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The paper highlights how significant characteristics of liver can be modeled in tissue-engineered constructs using unconventional scaffolds. Hepatic lobular organization and metabolic zonation can be mimicked with decellularized plant structures with vasculature resembling a native-hepatic lobule vascular arrangement or silk blend scaffolds meticulously designed for guided cellular arrangement as hepatic patches or metabolic activities. The functionality of hepatocytes can be enhanced and maintained for long periods in naturally fibrous structures paving way for bioartificial liver development. The phase I enzymatic activity in hepatic models can be raised exploiting the microfibrillar structure of paper to allow cellular stacking creating hypoxic conditions to induce in vivo -like xenobiotic metabolism. Lastly, the paper introduces amalgamation of carbon-based nanomaterials into existing scaffolds in liver tissue engineering.

Development of cheap and portable 3D liver models is a need of an hour for drug screening applications in the healthcare and diagnostic sector. An appropriate 3D liver model would support adhesion, proliferation, viability and functionality of the liver cells. With this perspective, the present study delineates the fabrication and characterization of PAMAM conjugated cellulose filter paper-based 3D liver model. Due to the absence of any cell adhesion motif, paper cannot directly be used for cell culture applications, thus, it was functionalized with PAMAM dendrimer using glutaraldehyde. PAMAM derivatized paper (PF) supported significantly higher adhesion, proliferation, and viability of the HepG2 cells in comparison to non-functionalized paper. Moreover, HepG2 cells maintained their functional aspects i.e., expression of mature hepatocyte markers albumin, CK19, CYP3 A4, MDR1 and SULT2 A1 on PF. Further, we showed the application of the PF-based 3D liver model for drug toxicity evaluations against hepatotoxins. The results showed a significantly higher sensitivity of the HepG2 cells in paper-based 3D culture as compared to 2D monolayer culture, which is similar to that of physiological drug-induced responses. In conclusion, PAMAM functionalized filter paper could serve as an efficient biomaterial platform for the development of microscale technologies, liver-associated diagnostics, and drug screening applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

New ultrasound methods that can be used to quantitatively assess liver fat content have recently been developed. These quantitative ultrasound (QUS) methods are based on the analysis of radiofrequency echoes detected by the transducer, allowing calculation of parameters for quantifying the fat in the liver. In this position paper, after a section dedicated to the importance of quantifying liver steatosis in patients with non-alcoholic fatty liver disease and another section dedicated to the assessment of liver fat with magnetic resonance, the current clinical studies performed using QUS are summarized. These new methods include spectral-based techniques and techniques based on envelope statistics. The spectral-based techniques that have been used in clinical studies are those estimating the attenuation coefficient and those estimating the backscatter coefficient. Clinical studies that have used tools based on the envelope statistics of the backscattered ultrasound are those performed by using the acoustic structure quantification or other parameters derived from it, such as the normalized local variance, and that performed by estimating the speed of sound. Experts' opinions are reported., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Valnemulin (VAL) and tiamulin (TIA) are pleuromutilin antibiotics used primarily for treating bacterial infections in swine or other food animals. Furthermore, VAL and TIA are also employed as feed additives to promote animal growth. However, the illegal use of VAL and TIA could cause a series of hazards to consumers. Here, VAL was designed to be conjugated with bovine serum protein to prepare immunogen. A highly sensitive monoclonal antibody that recognized both VAL and TIA has been successfully produced. Moreover, an immunochromatographic strip assay for rapidly screening VAL and TIA in porcine liver was established with visual detection limits (cutoff values) of 50 and 25 ng/g, respectively. The IC 50 values calculated from the equation of the standard curve were 6.06 and 3.45 ng/g and the limits of detection were 0.96 and 0.29 ng/g for VAL and TIA. According to the recovery experiment results, the test strip exhibited acceptable accuracy and precision. Generally, the proposed strip provided a practical tool for the detection of VAL and TIA. PRACTICAL APPLICATION: We produced a highly sensitive monoclonal antibody and developed an immunoassay strip for simultaneously monitoring TIA and VAL. Additionally it was preliminarily confirmed that the rapid detection tool was suitable for screening TIA and VAL in porcine liver., (© 2020 Institute of Food Technologists®.)

Despite numerous studies on microplastics, the biological impacts of polypropylene microplastics (PP-MPs) and its toxicity on freshwater fish have yet to be fully revealed. The purpose of this research was to look at the potentially harmful effects of PP-MPs in freshwater African catfish Clarias gariepinus and bioremediation using Spirulina. After acclimatization to laboratory conditions, 108 fish (125 ± 3 gm and 27 ± 2 cm) were assigned into triplicate six experimental groups (12 fish/group), a control group, Spirulina group (SP), PP-MP-treated groups (0.14 and 0.28 mg/l PP-MPs), and PP-MP + Spirulina-treated groups (0.14 mg/l PP-MPs + 200 mg/L SP and 0.28 mg/l PP-MPs +200 mg/L SP) for 15-day exposure and 45-day recovery after that. The hematological parameters exhibiting significance (RBCs, Hct, Hb, and MCV) or non-significance (MCH and MCHC) either decreased with the increase in PP-MP doses from 0.0 in the control to 0.28 mg/L red blood cells (RBCs), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hb) and platelets or increased with such an increase in doses (mean corpuscular volume (MCV)). The liver enzyme activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) exhibited non-significant (p ≥ 0.05) or significant (p < 0.05) increases in (0.14 and 0.28 mg/L) PP-MP-exposed groups, respectively, except ALP. Furthermore, there was a significant (p < 0.05) or non-significant (p ≥ 0.05) increase in 0.14 and 0.28 mg/l PP-MP +200 mg/L-exposure groups, respectively, compared to the control group and the same exposure group without Spirulina. In comparison to the control group, PP-MPs (0.14 and 0.28 mg/L) induced a significant (p < 0.05) increase in the percentage of poikilocytosis and nuclear abnormalities of RBCs. The liver tissue from fish exposed to PP-MPs exhibited varying degrees of pathological changes. These results indicated that these pathological changes increased with PP-MP concentration, suggesting that the effect of PP-MPs was dose-dependent. After 45 days of recovery under normal conditions, it was obvious that there was a significant improvement in the percentage of poikilocytosis and nuclear abnormalities of RBCs, as well as a non-significant improvement in hemato-biochemical parameters and liver tissue.

While many studies have shown that pulp mill effluents can affect ovarian physiology in fish, far fewer studies have considered the effects in males. We conducted a lab study to examine the effects of effluent from a Brazilian pulp and paper mill on hepatic and testicular morphology and various aspects of testicular physiology in the zebrafish Danio rerio. Males were exposed to lab water (control) or 4% effluent for 14 days. Effluent exposure did not affect testis size as measured by the gonadosomatic index, but contributed to morphological changes in the seminiferous tubules. The number of cysts with histopathological changes was elevated in effluent-exposed fish and the number of cysts containing spermatids was significantly reduced. The testis of effluent exposed fish had reduced levels of lactate, elevated lactate dehydrogenase activity, increased levels of reactive oxygen species and reduced levels of phosphorylated P38 mitogen-activated protein kinase (pP38 MAPK). Separate studies showed that the addition of lactate to testicular tissue incubated in vitro increased the activation of P38 MAPK. Effluent exposure also increased vacuolization, necrosis, apoptosis, hyperemia, and fat infiltration of the hepatocytes. Collectively, we provide evidence of short term effects of pulp mill effluent on testicular and hepatic physiology and biochemistry in the zebrafish., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Microwave ablation (MWA) is a minimally invasive alternative for the treatment of unresectable liver tumors. To verify the effectiveness and safety of MWA, it is critical to measure the temperature variation and assess the regions of the microwave-induced thermal lesions., Purpose: Recent studies have indicated that the locations of optimally matched Gabor atoms (LOMGA) from ultrasound radiofrequency (RF) echo signals allow accurate and stable scatterer spacing estimation. Herein, a harmonic-based LOMGA method is proposed to estimate the scatterer spacing for improving the assessment of microwave-induced thermal lesions., Methods: The mean scatterer spacing (MSS) is estimated via the LOMGA method incorporating the selection of concise atoms from separated second-harmonic RF echo signals with the pulse-inversion algorithm for thermal lesion evaluation. In vitro experiments, 10 fresh porcine liver samples were ablated at different time nodes during the ablation period, and 200 sets of second-harmonic and fundamental RF echo signals were randomly selected from the regions of interest in the coagulated liver samples for MSS estimation. The means and standard deviations of the MSSs, as well as the linear regression for the mean MSSs, were calculated from fundamental and second-harmonic signals for comparison and evaluation, the receiver operating characteristic (ROC) curves for the 200 sets of fundamental-based and harmonic-based MSS estimates from the 10 liver samples at five pairs of adjacent time nodes were calculated, and one-way analysis of variance (ANOVA) tests were performed for the five pairs of adjacent time nodes. The fundamental and harmonic-based p-values in the ANOVA tests and the areas under the ROC curves (AUCs) were calculated to statistically analyze the differences in the MSSs between adjacent time nodes., Results: The harmonic-based increments in the intensity variation and coherent components were larger than the fundamental-based increments with the increasing ablation time. The harmonic-based MSSs from the 10 liver samples at five pairs of adjacent time nodes were found to be highly statistically significant (p < 0.01). Thus, the harmonic-based MSSs had greater variations. Compared with the fundamental-based results, for the five preset ST values, the average increment in the harmonic-based mean slopes was 69.22% and the average decrement in the mean standard deviations was 11.67% for the linear-fitting MSS results, and the results were statistically significant (p < 0.05)., Conclusion: Harmonic-based MSSs are more sensitive and robust to variations in coagulated tissues, which is advantageous for the assessment of microwave-induced thermal lesions., (© 2024 American Association of Physicists in Medicine.)

Simple Summary: This review paper deals with incidentally found focal liver lesions (IFLLs) in otherwise healthy subjects, which is a frequent occurrence in daily practice. The clinical presentation and the imaging aspects play an important role in deciding whether and what further evaluation is required. In low-risk patients (i.e., those without a history of malignant or chronic liver disease or related symptoms, younger than 40 years old), more than 95% of IFLLs are benign. Shear Wave liver Elastography of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on a B-mode ultrasound of a benign lesion, no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed. [ABSTRACT FROM AUTHOR]

Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.

Partial Fourier encoding is popular in single-shot (ss) diffusion-weighted (DW) echo planar imaging (EPI) because it enables a shorter echo time (TE) and, hence, improves the signal-to-noise-ratio. Motion during diffusion encoding causes k-space shifting and dispersion, which compromises the quality of the homodyne reconstruction. This work provides a comprehensive understanding of the artifacts in homodyne reconstruction of partial Fourier ss-DW-EPI data in the presence of motion-induced phase and proposes the motion-induced phase-corrected homodyne (mpc-hdyne) reconstruction method to ameliorate these artifacts. Simulations with different types of motion-induced phase were performed to provide an understanding of the potential artifacts that occur in the homodyne reconstruction of partial Fourier ss-DW-EPI data. To correct for the artifacts, the mpc-hdyne reconstruction is proposed. The algorithm recenters k-space, updates the partial Fourier factor according to detected global k-space shifts, and removes low-resolution nonlinear phase before the conventional homodyne reconstruction. The mpc-hdyne reconstruction is tested on both simulation and in vivo data. Motion-induced phase can cause signal overestimation, worm artifacts, and signal loss in partial Fourier ss-DW-EPI data with the conventional homodyne reconstruction. Simulation and in vivo data showed that the proposed mpc-hdyne reconstruction ameliorated artifacts, yielding higher quality DW images compared with conventional homodyne reconstruction. Based on the understanding of the artifacts in homodyne reconstruction of partial Fourier ss-DW-EPI data, the mpc-hdyne reconstruction was proposed and showed superior performance compared with the conventional homodyne reconstruction on both simulation and in vivo data., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Segmentation of organs and lesions could be employed for the express purpose of dosimetry in nuclear medicine, assisted image interpretations, and mass image processing studies. Deep leaning created liver and liver lesion segmentation on clinical 3D MRI data has not been fully addressed in previous experiments. To this end, the required data were collected from 128 patients, including their T1w and T2w MRI images, and ground truth labels of the liver and liver lesions were generated. The collection of 110 T1w-T2w MRI image sets was divided, with 94 designated for training and 16 for validation. Furthermore, 18 more datasets were separately allocated for use as hold-out test datasets. The T1w and T2w MRI images were preprocessed into a two-channel format so that they were used as inputs to the deep learning model based on the Isensee 2017 network. To calculate the final Dice coefficient of the network performance on test datasets, the binary average of T1w and T2w predicted images was used. The deep learning model could segment all 18 test cases, with an average Dice coefficient of 88% for the liver and 53% for the liver tumor. Liver segmentation was carried out with rather a high accuracy; this could be achieved for liver dosimetry during systemic or selective radiation therapies as well as for attenuation correction in PET/MRI scanners. Nevertheless, the delineation of liver lesions was not optimal; therefore, tumor detection was not practical by the proposed method on clinical data., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Fontan-type surgery is the final step in the sequential palliative surgical treatment of infants born with a univentricular heart. The resulting long-term haemodynamic changes promote liver damage, leading to Fontan-associated liver disease (FALD), in virtually all patients with Fontan circulation. Owing to the lack of a uniform definition of FALD and the competitive risk of other complications developed by Fontan patients, the impact of FALD on the prognosis of these patients is currently debatable. However, based on the increasing number of adult Fontan patients and recent research interest, the European Association for The Study of the Liver and the European Reference Network on Rare Liver Diseases thought a position paper timely. The aims of the current paper are: (1) to provide a clear definition and description of FALD, including clinical, analytical, radiological, haemodynamic, and histological features; (2) to facilitate guidance for staging the liver disease; and (3) to provide evidence- and experience-based recommendations for the management of different clinical scenarios. [ABSTRACT FROM AUTHOR]

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.)

Abstract: The purpose of this study is to investigate the diagnostic accuracy of a new noninvasive imaging technique, ultrasound-guided attenuation parameter (UGAP), in diagnosing hepatic steatosis. This single-center retrospective study included 81 UGAP studies performed to guide therapy between July 2022 and June 2023 at a large academic medical center. Patients with either liver biopsy or Magnetic resonance-based proton-density fat fraction (MRI-PDFF) within 12 months of US-UGAP imaging, irrespective of order, were included. Patient demographics, body mass index, liver function tests, UGAP values, MRI-PDFF values, and liver biopsy results were obtained from a review of the medical records. Presence of steatosis was defined as PDFF >5.2% or >5% of hepatocytes with steatosis at pathology. Area under the ROC curve (AUROC) was used to measure UGAP accuracy for the detection of hepatic steatosis with statistical significance P < 0.05. There was a significant positive correlation between UGAP and MRI-PDFF (r = 0.463; P < 0.001; confidence interval [CI]: 0.220;0.651). The AUROC to differentiate absence of steatosis (n = 21) from presence of steatosis (n = 32) for UGAP with MRI as the gold standard was 0.760 (P < 0.001; CI: 0.623;0.867). A UGAP value >0.66 had 78% sensitivity and 67% specificity to identify steatosis presence on MRI-PDFF. The AUROC to differentiate absence of steatosis (n = 11) from presence of steatosis (n = 21) for UGAP with pathology as the gold standard was 0.894 (P < 0.001; CI: 0.734;0.974). A UGAP value >0.57 had 100% sensitivity and 64% specificity to identify steatosis presence at pathology. UGAP is an accurate measure for detecting the presence of hepatic steatosis and may be a noninvasive method for metabolic dysfunction-associated steatotic liver disease diagnosis and follow-up., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aspirin is one of the most frequently detected non-steroidal anti-inflammatory drugs in aquatic environments. Despite its prevalence, toxicity possessed by aspirin to non-target organisms like fish is poorly explored. In the present study, cell death induced by different concentrations of aspirin (1, 10, and 100 µg/L) has been investigated in the liver of fish, Labeo rohita exposed for 28 days. A significant increase (p < 0.05) in the density of caspase-3 positive cells in a dose and duration-dependent manner assessed through immunofluorescent staining indicates caspase-dependent pathway of cell death which may be either through intrinsic or extrinsic pathway. The flow cytometric analysis, in addition, revealed a significant (p < 0.05) decline in the live cells and an increase in apoptotic cells in the liver of fish exposed to aspirin. Cell death due to apoptosis is further indicated by a significant increase (p < 0.05) in the Kupffer cells and tumor necrosis factor-α. The decrease in the activity of cyclooxygenase (COX) enzyme significantly (p < 0.05) in all three exposure concentrations of aspirin suggests COX-dependent pathway of cell death. The present study provides in-depth insights into aspirin-induced cell death in the liver of fish at environmentally realistic concentrations., Competing Interests: Declarations Ethical approval The experiments were carried out under the guidance of ethical regulations from the institutional animal care and use committee (Ref No. BHU/DoZ/IAEC/2021–2022/022, dated 15/02/2022). Consent to participate and consent to publish All the authors have equally participated in this study and agreed to publish this work in this journal. Competing interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The aim of this study was to compare liver size measurements in different conventional B-mode ultrasound image (US) field views using magnetic resonance imaging (MRI) measurement as a reference., Methods: After receiving Institutional Review Board approval and informed consent, three operators measured the largest sagittal and transverse dimensions of adult livers on three US image field views (90°, 120°, and 140°) with a single curvilinear transducer. We analyzed the differences in liver size across three image field views using one-way analysis of variance (ANOVA) and examined the correlations between MRI and ultrasound measurements using Spearman regression. We used 95% Bland-Altman limits of agreement (95% LOA) to analyze the confidence interval for liver size measurements between MRI and US. Intra-observer and inter-observer reliability in measuring liver size were assessed using intraclass correlation coefficient (ICC)., Results: Based on sagittal liver length, 28 adult participants (7 men and 21 women, mean age 43 years) were divided into Group 1 (<17 cm, n = 10) or Group 2 (≥17 cm, n = 18). There was a significant difference in the liver size measurements across the three image field views (P < .001) in both groups. The highest correlation in liver size measurements between MRI and US was with ultra-wide-view (R 2  = .87 in sagittal; R 2  = .79 in transverse). Bland-Altman LOA also indicated good agreement between MRI and ultra-wide-view measurements. Intra-observer and inter-observer reliability in measuring liver size were good (ICC = 0.82-0.98)., Conclusion: The study suggests that ultrasound ultra-wide-view provides the most accurate liver size measurement and good intra- and inter-operator reliability., (© 2024 American Institute of Ultrasound in Medicine.)

Detergents are used as a part of our daily life routine. Though they are widely used but their active ingredients which are highly toxic and persist in the environment for long are an important cause of environmental pollution. In our current work, we have studied the harmful effects of a combination of some commonly used detergents which find their way into the water bodies especially the pond ecosystem through everyday activities like washing clothes, utensils, and bathing in water. This water is the home to many flora and fauna especially the fishes like Cirrhinus mrigala. In our work, we have analysed the levels of the hepatic enzymes Alanine Transaminase and Aspartate Aminotransferase as well as the histology of gill and liver tissues. We have also analysed the presence of micronucleus in the fish blood. It was observed that the presence of detergents has increased the enzyme level as well as resulted in destruction of gill and liver tissue morphology. Detergents also increased the presence of micronucleus in fish blood. These results are indicators of deterioration of fish health due to detergent pollution., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable for the current study. Consent for publication: Not applicable for the current study. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Microplastics (MPs) have attracted significant attention due to their global distribution in living environments. Although some studies have reported MP-induced hepatotoxicity in mouse models, a systematic approach to MP-mediated liver toxicity was still lacking. Therefore, we used a mouse model to study the sub-chronic effects of MP exposure on the liver. Female C57BL/6 mice, aged 6 weeks, received an oral administration of 0.3 mg of Nile Red-labeled polystyrene (PS) microplastics, with particle sizes of 0.5 µm (submicron) and 5 µm (micron), via gavage, while control mice received vehicle only. Each mouse was exposed to MPs twice a week for 12 weeks. After sacrifice, the levels of MP accumulation, oxidative stress, inflammation, and pathological changes were measured in the mouse liver, and blood samples were collected for serum biochemistry analysis. Our results demonstrated that 0.5 µm PS-MPs were accumulated in mouse livers post-MP exposure, but not in the 5 µm MP exposure group. Simultaneously, increased levels of glucose, triglyceride, alanine transaminase (ALT), aspartate transaminase (AST), superoxide dismutase, 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), interleukin-6, and lipid droplets were found in the 0.5 µm MP exposure group, while the fewer responses, including elevated liver weight index, glucose, high-density lipoprotein, AST, and decreased HNE-MA were observed in 5 µm MP exposure group. These results indicate that sub-chronic exposure to submicron MPs causes MP deposition in mouse livers, which further induces oxidative stress, increases inflammatory cytokines and perturbs glucose and lipid homeostasis, which might trigger more severe metabolic dysfunction or non-alcoholic steatohepatitis-like hepatotoxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Summary: During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, EASL and ESCMID published a position paper to provide guidance for physicians involved in the care of patients with chronic liver disease. While some healthcare systems are returning to a more normal routine, many countries and healthcare systems have been, or still are, overwhelmed by the pandemic, which is significantly impacting on the care of these patients. In addition, many studies have been published focusing on how COVID-19 may affect the liver and how pre-existing liver diseases might influence the clinical course of COVID-19. While many aspects remain poorly understood, it has become increasingly evident that pre-existing liver diseases and liver injury during the disease course must be kept in mind when caring for patients with COVID-19. This review should serve as an update on the previous position paper, summarising the evidence for liver disease involvement during COVID-19 and providing recommendations on how to return to routine care wherever possible.

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: Cirrhosis patients often exhibit clinical symptoms such as right liver atrophy, portal hypertension, spleen enlargement and increased blood supply, which exhibit considerable variation between the left and right liver sections. These differences are hypothesized to stem from disparities in blood flow within the left and right portal vein (PV) branches. However, rigorous quantitative evidence remains scarce., Purpose: We mainly aim at quantitatively revealing the relationship between the blood flow rates of two PV branches and liver volumes, and providing quantitative evidence and theoretical support for the diagnosis and treatment of cirrhosis from the perspective of hemodynamics., Methods: Five cirrhotic patients and two healthy volunteers from Beijing Friendship Hospital are investigated. Their PV blood flow models are established based on computed tomography (CT) images and finite volume simulations. The volume of the left and right liver lobes are measured in 3-matic. The distributions of blood source in the PV branches are tracked by streamline analysis. The blood flow rates are quantitatively counted by integrating the blood source velocities. Linear analysis is performed to build the relationship between liver volumes and PV blood flow distributions., Results: Streamline analysis reveals significant differences in blood distribution between the left and right PV branches. The majority of blood from the superior mesenteric vein (SMV) flowed into the right portal vein (RPV), while most blood from the splenic vein (SV) entered the left portal vein (LPV). The main PV pressure drop linearly increases with the SV blood velocity for all PV structures of patients and healthy volunteers. The flow rate ratio Q RPV /Q LPV demonstrates an increase in tandem with the volume ratio V R /V L , exhibiting a linear correlation with the Pearson correlation coefficient being 0.93., Conclusion: The differences in the blood distributions are consistent with the clinicians' knowledge and validate our simulations. We demonstrated a linear increase in PV pressure with elevated SV blood velocity. Additionally, the volumes of the left and right hepatic lobes exhibited a positive correlation with blood flow rates in the corresponding PV branches., (© 2024 American Association of Physicists in Medicine.)

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.)

Acute liver injury is a life-threatening disease. Although immune responses are involved in the development and exacerbation of acute liver injury, the cellular and molecular mechanisms are not fully understood. Intravenous administration of the plant lectin concanavalin A (ConA) is widely used as a model of acute liver injury. ConA triggers T cell activation and cytokine production by crosslinking glycoproteins, including the T cell receptor, leading to the infiltration of myeloid cells into the liver and the subsequent amplification of inflammation in the liver. Thus, the pathogenesis of ConA-induced acute liver injury is considered a model of immune-mediated acute liver injury or autoimmune hepatitis in humans. However, the severity of the liver injury and the analyses of immune cells and non-hematopoietic cells in the liver following ConA injection are significantly influenced by the experimental conditions. This article outlines protocols for ConA-induced acute liver injury in mice and evaluation methods for liver injury, immune cells, and non-hematopoietic cells in the liver. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Induction of acute liver injury by ConA injection Basic Protocol 2: Evaluation of inflammatory cytokines in mouse plasma Basic Protocol 3: Preparation of liver sections and histological analysis of liver injury Basic Protocol 4: Preparation of liver immune cells Basic Protocol 5: Preparation of hepatocytes, endothelial cells, and hepatic stellate cells Basic Protocol 6: Flow cytometry of immune and non-hematopoietic liver cells Basic Protocol 7: Flow cytometric sorting of endothelial cells and hepatic stellate cells Basic Protocol 8: Quantitative reverse transcription polymerase chain reaction., (© 2024 Wiley Periodicals LLC.)

Objectives: To assess whether meal or water intake may affect the measurement of the ultrasound (US) attenuation coefficient (AC) imaging, a parameter that is directly related to liver fat content., Methods: The study was performed in two centers (Italy and USA). AC was obtained using the ATI algorithm implemented in the Aplio i-series US systems (Canon Medical Systems, Japan) by one operator at each center. Measurements were performed at baseline and 5, 15, 30, 45 minutes after drinking 500 mL of water (group 1), or 30, 45, 60, 90, 120 minutes after eating a meal of about 600 kcal (group 2). Multilevel generalized estimating equations for repeated measures were used for the statistical analysis to consider the clustered nature of the data., Results: Twenty-six individuals were enrolled: 11 (10 females; age, 43.7 ± 12.5 years) in Italy and 15 (10 females; age, 60.7 ± 6.3 years) in USA. At B-mode US, 10 (38.5%) had liver steatosis. The baseline AC values, in decibel/centimeter/megahertz, were 0.64 (0.12) in group 1 and 0.66 (0.13) in group 2. There was not any significant difference in AC values at every time-point after water or meal intake either in group 1 or group 2. This result did not change including sex, age, and skin-to-liver capsule into the models., Conclusions: The measurement of the AC, which is a biomarker of liver steatosis, does not require a fasting state and drinking water does not affect the result., (© 2024 American Institute of Ultrasound in Medicine.)

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (P interaction  = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background and Purpose: Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR), and exert adverse effects on mitochondrial function, although the mechanisms underlying these effects remain unclear. We used a tamoxifen-induced Hmgcr-knockout (KO) mouse model, a multi-omics approach and mitochondrial function assessments to investigate whether decreased HMGCR activity impacts key liver energy metabolism pathways., Experimental Approach: We established a new mouse strain using the Cre/loxP system, which enabled whole-body deletion of Hmgcr expression. These mice were crossed with Rosa26 Cre mice and treated with tamoxifen to delete Hmgcr in all cells. We performed transcriptomic and metabolomic analyses and thus evaluated time-dependent changes in metabolic functions to identify the pathways leading to cell death in Hmgcr-KO mice., Key Results: Lack of Hmgcr expression resulted in lethality, due to acute liver damage caused by rapid disruption of mitochondrial fatty acid β-oxidation and very high accumulation of long-chain (LC) acylcarnitines in both male and female mice. Gene expression and KO-related phenotype changes were not observed in other tissues. The progression to liver failure was driven by diminished peroxisome formation, which resulted in impaired mitochondrial and peroxisomal fatty acid metabolism, enhanced glucose utilization and whole-body hypoglycaemia., Conclusion and Implications: Our findings suggest that HMGCR is crucial for maintaining energy metabolism balance, and its activity is necessary for functional mitochondrial β-oxidation. Moreover, statin-induced adverse reactions might be rescued by the prevention of LC acylcarnitine accumulation., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The histopathological changes in the liver and kidney of Rasbora daniconius have been investigated after exposed to sublethal concentration of paper mill effluent. The result of acute toxicity shows that the paper mill effluent was highly toxic. The fish, Rasbora daniconius were exposed two sub-lethal concentrations of paper mill effluent [1.9% (1/5) and 0.95 % (1/10) LC50 of 96hr] for 30 days to study the impacts on the histology of liver and kidney. Histopathological examination reveled, swollen hepatocytes, nuclear hypertrophy, rupture sinusoids, hemorrhages, vacuolation in hepatic cells and broken central vein in liver. Kidney showed hypertrophy of hematopoietic tissues, cell necrosis, blocked glomerules with full of blood stain, dilated renal tubules with pyknotic nuclei and tubular necrosis. Histopathological changes were dose dependent. The results of histopathological changes in liver and kidney of Rasbora daniconius shows that, fish were under high stress during exposure to sublethal concentration of paper mill effluent. [ABSTRACT FROM AUTHOR]

Recently, we characterized the ferroptotic phenotype in the liver of diabetic mice and revealed nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2) inactivation as an integral part of hepatic injury. Here, we aim to investigate whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes-induced hepatic ferroptosis and the mechanisms involved. Male C57BL/6 mice were divided into four groups: control (vehicle-treated), diabetic (streptozotocin-induced; 40 mg/kg, from Days 1 to 5), diabetic sulforaphane-treated (2.5 mg/kg from Days 1 to 42) and non-diabetic sulforaphane-treated group (2.5 mg/kg from Days 1 to 42). Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic molecules critical for antioxidative defense (catalase, superoxide dismutases, thioredoxin reductase), iron metabolism (ferritin heavy chain (FTH1), ferroportin 1), glutathione (GSH) synthesis (cystine-glutamate antiporter system, cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine ligase modifier subunit, glutathione synthetase), and GSH recycling - glutathione reductase (GR) were reversed/increased by sulforaphane treatment. In addition, we found that the ferroptotic phenotype in diabetic liver is associated with increased ferritinophagy and decreased FTH1 immunopositivity. The antiferroptotic effect of sulforaphane was further evidenced through the increased level of GSH, decreased accumulation of labile iron and lipid peroxides (4-hydroxy-2-nonenal, lipofuscin), decreased ferritinophagy and liver damage (decreased fibrosis, alanine aminotransferase, and aspartate aminotransferase). Finally, diabetes-induced increase in serum glucose and triglyceride level was significantly reduced by sulforaphane. Regardless of the fact that this study is limited by the use of one model of experimentally induced diabetes, the results obtained demonstrate for the first time that sulforaphane prevents diabetes-induced hepatic ferroptosis in vivo through the activation of Nrf2 signaling pathways. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related pathologies., (© 2024 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

The liver is one of the most important organs in the human body. It performs many important functions, including being responsible for the metabolism of most drugs, which is often associated with its drug-induced damage. Currently, there are no ideal pharmacological models that would allow the evaluation of the effect of newly tested drugs on the liver in preclinical studies. Moreover, the influence of hepatic metabolism on the effectiveness of the tested drugs is rarely evaluated. Therefore, in this work we present an advanced model of the liver, which reflects most of the morphologically and metabolically important features of the liver in vivo, namely: three-dimensionality, cellular composition, presence of extracellular matrix, distribution of individual cell types in the structure of the liver model, high urea and albumin synthesis efficiency, high cytochrome p450 activity. In addition, the work, based on the example of commonly used anticancer drugs, shows how important it is to take into account hepatic metabolism in the effective assessment of their impact on the target organ, in this case cancer. In our research, we have shown that the most similar to liver in vivo are 3D cellular aggregates composed of three important liver cells, namely hepatocytes (HepG2), hepatic stellate cells (HSCs), and hepatic sinusoidal endothelial cells (HSECs). Moreover, we showed that the cells in 3D aggregate structure need time (cell-cell interactions) to improve proper liver characteristic. The triculture model additionally showed the greatest ability to metabolize selected anticancer drugs., (© 2024 Wiley‐VCH GmbH.)

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).)