounding 1 year of first event of EGV bleeding was significantly lower in MASLD patients compared to all other etiologies (p = 0.02). At a MELD-Na score of 11–20, cumulative survival rate was significantly lower in MASLD patients compared to all other etiologies (log rank p < 0.01). MASLD patients present with EGV bleeding at lower MELD-Na scores compared to other etiologies of CLD. MELD-Na score may therefore underestimate disease severity and risk of death in patients with MASLD and CSPH. [ABSTRACT FROM AUTHOR]

Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field. [ABSTRACT FROM AUTHOR]

Non-cancer deaths are now becoming a great threat to the health of cancer survivors. There are no comprehensive and systematic reports on chronic liver disease and cirrhosis mortality (CLDCM) among patients with digestive system cancers (DSCs). This research aimed to quantitatively assess the risks and patterns of CLDCM among patients with DSCs. From the surveillance, epidemiology and end results (SEER) program, we extracted the data of patients diagnosed with DSCs between 2000 and 2017. Trends in incidence-based mortality rate (IBMR) were calculated using Joinpoint software. The standardized mortality ratio (SMR) was obtained based on the reference of the general United States population. The cumulative incidence function curves were constructed by all causes of death. Independent indicators were identified using the multivariate Fine and Gray competing risk model. We included 906,292 eligible patients from the SEER program, of which 3068 (0.34%) died from chronic liver disease and cirrhosis (CLDC). The IBMR of CLDC continued to increase during the study period [average annual percent change (APC): 6.7%; 95% confidence interval (CI) 5.1–8.2] and the SMR was significantly increased (SMR: 3.19; 95% CI 3.08–3.30). The cumulative mortality of CLDC was the lowest in all causes of death. Furthermore, the age at diagnosis, race, gender, marital status, year of diagnosis, SEER stage, surgery, chemotherapy and radiotherapy were identified as independent indicators. Better screening, diagnostic and management approaches need to be implemented as a preferred method to protect the liver among patients with DSCs. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the prognosis and pharmacological therapy sensitivity of epithelial mesenchymal transition-related genes (EMTRGs) that obtained from the EMTome database in hepatocellular carcinoma (HCC) using bioinformatical method. The expression status of EMTRGs were also investigated using the clinical information of HCC patients supported by TCGA database and the ICGC database to establish the TCGA cohort as the training set and the ICGC cohort as the validation set. Analyze the EMTRGs between HCC tissue and liver tissue in the TCGA cohort in the order of univariate COX regression, LASSO regression, and multivariate COX regression, and construct a risk model for EMTRGs. In addition, enrichment pathways, gene mutation status, immune infiltration, and response to drugs were also analyzed in the high-risk and low-risk groups of the TCGA cohort, and the protein expression status of EMTRGs was verified. The results showed a total of 286 differentially expressed EMTRGs in the TCGA cohort, and EZH2, S100A9, TNFRSF11B, SPINK5, and CCL21 were used for modeling. The TCGA cohort was found to have a worse outcome in the high-risk group of HCC patients, and the ICGC cohort confirmed this finding. In addition, EMTRGs risk score was shown to be an independent prognostic factor in both cohorts by univariate and multivariate COX regression. The results of GSEA analysis showed that most of the enriched pathways in the high-risk group were associated with tumor, and the pathways enriched in the low-risk group were mainly associated with metabolism. Patients in various risk groups had varying immunological conditions, and the high-risk group might benefit more from targeted treatments. To sum up, the EMTRGs risk model was developed to forecast the prognosis for HCC patients, and the model might be useful in assisting in the choice of treatment drugs for HCC patients. [ABSTRACT FROM AUTHOR]

Methods: HS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed. Results: It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 μm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%. Conclusions: The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect. Key points: The diameter of HepaSphere microspheres can be reduced effectively by using a new loading method. In vivo study on the rabbit VX2 liver cancer model suggests that the new loading method can increase anticancer drug concentration in tumor and hence exert better effect. [ABSTRACT FROM AUTHOR]

Hepatic venous pressure gradient (HVPG) is an accurate measure of portal hypertension in cirrhosis. However, the effect of catheter tip distance from hepatic vein ostium (HVO) on HVPG is unknown. We performed a retrospective study on 228 patients with 307 HVPGs in our institution. The objectives of this study were to assess the effect of catheter position on the validity of HVPG and its prognostication in cirrhosis. In this study, free hepatic vein pressure (FHVP) was considered optimal when difference between FHVP and inferior vena cava pressure was ≤ 2 mmHg. HVPG progressively decreased (p < 0.001) when measured at increasing distance from HVO due to an increasing FHVP (p = 0.036) but an unchanged wedged hepatic vein pressure (p = 0.343). Catheter tip distance > 5 to ≤ 8 cm [odds ratio {OR} 0.16 (95% CI 0.05–0.47), p = 0.001] and > 8 cm [OR 0.14 (95% CI 0.04–0.47), p = 0.002] compared to ≤ 3 cm from HVO were independent predictors of not achieving optimal FHVP. Baseline HVPG ≥ 16 mmHg was strongly associated with deaths due to cirrhosis and liver transplantation for end-stage liver disease compared to HVPG < 16 mmHg when FHVP was optimal (p < 0.001) but not when it was suboptimal (p = 0.359). Our study showed that FHVP is spuriously elevated when measured at > 5 cm from HVO, resulting in inaccurately low HVPG. [ABSTRACT FROM AUTHOR]

Purpose: Chronic hepatitis B-liver cirrhosis-hepatocellular carcinoma (CLH), commonly called the "liver cancer trilogy", is a crucial evolutionary phase in the emergence of hepatocellular carcinoma (HCC) in China. Previous studies on early diagnostic biomarkers of HCC were limited to the end-stage of HCC and did not focus on the evolutionary process of CLH. Methods: 11 monotonically changing differentially expressed genes (MCDEGs) highly correlated with CLH were screened through bioinformatic analysis and KPNA2 was identified for further research. The serum KPNA2 expression in different CLH states was detected by Enzyme linked immunosorbent assay (ELISA). A nomogram model was constructed using univariate and multivariate Cox regression methods. Results: The single-cell RNA-seq and bulk RNA-seq revealed that KPNA2 related to immune infiltration in HCC and may participate in cell cycle pathways in HCC. The serum KPNA2 expression was monotonically upregulated in CLH and was valuable for diagnosing different CLH states. Besides, chronic hepatitis B(CHB) patients, liver cirrhosis (LC) patients, and HCC patients were classified into subgroups with distinct serum KPNA2 expressions. Accordingly, patients with different serum KPNA2 expressions displayed various clinicopathological features. The AUC value of the nomogram model was 0.959 in predicting the likelihood of developing HCC in CHB patients or LC patients. Finally, we found that KPNA2 expression was negatively correlated with the IC50 of four chemotherapeutic drugs in HCC. Conclusion: KPNA2 was a novel serum biomarker for diagnosing different CLH states, monitoring the dynamic evolution of CLH, and a new therapeutic target for intervening in the progression of CLH. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to determine the role of Sound Touch Elastography [STE] technique in staging liver fibrosis and predicting clinically significant gastro-esophageal varices among patients with chronic liver disease [CLD] keeping aspartate aminotransferase to platelet ratio index [APRI] as the reference standard. Methods: A prospective short-term study including 60 eligible patients with CLD were staged as non-significant fibrosis [NSF], significant fibrosis [SF] and cirrhosis [C] based on APRI values. STE was performed on each patient obtaining multiple readings as per pre-defined standards. The intra-observer reliability between each measurement and its association with APRI staging was evaluated using relevant statistical variables. Further, Youden's index was used to define the optimum cut-off values on STE in differentiating the stages of fibrosis and in predicting clinically significant gastro-esophageal varices. Results: Based on APRI cut-off values, 41.7% [n = 25] of the study population had cirrhosis, while 45% [n = 27] had significant fibrosis and 13.3% [n = 8] had NSF. The STE values in kPa showed a positive correlation with APRI values [(rs) = 0.837, p < 0.001]. The intra-class correlation estimates based on a mean rating [k = 5] was found to be 0.97 [0.95–0.99], implying an excellent agreement between the measurements. Optimum cut-off values in staging SF and C were 7.26 kPa [J = 0.73, sensitivity—85.19%, specificity—87.5%; 95% CI] and 13.79 kPa [J = 0.84, sensitivity—96.0%, specificity—88.89%; 95% CI]. The AUROC for each of these stages were 0.926 [0.785–0.987] and 0.976 [0.890–0.999], respectively. 23.3% [n = 14] of the study population had clinically significant gastro-esophageal varices with a value above 18.84 kPa [J = 0.88] showing a sensitivity of 92.85% and a specificity of 95.65% in predicting the same. Conclusion: The novel STE technique shows good accuracy in staging liver fibrosis as determined by APRI values and in prediction of clinically significant gastro-esophageal varices with excellent reliability. It shows promising prospects and can be integrated widely in clinical practice for assessment and staging of fibrosis in CLD. [ABSTRACT FROM AUTHOR]

Purpose: The role of microRNA-146a (miR-146a) in defining the tumor immune microenvironment (TIME) is well established. The aim of this study was to evaluate circulating miR-146a as an early prognostic marker of 90Y-radioembolization (90Y-RE) in metastatic liver cancer and to assess the correlation between circulating miR-146a and TIME cellular composition in distant, yet untreated metastases. Methods: Twenty-one patients with bilobar liver lesions from gastro-intestinal cancer underwent lobar 90Y-RE. Biopsy of contralateral lobe abscopal tumors was acquired at the onset of a second treatment session at a median of 21 days after initial RE, immediately prior to ablation therapy of the contralateral lobe tumor. miR-146a was measured by RT-qPCR in plasma collected 24 h before (T1) and 48 h after (T2) initial unilobar 90Y-RE. The level of miR-146a was correlated with the infiltration of CD4 + , CD8 + , FoxP3 T cells, CD163 + M2 macrophages and immune-exhausted T cells in the abscopal tumor tissue acquired before the second treatment session. Results: Plasma samples collected at T2 showed a higher concentration of miR-146a with respect to T1 in 43% of the patients (p = 0.002). In these patients, tumors revealed a pro-tumorigenic immune composition with enrichment of Tim3 + immune exhausted cells (p = 0.021), in combination with a higher infiltration of CD163 + M2 macrophages and a lower infiltration of CD8 + T cells. Patients with a higher level of miR-146a after 90Y-RE showed a trend to shorter OS (p = 0.055). Conclusion: miR-146a may represent a novel prognostic biomarker for 90Y-radioembolization in metastatic liver cancer. [ABSTRACT FROM AUTHOR]

Changes in circulating platelets during different grades of malaria are of major concerns, and its etiology is poorly understood. We appraised and evaluated the role of circulating platelets in the determination of the severity of malaria among a cohort of outpatients living in Ilorin, Nigeria. A hospital-based case-control study of outpatients visiting public health facilities within the locality voluntarily enrolled for this study. Blood samples from 1162 malaise patients were screened using routine microscopy for Plasmodium parasite species identification, and their respective circulating platelet levels were determined. Seven hundred and seventy-five individuals (775, 66.7%, p<0.001) were malaria-positive. Samples from 387 (33.3%) uninfected healthy individuals were used as controls. Individuals with uncomplicated malaria (UCM) and complicated malaria (CM) across age group were notable (p<0.05). Children ≤5 years had the highest number of individuals with CM (103, 45.2%) with a relative risk ratio of 4.005 (95% CI: 2.964–5.413). UCM (471, 40.5%) occurred more than CM (304, 26.2%) (p>0.05) across the groups. The geometric mean, 95% CI, median, and IQR of populations with malaria thrombocytopenia were higher (181, 110.94±2.207, 106.59–115.30, 118.00, and 39.00) than thrombocytosis (78, 624.64±13.131, 598.49–650.79, 623.00, and 208). Seemingly, health controls recorded insignificant morbidity with respect to platelet counts. High P. falciparum parasitemia is inversely correlated with platelet count, and its' morbidity is associated with the manifestation of several malaria pathogenesis. Thrombocytopenia is a silent pathophysiological attribute that can trigger other cofactors during severe malaria disease. Although further studies are pertinent in order to specifically clarify its relevance to clinical disease spectrum. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of linezolid-induced thrombocytopenia (LIT) has been reported to vary widely across studies. We performed a meta-analysis to identify the risk factors for thrombocytopenia among patients who received linezolid treatment. Methods: The PubMed, Embase and Cochrane Library databases were searched from inception to November 2022 to identify eligible studies. Data on the potential predictors of incidence in LIT were pooled using a random effects model. Sensitivity analyses were performed to determine the robustness of the results when significant heterogeneity was observed. Results: Forty observational studies involving 6454 patients treated with linezolid were included in the analysis. LIT was estimated to occur in 37% of patients. The following important factors were associated with the incidence of LIT: advanced age, body mass index, concurrent renal impairment or liver disease, abnormal laboratory parameters (including white blood cell count, serum creatinine, baseline platelet count, albumin, creatinine clearance rate, and estimated glomerular filtration rate), treatment duration and renal replacement therapy. Conclusions: A variety of risk factors related to the occurrence of LIT were revealed in our analysis. Early identification of these factors could help patients improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) remains an incurable malignancy despite the treatment methods being continually updated. Matrix metalloproteinases (MMPs) promote the progression of HCC; however, no consensus exists on which MMP plays the predominant role in HCCs. In the present study, we analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the Cancer Genome Atlas database. The KEGG enrichment pathway using differentially expressed genes included extracellular matrix–receptor interaction, which was correlated with MMPs. We found that among the MMP family, only MMP1, MMP3, MMP8, MMP9, MMP11, MMP12, MMP14, MMP15, MMP20, MMP21, and MMP24 significantly increased in HCCs compared with adjacent tissues. Crucially, survival and univariate analyses indicated that only MMPs 1, 9, 12, and 14 predict poor overall survival; however, multivariate Cox analysis and a nomogram demonstrated that only MMP1 is a poor prognostic biomarker for HCCs. In addition, we observed significant enrichment of uncharacterized cells but decreased macrophages in HCC tissues. Consistent with decreased macrophages in HCCs, MMP1 was negatively associated with macrophages but positively correlated with uncharacterized cells, indicating that the main producer of MMP1 is uncharacterized cells. Furthermore, MMP1 expression was negatively correlated with immune responses of HCCs. Taken together, our findings indicated that MMP1 is a poor and predominant prognostic biomarker for patients with HCC and that anti-MMP1 may be a novel therapy that is worth studying in depth. [ABSTRACT FROM AUTHOR]

The systemic immune-inflammation index (SII), derived from neutrophil, platelet, and lymphocyte counts, has been associated with prognosis of patients with cancer. We performed a meta-analysis to evaluate the association between pretreatment SII and survival of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Cohort studies were identified by search of PubMed, Embase, Web of Science, CNKI, and Wanfang databases. Pooling the results was achieved with a random-effect model that incorporates potential heterogeneity between studies. Nine studies including 3557 patients with HCC contributed to the meta-analysis. Compared to patients with a lower SII, HCC patients with a higher pretreatment SII had poor overall survival (OS, hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.25–2.21, p < 0.001; I2 = 80%) and poor progression-free survival (PFS, HR 1.28, 95% CI 1.05–1.56, p = 0.01; I2 = 0%) after TACE treatment. Further subgroup analyses confirmed a significant association between a high pretreatment SII and poor OS after TACE, which was not significantly affected by study country, sample size, age of the patients, cutoff values for SII, and adjustment of Child–Pugh score or alpha fetoprotein (p for subgroup effect all < 0.05). However, a higher SII was associated with poor OS in studies with follow-up duration ≤ 24 months (HR 1.94, 95% CI 1.39–2.72, p < 0.001), but the association was not statistically significant in studies with follow-up duration > 24 months (HR 1.27, 95% CI: 0.96–1.68, p = 0.09). A higher pretreatment SII was correlated with poor survival of HCC patients after TACE. A preliminary measurement of SII may be valuable for the prediction of the prognosis in HCC patients after TACE. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively evaluate the potential of four-dimensional (4D) flow magnetic resonance imaging (MRI) in predicting treatment responses after transcatheter arterial chemoembolization (TACE) in cirrhotic patients with hepatocellular carcinoma (HCC). Methods: A total of 195 patients were classified into four groups (A–D): A, cirrhotic patients without HCC (n = 30); B, cirrhotic patients with HCC before TACE (n = 75); C, cirrhotic patients with HCC showing an incomplete response following TACE (n = 56); and D, cirrhotic patients with HCC achieving a complete response (CR) following TACE (n = 34). The patients were subjected to routine laboratory tests and 4D flow MRI using a 3-T MRI system to measure the quantitative parameters of blood flow in the portal vein (PV), splenic vein (SV), and superior mesenteric vein. The data collected by 4D flow MRI were compared among the groups using one-way analysis of variance. A multivariate analysis was performed to verify the association of clinical characteristics and 4D flow parameters with CR after TACE treatment. Results: The average through-plane velocity, peak velocity magnitude, average net flow, peak flow, and net forward volume in the PV and SV were significantly lower in groups B and C (P < 0.05) compared to those in group A. Moreover, average through-plane velocity and peak velocity magnitude in the PV in groups B and C were significantly lower than those in group D (P < 0.05). The multivariate analysis demonstrated that the average through-plane velocity and peak velocity magnitude in the PV were independently associated with CR in HCC patients after TACE (P < 0.05). Conclusion: The quantitative flow data obtained by 4D flow MRI may be useful for predicting CR after TACE in cirrhotic patients with HCC. [ABSTRACT FROM AUTHOR]

Although splenectomy causes significant increase in platelet count, little is known about its kinetics and final status of platelet count. This study sought to revisit the kinetics of post-splenectomy platelet count and attempted to establish a prediction model of post-splenectomy platelet count. Data of 103 consecutive patients who underwent splenectomy with or without resection of adjacent organs were reviewed. Postoperative kinetics of platelet count was investigated and prediction model of its final status was established. The study cohort consisted of patients with diseased liver group (n = 28) and with normal liver group (n = 75). Platelet count increased rapidly during the initial 1 month and reached plateau at approximately 3 months after splenectomy. The degree of increase in platelet count was significantly higher in the diseased liver group, while the final platelet count reached within normal range in both of the two groups. Regression analysis confirmed that platelet increase rate at 3 months was predictable with relatively high accuracy using the following formula: 1.667 + 0.006 × (spleen volume per body surface mL/m2)–0.030 × (preoperative platelet count, 104/mm3) (r = 0.849, P < 0.001). Acceptable performance of this formula was also confirmed in a validation cohort (r = 0.904, P < 0.001). Post-splenectomy increase in platelet count is significantly higher in patients with diseased liver. The final degree of increase in platelet count may be predictable with high accuracy using preoperative platelet count and spleen volume index. [ABSTRACT FROM AUTHOR]

Objective: In the present study, we aimed to identify potential predictors of intermediate-stage hepatocellular carcinoma (HCC) using whole-exome sequencing (WES) in patients undergoing transarterial chemoembolization (TACE). Materials and methods: In A total of 51 patients, newly diagnosed with intermediate-stage HCC between January 2013 and December 2020, were enrolled. Prior to treatment, histological samples were collected for western blotting and immunohistochemistry. The predictive roles of clinical indicators and genes in patient prognosis were analyzed using univariate and multivariate analyses. Finally, the correlation between imaging features and gene signatures was examined. Results: Using WES, we identified that bromodomain-containing protein 7 (BRD7) was significantly mutated in patients with different TACE responses. No significant difference in BRD7 expression was observed between patients with and without BRD7 mutations. HCC tumors exhibited higher BRD7 than normal liver tissues. Multivariate analysis revealed that alpha-fetoprotein (AFP), BRD7 expression, and BRD7 mutations were independent risk factors for progression-free survival (PFS). In addition, Child–Pugh class, BRD7 expression, and BRD7 mutations were independent risk factors for overall survival (OS). Patients with wild-type BRD7 and high BRD7 expression had worse PFS and OS, whereas those with mutated BRD7 and low BRD7 expression exhibited the best PFS and OS. The Kruskal–Wallis test revealed that wash-in enhancement on computed tomography might be an independent risk factor for high BRD7 expression. Conclusion: BRD7 expression may be an independent risk factor for prognosis in patients with HCC undergoing TACE. Imaging features such as wash-in enhancement are closely related to BRD7 expression. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are the most efficacious and common medications for gastric acid suppression. However, PPIs continue to perpetuate safety concerns due to the availability as an over-the-counter medication. This uncontrolled use of PPIs has recently been shown to be associated with the increased health risks. The inhibition of gastric acid production by irreversibly binding to and inhibiting the H+/K+ ATPase enzyme system can cause structural and physiologic changes in the GI microbiome, GI physiology, and pH. With the recent guideline updates from American Gastroenterological Association regarding deprescription of PPIs, this review focuses on the complications of long-term use of PPIs on various systems, gut microbiome, intestinal barrier and inflammatory bowel disease (IBD). Short conclusion: If PPI use in IBD patients is associated with increased risk of other adverse outcomes, considering the PPI-associated mineral, electrolyte and microbial alterations also needs rigorous evaluation. [ABSTRACT FROM AUTHOR]

Background: The data regarding the incidence of post-embolization syndrome after transarterial chemoembolization for hepatocellular carcinoma in Thailand are scarce. Therefore, this study aimed to determine the prevalence and predictors of post-embolization syndrome after transarterial chemoembolization for hepatocellular carcinoma in Thailand. Methods: This retrospective study collected data from patients undergoing transarterial chemoembolization for five years. Post-embolization syndrome was defined as fever and/or abdominal pain, and/or nausea or vomiting that occurred within three days after the transarterial chemoembolization procedure for hepatocellular carcinoma or hospital discharge. Pre-defined predictors for post-embolization syndrome were explored using Poisson regression analysis. Results: Of the 298 patients and 739 transarterial chemoembolization procedures, the incidence of post-embolization syndrome was 68.1% (203/298) and the incidence density was 53.9% (398/739). Tumor size, Barcelona Clinic Liver Cancer stages, and dose of chemotherapy showed no association with the occurrence of PES. However, a model for end-stage liver disease score was the only predictor for post-embolization syndrome [adjusted IRR 0.91 (0.84–0.98); p = 0.01]. There were three patients developing fever after transarterial chemoembolization due to infection. Conclusion: Post-embolization syndrome was common in patients undergoing transarterial chemoembolization for hepatocellular carcinoma. Patients with a lower model for end-stage liver disease scores were at increased risk of post-embolization syndrome. This study highlights the burden of post-embolization syndrome among patients with hepatocellular carcinoma receiving transarterial chemoembolization. [ABSTRACT FROM AUTHOR]

Purpose of Review: Clinically significant portal hypertension (CSPH) is a serious clinical condition causing decompensation and potentially fatal complications especially in the presence of advanced liver disease. This article aims to critically review the current literature on non-invasive assessment of CSPH. Recent Findings: The Baveno VII consensus encouraged non-invasive assessment of CSPH to identify patients at risk and avoid unnecessary screening endoscopies. Novel machine learning and omics-based laboratory scores have been introduced, which can be combined with liver stiffness measurement (LSM). Spleen stiffness measurement (SSM) is an increasingly used novel elastography modality. Elastography and cross-sectional imaging methods have reached similar predictive power, while the accuracy of non-invasive tests can only be improved when used sequentially. Summary: In this review, we provide a detailed discussion of advantages and limitations of non-invasive assessment of CSPH, highlighting their diagnostic accuracy, reproducibility, and feasibility in clinical practice. [ABSTRACT FROM AUTHOR]

Summary: The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna. Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy and one of the leading causes of cancer-related death. The biological process of HCC is complex, with multiple factors leading to the broken of the balance of inactivation and activation of tumor suppressor genes and oncogenes, the abnormal activation of molecular signaling pathways, the differentiation of HCC cells, and the regulation of angiogenesis. Due to the insidious onset of HCC, at the time of first diagnosis, less than 30% of HCC patients are candidates for radical treatment. Systematic antitumor therapy is the hope for the treatment of patients with middle-advanced HCC. Despite the emergence of new systemic therapies, survival rates for advanced HCC patients remain low. The complex pathogenesis of HCC has inspired researchers to explore a variety of biomolecular targeted therapeutics targeting specific targets. Correct understanding of the molecular mechanism of HCC occurrence is key to seeking effective targeted therapy. Research on biomarkers for HCC treatment is also advancing. Here, we explore the molecular mechanism that are associated with HCC development, summarize targeted therapies for HCC, and discuss potential biomarkers that may drive therapies. [ABSTRACT FROM AUTHOR]

Patients undergoing transplantation have an increased risk of developing infections such as tuberculosis, Pneumocystis carnii pneumonia, Candida infections or cytomegalovirus infections because of their immunosuppressive therapy with cyclosprin A, azathioprine and steroids. Mycobacterial infection is well recognized as a complication in the immunocompromised host but diagnosis and therapy are very difficult. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is a highly vascularized solid carcinoma and tumor vessel–targeted molecular imaging might be effective for early diagnosis of HCC. Herein, we developed a novel trimeric affibody (ZTRI) with highly specific binding to the platelet-derived growth factor receptor beta (PDGFRβ). The aim of this study is to evaluate the feasibility of 68Ga-radiolabeled ZTRI ([68Ga]Ga-DOTA-ZTRI) as PET tracer for diagnosis of HCC. Methods: The bioinformatics analysis of clinical database and immunoblotting of clinical specimens were performed to validate the potential of PDGFRβ as HCC biomarker. The trimeric affibody ZTRI was conjugated with DOTA-NHS-ester and radiolabeled with 68Ga to produce [68Ga]Ga-DOTA-ZTRI conjugate. Immunoreactivity and specific uptake of [68Ga]Ga-DOTA-ZTRI were assessed by dose-dependent cell binding, autoradiography, and biodistribution analysis. [68Ga]Ga-DOTA-ZTRI PET/CT scanning of diethylnitrosamine (DEN)-induced primary HCC rats and a rare case of idiopathical HCC rhesus monkey was performed to evaluate the imaging capability and radiation dosimetry of [68Ga]Ga-DOTA-ZTRI in vivo. Results: Excessive PDGFRβ was validated as a representative biomarker of HCC neovascularization. The radiolabeling of [68Ga]Ga-DOTA-ZTRI was achieved at more than 95% radiochemical yield. In vitro assays showed specific uptake of [68Ga]Ga-DOTA-ZTRI in HCC tumor vessels by autoradiography. Animal PET/CT imaging with [68Ga]Ga-DOTA-ZTRI successfully visualized the tumor lesions in primary HCC rats and rhesus monkey, and indicated radiation absorbed dose of 2.03E-02 mSv/MBq for each scanning. Conclusions: Our results demonstrated that [68Ga]Ga-DOTA-ZTRI conjugate could be applied as a promising PET tracer for early diagnosis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]