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Hepatic veno-occlusive disease-immunodeficiency syndrome

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hepatic veno-occlusive disease-immunodeficiency syndrome. Core disease mec...

2026-04-21
Asta MONDO:0009338 Model: Asta Scientific Corpus Retrieval 19 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hepatic veno-occlusive disease-immunodeficiency syndrome. Core disease mec...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 19
  • Snippets retrieved: 20

Relevant Papers

[1] Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

  • Authors: C. Mastroianni, M. Lichtner, C. Mascia, P. Zuccalà, V. Vullo
  • Year: 2014
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/22de2dd977b7f1302fb6dc29a174487ab88df54a
  • DOI: 10.3390/ijms15069184
  • PMID: 24865485
  • PMCID: 4100089
  • Citations: 96
  • Influential citations: 6
  • Summary: The evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.481) > Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

[2] Ten Cases of Hepatic Sinuses Obstruction Syndrome Caused by Sedum Uizoon

  • Authors: X. Wang, Wang Yg
  • Year: 2018
  • Venue: journal of Clinical Case Reports
  • URL: https://www.semanticscholar.org/paper/dc9e5e8ac06d4d77ef98bb9f5d3369a3e10ecee4
  • DOI: 10.4172/2165-7920.10001135
  • Summary: The clinical characteristics of HSOS caused by sedum uizoon were analyzed in detail, which provided clinical data for the diagnosis and treatment and the mechanism of the disease in the future.
  • Evidence snippets:
  • Snippet 1 (score: 0.469) > Hepatic sinuses obstruction syndrome (HSOS) also known as hepatic venule syndrome, refers to the injury of central lobe and sub-lobular vein of hepatic lobule, resulting in intrahepatic posterior sinus portal hypertension caused by lumen stenosis or occlusion. Currently the pathogenesis is not clear. It may be related to the drug, immunity and inflammation of the liver vein endothelial cells. The clinical manifestations are hepatomegaly, right upper abdominal pain, jaundice and ascites, with a high risk of mortality and poor prognosis for characteristics. Occurs because of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), adjuvant or neoadjuvant chemotherapy containing oxaliplatin for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, taking herbal remedies containing pyrrolizidine alkaloid and the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). In this paper, the clinical characteristics of HSOS caused by sedum uizoon were analyzed in detail, which provided clinical data for the diagnosis and treatment and the mechanism of the disease in the future.

[3] Sinusoidal Obstruction Syndrome Post-allogeneic Transplantation: A Complex Multisystem Challenge

  • Authors: Tomas Escobar Gil, Sushrruti Varatharaj, S. Rosenberg, G. J. Aguilar, David Santistevan et al.
  • Year: 2025
  • Venue: Cureus
  • URL: https://www.semanticscholar.org/paper/cce816feb22a5c8d5488aada4604332db94ed4ba
  • DOI: 10.7759/cureus.80078
  • PMID: 40190874
  • PMCID: 11970208
  • Summary: The case of a 41-year-old female with chronic myeloid leukemia (CML) in blast crisis who underwent haploidentical allogeneic stem cell transplantation highlights the need for early intervention, a tailored risk-benefit assessment of defibrotide, and multidisciplinary critical care strategies for high-risk patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.465) > Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a rare but severe complication of hematopoietic stem cell transplantation (HSCT) caused by endothelial injury within the hepatic sinusoids [1,2]. Clinically, it manifests as sinusoidal congestion, hepatomegaly, and hyperbilirubinemia, typically within three weeks after transplantation [3,4]. Several factors increase the risk of SOS, including myeloablative conditioning regimens, haploidentical donors, and preexisting liver dysfunction [5,6]. > The pathophysiology of SOS is multifactorial, involving endothelial injury, activation of coagulation pathways, inflammatory cytokines, and complement system dysregulation [3]. These mechanisms suggest potential targets for adjunct therapies, such as complement inhibitors, anti-inflammatory agents, or endothelial-protective strategies, which warrant further investigation [7,8]. For survivors of SOS, long-term complications, such as chronic liver disease and portal hypertension, remain significant concerns, with consistent follow-up becoming an important factor in the care of these patients after the event [1]. This case highlights the complexity of SOS in a post-transplant setting, emphasizing the challenges in diagnosis, therapeutic decision-making, and multidisciplinary care. Through this case, we aim to illustrate the clinical course, diagnostic criteria, and therapeutic challenges associated with SOS, contributing to a deeper understanding of this serious complication in hematopoietic stem cell transplantation.

[4] Lipophagy: Molecular Mechanisms and Implications in Hepatic Lipid Metabolism.

  • Authors: Sai Feng, Zeao Sun, Xiao Jia, Lingyun Li, Yijian Wu et al.
  • Year: 2023
  • Venue: Frontiers in bioscience
  • URL: https://www.semanticscholar.org/paper/05073e2380c667f7bdf193e0c71a30a8cfbdf55e
  • DOI: 10.31083/j.fbl2801006
  • PMID: 36722271
  • Citations: 19
  • Influential citations: 1
  • Summary: Increasing evidence suggests that lipophagy is an effective method to resolve liver diseases because of its role in lipid metabolism and the interaction betweenlipophagy and hepatic lipid metabolism.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > The liver is the central organ of lipid metabolism and plays a vital role in cellular metabolisms, such as lipid digestion, absorption, transport, and decomposition [1].Chronically disturbed hepatic metabolism may lead to obesity and metabolic syndrome, causing non-alcoholic fatty liver disease (NAFLD) [2].Approximately 1 in 30 patients diagnosed with NAFLD develops cirrhosis or a liverassociated complication [3].Autophagy plays a crucial role during hepatic lipid metabolism.Diet, environment, and drugs strongly affect hepatic lipid metabolism through autophagy [4].Therefore, a further understanding of the specific molecular mechanisms of autophagy and various cell types involved has been deeply explored.The current article reviews the main pathways and regulatory mechanisms of hepatic autophagy and the related effects on lipid metabolism.

[5] In vitro systems to study inborn errors of immunity using human induced pluripotent stem cells

  • Authors: Eirini Nikolouli, Janne Reichstein, G. Hansen, N. Lachmann
  • Year: 2022
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/50f330ee9584168734b8cc8a22dc702c4cbe8ec5
  • DOI: 10.3389/fimmu.2022.1024935
  • PMID: 36466870
  • PMCID: 9713844
  • Citations: 1
  • Summary: This review aims to provide an overview of the current available in vitro models used to study IEI and which could lay the foundation for new therapeutic approaches and elaborate in particular on the use of induced pluripotent stem cell-based systems.
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > of drug-resistant pathogens, which can cause lifethreatening infections. In some cases, like in the severe combined immunodeficiency (SCID) syndrome, allogenic hematopoietic stem cell transplantation (HSCT) (or autologous HSC-gene therapy) is the only curative therapy (6,7). However, HSCT always lurks the risk of immunological rejection or development of graft versus host disease with devastating consequences for the patient, pointing towards the need of suitable alternatives. > For these reasons, more targeted therapeutic approaches, which can directly modulate specific cell types or intracellular pathways, are preferred. These approaches include the use of specific inhibitors or biologics (antibodies or recombinant proteins). For the safe use of these emerging therapeutic agents, a detailed study of the pathophysiological mechanisms of the diseases is necessary. Given the rarity of IEI and the technical difficulties (obtaining sufficient samples from children or the low number of affected cells), the study of IEI-related diseases remains challenging. Thus, the development of novel systems to unravel the cellular and molecular mechanisms involved in the pathophysiology of the various IEI is of great importance.

[6] Basic and Clinical Advances in Chronic Liver Inflammation

  • Authors: H. Enomoto, A. Tamori, H. Yoshiji, E. Seki
  • Year: 2016
  • Venue: Mediators of Inflammation
  • URL: https://www.semanticscholar.org/paper/3d41abce2962c7757c197fb58e2c5ada322d6fb6
  • DOI: 10.1155/2016/1571457
  • PMID: 27006527
  • PMCID: 4783579
  • Summary: This special issue is proposed to provide recent basic and clinical findings in chronic liver inflammation and its complications, and introduces papers regarding the complications of progressed liver diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > Continuous liver inflammation causes fibrotic changes and leads to the development of liver cirrhosis and liver cancer. Recent biological and medical advances have clarified the mechanisms of chronic liver inflammation and succeeded in providing new therapies for various liver diseases. We proposed this special issue to provide recent basic and clinical findings in chronic liver inflammation and its complications. > Regarding the diagnosis and treatment of liver inflammation, A. Tsutsui et al. showed the clinical utility of the Digestive Disease Week Japan 2004 (DDW-J) scale, which has been used as an objective diagnostic tool for drug-induced liver injury in Japan. A. Tamori et al. reviewed remarkable progression in antiviral treatments for hepatitis C virus (HCV), including DAAs (direct-acting antivirals or direct antiviral agents). > We also introduce papers regarding the complications of progressed liver diseases in this special issue. The prognoses of cirrhotic patients are highly dependent on their liver function, and A. Hassan et al. showed that L-carnitine administration helps maintain and improve liver functions after transarterial chemoembolization. Additionally, malnutrition is a frequently observed complication which is known to be associated with a poor prognosis. Y. Osaki and H. Nishikawa reviewed the nutritional problems of cirrhosis, focusing on a recent hot topic “sarcopenia.” Portal hypertension is a major problem along with the progression of chronic liver disease. The paper by K. Kotani et al. suggested the association of the immune system with the development of portal hypertension. Hepatocellular carcinoma is also a prognosis-determining complication of patients with chronic liver inflammation. K. Shindo et al. showed the clinical utility of a semiannual imaging surveillance program in patients without hepatitis viral infection. > With regard to the basic mechanisms of chronic liver inflammation, H. Tsutsui et al. reviewed the roles of IL-1 family cytokines in the development of various liver diseases, including IL-1 family cytokine-mediated molecular and cellular networks. Coinfection of HCV and human immunodeficiency virus (HIV) cooperatively leads to the progression of liver disease. Along this viewpoint, the paper by M. C. Liberto et al., which described the specific

[7] Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

  • Authors: Hao Xiong, Jinsheng Guo
  • Year: 2025
  • Venue: Pharmaceuticals
  • URL: https://www.semanticscholar.org/paper/76e92127053136900f7e3f10e2c9278251ced5d2
  • DOI: 10.3390/ph18040507
  • PMID: 40283943
  • PMCID: 12030350
  • Citations: 8
  • Summary: HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects.
  • Evidence snippets:
  • Snippet 1 (score: 0.422) > Significant progress has been made in elucidating the cellular and molecular mechanisms of liver fibrosis; however, only a few findings have been successfully translated into clinical applications. Firstly, the high cost of drug development and target validation necessitates prolonged timelines and substantial financial investment. Secondly, as regulatory requirements become more stringent, there is an increasing demand for drugs with well-defined clinical efficacy and safety profiles. Moreover, the efficacy observed in animal models often fails to fully translate to clinical settings due to differences in pharmacokinetics, extracellular matrix (ECM) cross-linking, and disease pathophysiology. Despite advancements in anti-fibrotic drug development, accurately identifying ideal noninvasive biomarkers for fibrotic activity and establishing consensus on optimal clinical endpoints remain significant challenges [113,114]. > Currently, addressing the underlying cause remains the only proven strategy to halt or reverse liver fibrosis progression, while the development of effective anti-fibrotic therapies continues to pose a major challenge in liver disease management. Over the past few decades, substantial progress has been made in elucidating the cellular and molecular mechanisms underlying liver fibrosis. Liver fibrosis is a complex pathological change involving multiple cells, factors, and pathways, and the study of the cellular and molecular mechanisms of its occurrence and development provides an important theoretical basis and therapeutic target for clinical drug development. It is anticipated that improved animal models and well-designed clinical trials will facilitate the successful translation of anti-fibrotic research into effective clinical treatments in the near future.

[8] Hepatic veno-occlusive disease-immunodeficiency syndrome

  • Authors: Unknown authors
  • Year: 2020
  • Venue: Definitions
  • URL: https://www.semanticscholar.org/paper/ca0179047b364e90ddc74672dc7abb73baacfa72
  • DOI: 10.32388/u9la32
  • Summary: Hepatic veno-occlusive disease-immunodeficient syndrome is characterized by the association of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic venO-OCclusive disease.
  • Evidence snippets:
  • Snippet 1 (score: 0.419) > Hepatic veno-occlusive disease-immunodeficiency syndrome is characterized by the association of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease.
  • Snippet 2 (score: 0.410) > Hepatic veno-occlusive disease-immunodeficiency syndrome

[9] Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies

  • Authors: Jeysson E Mejía-Guzmán, Ramón A. Belmont-Hernández, Norberto C. Chávez-Tapia, M. Uribe, N. Nuño-Lámbarri
  • Year: 2025
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/4c63d1bff27c7cfbe5c3091c5eb3445a0a04f186
  • DOI: 10.3390/ijms26072959
  • PMID: 40243565
  • PMCID: 11988898
  • Summary: This review delves into the molecular mechanisms driving MASLD pathogenesis, including dysregulation of lipid metabolism, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota alterations.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > MASLD and MASH are increasingly recognized as central components of the broader cardiometabolic disease spectrum. The recently proposed Cardiovascular-Renal-Hepatic-Metabolic syndrome expands upon the earlier Cardiovascular-Kidney-Metabolic model by integrating the liver as a critical organ involved in the interconnected pathophysiology linking metabolic, cardiovascular, renal, and hepatic health. This holistic framework acknowledges the bidirectional interactions between MASLD and other cardiometabolic disorders, emphasizing shared mechanisms such as meta-inflammation, adipokine dysregulation, insulin resistance, oxidative stress, and neurohormonal activation. By incorporating MASLD into the broader cardiometabolic landscape, the CRHM syndrome offers a clinically relevant and scientifically grounded framework to address the global burden of cardiometabolic disorders more effectively [16]. > Regarding oncological outcomes, MASLD has also been associated with an elevated risk of both hepatic and extrahepatic cancers. While the primary hepatic cancers are often driven by cirrhosis, an increased risk has also been observed in patients with the condition. Furthermore, MASLD has also been linked to extrahepatic malignancies, particularly colorectal cancer, where the risk is approximately 50% higher compared to patients without MASLD [14,17]. > Understanding the molecular pathophysiology and diverse clinical manifestations of these conditions is essential for effective treatment. Early diagnosis and targeted molecular interventions addressing the underlying mechanisms can halt disease progression and significantly improve patient outcomes.

[10] Coagulation disturbances in paediatric patients with hepatic veno-occlusive disease after stem cells transplantation.

  • Authors: D. Jevtić, D. Vujic, Željko Zečević, D. Veljković, S. Gazikalović et al.
  • Year: 2010
  • Venue: Srpski arhiv za celokupno lekarstvo
  • URL: https://www.semanticscholar.org/paper/3ea4487128c4d63501c2fc57baa3962200940ec1
  • DOI: 10.2298/SARH10S1033J
  • PMID: 20229680
  • Citations: 4
  • Summary: It is suggested that monitoring coagulation parameters levels in the first five days from the establishment of diagnosis may have a significant predictive value for VOD outcome.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > Liver veno-occlusive disease (VOD) is a clinical syndrome characterized by hepatomegaly, fluid retention and hyperbilirubinaemia [1]. It is a serious complication after high doses of chemotherapy and/or radiotherapy and immunosuppressive treatment. Also, it is an early complication after stem cells transplantation (SCT), one of the most frequent complication and one of the leading causes of death in this group of patients [2]. In paediatric population the incidence of VOD is between 5-40%, mortality rate around 40% and, according to the recent studies, it is several times higher comparing with adults [2,3]. > The precise mechanism of VOD and the place of damage are not completely clear yet; it is, most probably, the result of sinusoidal endothelial cell damage followed by hepatocyte necrosis and coagulation activation. All these thee processes are highly increased after being followed by cytokine activation, especially tumour necrosis factor α and interleukin 1β [1]. First pathohistological findings have been seen in zone 3 of hepatic acinus as a progressive and concentric narrowing of small intrahepatic venules associated with necrosis of hepatocytes in the centrilobular areas. A lasting sinusoidal obstruction with cell detritus and erythrocytes consecutively leads to sinusoidal fibrosis and obliteration [4]. > The diagnosis of VOD relies on the combination of certain clinical signs, and most of transplantation teams use Seattle or Baltimore criteria, which are similar. The Seattle criteria requires two of the following three physical or laboratory findings: 1) jaundice or bilirubin level >34 μmol\l; 2) hepatomegaly or right upper quadrant pain of liver origin or; 3) sudden weight gain of more than 5% above baseline caused by either fluid accumulation or ascites [5]. For clinical practise it is very useful to add ultrasound findings of gallbladder thickening of more than 4 mm and platelet transfusion dependency together with the mentioned well known clinical signs [6].

[11] 18O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

  • Authors: E. Nemutlu, Song Zhang, N. Juranic, A. Terzic, S. Macura et al.
  • Year: 2012
  • Venue: Croatian Medical Journal
  • URL: https://www.semanticscholar.org/paper/880f053c7f060db4b990e447d0a22c4b69372ddb
  • DOI: 10.3325/cmj.2012.53.529
  • PMID: 23275318
  • PMCID: 3541579
  • Citations: 28
  • Summary: The potential use of dynamic phosphometabolomic platform for disease diagnostics currently under development at Mayo Clinic is described and discussed briefly.
  • Evidence snippets:
  • Snippet 1 (score: 0.401) > Living cells represent an integrated and interacting network of genes, transcripts, proteins, small signaling molecules, and metabolites that define cellular phenotype and function. Traditionally the focus of biomedical research was on individual genes, single protein targets, single metabolites, and metabolic or signaling pathways. This "molecular reductionist" paradigm was based on the assumption that identifying genetic variations and molecular components would lead to discovery of cures for human diseases. However, most of diseases are complex and multi-factorial and the disease phenotype is determined by the alterations of multiple genes, pathways, proteins and metabolites (at cellular, tissue, and organismal levels). Therefore, an integrated "omics" approach is more viable direction for uncovering alterations in metabolic networks, disease mechanisms, and mechanisms of drug effects. > Recent advent of large-scale metabolomics and fluxomic (metabolite dynamics and metabolic flux analysis) completed the "omics revolution" (Figure 1), where genomics, transcriptomics, proteomics, metabolomics, and fluxomics all together complement phenotype determination of living organism. Such integrated "omics" cascades provide a framework for advances in system and network biology, integrative physiology, and system medicine as well as system pharmacology and regenerative medicine. Noteworthy is the "reverse omic" approach or "metabolomicsinformed pharmacogenomics, " where discovery of specific metabolite changes have led to discovery of genetic alterations (2). Therefore, bringing new "omics" technologies to clinical practice will improve disease diagnostics and treatment by targeting drugs and procedures for each unique transcriptomic and metabolomic profiles.

[12] Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

  • Authors: S. Putta, B. Young, J. Levine, R. Reshef, R. Nakamura et al.
  • Year: 2022
  • Venue: Transplantation and cellular therapy
  • URL: https://www.semanticscholar.org/paper/6f56766841865b8c6fdb47f19384cd61b9a4e77b
  • DOI: 10.1016/j.jtct.2022.11.024
  • PMID: 36574581
  • PMCID: 10116945
  • Citations: 7
  • Summary: Multivariate analysis suggests that a combination of up to 5 protein biomarkers may provide a prognostic tool for identifying patients at risk for VOD/SOS shortly after HCT.
  • Evidence snippets:
  • Snippet 1 (score: 0.399) > Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication observed after hematopoietic cell transplantation (HCT) often characterized by ascites, hepatomegaly, weight gain, and hyperbilirubinemia [1,2]. Severe VOD/SOS with multiorgan dysfunction is associated with high mortality (>80%) if untreated [3]. The incidence of VOD/SOS following HCT ranges from 5% to 60% [3,4] and varies depending on clinical risk factors, such as conditioning regimen intensity, type of transplant, graft-versus-host disease (GVHD) prophylaxis, and such patient characteristics as age, advanced malignancy, and history of hepatitis B or C infection [4][5][6]. > The pathogenesis of VOD/SOS is complex, but damage to the endothelial cells (ECs) lining hepatic sinusoids resulting from accumulation of toxic metabolites produced by HCT conditioning is likely the inciting event [5]. EC injury induces the expression of procoagulant factors, inflammatory cytokines, and metalloproteinases and the release of heparanase, which results in a loss of cytoskeletal integrity, opening of the endothelial paracellular pathways [7,8], and extravasation of cellular and extracellular debris into the space of Disse. This in turn leads to extraluminal compression of sinusoidal vessels [7,9] and culminates in postsinusoidal hypertension, reduction or reversal of sinusoidal flow, and ultimately sinusoidal obstruction and/or central vein occlusion, the pathologic hallmarks of VOD/SOS [5]. > VOD/SOS typically manifests within 3 weeks after HCT but occurs later in approximately 20% of patients [10,11].

[13] Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment

  • Authors: A. Gruevska, Ángela B. Moragrega, A. Cossarizza, J. Esplugues, A. Blas-García et al.
  • Year: 2021
  • Venue: Cells
  • URL: https://www.semanticscholar.org/paper/dfb9e730d9161be4832d28d9affecd8eef223c4e
  • DOI: 10.3390/cells10020410
  • PMID: 33669403
  • PMCID: 7920460
  • Citations: 14
  • Summary: The evidence and potential mechanisms involved in the apoptosis of hepatocytes induced by HIV, HIV-encoded proteins, or cART are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.397) > Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infections, HIV itself and the adverse effects of cART are the main factors that contribute to hepatic cell injury, inflammation, and fibrosis. Among the molecular mechanisms that are activated in the liver during HIV infection, apoptotic cell death of hepatocytes stands out as a key pathogenic player. In this review, we will discuss the evidence and potential mechanisms involved in the apoptosis of hepatocytes induced by HIV, HIV-encoded proteins, or cART. Some antiretroviral drugs, especially the older generation, can induce apoptosis of hepatic cells, which occurs through a variety of mechanisms, such as mitochondrial dysfunction, increased production of reactive oxygen species (ROS), and induction of endoplasmic reticulum (ER) stress and unfolded protein response (UPR), all of which ultimately lead to caspase activation and cell death.

[14] The potential roles of gut microbiome in porto-sinusoidal vascular disease: an under-researched crossroad

  • Authors: Yangjie Li, Lingna Lyu, Huiguo Ding
  • Year: 2025
  • Venue: Frontiers in Microbiology
  • URL: https://www.semanticscholar.org/paper/7fc2f5ae990d46892b846143a3a862fe435360f2
  • DOI: 10.3389/fmicb.2025.1556667
  • PMID: 40099185
  • PMCID: 11911366
  • Citations: 1
  • Summary: The current understanding of the gut microbiome's potential role in the pathogenesis of hepatic microvascular abnormalities and thrombosis is summarized and the insights into gut microbiota and their potential influence on the onset and progression of PSVD may pave the way for new diagnostic, prognostic, and therapeutic strategies.
  • Evidence snippets:
  • Snippet 1 (score: 0.395) > The diagnosis of PSVD remains challenging, which primarily relies on clinical signs of portal hypertension combined with specific histological features involving the porto-sinusoidal vascular abnormalities (obliterative portal venopathy, portal tract hypervascularization, and abnormal periportal vessels) as well as parenchymal abnormalities (Gioia et al., 2024;De Gottardi et al., 2022). Moreover, the pathophysiology responsible for PSVD is complex and hinders the development of treatments capable of altering the natural history of the disease. A better insight into the biological processes and pathophysiological mechanisms involved in PSVD is essential for identifying disease drivers and developing new diagnostic and therapeutic strategies. > Gut microbiome plays critical roles in the development of several vascular disease phenotypes by activating vascular endothelial cells, platelets, and innate immune cells (Hasan et al., 2020). Since the liver yields most of its blood supply via the portal circulation, the hepatic microcirculation constantly encounters gut-derived components, metabolites, and signals. These factors can induce changes in the liver sinusoidal endothelium, affecting the immune partitioning of the sinusoids and influencing portal hypertension (Kiouptsi et al., 2023). Although the exact pathogenesis of PSVD remains unclear, it is hypothesized to result from injuries and occlusion of the intrahepatic portal microvasculature, leading to increased resistance to portal blood flow and subsequent presinusoidal type of portal hypertension (Jin and Choi, 2023). Predisposing conditions of PSVD are related to immune disorders, infections, prothrombotic conditions, congenital or hereditary defects, drug exposure, and inherited vascular remodeling disorders (Kmeid et al., 2021). The link between gut microbiome, portal hypertension, and predisposing conditions of PSVD have supported that gut microbiota translocation into the sinusoids may impact on the pathophysiology of PSVD (Fiordaliso et al., 2023).

[15] LifeTime and improving European healthcare through cell-based interceptive medicine

  • Authors: N. Rajewsky, G. Almouzni, S. Gorski, S. Aerts, I. Amit et al.
  • Year: 2020
  • Venue: Nature
  • URL: https://www.semanticscholar.org/paper/d626a4acb560c1ef16ea394cb4dccf277882d119
  • DOI: 10.1038/s41586-020-2715-9
  • PMID: 32894860
  • PMCID: 7656507
  • Citations: 138
  • Influential citations: 2
  • Summary: The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe over the next decade.
  • Evidence snippets:
  • Snippet 1 (score: 0.393) > , a major challenge is a lack of understanding of the early events in disease onset to enable the development of disease-modifying therapies. The lack of access to longitudinal samples from patients necessitates the establishment of cohorts of patient-derived disease models to understand the cellular heterogeneity associated with disease. The discovery of pathways and biomarkers that will allow the stratification of patients on the basis of the cellular mechanisms that drive a disease will make it possible to design new clinical trials to reevaluate drugs that were previously tested without such stratification, and to broaden the drug target portfolio. > As seen during the coronavirus disease 2019 (COVID-19) pandemic, it is important to be able to understand infection mechanisms and the host response in order to rapidly identify the most likely effective treatment for an infection. At the same time, the continuous rise of antimicrobial resistance requires the discovery of new therapeutic strategies. A key medical challenge for infectious diseases is to understand the cellular response to infections and to develop precision, immune-based therapeutic strategies to combat infections. > Chronic inflammatory diseases impose a high burden owing to their long-term debilitating consequences, which result from the structural destruction of affected organs or tissues. Current therapies treat the symptoms but do not cure or fully control the chronic inflammatory pathophysiology. While different targeted therapies exist, they are expensive and their success is limited by high rates of non-response to treatment. Consequently, there is an urgent need to explore and understand how cellular heterogeneity contributes to the pathology of inflammatory diseases 61 and how this relates to the predicted course of disease and the response of a patient to one of the numerous available therapies. > Many cardiovascular and metabolic diseases lack effective therapies owing to a lack of knowledge of their underlying causes and the link between abnormal cardiac cell structure or function and pathophysiology. The identified medical priority is to understand the cellular and molecular mechanisms involved, in order to enable early diagnosis and the design of new mechanism-based therapies for precise clinical treatment. > The LifeTime disease roadmaps can be divided broadly into three phases 7 : first, immediate research into the identified medical challenges using established, scaled single-cell technologies, computational tools and disease models; second, the development of new technologies that are required

[16] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

  • Authors: M. Uzti̇mür, C. N. Ünal, Gurler Akpinar
  • Year: 2025
  • Venue: Journal of Veterinary Internal Medicine
  • URL: https://www.semanticscholar.org/paper/4b9c488b5dbd65d7b26fd2ad9aed70e8c4b59942
  • DOI: 10.1111/jvim.70139
  • PMID: 40492724
  • PMCID: 12150350
  • Summary: Understanding the serum proteome profiles of goats with pregnancy toxemia might help identify the proteomes and pathways responsible for the development of this disease and improve diagnosis and treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.392) > The pathophysiology and progression of this disease are not fully understood. > Traditional biomedical research has focused on the analysis of single genes, proteins, metabolites, or metabolic pathways in diseases. This molecular reductionist approach is based on the assumption that identifying genetic variations and molecular components will lead to new treatments for diseases [13][14][15][16]. However, many diseases are complex and multifactorial, and in order to determine the phenotype of such diseases, it is necessary to understand the changes that occur in more than one gene, pathway, protein, or metabolite at the cellular, tissue, and organismal levels [17][18][19]. Therefore, in recent years, proteomics, as one field of multi-omics technologies, has helped in evaluating the complex pathogenetic mechanisms of different diseases from a broad perspective and has made substantial contributions [20,21]. In veterinary medicine, proteomic analysis of metabolic diseases such as ketosis [16], hypocalcemia [22], and fatty liver [23] in dairy cows has contributed valuable insights for the definition of new pathophysiological pathways and new diagnosis and treatment protocols for these diseases. The proteomic approach can contribute importantly to a broad and detailed understanding of the changes that occur at the organismal level associated with the increase in BHBA concentration in goats with pregnancy toxemia. Our aim was to evaluate the serum protein profiles of goats with SPT or CPT using proteomic techniques to determine the proteomic profiles of these animals and to identify the relevant pathophysiological mechanisms.

[17] Pathology Competencies in Medical Education and Educational Cases: Update 2023

  • Authors: B. Knollmann-Ritschel, A. Huppmann, M. Borowitz, R. Conran
  • Year: 2023
  • Venue: Academic Pathology
  • URL: https://www.semanticscholar.org/paper/4ffbccfbf055a43c6344d7de3c8f40ded1bbccd0
  • DOI: 10.1016/j.acpath.2023.100086
  • PMID: 37496887
  • PMCID: 10366624
  • Citations: 17
  • Summary: The learning goals and learning objectives of the PCME that were first published in 2017 have been carefully revised and updated and will allow for continued linking of previous and new educational cases to the revised learning objectives.
  • Evidence snippets:
  • Snippet 1 (score: 0.390) > Apply knowledge of basic mechanisms of immunology to explain how dysfunction can produce cellular injury, acute and chronic inflammation, autoimmunity, allergic reactions, and susceptibility to infection; how these changes affect organ function and the health of the organism; and how therapeutic intervention can mitigate these effects. Objective IM1.5: Complement. Discuss how the complement cascade is activated, the role its activation plays in both inflammation and cellular cytotoxicity, and how abnormalities in complement function can produce disease. > Objective IM1.6: Immune Tolerance. Define immunological tolerance and describe the role that failure of tolerance plays in the development of autoimmune diseases. > Objective IM1.7: Human Leukocyte Antigen (HLA). Discuss the structure and function of human histocompatibility antigens and describe the role of this system in both transplantation and susceptibility to certain diseases. > Objective IM1.8: Tissue Transplantation. Discuss the complications of tissue transplantation, including the risk of infection and neoplasia, and the pathophysiology and clinicopathologic findings of hyperacute, acute, and chronic rejection. > Objective IM1.9: Primary Immunodeficiencies. Compare and contrast the genetic basis and inheritance patterns of the well-defined primary immunodeficiency syndromes, discuss the pathogenesis and clinical manifestations of these disorders, and describe therapeutic interventions that can mitigate or correct them. > Objective IM1.10: Secondary Immune Deficiencies. Describe the etiology, mechanisms of action, and possible clinical consequences of secondary immune deficiencies. > Objective IM1.11: Bone Marrow Transplantation. Discuss common complications of bone marrow allograft transplantation, including the pathophysiologic and clinicopathologic features of acute and chronic graftversus-host disease.

[18] Editorial: The Role of Microbiota in the Onset and Development of Intestine and Liver Diseases and Cancer: Molecular and Cell Mechanisms

  • Authors: F. Andreola, Camilla Moliterni, Andrea Quagliariello, F. Scaldaferri, M. Fidaleo
  • Year: 2022
  • Venue: Frontiers in Cell and Developmental Biology
  • URL: https://www.semanticscholar.org/paper/833e6db5d680891640f1470827bb4281059ee288
  • DOI: 10.3389/fcell.2022.852188
  • PMID: 35356278
  • PMCID: 8959644
  • Summary: Liver Failure Group, Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, United Kingdom and Sapienza University of Rome, Rome, Italy.
  • Evidence snippets:
  • Snippet 1 (score: 0.388) > The Role of Microbiota in the Onset and Development of Intestine and Liver Diseases and Cancer: Molecular and Cell Mechanisms > In the last decades, numerous studies highlighted the huge taxonomic and functional complexity that characterizes the human microbiota, demonstrating its role in several physiological processes necessary for host survival. This evidence supports the hypothesis that the microbiota constitutes an "essential organ" instead of a "simple" conglomerate of microbial symbionts. Furthermore, findings point out a mutual host-microbiota interaction, whose imbalance can trigger dysbiosis and, in turn, the onset of illnesses or vice versa. In the latter case, dysbiosis can magnify sicknesses. Several factors can alter microbiota homeostasis and the present Research Topic collects seven reviews and four original contributions focused on the cellular and molecular mechanisms involved in the interaction between host and microbiota which can help to unravel the possible cause of disease and find new therapeutic approaches. Soffientini et al. and Bi et al. describe new cellular and molecular mechanisms that strengthen the role of the gut microbiota in pathogenesis and progression of liver diseases. > Using a mouse model, Soffientini et al. reported that the deficiency of caspase-11, a protease involved in the intracellular LPS sensing and triggering cell death pathways, gives protection against multi-organ injury induced by low-dose injection of LPS in CCl4-induced hepatic fibrosis. Furthermore, they found that high levels of the human orthologue, caspase-4, in the liver of patients with acute decompensation of cirrhosis is correlated with the degree of injury and clinical outcome. Overall, these data showed for the first time a causal relationship between translocation of gut-derived bacterial products and multi-organ injury in cirrhosis. > Bi et al. provided theoretical support for future clinical practice, discussing the more recent findings regarding the immuno-molecular mechanisms of the gut microbiota and their metabolites in the occurrence and development of liver cancer. They pointed out that a balanced composition in the gut microbiota is able to improve chemotherapy treatment in liver cancer and to reduce adverse reactions.

[19] Hepatic wound repair

  • Authors: M. Parola, M. Pinzani
  • Year: 2009
  • Venue: Fibrogenesis & Tissue Repair
  • URL: https://www.semanticscholar.org/paper/1fdf786492f33c80ec4814220e66012ca1da8f98
  • DOI: 10.1186/1755-1536-2-4
  • PMID: 19781064
  • PMCID: 2760508
  • Citations: 61
  • Influential citations: 1
  • Summary: Emerging mechanisms and concepts related to liver fibrogenesis may significantly contribute to clinical management of patients affected by CLDs, thus extending the complication-free patient survival time and reducing the need for liver transplantation.
  • Evidence snippets:
  • Snippet 1 (score: 0.387) > BackgroundHuman chronic liver diseases (CLDs) with different aetiologies rely on chronic activation of wound healing that represents the driving force for fibrogenesis progression (throughout defined patterns of fibrosis) to the end stage of cirrhosis and liver failure.IssuesFibrogenesis progression has a major worldwide clinical impact due to the high number of patients affected by CLDs, increasing mortality rate, incidence of hepatocellular carcinoma and shortage of organ donors for liver transplantation.Basic science advancesLiver fibrogenesis is sustained by a heterogeneous population of profibrogenic hepatic myofibroblasts (MFs), the majority being positive for α smooth muscle actin (αSMA), that may originate from hepatic stellate cells and portal fibroblasts following a process of activation or from bone marrow-derived cells recruited to damaged liver and, in a method still disputed, by a process of epithelial to mesenchymal transition (EMT) involving cholangiocytes and hepatocytes. Recent experimental and clinical data have identified, at tissue, cellular and molecular level major profibrogenic mechanisms: (a) chronic activation of the wound-healing reaction, (b) oxidative stress and related reactive intermediates, and (c) derangement of epithelial-mesenchymal interactions.Clinical care relevanceLiver fibrosis may regress following specific therapeutic interventions able to downstage or, at least, stabilise fibrosis. In cirrhotic patients, this would lead to a reduction of portal hypertension and of the consequent clinical complications and to an overall improvement of liver function, thus extending the complication-free patient survival time and reducing the need for liver transplantation.ConclusionEmerging mechanisms and concepts related to liver fibrogenesis may significantly contribute to clinical management of patients affected by CLDs.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.