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18 pages, 26299 KB  
Review
Schistosoma Mansoni and Haematobium: Radiological Diagnostic Clues and Pathophysiology
by Sultan Abdulwadoud Alshoabi, Abdullatif O. Magram, Abdulaziz H. Alkalady, Rafat Rashed Al-Maqtari, Khaled M. Almas, Khaled Mohammed Al-Sayaghi, Abdullgabbar M. Hamid, Fahad H. Alhazmi, Abdulaziz A. Qurashi, Walaa Alsharif, Amirah Alsaedi, Ezzat AbuAzzah, Abdulkareem Algahtani, Khaled A. Alqfail and Khalid M. Alshamrani
Pathogens 2026, 15(5), 536; https://doi.org/10.3390/pathogens15050536 - 15 May 2026
Viewed by 357
Abstract
Schistosomiasis (bilharzia) is a parasitic infection caused by trematodes of the Schistosoma genus and remains a significant health burden in endemic regions. Granulomatous host responses to deposited Schistosoma eggs in small veins and tissues result in progressive changes and characteristic imaging findings. This [...] Read more.
Schistosomiasis (bilharzia) is a parasitic infection caused by trematodes of the Schistosoma genus and remains a significant health burden in endemic regions. Granulomatous host responses to deposited Schistosoma eggs in small veins and tissues result in progressive changes and characteristic imaging findings. This diagnostic radiological review synthesizes the published literature and highlights key and robust imaging findings that facilitate the diagnosis of Schistosoma mansoni and Schistosoma haematobium, with emphasis on modality-specific patterns and disease staging. Schistosoma mansoni primarily affects the liver, causing periportal fibrosis visible as “pipe-stem” echogenic thickening upon ultrasonography, which may progress to portal hypertension and chronic liver disease. Liver cirrhosis is the end-stage disease manifested as an irregular liver contour with surface nodularity and lobar redistribution as right lobe atrophy with left and/or caudate lobe hypertrophy. Schistosoma haematobium predominantly affects the genitourinary system, causing urinary bladder wall thickening and calcification. Early disease, within three months of infection, may present with fine calcification, firstly in the bladder base and then extending to the whole bladder and even to the ureters. Calcification appears as a line or two parallel lines on radiography and as a circle in axial computed tomography (CT) images, which is pathognomonic for early-stage Schistosomiasis. In contrast studies, including conventional urography and CT urography, Schistosoma eggs appear as bubble-like filling defects in the ureter, kidney, and bladder, manifested as ureteritis, pyelitis, and cystitis cystica. Late stages appear as coarse calcification, fibrosis, strictures, and reduced bladder capacity and are associated with an increased risk of bladder squamous cell carcinoma. Moreover, Schistosomiasis calcification can present in genital organs, especially in the seminal vesicles; in the prostate in males; and in the vulva, cervix, and perineum in females. Ultimately, Schistosoma mansoni and haematobium eggs can reach the spinal cord, leading to acute myelopathy with paraparesis, urinary retention, or paraplegia. Recognition of characteristic imaging patterns of Schistosomiasis is essential for early diagnosis, accurate staging, and prevention of long-term complications. Full article
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15 pages, 2165 KB  
Article
Morphological and Immunohistochemical Characteristics of Liver Inflammation in Patients with a History of COVID-19
by Ilze Strumfa, Ludmila Viksna, Oksana Kolesova, Ieva Vanaga, Haralds Plaudis, Jelena Storozenko, Boriss Strumfs, Janis Pavulans and Romans Uljanovs
Viruses 2026, 18(1), 68; https://doi.org/10.3390/v18010068 - 2 Jan 2026
Viewed by 962
Abstract
The COVID-19 pandemic caused more than seven million deaths, mostly via acute respiratory distress syndrome with microvascular thrombosis. Compared to the amount of information about pulmonary pathology, information about COVID-19-induced liver lesions is scarce, especially with regard to the long-term consequences. The aim [...] Read more.
The COVID-19 pandemic caused more than seven million deaths, mostly via acute respiratory distress syndrome with microvascular thrombosis. Compared to the amount of information about pulmonary pathology, information about COVID-19-induced liver lesions is scarce, especially with regard to the long-term consequences. The aim of our study was to evaluate inflammatory, vascular and fibrotic changes in hepatobiliary tissues of patients with a history of COVID-19 (post-COVID-19 patients). Based on the Knodell score, moderate portal inflammation was observed in 41.2% of post-COVID-19 patients, contrasting with 14.3% of control cases (p = 0.06). Moderate periportal inflammation was present in 26.5% and 7.1% of patients, respectively (p = 0.08). Post-COVID-19 patients showed higher counts of CD3+ lymphocytes (p = 0.02) and lower counts of CD68+ macrophages (p = 0.04), as well as more frequent and extensive regenerative changes in hepatocytes and the biliary epithelium (p = 0.0007). We did not find significant fibrosis or pathological changes in blood vessels, and only mild steatosis was observed in both groups. Full article
(This article belongs to the Special Issue Coronavirus Pathogenesis and Virus-Host Interaction)
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16 pages, 2002 KB  
Article
Deep Learning for Automated Detection of Periportal Fibrosis in Ultrasound Imaging: Improving Diagnostic Accuracy in Schistosoma mansoni Infection
by Alex Mutebe, Bakhtiyar Ahmed, Agnes Natukunda, Emily Webb, Andrew Abaasa, Simon Mpooya, Moses Egesa, Ayoub Kakande, Alison M. Elliott and Samuel O. Danso
Appl. Sci. 2026, 16(1), 87; https://doi.org/10.3390/app16010087 - 21 Dec 2025
Cited by 1 | Viewed by 945
Abstract
This study investigates advanced deep learning methods to improve the detection of periportal fibrosis (PPF) in medical imaging. Schistosoma mansoni infection affects over 54 million individuals globally, predominantly in sub-Saharan Africa, with around 20 million experiencing chronic complications. PPF, present in up to [...] Read more.
This study investigates advanced deep learning methods to improve the detection of periportal fibrosis (PPF) in medical imaging. Schistosoma mansoni infection affects over 54 million individuals globally, predominantly in sub-Saharan Africa, with around 20 million experiencing chronic complications. PPF, present in up to 42% of these cases, is a leading outcome of chronic liver disease, significantly contributing to morbidity and mortality. Early and accurate detection is critical for timely intervention, yet conventional ultrasound diagnosis remains highly operator-dependent. We adapted and trained a convolutional neural network (CNN) using ultrasound images to automatically identify and classify PPF severity. The proposed approach achieved a diagnostic accuracy of 80%. Sensitivity and specificity reached 84% and 76%, respectively, demonstrating robust generalisability across varying image qualities and acquisition settings. These findings highlight the potential of deep learning to reduce diagnostic subjectivity and support scalable screening programmes. Future work will focus on validation with larger datasets and multi-class fibrosis grading to enhance clinical utility. Full article
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15 pages, 6091 KB  
Article
Could Different Doses of Dexmedetomidine Be as Effective as Amifostine Against Radiotherapy-Induced Liver Injury in Rats? Evidence from Mitotic, Apoptotic, Oxidative, and Neurogenic Insights
by Hatice Beyazal Polat, Hamit Yilmaz, Kasım Demir, Kagan Kilinc, Belemir Gülhan, Sema Yilmaz Rakici and Levent Tumkaya
J. Clin. Med. 2025, 14(22), 8238; https://doi.org/10.3390/jcm14228238 - 20 Nov 2025
Viewed by 654
Abstract
Background/Objectives: Radiotherapy (RT) induces oxidative stress and structural damage in solid tissues, including the liver. This study aimed to investigate the histological and immunohistochemical effects of dexmedetomidine (DEX) and amifostine on their potential protective and regenerative properties against liver injury induced by [...] Read more.
Background/Objectives: Radiotherapy (RT) induces oxidative stress and structural damage in solid tissues, including the liver. This study aimed to investigate the histological and immunohistochemical effects of dexmedetomidine (DEX) and amifostine on their potential protective and regenerative properties against liver injury induced by radiation therapy. Methods: This study consisted of five randomized groups: control, RT, RT-D100, RT-D200, and RT-A (Amifostine). A total of 100 µg/kg DEX, 200 µg/kg DEX, and 200 µg/kg amifostine were administered before radiotherapy as per the experimental design. After RT, liver specimens were analyzed for histological alterations, including periportal and perisinusoidal fibrosis, vacuolization, and pyknotic nuclei. Furthermore, immunohistochemistry investigations were conducted to evaluate apoptosis, mitosis, oxidative stress, and neural regeneration in non-neuronal liver tissue following radiotherapy and subsequent treatment. Results: The control group’s liver tissue exhibited standard histological architecture, whereas the RT group displayed severe cellular degeneration, periportal and perisinusoidal fibrosis, cytoplasmic vacuolization, and an increase in pyknotic nuclei. The apoptotic index was markedly reduced in the RT-D100 and RT-D200 groups relative to the RT group. Furthermore, caspase-3 immunoactivity was negligible in the control group, while a significant increase was observed in the RT group. The administration of amifostine significantly increased GAP-43 levels. Conclusions: DEX mitigates RT-induced hepatic injury chiefly through antioxidant and anti-apoptotic pathways, whereas amifostine promotes hepatic regeneration by modulating GAP-43. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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30 pages, 7740 KB  
Article
Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells
by Hui-Hsuan Lin, Pei-Rong Yu, Chiao-Yun Tseng, Ming-Shih Lee and Jing-Hsien Chen
Antioxidants 2025, 14(5), 595; https://doi.org/10.3390/antiox14050595 - 16 May 2025
Cited by 4 | Viewed by 2445
Abstract
Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod [...] Read more.
Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment–insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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14 pages, 5075 KB  
Article
Time-Dependent Changes in Performance, Biochemistry, and Histology in Dairy Calves with Acute Aflatoxicosis
by María Carolina de Luna-López, Arturo G. Valdivia-Flores, Erika Janet Rangel-Muñoz, Emmanuel Hernández-Valdivia, Teódulo Quezada-Tristán, Fernando Jaramillo-Juárez and Raúl Ortiz-Martínez
Vet. Sci. 2025, 12(3), 273; https://doi.org/10.3390/vetsci12030273 - 14 Mar 2025
Cited by 2 | Viewed by 1911
Abstract
Aflatoxins (AFs) are secondary metabolites of Aspergillus spp. They are highly toxic, carcinogenic, and immunosuppressive; AFs cause nonspecific disorders in humans and animals, which makes their diagnosis complex. The objective was to describe the time course of toxic effects of a single exposure [...] Read more.
Aflatoxins (AFs) are secondary metabolites of Aspergillus spp. They are highly toxic, carcinogenic, and immunosuppressive; AFs cause nonspecific disorders in humans and animals, which makes their diagnosis complex. The objective was to describe the time course of toxic effects of a single exposure to AFs-contaminated feed. Fifteen male calves (2 weeks old) were examined over 30 days for clinical, biochemical, and pathological changes resulting from the ingestion of AF-contaminated feed (1.0 mg/kg BW). Compared with 15 unexposed calves, exposed calves showed transient depression and rough coat; BW gain, dry matter intake, albumin, total plasma protein, and hepatic and renal glutathione-S-transferase concentrations progressively decreased. However, conversion ratio (feed/BW), total bilirubin, direct bilirubin, alkaline phosphatase, reduced glutathione, gamma-glutamyltransferase, and alanine and aspartate aminotransferases progressively increased. Necropsy and histology at 7 days postexposure (dpe) showed liver with multifocal hemorrhages, yellowish coloration, friable consistency, periportal fibrosis, and steatosis. Kidneys were hemorrhagic, with brush border losses, glomerular atrophy, sclerotic glomerulonephritis, and lymphocytic infiltration. However, at 30 dpe, the liver showed pale discoloration, diffuse macrovesicular steatosis, and periportal fibrosis. The kidneys had mottled appearance and firm consistency, fibrosis, loss of normal architecture, and thickening of Bowman’s capsule. These results suggest that the identification of alterations in animal performance and biochemical and histological characteristics could be useful for integrating a proper diagnosis of bovine aflatoxicosis. Full article
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8 pages, 304 KB  
Article
Seroprevalence of Hepatitis E Virus Among Schistosomiasis mansoni Patients Residing in Endemic Zone in Brazil
by Cristiane Tiburtino de Oliveira Gomes, Carolline Araujo Mariz, Andrea Dória Batista, Clarice Neuenschwander Lins de Morais, Lílian Araújo, Ana Virgínia Matos Sá Barreto, Michele Soares Gomes-Gouvêa, Ana Lúcia Domingues and Edmundo Pessoa Lopes
Trop. Med. Infect. Dis. 2024, 9(12), 310; https://doi.org/10.3390/tropicalmed9120310 - 20 Dec 2024
Cited by 1 | Viewed by 1833
Abstract
The occurrence of hepatitis E virus (HEV) in patients with Schistosomiasis mansoni (SM) is still poorly understood in Brazil. The objective of this study was to estimate the seroprevalence of anti-HEV IgG in patients with SM and its association with the periportal fibrosis [...] Read more.
The occurrence of hepatitis E virus (HEV) in patients with Schistosomiasis mansoni (SM) is still poorly understood in Brazil. The objective of this study was to estimate the seroprevalence of anti-HEV IgG in patients with SM and its association with the periportal fibrosis (PPF), assessed by serum markers and ultrasound criteria. This cross-sectional study was carried out in an endemic area in Pernambuco, Brazil, with schistosomal patients who underwent coproscopic survey. Anti-HEV antibody IgG were evaluated by using ELISA (Euroimmun®, Lübeck, Germmany). In positive cases, HEV-RNA was tested by using real-time PCR. Among the 286 patients (60.8% women; 56% 18–44 years), 116 (40.6%) had advanced PPF (Niamey pattern D/E/F). Anti-HEV IgG was positive in 15 (5.24%), and all were HEV-RNA negative. Anti-HEV IgG was more frequent in patients with an advanced PPF (D/E/F) pattern (p = 0.034) and those with the largest spleen diameter (p = 0.039). In this study, the occurrence of anti-HEV IgG in patients with SM was higher than described in the same region and more frequent among patients with evidence of advanced liver fibrosis. Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
10 pages, 1321 KB  
Article
AI Digital Pathology Using qFibrosis Shows Heterogeneity of Fibrosis Regression in Patients with Chronic Hepatitis B and C with Viral Response
by Feng Liu, Yameng Sun, Dean Tai, Yayun Ren, Elaine L. K. Chng, Aileen Wee, Pierre Bedossa, Rui Huang, Jian Wang, Lai Wei, Hong You and Huiying Rao
Diagnostics 2024, 14(16), 1837; https://doi.org/10.3390/diagnostics14161837 - 22 Aug 2024
Cited by 3 | Viewed by 2224
Abstract
This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and [...] Read more.
This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and C (CHC; n = 58) were examined. qFibrosis was employed with artificial intelligence (AI) to analyze the fibrosis dynamics in the portal tract (PT), periportal (PP), midzonal, pericentral, and central vein (CV) regions. All patients with CHB achieved a virological response after 78 weeks of treatment, whereas patients with CHC achieved a sustained viral response after 24 weeks. For patients initially staged as F5/6 (Ishak system) at baseline, the post-treatment cases exhibited a significant reduction in the collagen proportionate area (CPA) (25–69%) and number of collagen strings (#string) (9–72%) across all regions. In contrast, those initially staged as F3/4 at baseline showed a similar CPA and #string trend at 24 weeks. For regression patients, 27 parameters (25 in the CV region) in patients staged as F3/4 and 15 parameters (three in the PT and 12 in the PP regions) in those staged as F5/6 showed significant differences between the CHB and CHC groups at baseline. Following successful antiviral treatment, the pre- and post-treatment liver samples provided quantitative evidence of the heterogeneity of fibrotic features. qFibrosis has the potential to provide new insights into the characteristics of fibrosis regression in both patients with CHB and CHC as early as 24 weeks after antiviral therapy. Full article
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12 pages, 1881 KB  
Article
COVID-19-Related Cholangiopathy: Histological Findings
by Valéria F. A. Borges, Helma P. Cotrim, Antônio Ricardo C. F. Andrade, Liliana S. C. Mendes, Francisco G. C. Penna, Marcelo C. Silva, Frederico C. Salomão and Luiz A. R. Freitas
Diagnostics 2024, 14(16), 1804; https://doi.org/10.3390/diagnostics14161804 - 19 Aug 2024
Viewed by 2550
Abstract
Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. Methods: We [...] Read more.
Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. Methods: We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. Results: All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51–60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390–1256); GGT 925 (664–2169); ALT 100 (86–113); AST 87 (68–106); and bilirubin 4 (1–9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150–249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. Conclusions: The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable. Full article
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13 pages, 497 KB  
Review
Liver Stiffness Evaluation in Chronic Hepatitis C Patients with Cirrhosis before and after Direct-Acting Antivirals
by Cristina Stasi and Stefano Brillanti
Microorganisms 2024, 12(7), 1418; https://doi.org/10.3390/microorganisms12071418 - 12 Jul 2024
Cited by 1 | Viewed by 3372
Abstract
After the introduction of direct-acting antivirals, parallel significant clinical progress has been achieved in the assessment of liver fibrosis progression/regression before treatment and during the follow-up of the cirrhotic patients with chronic hepatitis C virus (HCV) infection. The evolution of chronic hepatitis C [...] Read more.
After the introduction of direct-acting antivirals, parallel significant clinical progress has been achieved in the assessment of liver fibrosis progression/regression before treatment and during the follow-up of the cirrhotic patients with chronic hepatitis C virus (HCV) infection. The evolution of chronic hepatitis C into liver cirrhosis is correlated with an extensive accumulation of the extracellular matrix, leading to the formation of large amounts of fibrotic tissues that, initially, are concentrated in periportal areas and, in the later stages, surround the nodules of regenerating hepatocytes. The progressive increase in the fibrotic matrix contributes to vascular disturbances (favoring the development of portal hypertension) and to microenvironmental changes. The four clinical stages of liver cirrhosis are predictors for different clinical scenarios. The wide-ranging functions of the liver require different methods for their assessment. The non-invasive evaluation using transient elastography is useful in determining the longitudinal modifications of fibrosis during and after treatment with direct-acting antivirals. The liver stiffness evaluation, known to have a wide range of values in cirrhotic patients, can offer different prognostic implications after sustained virological response. This review discusses the different time points of liver stiffness evaluation that appear to show a more well-defined propensity to identify adequate monitoring schedules for these patients. Full article
(This article belongs to the Special Issue Human Infectious Diseases)
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20 pages, 1215 KB  
Review
Ductular Reactions in Liver Injury, Regeneration, and Disease Progression—An Overview
by Nirmala Mavila, Mallikarjuna Siraganahalli Eshwaraiah and Jaquelene Kennedy
Cells 2024, 13(7), 579; https://doi.org/10.3390/cells13070579 - 26 Mar 2024
Cited by 18 | Viewed by 7064
Abstract
Ductular reaction (DR) is a complex cellular response that occurs in the liver during chronic injuries. DR mainly consists of hyper-proliferative or reactive cholangiocytes and, to a lesser extent, de-differentiated hepatocytes and liver progenitors presenting a close spatial interaction with periportal mesenchyme and [...] Read more.
Ductular reaction (DR) is a complex cellular response that occurs in the liver during chronic injuries. DR mainly consists of hyper-proliferative or reactive cholangiocytes and, to a lesser extent, de-differentiated hepatocytes and liver progenitors presenting a close spatial interaction with periportal mesenchyme and immune cells. The underlying pathology of DRs leads to extensive tissue remodeling in chronic liver diseases. DR initiates as a tissue-regeneration mechanism in the liver; however, its close association with progressive fibrosis and inflammation in many chronic liver diseases makes it a more complicated pathological response than a simple regenerative process. An in-depth understanding of the cellular physiology of DRs and their contribution to tissue repair, inflammation, and progressive fibrosis can help scientists develop cell-type specific targeted therapies to manage liver fibrosis and chronic liver diseases effectively. Full article
(This article belongs to the Section Cellular Pathology)
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16 pages, 6170 KB  
Article
Spatial Computational Hepatic Molecular Biomarker Reveals LSEC Role in Midlobular Liver Zonation Fibrosis in DILI and NASH Liver Injury
by Munish Puri
Int. J. Transl. Med. 2024, 4(2), 208-223; https://doi.org/10.3390/ijtm4020012 - 23 Mar 2024
Cited by 1 | Viewed by 5650
Abstract
The liver is structurally organized into zonation, where Liver Sinusoidal Endothelial Cells (LSECs) play a crucial role during chronic liver injury and the early stages of fibrosis. Fibrosis can be reversed if diagnosed early at the molecular level in zonation before progressing to [...] Read more.
The liver is structurally organized into zonation, where Liver Sinusoidal Endothelial Cells (LSECs) play a crucial role during chronic liver injury and the early stages of fibrosis. Fibrosis can be reversed if diagnosed early at the molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in a normal and diseased fibrotic human liver. DGE analysis was performed over LSECs, and we identified the top 20 expressed genes in the periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells showed OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, and CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, and CTSL genes as expressed in DILI and NASH EC populations. The connection between LSEC marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases. Full article
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19 pages, 4738 KB  
Article
The Development of Nonalcoholic Fatty Liver Disease and Metabolic Syndromes in Diet-Induced Rodent Models
by Bayan Abdulhafid Aljahdali, Adnan Salem Bajaber, Doha M. Al-Nouri, Abdulrahman Saleh Al-Khalifah, Shaista Arzoo and Abeer Abdullah Alasmari
Life 2023, 13(6), 1336; https://doi.org/10.3390/life13061336 - 7 Jun 2023
Cited by 5 | Viewed by 5970
Abstract
Dietary macronutrients are essential for metabolic regulation and insulin function. The present study examined the effects of different high-fat diets (HFDs) and high-carbohydrate diets (HCDs) on the development of non-alcoholic fatty liver disease and metabolic syndrome indices in healthy adult male Wistar albino [...] Read more.
Dietary macronutrients are essential for metabolic regulation and insulin function. The present study examined the effects of different high-fat diets (HFDs) and high-carbohydrate diets (HCDs) on the development of non-alcoholic fatty liver disease and metabolic syndrome indices in healthy adult male Wistar albino rats. Forty-two rats were distributed into six groups (n = 7), which were fed the following for 22 weeks: (1) a control diet; (2) a high-carbohydrate, low-fat diet (HCD-LFD); (3) high-saturated-fat, low-carbohydrate diet (HSF-LCD); (4) a high-monounsaturated-fat diet (HMUSF); (5) a high medium-chain fat diet (HMCF); and a (6) a high-carbohydrate, high-fiber diet (HCHF). In comparison to the control, the body weight increased in all the groups. The HSF-LCD group showed the highest levels of cholesterol, triglyceride, low-density lipoprotein, hepatic enzyme, insulin resistance, and Homeostatic Model Assessment for Insulin Resistance. A liver histology analysis of the HSF-LCD group showed macrovesicular hepatic steatosis associated with large hepatic vacuolation. Additionally, it showed marked periportal fibrosis, especially around the blood vessels and blood capillaries. The lowest levels of fasting glycemia, insulin, and HOMA-IR were observed in the HCHF group. In conclusion, these findings show that dietary saturated fat and cholesterol are principal components in the development and progression of non-alcoholic fatty liver disease in rats, while fiber showed the greatest improvement in glycemic control. Full article
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12 pages, 900 KB  
Article
Laparoscopic Right Hemihepatectomy after Future Liver Remnant Modulation: A Single Surgeon’s Experience
by Tijs J. Hoogteijling, Jasper P. Sijberden, John N. Primrose, Victoria Morrison-Jones, Sachin Modi, Giuseppe Zimmitti, Marco Garatti, Claudio Sallemi, Mario Morone and Mohammad Abu Hilal
Cancers 2023, 15(10), 2851; https://doi.org/10.3390/cancers15102851 - 21 May 2023
Cited by 4 | Viewed by 2945
Abstract
Background: Laparoscopic right hemihepatectomy (L-RHH) is still considered a technically complex procedure, which should only be performed by experienced surgeons in specialized centers. Future liver remnant modulation (FLRM) strategies, including portal vein embolization (PVE), and associating liver partition and portal vein ligation for [...] Read more.
Background: Laparoscopic right hemihepatectomy (L-RHH) is still considered a technically complex procedure, which should only be performed by experienced surgeons in specialized centers. Future liver remnant modulation (FLRM) strategies, including portal vein embolization (PVE), and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), might increase the surgical difficulty of L-RHH, due to the distortion of hepatic anatomy, periportal inflammation, and fibrosis. Therefore, this study aims to evaluate the safety and feasibility of L-RHH after FLRM, when compared with ex novo L-RHH. Methods: All consecutive right hemihepatectomies performed by a single surgeon in the period between October 2007 and March 2023 were retrospectively analyzed. The patient characteristics and perioperative outcomes of L-RHH after FLRM and ex novo L-RHH were compared. Results: A total of 59 patients were included in the analysis, of whom 33 underwent FLRM. Patients undergoing FLRM prior to L-RHH were most often male (93.9% vs. 42.3%, p < 0.001), had an ASA-score >2 (45.5% vs. 9.5%, p = 0.006), and underwent a two-stage hepatectomy (45.5% vs. 3.8% p < 0.001). L-RHH after FLRM was associated with longer operative time (median 360 vs. 300 min, p = 0.008) and Pringle duration (31 vs. 24 min, p = 0.011). Intraoperative blood loss, unfavorable intraoperative incidents, and conversion rates were similar in both groups. There were no significant differences in length of hospital stay and 30-day overall and severe morbidity rates. Radical resection margin (R0) and textbook outcome rates were equal. One patient who underwent an extended RHH in the FLRM group deceased within 90 days of surgery, due to post-hepatectomy liver failure. Conclusion: L-RHH after FLRM is more technically complex than L-RHH ex novo, as objectified by longer operative time and Pringle duration. Nevertheless, this procedure appears safe and feasible in experienced hands. Full article
(This article belongs to the Special Issue Advances in Minimally Invasive Liver Resection for Cancer Therapies)
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17 pages, 1830 KB  
Article
Imaging Phenotypes and Evolution of Hepatic Langerhans Cell Histiocytosis on CT/MRI: A Retrospective Study of Clinical Cases and Literature Review
by Luwen Hao, Yuanqiu Li, Ziman Xiong, Yuchen Jiang, Xuemei Hu, Daoyu Hu, Zhen Li and Yaqi Shen
Bioengineering 2023, 10(5), 598; https://doi.org/10.3390/bioengineering10050598 - 16 May 2023
Cited by 2 | Viewed by 3452
Abstract
(1) Background: pathological changes in hepatic Langerhans cell histiocytosis (LCH) have been observed; however, corresponding imaging findings can appear vague to physicians and radiologists. The present study aimed to comprehensively illustrate the imaging findings of hepatic LCH and to investigate the evolution of [...] Read more.
(1) Background: pathological changes in hepatic Langerhans cell histiocytosis (LCH) have been observed; however, corresponding imaging findings can appear vague to physicians and radiologists. The present study aimed to comprehensively illustrate the imaging findings of hepatic LCH and to investigate the evolution of LCH-associated lesions. (2) Methods: LCH patients with liver involvement treated at our institution were retrospectively reviewed along with prior studies in PubMed. Initial and follow-up computed tomography (CT) and magnetic resonance imaging (MRI) were systematically reviewed, and three imaging phenotypes were created based on the lesion distribution pattern. Clinical features and prognoses were compared among the three phenotypes. Liver fibrosis was evaluated visually on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values of the fibrotic areas were measured. Descriptive statistics and a comparative analysis were used to analyze the data. (3) Results: based on the lesion distribution pattern on CT/MRI scans, patients with liver involvement were categorized as the disseminated lesion phenotype, scattered lesion phenotype, and central periportal lesion phenotype. Patients with scattered lesion phenotype were typically adults, and only a few of them had hepatomegaly (npresent = 1, 1/6, 16.7%) and liver biochemical abnormalities (npresent = 2, 2/6, 33.3%); patients with central periportal lesion phenotype were typically young children, and hepatomegaly and biochemical abnormalities were more apparent in these patients than those with another phenotype; and those with the disseminated lesion phenotype were found in all age groups, and the lesions evolved rapidly on medical imaging. Follow-up MRI scans show more details and can better document the evolution of lesions than CT. T2-hypointense fibrotic changes, including the periportal halo sign (npresent = 2, 2/9, 22.2%), patchy liver parenchyma changes (npresent = 6, 6/9, 66.7%), and giant hepatic nodules close to the central portal vein (npresent = 1, 1/9, 11.1%), were found, while fibrotic changes were not observed in patients with the scattered lesion phenotype. The mean ADC value for the area of liver fibrosis in each patient was lower than the optimal cutoff for significant fibrosis (METAVIR Fibrosis Stage ≥ 2) in a previous study that assessed liver fibrosis in chronic viral hepatitis. (4) Conclusions: The infiltrative lesions and liver fibrosis of hepatic LCH can be well characterized on MRI scans with DWI. The evolution of these lesions was well demonstrated on follow-up MRI scans. Full article
(This article belongs to the Section Biosignal Processing)
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