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Background and Aims: This study prospectively compared the diagnostic accuracies of the improved Attenuation Measurement (iATT) algorithm and the Controlled Attenuation Parameter (CAP) and assessed the interchangeability of iATT with magnetic resonance imaging-derived proton density fat fraction (MRI-derived PDFF)., Methods: Patients with chronic liver disease were prospectively enrolled and underwent iATT, CAP and MRI-derived PDFF measurements for hepatic steatosis evaluation. According to MRI-derived PDFF values, steatosis grades were categorised as steatosis (S)0 (< 5.2%), S1 (≥ 5.2%, < 11.3%), S2 (≥ 11.3%, < 17.1%) and S3 (≥ 17.1%). Correlation coefficients (CCs) were determined, diagnostic performances were compared by the area under the receiver operating characteristic curve (AUROC) and agreement was evaluated using the calculated percentage error (PE) and expected limit of agreement (LOA)., Results: A total of 414 patients (median age 64 years, 203 females) were evaluated. The CC between iATT and MRI-derived PDFF was 0.727 (95% confidence interval [CI] 0.678-0.770), which was higher than that between CAP and MRI-derived PDFF at 0.615 (95% CI 0.551-0.672) (p < 0.001). The AUROCs of iATT for ≥ S1, ≥ S2 and ≥ S3 were 0.901 (95% CI 0.870-0.931), 0.878 (95% CI 0.846-0.910) and 0.839 (95% CI 0.794-0.883), respectively. The diagnostic performances of iATT for ≥ S1 and ≥ S2 showed significantly higher AUROCs than those of CAP (p < 0.001, p = 0.036, respectively). The calculated PE and the expected LOA for CAP and iATT were 38.94% and 22.66% and 32.94% and 30.03%, respectively., Conclusions: iATT was superior to CAP and comparable to MRI-derived PDFF in assessing hepatic steatosis., Trial Registration: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000047411)., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference., Methods: Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis., Results: The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73)., Conclusions: Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetes mellitus (T2DM). Previous studies have identified a link between β-cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic β-cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic β-cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of β-cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic β-cell dysfunction., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD., Methods: The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD., Results: A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up., Conclusions: PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lentiviral vectors (LV) are efficient vehicles for in vivo gene delivery to the liver. LV integration into the chromatin of target cells ensures their transmission upon proliferation, thus allowing potentially life-long gene therapy following a single administration, even to young individuals. The glycoprotein of the vesicular stomatitis virus (VSV.G) is widely used to pseudotype LV, as it confers broad tropism and high stability. The baculovirus-derived GP64 envelope protein has been proposed as an alternative for in vivo liver-directed gene therapy. Here, we perform a detailed comparison of VSV.G- and GP64-pseudotyped LV in vitro and in vivo. We report that VSV.G-LV transduced hepatocytes better than GP64-LV, however the latter showed improved transduction of liver sinusoidal endothelial cells (LSEC). Combining GP64-pseudotyping with the high surface content of the phagocytosis inhibitor CD47 further enhanced LSEC transduction. Coagulation factor VIII (FVIII), the gene mutated in hemophilia A, is naturally expressed by LSEC, thus we exploited GP64-LV to deliver a FVIII transgene under the control of the endogenous FVIII promoter and achieved therapeutic amounts of FVIII and correction of hemophilia A mice., (© 2024. The Author(s).)

Few instances of neoplastic formations in the liver of chinchillas have been found, even though the species is widely used in different scientific experiments. In the present article we investigate the anatomical features of the chinchilla's liver using CT and three dimension (3D) imaging. For the trials we used 12 (six males and six females) clinically healthy chinchillas all at 18 months of age. The animals were positioned in dorsal recumbency. We used Th8 to L2 vertebrae and the sternum as bone markers for the transverse CT study. The investigated anatomical landmarks for the CT coronal study were the vertebrae, costal arch, soft abdominal wall, diaphragm, stomach and the right kidney. 3D reconstructions were accomplished with a specific imaging software. On transverse and coronal CT images, the chinchilla's liver was composed of lobus hepatis sinister lateralis, 'middle lobe'-without proper Latin term in NAV 2017, lobus hepatis dexter and lobus caudatus. The 'middle lobe' was separated into the 'left middle lobe' and the 'right middle lobe'. Lobus hepatis dexter consisted of lobus hepatis dexter medialis and lobus hepatis dexter lateralis. There was an anatomical relation between the liver, fundus ventriculi and corpus ventriculi. Proc. caudatus was in close contact with the right kidney. Vesica fellea was elongated and ellipsoid. 3D reformatted images confirmed the results obtained by transverse and coronal CT studies. The CT density of the liver in HU was 195.6 ± 73.1. The CT and 3D reconstructed images were visualized at high resolution. This data could be used as a basis for further morphological and imaging studies., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP., Methods: To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded., Results: Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r 2  = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO 2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO 2 ) and VO 2 . Lactate clearance was correlated to transaminase levels and DO 2 -normalized lactate clearance was the parameter best discriminating between study groups., Conclusions: DO 2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background & Aims: We examined the diagnostic performance of plasma N-terminal propeptide of type III procollagen (PIIINP) levels, aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for predicting non-alcoholic steatohepatitis (NASH) and liver fibrosis stage in children/adolescents with non-alcoholic fatty liver disease (NAFLD)., Methods: We enrolled 204 children/adolescents with biopsy-proven NAFLD at the "Bambino Gesù" Children's Hospital. We measured plasma PIIINP levels using a commercially available enzyme-linked immunosorbent assay kit and calculated APRI and FIB-4 scores using standard methods., Results: Children with NASH had higher plasma PIIINP levels, APRI and FIB-4 scores compared with those without NASH (all P < .001). However, PIIINP levels had much better diagnostic performance and accuracy than APRI and FIB-4 scores for predicting liver fibrosis stage. PIIINP levels correlated with the total NAFLD activity score (NAS) and its constituent components (P < .0001). The risk of either NASH or F ≥ 2 fibrosis progressively increased with increasing PIIINP levels (P < .0001), independent of age, gender, adiposity measures, insulin resistance, NAS score and the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. For every 3.6 ng/mL increase in PIIINP levels, the likelihood of having F ≥ 2 fibrosis increased by ~14-fold (adjusted-odds ratio 14.1, 95% CI 5.50-35.8, P < .0001) after adjustment for the aforementioned risk factors. The area under the receiver operating characteristics curve was 0.921 (95% CI 0.87-0.97) for F ≥ 2 fibrosis, and 0.993 (95% CI 0.98-1.0) for F3 fibrosis respectively., Conclusions: Unlike APRI and FIB-4 scores, plasma PIIINP levels are a promising, non-invasive biomarker for diagnosing liver fibrosis stage in children/adolescents with biopsy-proven NAFLD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cell junctions, including anchoring, occluding and communicating junctions, play an indispensable role in the structural and functional organization of multicellular tissues, including in liver. Specifically, hepatic cell junctions mediate intercellular adhesion and communication between liver cells. The establishment of the hepatic cell junction network is a prerequisite for normal liver functioning. Hepatic cell junctions indeed support liver-specific features and control essential aspects of the hepatic life cycle. This review paper summarizes the role of cell junctions and their components in relation to liver physiology, thereby also discussing their involvement in hepatic dysfunctionality, including liver disease and toxicity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Liver cancer presents a growing global health concern, necessitating advanced approaches for intervention. This review investigates the use and effectiveness of software navigation in interventional radiology for liver tumour procedures. Methods: In accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) guidelines, a scoping review was conducted of the literature published between 2013 and 2023 sourcing articles through MEDLINE, Scopus, CINAHL and Embase. Eligible studies focused on liver cancer, utilised cone‐beam computed tomography (CBCT), and employed software for intervention. Twenty‐one articles were deemed eligible for data extraction and analysis. Results: Categorised by type, software applications yielded diverse benefits. Feeder detection software significantly enhanced vessel identification, reducing non‐target embolisation by up to 43%. Motion correction software demonstrated a 20% enhancement in image quality, effectively mitigating breathing‐induced motion artefacts. Liver perfusion software facilitated efficient tumour targeting while simultaneously reducing the occurrence of side effects. Needle guide software enabled precise radiofrequency ablation needle placement. Additionally, these software applications provided detailed anatomical simulations. Overall, software integration resulted in shorter procedures, reduced radiation exposure and decreased contrast media usage. Conclusion: This scoping review highlights the innovative yet relatively underexplored role of software navigation for liver tumour procedures. The integration of software applications not only enhances procedural efficiency but also bolsters operator confidence, and contributes to improved patient outcomes. Despite the current lack of uniformity and standardisation, these software‐driven advancements hold significant promise for transforming liver tumour interventions. To realise these benefits, further research is needed to explore the clinical impact and optimal utilisation of software navigation tools in interventional radiology. [ABSTRACT FROM AUTHOR]

Numerous complementary feeds to support liver function are commercially available for small animals. Aiming to furnish a scientific support for clinicians/nutritionists that necessitate a complementary feed to support liver function in dogs and cats, with the present paper, we analyzed scientific evidences supporting the use, for this purpose, of ingredients/additives such as artichoke (Cynara scolymus), curcumin, dandelion (Taraxacum officinale), milk thistle (Silybum marianum), phosphatidylcholine, and S-adenosylmethionine. Although sustained by significant results, our review found only few scientific papers, and albeit we believe that they represent a significant aid in handling hepatopathies, in the authors' opinion, this topic probably deserves, and would benefit of, further studies. [ABSTRACT FROM AUTHOR]

Liver, an important regulator of metabolic homeostasis, is critical for healthy brain function. In particular, age‐related neurodegenerative diseases seriously reduce the quality of life for the elderly. As population aging progresses rapidly, unraveling the mechanisms that effectively delay aging has become critical. Appropriate exercise is reported to improve aging‐related cognitive impairment. Whereas current studies focused on exploring the effect of exercise on the aging brain itself, ignoring the persistent effects of peripheral organs on the brain through the blood circulation. The aim of this paper is to summarize the communication and aging processes of the liver and brain and to emphasize the metabolic mechanisms of the liver–brain axis about exercise ameliorating aging‐related neurodegenerative diseases. A comprehensive understanding of the potential mechanisms about exercise ameliorating aging is critical for improving adaptation to age‐related brain changes and formulating effective interventions against age‐related cognitive decline. [ABSTRACT FROM AUTHOR]

Hepatic ischemia/reperfusion injury (IRI) remains a severe threat during liver surgery and transplantation, accounting for unfavorable clinical outcomes. Modafinil (MOD), a wakefulness‐inducing compound, is increasingly disclosed to protect against IRI. However, the specific literatures covering the association between MOD and hepatic IRI are few. Here, this paper is committed to unraveling the role and response mechanism of MOD in hepatic IRI. After the establishment of hepatic IRI mice model and cell model, relevant assay kits measured the concentrations of biochemical indicators of hepatotoxicity and hematoxylin and eosin staining estimated liver morphology. Enzyme‐linked immunosorbent assay, reverse‐transcription quantitative polymerase chain reaction, and western blot evaluated inflammatory levels. Terminal‐deoxynucleoitidyl transferase‐mediated nick end labeling assay and western blot appraised apoptosis. Western blot also analyzed the expression of Toll‐like receptor 9 (TLR9)/myeloid differentiation primary response gene 88 (MyD88)/p38 signaling‐associated proteins. Cell counting kit‐8 method judged cell viability. MOD was discovered to mitigate liver dysfunction and morphological damage, inflammatory response, apoptosis in vivo and improve cell viability, suppress inflammatory response and apoptosis in vitro. In addition, MOD inactivated TLR9/Myd88/p38 signaling both in vitro and in vivo. Further, TLR9 elevation reversed the inhibitory role of MOD in inflammatory response and cell apoptosis in vitro. Anyway, MOD blocked TLR9/Myd88/p38 signaling to exhibit anti‐inflammatory and anti‐apoptotic properties in hepatic IRI. [ABSTRACT FROM AUTHOR]

Summary: The SIMulation supported LIVer Assessment for donor organs (SimLivA) project aims to develop a mathematical model to accurately simulate the influence of mechanical alterations in marginal liver grafts (specifically steatotic ones) and cold ischemia on early ischemia‐reperfusion injury (IRI) during liver transplantation. Our project tackles significant research challenges, including the co‐development of computational methodologies, experimental studies, clinical processes, and technical workflows. We aim to refine a continuum‐biomechanical model for enhanced IRI prediction, collect pivotal experimental and clinical data, and assess the clinical applicability of our model. Our efforts involve augmenting and tailoring a coupled continuum‐biomechanical, multiphase, and multi‐scale partial differential equation‐ordinary differential equation (PDE‐ODE) model of the liver lobule, allowing us to numerically simulate IRI depending on the degree of steatosis and the duration of ischemia. The envisaged model will intertwine the structure, perfusion, and function of the liver, serving as a crucial aid in clinical decision‐making processes. We view this as the initial step towards an in‐silico clinical decision support tool aimed at enhancing the outcomes of liver transplantation. In this paper, we provide an overview of the SimLivA project and our preliminary findings, which include: a cellular model that delineates critical processes in the context of IRI during transplantation; and the integration of this model into a multi‐scale PDE‐ODE model using a homogenized, multi‐scale, multi‐component approach within the Theory of Porous Media (TPM) framework. The model has successfully simulated the interconnected relationship between structure, perfusion, and function—all of which are integral to IRI. Initial results show simulations at the cellular scale that describe critical processes related to IRI during transplantation. After integrating this model into a multiscale PDE‐ODE model, first simulations were performed on the spatial distribution of key functions during warm and cold ischaemia. In addition, we were able to study the effect of tissue perfusion and temperature, two critical parameters in the context of liver transplantation and IRI. [ABSTRACT FROM AUTHOR]

Purpose: The liver segments divided by Couinaud classification method are used to understand the functional anatomy of liver, which is significant in hepatic resection surgery. In Couinaud classification method, each third‐order branch of the portal vein (PV) defines the supplied territory of a corresponding liver segment. However, the accuracies of the reconstruction and classification of PV are affected by the complicated structure of the vein. The purpose of this paper is to develop a separation and classification method that can accurately extract the liver segments. Methods: In this paper, a multiple feature‐based method is proposed to obtain liver segments. Because the portal and hepatic veins usually connect in the vessel segmentation result, the PV is first completely separated based on the different strategies for minimal node cut using fused features of topology and appearance. Meanwhile, all bifurcation nodes of PV are detected. The bifurcation nodes are initial ordered through their linkages to classify the branches. Then, the feature of the vascular topology is used to refine the orders of bifurcation nodes. The bifurcation nodes with the refined orders classify the branches between them, and the third‐order branches of PV are obtained. The liver segments are eventually obtained through the third‐order branches. Results: The separation and classification in the proposed method are evaluated on the CT and MR datasets. The average values of Dice, Jaccard, Recall, and Precision obtained by the proposed method are 93.00%, 87.90%, 93.47%, and 93.19%, respectively. Compared with the state‐of‐the‐art methods, the separation results obtained by the proposed method are more accurate. The branches of PV are classified based on the separation result. According to the third‐order branches, eight liver segments correspond to the different functional areas are precisely extracted. Conclusions: The proposed method achieves a high accuracy for the liver segment extraction. And the extracted liver segments are significant for the preplanning of resection surgery. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kuo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17637 and https://doi.org/10.1111/apt.17677 [ABSTRACT FROM AUTHOR]

Liver cultures may be used for disease modeling, testing therapies, and predicting drug‐induced injury. The complexity of the liver cultures has evolved from hepatocyte monocultures to co‐cultures with non‐parenchymal cells and finally to precision‐cut liver slices. The latter culture format retains liver's native biomolecular and cellular complexity and therefore holds considerable promise for in vitro testing. However, liver slices remain functional for ≈72 h in vitro and display limited utility for some disease modeling and therapy testing applications that require longer culture times. This paper describes a microfluidic device for longer‐term maintenance of functional organotypic liver cultures. This microfluidic culture system is designed to enable direct injection of liver tissue into a culture chamber through a valve‐enabled side port. Liver tissue is embedded in collagen and remained functional for up to 31 days, highlighted by continued production of albumin and urea. These organotypic cultures also express several enzymes involved in xenobiotic metabolism. Conversely, matched liver tissue embedded in collagen in a 96‐well plate loses its phenotype and function within 3–5 days. The microfluidic organotypic liver cultures described here represent a significant advance in liver cultivation and may be used for future modeling of liver diseases or for individualized liver‐directed therapies. [ABSTRACT FROM AUTHOR]

Microgravity as experienced during spaceflight affects a number of physiological processes in various organs. However, effects on the liver have yet been poorly documented. Nevertheless, the liver is a metabolically highly active organ involved in carbohydrate metabolism, lipid metabolism and xenobiotic biotransformation. The present paper provides an overview of the effects of microgravity on the liver observed in experimental animals during actual spaceflight and upon simulation of microgravity on Earth. These include (i) induction of liver injury and inflammation associated with apoptosis and oxidative stress, (ii) changes in liver carbohydrate metabolism resulting in the onset of a diabetogenic phenotype, (iii) modifications in hepatic lipid metabolism leading to early non‐alcoholic fatty liver disease and (iv) alterations of the hepatic xenobiotic biotransformation machinery. Although most of these observations remain to be fully validated in humans, appropriate measures to counteract liver pathogenesis should be considered, especially in view of long‐term space missions. [ABSTRACT FROM AUTHOR]

Glycyrrhizae Radix et Rhizoma (GRER) has been used as a medicinal plant and dietary supplements for its beneficial effect in immunomodulatory effects. Sulfur fumigation (SF) processing was widely used in the storage and maintenance of Chinese medicine because of its convenience and cheapness. However, the disadvantage of SF has been reported, but the systematic study of SF on GRER was deficient. In this paper, the active ingredients, sulfur-fumigated products, immunomodulatory effect, and liver injury of SF-GRER were studied. After SF, the liquiritin decreased from 4.49 ± 0.03 mg/g to 3.94 ± 0.08 mg/g (P < 0.01). Compared with the NSF-GRER group, the SF-GRER group showed a decreased immunoregulation in the thymus index, spleen index, and serum IL-6 and SOD levels (P < 0.05). After 2 weeks of continuous intragastric administration of SF-GRER in healthy mice, the level of serum aspartate aminotransferase (AST) significantly increased (P < 0.05) and the area of liver lesion significantly increased compared with the NSF-GRER (P < 0.05) group. The sulfonated products (m/z, 631.13) corresponding to liquiritin apioside (m/z, 551.17) and isoliquiritin apioside (m/z, 551.17) were screened out in SF-GRER by using UPLC-Orbitrap-MS. The sulfonated products provided in this paper were discovered for the first time and could be powerfully applied for the identification of SF-GRER. SF destroyed the chemical composition of GRER, inhibited immunoregulation, and induced liver injury. The feasibility of this processing method needs to be reconsidered. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) typically presents with hepatic fibrosis in advanced disease, resulting in increased liver stiffness. A subset of patients further develops liver cirrhosis and hepatocellular carcinoma. Cardiovascular disease is a common comorbidity in patients with MASLD and its prevalence is increasing in parallel. Recent evidence suggests that especially liver stiffness, whether or not existing against a background of MASLD, is associated with heart diseases. We conducted a narrative review on the role of liver stiffness in the prediction of highly prevalent heart diseases including heart failure, cardiac arrhythmias (in particular atrial fibrillation), coronary heart disease, and aortic valve sclerosis. Research papers were retrieved from major scientific databases (PubMed, Web of Science) until September 2023 using 'liver stiffness' and 'liver fibrosis' as keywords along with the latter cardiac conditions. Increased liver stiffness, determined by vibration-controlled transient elastography or hepatic fibrosis as predicted by biomarker panels, are associated with a variety of cardiovascular diseases, including heart failure, atrial fibrillation, and coronary heart disease. Elevated liver stiffness in patients with metabolic liver disease should lead to considerations of cardiac workup including N-terminal pro-- B-type natriuretic peptide/B-type natriuretic peptide determination, electrocardiography, and coronary computed tomography angiography. In addition, patients with MASLD would benefit from heart disease case-finding strategies in which liver stiffness measurements can play a key role. In conclusion, increased liver stiffness should be a trigger to consider a cardiac workup in metabolically compromised patients. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative T1ρ imaging is an emerging technique to assess the biochemical properties of tissues. In this paper, we report our observation that liver iron content (LIC) affects T1ρ quantification of the liver at 3.0T field strength and develop a method to correct the effect of LIC. Theory and Methods: On‐resonance R1ρ (1/T1ρ) is mainly affected by the intrinsic R2 (1/T2), which is influenced by LIC. As on‐resonance R1ρ is closely related to the Carr–Purcell–Meiboom–Gill (CPMG) R2, and because the calibration between CPMG R2 and LIC has been reported at 1.5T, a correction method was proposed to correct the R2 contribution to the R1ρ. The correction coefficient was obtained from the calibration results and related transformed factors. To compensate for the difference between CPMG R2 and R1ρ, a scaling factor was determined using the values of CPMG R2 and R1ρ, obtained simultaneously from a single breath‐hold from volunteers. The livers of 110 subjects were scanned to validate the correction method. Results: LIC was significantly correlated with R1ρ in the liver. However, when the proposed correction method was applied to R1ρ, LIC and the iron‐corrected R1ρ were not significantly correlated. Conclusion: LIC can affect T1ρ in the liver. We developed an iron‐correction method for the quantification of T1ρ in the liver at 3.0T. [ABSTRACT FROM AUTHOR]

Background: Several options have been proposed for the treatment of congenital extrahepatic portosystemic shunts (cEHPSS) in dogs, but formal comparisons among different treatment options are currently unavailable. A previous evidence‐based review (2012) found low quality of evidence for papers assessing the treatment of cEHPSS in dogs. Objectives: To assess the quality of evidence available in the treatment of cEHPSS, summarize the current state of knowledge with respect to outcome after cEHPSS management, and compare different treatment techniques. Animals: Not used. Methods: A bibliographic search was performed without date or language restrictions. Studies were assessed for quality of evidence (study design, study group sizes, subject enrollment quality, and overall risk of bias) and outcome measures reported (perioperative outcome, clinical outcome, and surgical or interventional outcome), all reported with 95% confidence intervals. A network meta‐analysis was performed. Results: Forty‐eight studies were included. Six retrospective studies (grade 4b) compared 2 techniques and 7 were abstracts (grade 5). The quality of evidence was low and risk of bias high. Regarding surgical outcome, statistically significant superiority of ameroid constrictor over thin film band was observed (P =.003). No other comparisons were statistically significant. Conclusions and Clinical Importance: The evidence base of choice of treatment of cEHPSS in dogs remains weak despite recent publications on the subject. Ameroid is superior to thin film band in causing EHPSS closure. Blinded randomized studies comparing different treatment modalities, which routinely include postoperative imaging to assess cEHPSS closure and acquired portosystemic shunt development are essential. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kaur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18202 and https://doi.org/10.1111/apt.18238 [ABSTRACT FROM AUTHOR]

The article titled "Correction to 'Attenuative role of mangiferin in oxidative stress mediated liver dysfunction in arsenic intoxicated murines'" discusses an editing error in Figure 5A of the original paper. The error involved the duplication of the "Normal" liver subpanel, which slightly overlapped. The authors confirm that this error does not affect the experimental results or conclusions mentioned in the paper. The corrected Figure 5A shows the normal hepatic architecture and the effects of mangiferin treatment on liver dysfunction caused by arsenic intoxication. The authors apologize for the error. [Extracted from the article]

In this paper, we propose a new method to reduce the computational complexity of calculating the tangential stiffness matrix in a nonlinear finite element formulation. Our approach consists in partially updating the tangential stiffness matrix during a classic Newton–Raphson iterative process. The complexity of such an update process has the order of the number of mesh vertices to the power of two. With our approach, this complexity is reduced to the power of two of only the number of updated vertices. We numerically study the convergence of the solution with our modified algorithm. We describe the deformation through a strain energy density function which is defined with respect to the Lagrangian strain. We derive the conditions of convergence for a given tangential stiffness matrix and a given set of updated vertices. We use nonlinear geometric deformation and the nonlinear Mooney‐Rivilin model with both tetrahedron and hexahedron element meshing. We provide extensive results using a cube with small and large number of elements. We provide results on nonlinearly deformed liver with multiple deformation ranges of updated vertices. We compare the proposed method to state‐of‐the‐art work and we prove its efficiency at three levels: accuracy, speed of convergence and small radius of convergence. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kuo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17637 and https://doi.org/10.1111/apt.17742 [ABSTRACT FROM AUTHOR]

Purpose: Liver disease causes significant morbidity and mortality worldwide. Liver imaging plays an essential role in the noninvasive liver disease evaluation because of the limitation of liver biopsy. This paper aims to image in vivo liver with thermoacoustic imaging (TAI) and demonstrate this liver imaging technique with a cross‐validation method. Methods: The imaging system composed of a large aperture antenna and a flexible transducer array was used, and we performed the position calibration using the delay and sum algorithm. The localization wire was utilized in the cross‐validation of in vivo liver TAI. Results: We successfully validated in vivo liver TAI. In vivo images of different liver lobes without labels were observed. The imaging depth reached about 4 cm. Conclusions: TAI has the potential to image the liver and provide useful dielectric properties of the liver tissue. This study realized the first in vivo liver TAI, suggesting its prospect in detecting liver disease noninvasively. [ABSTRACT FROM AUTHOR]

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Type 2 diabetes mellitus is the most common type of diabetes, and insulin resistance (IR) is its core pathological mechanism. Proteomics is an ingenious and promising Omics technology that can comprehensively describe the global protein expression profiling of body or specific tissue, and is widely applied to the study of molecular mechanisms of diseases. In this paper, we focused on insulin target organs: adipose tissue, liver, and skeletal muscle, and analyzed the different pathological processes of IR in these three tissues based on proteomics research. By literature studies, we proposed that the main pathological processes of IR among target organs were diverse, which showed unique characteristics and focuses. We further summarized the differential proteins in target organs which were verified to be related to IR, and discussed the proteins that may play key roles in the emphasized pathological processes, aiming at discovering potentially specific differential proteins of IR, and providing new ideas for pathological mechanism research of IR. [ABSTRACT FROM AUTHOR]

One of the most used painkillers is acetaminophen (APAP), which is safe at the right dose. However, several studies have described populations susceptible to APAP‐induced liver damage, mainly in livers with steatosis. Thus, clinicians should consider the presence of obesity and other chronic liver diseases like nonalcoholic fatty liver disease (NAFLD) when indicating treatment with APAP. Liver damage from this drug is generated through its metabolite N‐acetyl‐p‐benzoquinone imine, which is detoxified with glutathione (GSH). Prior depletion of GSH in steatotic hepatocytes plays a key role in APAP‐induced hepatotoxicity in people with obesity and NAFLD. The knowledge about the damage to the liver or APAP in susceptible people like the obese and those with NAFLD is of great relevance for the sanitary sector because it would imply strategies of different therapeutic approach in such patients. This paper reviews the role of APAP in liver damage in the presence of obesity, NAFLD, and nonalcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Hepatic hemangioma is the most common hepatic tumor with a prevalence of approximately 3%. It is typically supplied by the hepatic artery as evident from findings of abdominal angiography, contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging. However, few cases of hepatic hemangioma supplied by the portal vein have been reported. In this paper, we report a rare case of hepatic hemangioma supplied by the portal vein as shown on CEUS and CT arterioportography. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients' compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR. [ABSTRACT FROM AUTHOR]

What is known and objective: Statins, also known as 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitors, and antidepressant drugs are frequently used in combination due to the high and growing incidence of cardiovascular diseases and psychiatric disorders worldwide. Several aspects on management, the risk of adverse events (AEs) occurrence and the potential clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug‐drug interactions (DDIs) between these two classes have not been well investigated. The aim of the present review was to describe the PK and PD interactions, of clinical relevance, between statins and antidepressant drugs and provide a comprehensive overview of their pharmacological features for appropriate multiple drug regimens. Methods: Relevant studies were identified through a literature search of PubMed and the Cochrane databases focusing on clinically relevant DDIs between statins and antidepressants. Only papers in English were included in the search. Results and discussion: Pharmacodynamic (PD) drug‐drug interactions (DDIs) are unlikely to occur as statins are highly selective inhibitors of HMG‐CoA reductase with no relevant effect on other enzymes or receptor systems. Despite the numerous PK studies on individual drugs belonging to statins and antidepressant agents, only a few case reports regarding specific DDIs are present in the literature and no clinical studies have been performed. PK data allow to speculate on potential DDIs, comparing the metabolic pathways, intestinal and liver transporters and elimination routes. Overall, second‐generation antidepressants, in particular citalopram, escitalopram, mirtazapine, reboxetine and venlafaxine, have weak inhibitory effects on various cytochrome (CYP) isozymes and seem to have a more advantageous DDIs profile in vivo. Conversely, nefazodone, fluoxetine, paroxetine and fluvoxamine influence considerably CYPs activity with potential effects on statins plasma levels, although pravastatin, pitavastatin and rosuvastatin are not susceptible to inhibition by any CYP. Albeit no studies have been performed on P‐glycoprotein (P‐gp), interactions of clinical relevance are unlikely. What is new and conclusion: Although DDIs with antidepressants are potentially, but rarely clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. An evaluation on DDIs between these drugs can be useful for future PK/PD studies on drug‐drug interaction to provide clinicians with more data for appropriate multiple drug regimens. [ABSTRACT FROM AUTHOR]

Investigational agents that reduce or eliminate covalently closed circular DNA (cccDNA) or enhance host immunity against hepatitis B virus (HBV)‐infected hepatocytes are intended to induce a durable off‐treatment clearance of hepatitis B surface antigen (HBsAg) (referred to as functional cure). The aim of this paper was to highlight challenges in interpreting liver safety data in clinical trials of these agents when given alone or in combination regimens. The incidence, grading and management of spontaneous serum ALT flares in untreated chronic HBV patients are reviewed along with a summary of serum ALT flares observed during the registration trials for peginterferon and nucleos(t)ide reverse transcriptase inhibitors. Recommendations regarding the detection, management and interpretation of liver safety biomarker data in future clinical trials as well as suggested inclusion and exclusion criteria for phase 1/2 vs phase 3 studies are provided. Criteria to help classify liver safety signals as being due to the intended therapeutic response, emergence of drug‐resistant HBV virions, or idiosyncratic drug‐induced liver injury are provided along with a review of the role of an expert hepatic adjudication panel in assessing a compound's hepatotoxicity profile. Finally, an algorithmic approach to the differential diagnosis and recommended medical evaluation and management of individual clinical trial patients that develop a liver safety signal is provided along with the rationale to collect and test research blood samples for future mechanistic studies. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Idalsoaga et al papers. To view these articles, visit https://doi.org/10.1111/apt.18193 and https://doi.org/10.1111/apt.18220 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Eunice et al papers. To view these articles, visit https://doi.org/10.1111/apt.17914 and https://doi.org/10.1111/apt.17951 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Dominik et al paper. To view this article, visit https://doi.org/10.1111/apt.17945 [ABSTRACT FROM AUTHOR]

Summary: Non‐alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion‐dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty‐five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2‐MRI‐liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron‐related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: After pediatric split liver transplantation, intra‐abdominal loss of domain due to large‐for‐size left lateral grafts is a frequent problem for fascial closure and potentially leads to reduced liver perfusion and abdominal compartment syndrome. Therefore, delayed fascial closure with the use of temporary silastic meshes and reoperation or alternative fascial bridging procedures are necessary. Methods: Between March 2019 and October 2021, biologic meshes were used for abdominal wall expansion in 6 cases of pediatric split liver transplantation. These cases were analyzed retrospectively. Results: One male and 5 female children with median age of 6 months (range: 0–57 months) and weight of 6 kg (range: 3.5–22 kg) received a large‐for‐size left lateral graft. Graft‐to‐recipient weight ratio (GRWR) was 4.8% (range: 1.5%–8.5%) in median. Biologic mesh implantation for abdominal wall expansion was done in median 7 days (range: 3–11 days) after transplantation when signs of abdominal compartment syndrome with portal vein thrombosis in 3 and of the liver artery in 1 case occurred. In 2 cases, bovine acellular collagen matrix and 4 cases ovine reinforced tissue matrix was used. Median follow‐up was 12.5 months (range: 4–28 months) and showed good liver perfusion by sonography and normal corporal development without signs of ventral hernia. One patient died because of fulminant graft rejection and emergency re‐transplantation 11 months after the initial transplantation. Conclusions: Biologic meshes can be used as safe method for abdominal wall expansion to achieve fascial closure in large‐for‐size liver transplant recipients. Usage for primary fascial closure can be considered in selected patients. [ABSTRACT FROM AUTHOR]

Purpose: Phantom-based objective image quality assessment methods are widely used in the medical physics community. For a filtered backprojection (FBP) reconstruction-based linear or quasilinear imaging system, the use of this methodology is well justified. Many key image quality metrics acquired with phantom studies can be directly applied to in vivo human subject studies. Recently, a variety of image quality metrics have been investigated for model-based iterative image reconstruction (MBIR) methods and several novel characteristics have been discovered in phantom studies. However, the following question remains unanswered: can certain results obtained from phantom studies be generalized to in vivo animal studies and human subject studies? The purpose of this paper is to address this question. Methods: One of the most striking results obtained from phantom studies is a novel power-law relationship between noise variance of MBIR (σ²) and tube current-rotation time product (mAs): σ² ∝ (mAs)-0.4 [K. Li et al., "Statistical model based iterative reconstruction (MBIR) in clinical CT systems: Experimental assessment of noise performance," Med. Phys. 41, 041906 (15pp.) (2014)]. To examine whether the same power-law works for in vivo cases, experimental data from two types of in vivo studies were analyzed in this paper. All scans were performed with a 64-slice diagnostic CT scanner (Discovery CT750 HD, GE Healthcare) and reconstructed with both FBP and a MBIR method (Veo, GE Healthcare). An Institutional Animal Care and Use Committee-approved in vivo animal study was performed with an adult swine at six mAs levels (10-290). Additionally, human subject data (a total of 110 subjects) acquired from an IRB-approved clinical trial were analyzed. In this clinical trial, a reduced-mAs scan was performed immediately following the standard mAs scan; the specific mAs used for the two scans varied across human subjects and were determined based on patient size and clinical indications. The measurements of σ² were performed at different mAs by drawing regions-of-interest (ROIs) in the liver and the subcutaneous fat. By applying a linear least-squares regression, the β values in the power-law relationship σ² ∝ (mAs)-β were measured for the in vivo data and compared with the value found in phantom experiments. Results: For the in vivo swine study, an exponent of &#946 = 0.43 was found for MBIR, and the coefficient of determination (R²) for the corresponding least-squares power-law regression was 0.971. As a reference, the β and R² values for FBP were found to be 0.98 and 0.997, respectively, from the same study, which are consistent with the well-known σ² ?∝ (mAs)-1.0 relationship for linear CT systems. For the human subject study, the measured β values for the MBIR images were 0.41?±0.12 in the liver and 0.37?±0.12 in subcutaneous fat. In comparison, the β values for the FBP images were 1.04±0.10 in the liver and 0.97±0.12 in subcutaneous fat. The β values of MBIR and FBP obtained from the in vivo studies were found to be statistically equivalent to the corresponding β values from the phantom study within an equivalency interval of [-0.1, 0.1] (p < 0.05); across MBIR and FBP, the difference in β was statistically significant (p < 0.05). Conclusions: Despite the nonlinear nature of the MBIR method, the power-law relationship, σ² ẙ (mAs)-0.4, found from phantom studies can be applied to in vivo animal and human subject studies. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Higuchi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16745 and https://doi.org/10.1111/apt.16792 [ABSTRACT FROM AUTHOR]

Lead, a heavy metal, has emerged as one of the most significant pollutants, bearing irreversible consequences on human and animal health in conjunction with industrial development. Presently, the use of medicinal plants to alleviate the adverse effects of heavy metal toxicity has captured the attention of researchers. Hence, the objective of this study was to assess the impact of levamisole and broccoli extract on the electrophoretic pattern of serum proteins, hematological parameters, and histopathological alterations in the liver, kidney, and spleen tissues within a lead poisoning model of rats. This experimental investigation spanned 28 days, involving 42 male Wistar rats categorized into seven groups: a control group, a lead acetate (AL) group administered at 1000 ppm in drinking water, a broccoli (B) group at 300 mg/kg/day, a levamisole (LE) group at 2.5 mg/kg/day, and combination groups of lead and broccoli (AL + B), lead and levamisole (AL + LE), and lead, broccoli, and levamisole (AL + LE + B). Upon completion of the study, hematological and biochemical parameters were assessed, and serum protein concentrations were analyzed using electrophoresis. Liver, kidney, and spleen tissues were fixed and subjected to histopathological examination with H&E staining. The findings indicated a significant decrease in white blood cells (WBC), red blood cells (RBC), and hemoglobin (Hb) levels in the AL group compared to other groups (p < 0.01). Conversely, the B group exhibited a notable increase in RBC and WBC compared to the AL group (p < 0.05). The most pronounced lead‐induced damage was observed in the liver, resulting in elevated levels of specific enzymes such as AST and ALT in the AL group, accompanied by a decline in albumin and total protein (p < 0.001). A reduction in globulin levels, including Beta‐2 globulin, was noted in the AL + B and AL + LE groups compared to the AL group (p < 0.001, p < 0.05). Histopathological findings also unveiled increased infiltration of inflammatory cells and hemorrhage in the liver tissue, followed by the spleen, significantly higher in the AL group compared to other experimental groups (p < 0.05). Additionally, congestion and inflammation were evident in the spleen tissue compared to other groups. These tissue damages were mitigated in other combination treatment groups. Based on the aforementioned results, the combination of broccoli and levamisole is deemed effective in ameliorating liver and spleen injuries caused by lead and enhancing biochemical parameters and serum proteins. [ABSTRACT FROM AUTHOR]

The protective effect of Fe against Cd‐induced toxicity in the liver and kidney of rats during concurrent administration of both metals was investigated in this study. Fifty female rats (130–150 g) were distributed into five groups of 10 rats each (n = 10): Group I (control), received normal saline solution; Group II (1.2 mg CdCl2/kg b.w.); Group III (1.2 mg CdCl2 + 0.25 mg FeCl2/kg b.w.); Group IV (1.2 mg CdCl2 + 0.75 mg FeCl2/kg b.w.); and Group V (1.2 mg CdCl2 + 1.5 mg FeCl2/kg b.w.). Administration of both tested substances lasted for 47 days. Cd was injected intraperitoneally once a week, while Fe was administered to the Cd‐exposed animals by oral gavage thrice weekly. The animals were killed at the end of the study, their blood was collected, and their liver and kidneys were harvested for biochemical and histological analysis. Following Cd administration, the kidney and liver showed a significant increase in Cd concentration, while Fe concentration in the kidney decreased. However, cotreatment with Fe decreased Cd concentration in the kidney and liver and increased Fe concentration in the kidney but not the liver, and the effect was more pronounced in the higher than lower doses. In the kidney, cotreatment with Fe especially at higher doses inhibited Cd‐induced lipid peroxidation and plasma uric acid concentration. In the liver, lipid peroxidation which Cd did not alter was found to be elevated after cotreatment with the highest dose Fe. Inflammatory cell infiltrations of the central vein and renal tubular and glomeruli injury induced by Cd were not obviated by Fe cotreatment. It seems that both tissues respond differently to the concurrent administration of these metals and that Fe protected the kidney against oxidative injury‐induced by Cd but not histopathological changes in both tissues. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16633 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16672 [ABSTRACT FROM AUTHOR]

Purpose: Liver is one of the organs with a high incidence of tumors in the human body. Malignant liver tumors seriously threaten human life and health. The difficulties of liver tumor segmentation from computed tomography (CT) image are: (a) The contrast between the liver tumors and healthy tissues in CT images is low and the boundary is blurred; (b) The image of liver tumor is complex and diversified in size, shape, and location. Methods: To solve the above problems, this paper focused on the human liver and liver tumor segmentation algorithm based on convolutional neural network (CNN), and specially designed a three‐dimensional dual path multiscale convolutional neural network (TDP‐CNN). To balance the performance of segmentation and requirement of computational resources, the dual path was used in the network, then the feature maps from both paths were fused at the end of the paths. To refine the segmentation results, we used conditional random fields (CRF) to eliminate the false segmentation points in the segmentation results to improve the accuracy. Results: In the experiment, we used the public dataset liver tumor segmentation (LiTS) to analyze the segmentation results qualitatively and quantitatively. Ground truth segmentation of liver and liver tumor was manually labeled by an experienced radiologist. Quantitative metrics were Dice, Hausdorff distance, and average distance. For the segmentation results of liver tumor, Dice was 0.689, Hausdorff distance was 7.69, and the average distance was 1.07; for the segmentation results of the liver, Dice was 0.965, Hausdorff distance was 29.162, and the average distance was 0.197. Compared with other liver and liver tumor segmentation algorithms in Medical Image Computing and Intervention (MICCAI) 2017 competition, our method of liver segmentation ranked first, and liver tumor segmentation ranked second. Conclusions: The experimental results showed that the proposed algorithm had good performance in both liver and liver tumor segmentation. [ABSTRACT FROM AUTHOR]

Aim. The aim of this paper is to investigate the effects of ethyl pyruvate (EP) on experimental liver fibrosis induced by bile duct ligation (BDL) and explore the underlying molecular mechanisms. Material and Method. Rats were randomly divided into three groups: the sham group, the BDL group, and the BDL+EP group. Liver fibrosis was induced by common bile duct ligation and was evaluated by serum biochemical parameter levels, Masson's trichrome staining, α-SMA expression, and collagen I deposition. The levels of Nrf2 signaling pathway-related antioxidant genes (Nrf2, SOD2, NQO1, and GSH-Px) in liver tissues were also measured. Meanwhile, the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27 were analyzed. In BDL-induced liver fibrosis rats, the successfully established model was confirmed by the significant increase of serum ALT and AST levels, the high liver fibrosis score, α-SMA expression, and collagen deposition. Results. Compared with the BDL group, EP administration could diminish fibrosis level and substantially increase the expression of Nrf2 signaling pathway-related antioxidant genes. Furthermore, EP significantly suppressed the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27. Conclusions. The results suggested that EP administration could effectively inhibit the liver fibrosis induced by BDL in rat, which may be associated with the enhanced activity of Nrf2 to mediate antioxidant enzyme system and downregulate the inflammatory genes. [ABSTRACT FROM AUTHOR]

For several years, research has been carried out on the effectiveness of solutions for perfusion and preservation of organs, including the liver. There is a search for an optimal pharmacological composition of these solutions, allowing to preserve or improve vital functions of the organ for as long as possible until it is transplanted into a recipient. Hormones due to their properties, often resulting from their pleiotropic effects, may be a valuable component for optimizing the composition of liver perfusion and preservation solutions. The paper presents the current state of knowledge on liver perfusion and preservation solutions modified with hormones. It also shows the characteristics of the hormones evaluated, taking into account their physiological functions in the body. [ABSTRACT FROM AUTHOR]

Summary: Background: Direct‐acting anti‐viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross‐sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan‐Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow‐up from start of DAA therapy was 32.4 months. Twenty‐eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64‐5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. Linked Content This article is linked to Hollande and Pol paper. To view this article, visit https://doi.org/10.1111/apt.15328. [ABSTRACT FROM AUTHOR]

Background: Initial treatment of autoimmune hepatitis (AIH) with prednisolone ± azathioprine is based on randomised controlled trials. Many patients receive long‐term immunosuppressive treatment to prevent disease relapse; this strategy has a weaker evidence base. Aim: To consider whether immunosuppressive treatment (IST) withdrawal in AIH is justified and to develop a rationale for patient selection. Methods: We reviewed published papers between 1972 and 2018, which addressed the outcomes of IST withdrawal and/or complications of IST in AIH. Results: (1) AIH relapse rates after withdrawal of IST vary between 25% and 100%. There is heterogeneity in these studies regarding relapse definition, IST duration prior to withdrawal and criteria for biochemical and histological remission prior to withdrawal. (2) Factors associated with relapse following IST withdrawal include: (a) absence of an identifiable initial disease trigger, (b) presence of other autoimmune diseases, (c) longer time to biochemical remission and (d) elevated serum transaminases on treatment withdrawal. Reports of associations between relapse and age, IST duration and failure of histological remission have been inconsistent. (3) Continued IST reduces risk of AIH relapse over at least 5 years. However, there is no evidence that routine (as opposed to selective) long‐term IST improves disease outcome. (4) Patients with AIH have an increased risk of extrahepatic cancer, notably non‐melanoma skin cancer, to which long‐term IST may contribute. Long‐term corticosteroid therapy is associated with weight gain, low‐trauma fractures, diabetes and possibly vascular disease. Conclusions: While further studies are needed, evidence supports a strategy of IST withdrawal in some patients with AIH who have achieved remission. [ABSTRACT FROM AUTHOR]