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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®.)

This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase, ALP, and aspartate aminotransferase, AST) and total serum protein. A device consists of four components: (i) a top plastic sheet, (ii) a filter membrane, (iii) a patterned paper chip containing the reagents necessary for analysis, and (iv) a bottom plastic sheet. The device performs both the sample preparation (separating blood plasma from erythrocytes) and the assays; it also enables both qualitative and quantitative analysis of data. The data obtained from the paper-microfluidic devices show standard deviations in calibration runs and "spiked" standards that are acceptable for routine clinical use. This device illustrates a type of test useable for a range of assays in resource-poor settings.

This study investigates whether pulse exposure to Chilean pulp and paper mill effluent solid phase extracted (SPE) extracts via intraperitoneal injection (IP), would result in changes in the activities of the respiratory metabolic enzymes citrate synthase (CS) and lactate dehydrogenase (LDH) in rainbow trout livers. It also investigated if an alteration in liver metabolic capacity influenced the liver detoxification processes and estrogenic effects previously reported. Besides, a comparison of those enzymatic activities with fish IP injected with SPE extracts of two model effluents coming from industries that process 100% different type of feedstock (softwood, SW and hardwood, HW) was also evaluated. An initial induction of the anaerobic metabolism (increase in LDH enzymatic activity) was detected in all Chilean pulp mill effluent extracts evaluated, contrary to the initial unaltered aerobic metabolism (CS enzymatic activity) observed. A compensatory relationship in energy metabolism (Pasteur effect) was observed when comparing both enzymatic activities of fish exposed to those effluent extracts. LDH and CS activities observed in fish injected with Chilean extracts seem to be related to the effects observed in fish injected with SW extracts. This study showed that intraperitoneal injection of pulp and paper mill effluent extracts affected the anaerobic and aerobic metabolic capacities in rainbow trout livers, but this metabolic alteration did not affect detoxification capability or estrogenic effect previously reported., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Wood extractives present in pulp and paper mill effluents may cause reproductive disturbances in fish. A chronic-exposure toxicity experiment using immature rainbow trout (Oncorhynchus mykiss) was conducted in order to assess the endocrine disrupting effects of two Chilean pulp and paper mill specific extracts (solid phase extraction, SPE) obtained from primary and secondary treated effluents. The (anti)estrogenic potencies and toxicity of the wood extractives regularly present in pulp mill effluent such as dehydroabietic acid (DHAA), beta-sitosterol (BS), and model estrogen 17beta-estradiol (E2) were evaluated by analysis of plasma vitellogenin (VTG) levels, gonadal somatic index (GSI) and liver ethoxyresorufin-O-deethylase (EROD) activity, respectively. The protocol involved the use of multiple intra-peritoneal injections (1 injection every 7 days for a total exposure period of 28 days). Analysis of variance/covariance, demonstrated no differences associated with fish gender other than GSI. The phytosterol BS, E2 and both pulp mill effluent extracts showed significant inductions of EROD and increased VTG levels after 4, 7, 14, 21 and 28 of exposure. While fish injected with secondary treated effluent extract showed a delayed induction in VTG levels compared to primary effluent injected fish, no effects on VTG and EROD levels were observed in DHAA injected fish. Moreover simultaneous injection of DHAA+E2 reduced the VTG levels found in E2 injected fish, indicating a potential indirect anti-estrogenic effect of this resin acid. The results of this study indicate that Chilean pulp and paper mill effluent extracts are estrogenic in rainbow trout males and females., ((c) 2010 Elsevier B.V. All rights reserved.)

Eight phenolics were detected in samples collected from areas where paper-recycling process water is discharged. The detected concentration levels were up to 270 microg/L and 230 microg/g in water samples and sediment samples, respectively, obtained from both the outfall of the paper-recycling process water and its downstream areas. In particular, totarol (compound 4), 2,4-bis(1-phenylethyl)phenol (compound 6), 4,4'-butylidenebis(6-t-butyl-m-cresol) (compound 7), 2,4-bis(1-phenylethyl)-6-chlorophenol (compound 8), and 4-hydroxy-4'-isopropoxydiphenyl sulfone (compound 9) were identified for the first time as environmental pollutants. The estrogenicities of the identified compounds were assessed by yeast two-hybrid assays incorporating either the human or medaka fish (Oryzias latipes) estrogen receptor alpha (hERalpha and medERalpha, respectively) and an estrogen receptor competitive enzyme-linked immunosorbent assay (ER-ELISA) both with and without metabolic activation by a rat liver S9 mix. Bisphenol A (compound 3) and 2-naphthol (compound 1) exhibited activity in the assays of both hERalpha and medERalpha without the S9 mix. The relative activity (%) to 17beta-estradiol was 0.0015% for compound 3 and 0.0009% for compound 1 in the hERalpha assay and 0.027% for compound 3 and 0.0093% for compound 1 in the medERalpha assay. These compounds were attenuated by the S9 mix. The binding affinity was evaluated using an ER-ELISA. Compounds 3, 4, 6, and 7 exhibited affinity without the S9 mix. After exposure to the S9 mix, however, the binding affinity of compound 7 was eliminated by the S9 mix; those of compounds 3, 4, and 6 were attenuated; and that of compound 8 exhibited affinity. A comprehensive assessment of the estrogenicities of the phenolics originating from thermal paper and their implications for an aquatic environment may require an examination of the components of the phenolics, as in the present study.

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.)

To develop an effective hybrid bioartificial liver (BAL) device, the material of the scaffold is very important to support hepatocytes that have both growth ability and hepatic differentiated functions. In this study we used paper (Kimwipe, Kimberly-Clark Corp., Roswell, GA, U.S.A.) as a scaffold. Primary hepatocytes isolated from a normal adult rat liver could proliferate on the paper. The secretion of albumin into culture medium by the cells on the paper increased with time in culture and, compared to the cells on dishes, the amount of 48 h albumin secretion at Day 10 was two times larger. Perpendicular sections of hepatocytes on the paper revealed that the cells fell into cavities made by intersecting fibers, piled up, and formed three to four layers. The piled-up cells changed their shape from flat to cuboidal and enlarged their cytoplasm, which was rich in organelles such as mitochondria and peroxisomes with a nucleoid. In addition, they formed bile canalicular structures between the cells. Their morphological appearance was similar to in vivo hepatocytes. Paper (Kimwipe) may be a good candidate as a scaffold to make a BAL device.

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.)

Toxic effects of unbleached (sulfate or sulfite) and bleached (sulfate) paper mill effluents were studied in a primary culture of rainbow trout liver cells. The effluents and control water from a clean area were extracted with diethyl ether and added to the cultures dissolved in dimethyl sulfoxide. Plasma membrane integrity was studied by measuring lactate dehydrogenase (LDH) leakage. The cellular content of glutathione (GSH) was used as an indicator of oxidative stress and the formation of reactive intermediates. Dose-response studies indicated that unbleached effluents contained more potent toxic substances than bleached effluents. Both unbleached and bleached effluents contained organic diethyl ether-extractable substances which increased cytochrome P450-dependent 7-ethoxyresorufin-O-deethylase (EROD) activities. The inducing effects were seen at concentrations substantially lower than those decreasing GSH content and increasing LDH leakage. Possible EROD inducing substances in bleached effluents are chlorinated organic compounds. Inducing compounds in unbleached effluents are yet to be identified. Furthermore, at higher concentrations the effluents contained substances that inhibited the cytochrome P450 system. The results show that the trout primary hepatocyte cultures afford a convenient in vitro method for screening cytochrome P450 inducing components extracted from industrial effluents to investigate mechanisms by which wastewaters cause injury in cells.

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]

Enzymatic and non-enzymatic antioxidants serve as an important biological defense against environmental oxidative stress. Information on antioxidant defense in fish is meager despite that fish are constantly exposed to a myriad of environmental stress including the oxidants. This study, therefore, assesses the activities of antioxidant enzymes viz., glutathione peroxidase, catalase and glutathione S-transferase and the non-enzymatic antioxidants viz., glutathione and metallothionein in various tissues of freshwater fish Channa punctatus (Bloch), in response to short-term and long-term exposures to paper mill effluent. The fish were exposed to the effluent at a concentration of 1.0% (v/v) for 15, 30, 60 and 90 days. The exposure caused a time-dependent increase in glutathione level (P < 0.001), activities of glutathione peroxidase (P < 0.05 to P < 0.001), glutathione S-transferase (P < 0.001) and a marginal initial decrease in catalase activity in the liver (P < 0.01 to P < 0.001). Metallothionein was induced in liver after 60 days of exposure. Two isoforms of metallothionein were detected. Catalase activity also increased 60 days afterwards. Antioxidant pattern was different in gill and kidney showing that liver was more resistant to oxidative damage as compared to gills and kidney. Our results demonstrate a pollutant-induced adaptive response in fish. In addition, levels of enzymatic and non-enzymatic tissue antioxidants may serve as surrogate markers of exposure to oxidant pollutants in fish.

Juvenile whitefish (Coregonus lavaretus L. s.l.) were exposed by caging in the field to diluted effluents from three operating pulp, paper, and paperboard mills in Southern Lake Saimaa, Finland. The expression of the vitellogenin gene, used as a biomarker of estrogenic contamination of effluents, was measured using a Northern blotting method. Increased mRNA levels, the most specific and reliable evidence for estrogen receptor-mediated actions in vivo, were found in fish caged in the vicinity of one of three mills studied. This mill was found to discharge wood-derived compounds, such as sterols and resin acids, into Lake Saimaa in amounts considerably exceeding those from the other two mills. The increased vitellogenin gene expression suggests that the effluent is a source of estrogenic contaminants., (Copyright 1999 Academic Press.)

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.)

Children comprise one-fifth of Europe's population. Promoting child health and development is of key importance for society and its future. This position paper highlights opportunities of investing in gastrointestinal, liver, and nutritional research to promote child health and delineates priorities for research. Investing in child health plays a key role in the promotion of population health, well-being, and disease prevention lifelong, with large health economic benefits. Major opportunities for improving knowledge and translational application arise from recent scientific and technological developments, for example, the long-term impact of early environmental cues interacting with genes. Personalised approaches to therapy and prevention should be enhanced. Deciphering the microbiome and its effects on functions can help in promoting long-term health. Epigenetic research can help to understand how early environmental factors influence later gastrointestinal and hepatic health and disease. A linked nutrition and physical activity strategy can promote health and prevent nutritional deficiencies, inactivity, and chronic noncommunicable diseases, such as diabetes, to ensure optimal health and cognition. Special attention should be devoted to populations with low socioeconomic status, migrant background, and ethnic minorities, and to critical life periods, including pregnancy, lactation, infancy, and childhood. Improved understanding of optimal nutrition and on maintaining gut and liver homeostasis throughout childhood will help prevent chronic diseases in later life.

Patients with hepatocellular carcinoma should be managed with a multidisciplinary approach framed in a network where all the diagnostic techniques and therapeutic resources are available in order to provide the optimal level of care. Given this assumption, the Coordinating Committee of the Italian Association for the Study of the Liver nominated a panel of experts to elaborate practical recommendations for the multidisciplinary management of hepatocellular carcinoma aiming to provide: (1) homogeneous and efficacious diagnostic and staging work-up, and (2) the best treatment choice tailored to patient status and tumour stage at diagnosis. The 2010 updated American Association for the Study of Liver Disease Guidelines for hepatocellular carcinoma were selected as the reference document. For each management issue, the American Association for the Study of Liver Disease recommendations were briefly summarised and discussed, according to both the scientific evidence published after their release and the clinical expertise of the Italian centres taking care of these patients. The Italian Association for the Study of the Liver expert panel recommendations are finally reported., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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.)

Many studies link pulp and paper mill effluent (PPME) exposure to adverse effects in fish populations present in the mill receiving environments. These impacts are often characteristic of endocrine disruption and may include impaired reproduction, development and survival. While these physiological endpoints are well-characterized, the molecular mechanisms causing them are not yet understood. To investigate changes in gene transcription induced by exposure to a PPME at several stages of treatment, male and female fathead minnows (FHMs) were exposed for 6 days to 25% (v/v) secondary (biologically) treated kraft effluent (TK) or 100% (v/v) combined mill outfall (CMO) from a mill producing both kraft pulp and newsprint. The gene expression changes in the livers of these fish were analyzed using a 22K oligonucleotide microarray. Exposure to TK or CMO resulted in significant changes in the expression levels of 105 and 238 targets in male FHMs and 296 and 133 targets in females, respectively. Targets were then functionally analyzed using gene ontology tools to identify the biological processes in fish hepatocytes that were affected by exposure to PPME after its secondary treatment. Proteolysis was affected in female FHMs exposed to both TK and CMO. In male FHMs, no processes were affected by TK exposure, while sterol, isoprenoid, steroid and cholesterol biosynthesis and electron transport were up-regulated by CMO exposure. The results presented in this study indicate that short-term exposure to PPMEs affects the expression of reproduction-related genes in the livers of both male and female FHMs, and that secondary treatment of PPMEs may not neutralize all of their metabolic effects in fish. Gene ontology analysis of microarray data may enable identification of biological processes altered by toxicant exposure and thus provide an additional tool for monitoring the impact of PPMEs on fish populations., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The feasibility of using liver impressions on Flinders Technology Associates (FTA filter paper for the collection, inactivation, and molecular analysis of fowl adenovirus (FAV) was evaluated. FAV I European Union (EU) serotype 1 spotted on FTA was shown to be inactivated using specific-pathogen-free (SPF) primary chicken embryo liver cell culture as indicated by absence of cytopathic effect. Sensitivity of the polymerase chain reaction (PCR) test using tenfold dilutions of allantoic fluid from 100 to 10-4 for the detection of adenovirus serotype 1 on FTA cards was determined to be 0.0005 mean tissue culture infectious dose per FTA spot. The stability of the DNA from liver impressions on the FTA was found to be 198 days when stored at -20 degrees C. In a trial, inclusion body hepatitis (IBH) was experimentally reproduced in SPF chickens inoculated with FAV I EU serogroup 1, 4, 8, or 11, which presented weakness, pallor, depression, dehydration, and mortality within 6 days after inoculation. PCR performed on FTA liver impressions from the inoculated birds was able to detect all four viruses, and the nucleotide sequence analysis of the amplified PCR products (1219 bp of the hexone gene) revealed the expected serotypes. In addition to the trial, 55 clinical samples were analyzed from liver impressions on FTA cards, and FAV was detected in 11 of 55 (20%). Sequencing analysis showed that the viruses were EU serotypes 4, 5, 9, and 10. The results demonstrate that FTA filter paper inactivates the FAV I and maintains the DNA template for molecular analysis.

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]

The studies were performed on perch (Perca fluviatilis) caught outside Husum and Iggesund kraft pulp mills in 1985 and 1987, respectively, and the results were compared to previous observations from 1984 to 1985 in the receiving waters of the Norrsundet kraft pulp mill. The studies revealed that the biochemical and physiological variables, i.e., EROD activity, gonad size, number of lymphocytes, carbohydrate metabolites, and plasma ion composition, can be used as sensitive and reliable indicators of toxic effects on natural populations of fish exposed to conventional chlorine-bleached kraft mill effluents. However; the effects were generally less pronounced and indicated less geographic extension than those seen in perch previously investigated in the receiving waters of the Norrsundet kraft pulp mill. Based on these studies on perch at Husum and Iggesund and the previous studies at Norrsundet it can be concluded that the chlorine-bleached kraft mill effluents cause serious disturbances to vital biochemical and physiological functions, which can affect the health status and presumably also the survival of the fish. Finally, the responses do not reflect the present situation in the receiving waters since all three mills have taken extensive measures for process alterations and discharge reductions after the time of the investigations.

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.)