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1.
Curr Mol Med ; 22(2): 151-164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33602084

RESUMO

Liver fibrosis is one of the leading causes of cirrhotic liver disease, and the lack of therapies to treat fibrotic liver is a major concern. Liver fibrosis is mainly occurred by activation of hepatic stellate cells, and some stem cell therapies had previously reported for treatment. However, due to some problems with cell-based treatment, a safe therapeutic agent is vehemently sought by the researchers. Extracellular vesicles are cell-derived nanoparticles that are employed in several therapeutic approaches, including fibrosis, for their ability to transfer specific molecules in the target cells. In this review, the possibilities of extracellular vesicles to inactivate stellate cells are summarized and discussed. According to several studies, extracellular vesicles from different sources can either have beneficial or detrimental effects by regulating the activation of stellate cells. Therefore, targeting extracellular vesicles for maximizing or inhibiting their production is a potential approach for fibrotic liver treatment. Extracellular vesicles from different cells can also inactivate stellate cells by carrying out the paracrine effects of those cells, working as the agents. They are also implicated as a smart carrier of anti-fibrotic molecules when their respective parent cells are engineered to produce specific stellate cell-regulating substances. A number of studies showed stellate cell activation can be regulated by up/downregulation of specific proteins, and extracellular vesicle-based therapies can be an effective move to exploit these mechanisms. In conclusion, EVs are advantageous nano-carriers with the potential to treat fibrotic liver by inactivating activated stellate cells by various mechanisms.


Assuntos
Vesículas Extracelulares , Hepatopatias , Vesículas Extracelulares/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Fígado/metabolismo , Cirrose Hepática/metabolismo
3.
BMC Gastroenterol ; 22(1): 227, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534800

RESUMO

BACKGROUND: Patients with acid sphingomyelinase deficiency (ASMD) may be referred to a hepatologist for liver manifestations. This study summarized the liver manifestations of patients with ASMD in the early disease course. METHODS: This study enrolled ASMD patients diagnosed by genetic tests between July 2016 and December 2020 in a national pediatric liver center. The significance of low High-density lipoprotein cholesterol (HDL-C) for aid diagnosis of ASMD in infancy was explored by reviewing 160 consecutive infants with liver manifestations, who underwent both genetic tests and lipid profile studies, between January 2020 and December 2020. RESULTS: A total of 7 patients were diagnosed as ASMD, and 10 known disease-causing variants were identified. Hepatosplenomegaly, elevated transaminases, and liver foam cells were observed in all the 7 patients at age ranging from 4 to 31 months. Low HDL-C was detected in 5 patients, cherry red spot in 4 patients, development delay in 3 patients, and interstitial lung diseases in 1 patient. Three ASMD patients developed cholestasis around 1 month of age, and bilirubin levels normalized at age ranging from 3 to 10 months. They had persistently elevated transaminases and hepatosplenomegaly, and died within 4 years of age. Among the 160 infants with liver manifestations, 125 (78.1%) had low HDL-C. Fifty-four had both low HDL-C and splenomegaly, including 48 cholestatic infants, but only 1 (1.9%, 1/54) infant without cholestasis was diagnosed as ASMD. CONCLUSIONS: ASMD can manifest as neonatal cholestasis in the early disease course. Cholestasis is a pitfall when low HDL-C is used for aid diagnosis of ASMD in infants with splenomegaly.


Assuntos
Colestase , Hepatopatias , Doença de Niemann-Pick Tipo A , Doenças de Niemann-Pick , Criança , Pré-Escolar , Hepatomegalia/etiologia , Humanos , Lactente , Recém-Nascido , Doenças de Niemann-Pick/genética , Esplenomegalia/etiologia , Transaminases
4.
Stem Cell Res Ther ; 13(1): 179, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505419

RESUMO

Mesenchymal stem cell (MSC) transplantation, as an alternative strategy to orthotopic liver transplantation, has been evaluated for treating end-stage liver disease. Although the therapeutic mechanism of MSC transplantation remains unclear, accumulating evidence has demonstrated that MSCs can regenerate tissues and self-renew to repair the liver through differentiation into hepatocyte-like cells, immune regulation, and anti-fibrotic mechanisms. Multiple clinical trials have confirmed that MSC transplantation restores liver function and alleviates liver damage. A sufficient number of MSCs must be home to the target tissues after administration for successful application. However, inefficient homing of MSCs after systemic administration is a major limitation in MSC therapy. Here, we review the mechanisms and clinical application status of MSCs in the treatment of liver disease and comprehensively summarize the molecular mechanisms of MSC homing, and various strategies for promoting MSC homing to improve the treatment of liver disease.


Assuntos
Hepatopatias , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Diferenciação Celular , Humanos , Cirrose Hepática/terapia , Hepatopatias/terapia
5.
Parasit Vectors ; 15(1): 154, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505421

RESUMO

BACKGROUND: The activation of immune response driven by the eggs of Schistosoma japonicum and the subsequent secretions is the culprit behind granulomatous inflammation and liver fibrosis. Evidence suggests that PKCλ/ι participates in a variety of physiological and pathological processes, including the regulation of metabolism, growth, proliferation and differentiation of cells. However, the role of PKCλ/ι in liver disease caused by Schistosoma japonicum remains unclear. METHODS: In the present study, we observe the pathological changes of egg-induced granulomatous inflammation and fibrosis in the liver of mice infected by Schistosoma japonicum by using conditional PKCλ/ι-knockout mice and wild-type control. Immune cytokines and fibrogenic factors were analyzed by performing flow cytometry and real-time fluorescence quantitative PCR. RESULTS: The results of H&E and Masson staining show that the degree of granulomatous lesions and fibrosis in the liver of the infected PKCλ/ι-knockout mice was significantly reduced compared with those of the infected wild-type mice. The mean area of single granuloma and hepatic fibrosis in the PKCλ/ι-knockout mice was significantly lower than that of the wild-type mice (85,295.10 ± 5399.30 µm2 vs. 1,433,702.04 ± 16,294.01 µm2, P < 0.001; 93,778.20 ± 8949.05 µm2 vs. 163,103.01 ± 11,103.20 µm2, P < 0.001), respectively. Serological analysis showed that the ALT content was significantly reduced in the infected knockout mice compared with infected wild-type mice. RT-PCR analysis showed that IL-4 content in knockout mice was significantly increased after Schistosoma japonicum infection, yet the increase was less than that in infected wild-type mice (P < 0.05). PKCλ/ι deficiency led to reduced expression of fibrosis-related factors, including TGF-ß1, Col-1, Col-3, α-SMA and liver DAMP factor HMGB1. Flow cytometry analysis showed that the increasing percentage of Th2 cells, which mainly secrete IL-4 cytokines in spleen cells, was significantly lower in PKCλ/ι-deficient mice compared with wild-type mice after infection (P < 0.05). CONCLUSIONS: Our data demonstrate that PKCλ/ι deficiency alleviating granulomatous inflammation and fibrosis in the liver of mice with S. japonicum infection by downregulating Th2 immune response is the potential molecular mechanism behind the role of PKCλ/ι in schistosomiasis.


Assuntos
Hepatopatias , Schistosoma japonicum , Esquistossomose Japônica , Animais , Citocinas/metabolismo , Fibrose , Granuloma , Inflamação , Interleucina-4 , Cirrose Hepática , Camundongos , Camundongos Knockout
6.
Sci Rep ; 12(1): 7311, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508514

RESUMO

Nalfurafine hydrochloride, a selective κ-opioid receptor agonist has been approved for pruritus in patients with chronic liver disease. However, not all patients respond to nalfurafine hydrochloride. The aim of this study was to clarify the efficacy of nalfurafine hydrochloride. The subjects were patients with chronic liver disease complicated by pruritus who were treated with nalfurafine hydrochloride between May, 2015, and May, 2021. The degree of pruritus was evaluated based on the Visual Analog Scale (VAS) score and the Kawashima's pruritus score. Nalfurafine hydrochloride 2.5 µg was orally administered once a day for 12 weeks. A decrease in the VAS score of ≥ 25 mm or the Kawashima's pruritus score of ≥ 1 scores was designated as relevant response. The former of ≥ 50 mm or the latter of ≥ 2 scores as remarkable response. The 326 patients who were evaluated the efficacy at 12 weeks. The median time suffering from pruritus to administration of nalfurafine hydrochloride was 4 months. The median VAS score improved from 70.0 mm before administration to 40.0 and 30.0 mm at 4 and 12 weeks of treatment, respectively. On multivariate analysis, shorter itching period and lower FIB-4 index value were extracted as the independent factors related to remarkable responder. On multivariate analysis, shorter itching period was extracted as the only independent factor related to relevant responder. In conclusion, this study suggested nalfurafine hydrochloride treatment markedly improves pruritus in patients with chronic liver disease. A short pruritus period and less-advanced fibrosis were associated with response to nalfurafine hydrochloride.


Assuntos
Hepatopatias , Morfinanos , Compostos de Espiro , Humanos , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Morfinanos/uso terapêutico , Prurido/complicações , Prurido/etiologia , Receptores Opioides kappa/agonistas , Compostos de Espiro/uso terapêutico
7.
Front Immunol ; 13: 818612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493503

RESUMO

Background & Aim: Men have a higher prevalence of liver disease. Liver myeloid cells can regulate tissue inflammation, which drives progression of liver disease. We hypothesized that sex alters the responsiveness of liver myeloid cells, predisposing men to severe liver inflammation. Methods: Luminex was done on plasma from Hepatitis B Virus infected patients undergoing nucleoside analogue cessation in 45 male and female patients. We collected immune cells from the sinusoids of uninfected livers of 53 male and female donors. Multiparametric flow cytometry was used to phenotype and characterize immune composition. Isolated monocytes were stimulated with TLR ligands to measure the inflammatory potential and the expression of regulators of TLR signaling. Results: We confirmed that men experienced more frequent and severe liver damage upon Hepatitis B Virus reactivation, which was associated with inflammatory markers of myeloid activation. No differences were observed in the frequency or phenotype of sinusoidal myeloid cells between male and female livers. However, monocytes from male livers produced more inflammatory cytokines and chemokines in response to TLR stimulation than female monocytes. We investigated negative regulators of TLR signaling and found that TOLLIP was elevated in female liver-derived monocytes. Conclusions: Our data show that enhanced responsiveness of myeloid cells from the male liver predisposes men to inflammation, which was associated with altered expression of negative regulators of TLR signaling.


Assuntos
Inflamação , Hepatopatias , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Hepatopatias/metabolismo , Masculino , Monócitos
8.
Med Clin North Am ; 106(3): 437-446, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35491064

RESUMO

Cirrhosis is a chronic condition resulting from inflammation and fibrosis of the liver. Patients with cirrhosis may have a myriad of physical examination findings that reflect the severity of the underlying liver disease. Although many signs and symptoms related to cirrhosis are nonspecific, such as abdominal pain, nausea, and malaise, some findings are more specific and point to complications of liver disease. In this article, key physical findings in patients with cirrhosis, including hepatomegaly, splenomegaly, jaundice, ascites, encephalopathy, dilated abdominal wall veins, spider nevi, palmar erythema, and others, are discussed.


Assuntos
Cirrose Hepática , Hepatopatias , Ascite/etiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico
9.
BMJ Open ; 12(5): e053204, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501093

RESUMO

INTRODUCTION: Chronic liver disease is a growing cause of morbidity and mortality in the UK. Acute presentation with advanced disease is common and prioritisation of resources to those at highest risk at earlier disease stages is essential to improving patient outcomes. Existing prognostic tools are of limited accuracy and to date no imaging-based tools are used in clinical practice, despite multiple anatomical imaging features that worsen with disease severity.In this paper, we outline our scoping review protocol that aims to provide an overview of existing prognostic factors and models that link anatomical imaging features with clinical endpoints in chronic liver disease. This will provide a summary of the number, type and methods used by existing imaging feature-based prognostic studies and indicate if there are sufficient studies to justify future systematic reviews. METHODS AND ANALYSIS: The protocol was developed in accordance with existing scoping review guidelines. Searches of MEDLINE and Embase will be conducted using titles, abstracts and Medical Subject Headings restricted to publications after 1980 to ensure imaging method relevance on OvidSP. Initial screening will be undertaken by two independent reviewers. Full-text data extraction will be undertaken by three pretrained reviewers who have participated in a group data extraction session to ensure reviewer consensus and reduce inter-rater variability. Where needed, data extraction queries will be resolved by reviewer team discussion. Reporting of results will be based on grouping of related factors and their cumulative frequencies. Prognostic anatomical imaging features and clinical endpoints will be reported using descriptive statistics to summarise the number of studies, study characteristics and the statistical methods used. ETHICS AND DISSEMINATION: Ethical approval is not required as this study is based on previously published work. Findings will be disseminated by peer-reviewed publication and/or conference presentations.


Assuntos
Hepatopatias , Projetos de Pesquisa , Humanos , Hepatopatias/diagnóstico por imagem , Programas de Rastreamento , Literatura de Revisão como Assunto
10.
Front Cell Infect Microbiol ; 12: 864933, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493732

RESUMO

Objective: The longitudinal effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the liver are unknown. This study aimed to characterize dynamic changes in liver function test abnormalities in patients with COVID-19 at the acute phase and recovery phase. Methods: A prospective cohort study involved patients with COVID-19 who were admitted to Shenzhen Third People's Hospital between January 11, 2020, and April 27, 2020. Patients underwent liver function tests at hospitalization and at the outpatient visit at the 1-month, 3-month, 6-month, and 12-month follow-ups. Results: Among 461 patients, 28.4% of patients had any kind of liver function tests abnormality at admission, manifested as elevated ALT (13.0%), AST (17.6%), and GGT (15.8%) levels. The trajectory analysis indicated a marked improvement in liver function after discharge, with any kind of liver function test abnormalities of 25.1% at 1 month, 13.2% at 3 months, 16.7% at 6 months, and 13.2% at 12 months after discharge. Persistent liver function abnormalities were observed in patients with pre-existing conditions during follow-up. A significantly higher prevalence of ultrasound determined fatty liver disease was found in those patients with more frequent LFT abnormalities at follow-up. Conclusion: In this study of patients with COVID-19, liver damage in COVID-19 was usually temporary and could return to normal at the end of the 12-month follow-up.


Assuntos
COVID-19 , Hepatopatias , Assistência ao Convalescente , Feminino , Humanos , Testes de Função Hepática , Alta do Paciente , Gravidez , Estudos Prospectivos , SARS-CoV-2
11.
Zentralbl Chir ; 147(2): 129-131, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-35378549

Assuntos
Cistos , Hepatopatias , Humanos
12.
Front Immunol ; 13: 865888, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464407

RESUMO

Various factors, including viral and bacterial infections, autoimmune responses, diabetes, drugs, alcohol abuse, and fat deposition, can damage liver tissue and impair its function. These factors affect the liver tissue and lead to acute and chronic liver damage, and if left untreated, can eventually lead to cirrhosis, fibrosis, and liver carcinoma. The main treatment for these disorders is liver transplantation. Still, given the few tissue donors, problems with tissue rejection, immunosuppression caused by medications taken while receiving tissue, and the high cost of transplantation, liver transplantation have been limited. Therefore, finding alternative treatments that do not have the mentioned problems is significant. Cell therapy is one of the treatments that has received a lot of attention today. Hepatocytes and mesenchymal stromal/stem cells (MSCs) are used in many patients to treat liver-related diseases. In the meantime, the use of mesenchymal stem cells has been studied more than other cells due to their favourable characteristics and has reduced the need for liver transplantation. These cells increase the regeneration and repair of liver tissue through various mechanisms, including migration to the site of liver injury, differentiation into liver cells, production of extracellular vesicles (EVs), secretion of various growth factors, and regulation of the immune system. Notably, cell therapy is not entirely excellent and has problems such as cell rejection, undesirable differentiation, accumulation in unwanted locations, and potential tumorigenesis. Therefore, the application of MSCs derived EVs, including exosomes, can help treat liver disease and prevent its progression. Exosomes can prevent apoptosis and induce proliferation by transferring different cargos to the target cell. In addition, these vesicles have been shown to transport hepatocyte growth factor (HGF) and can promote the hepatocytes'(one of the most important cells in the liver parenchyma) growths.


Assuntos
Vesículas Extracelulares , Hepatopatias , Células-Tronco Mesenquimais , Vesículas Extracelulares/metabolismo , Fibrose , Humanos , Imunomodulação , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/terapia , Células-Tronco Mesenquimais/metabolismo
13.
Genes (Basel) ; 13(4)2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35456379

RESUMO

Serving as the metabolic hub of the human body, the liver is a vital organ that performs a variety of important physiological functions. Although known for its regenerative potential, it remains vulnerable to a variety of diseases. Despite decades of research, liver disease remains a leading cause of mortality in the United States with a multibillion-dollar-per-year economic burden. Prior research with model systems, such as primary hepatocytes and murine models, has provided many important discoveries. However, progress has been impaired by numerous obstacles associated with these models. In recent years, induced pluripotent stem cell (iPSC)-based systems have emerged as advantageous platforms for studying liver disease. Benefits, including preserved differentiation and physiological function, amenability to genetic manipulation via tools such as CRISPR/Cas9, and availability for high-throughput screening, make these systems increasingly attractive for both mechanistic studies of disease and the identification of novel therapeutics. Although limitations exist, recent studies have made progress in ameliorating these issues. In this review, we discuss recent advancements in iPSC-based models of liver disease, including improvements in model system construction as well as the use of high-throughput screens for genetic studies and drug discovery.


Assuntos
Células-Tronco Pluripotentes Induzidas , Hepatopatias , Animais , Diferenciação Celular , Descoberta de Drogas , Hepatócitos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Hepatopatias/tratamento farmacológico , Hepatopatias/genética , Hepatopatias/metabolismo , Camundongos
15.
Ann Ital Chir ; 93: 224-228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478187

RESUMO

Hepatic cysts have become increasingly frequent findings thanks to the improvement in diagnostic investigations. Distinction has to be made between congenital hepatic cysts (like liver cyst, PLCD) and acquired forms (such as a parasitic cyst and a cyst occurring as part of a neoplastic process) (1). When a simple hepatic cyst becomes symptomatic, when its size is > 4 cm or when there is some radiological suspicion of malignancy (thick wall, peripheral enhancement on CT/MRI) surgical management is indicated and relies on a variety of techniques (2). Presently the two most common techniques are percutaneous aspiration with sclerotherapy and laparoscopic fenestration. The use of laparoscopic approach has achieved, in the last years, some great results, for it shortens hospital stay, involves minimal invasiveness and offers low recurrence rate. We report three cases of symptomatic hepatic cysts successfully treated by using laparoscopic procedure. KEY WORDS: Laparoscopic deroofing, Sclerotherapy, Simple hepatic cysts.


Assuntos
Cistos , Laparoscopia , Hepatopatias , Cistos/cirurgia , Humanos , Laparoscopia/métodos , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Escleroterapia/métodos
16.
PLoS One ; 17(4): e0267124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35482741

RESUMO

BACKGROUND: Thrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer. METHODS AND FINDINGS: Between August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7-11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0-3.7%) of controls. Patients <40 years or with pre-existing causes of thrombocytosis were then excluded. Subsequent analysis revealed a 10.8% (6.6-16.3%) incidence of cancer in thrombocytosis patients (n = 176) compared to 2.5% (1.2-4.6%, p = 0.00014) in patients with normal platelet count (PLT) (n = 398). When thrombocytosis is combined with elevated alkaline phosphatase (ALP), there is a positive predictive value (PPV) of 20% for cancer. These rules were subsequently applied to a validation cohort of 71,652 patients, of whom 458 had thrombocytosis and elevated ALP. There was a 30.6% cancer incidence, confirming the strong predictive value of the combined test of PLT and ALP. CONCLUSIONS: These findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated.


Assuntos
Hepatopatias , Neoplasias , Trombocitose , Humanos , Hepatopatias/complicações , Testes de Função Hepática , Neoplasias/complicações , Neoplasias/epidemiologia , Trombocitose/complicações
17.
Sci Rep ; 12(1): 6757, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474106

RESUMO

Liver disease remains a major critical challenge in Thailand due to viral hepatitis. Clinical management requires close monitoring of liver fibrosis severity. Non-invasive testing is an attractive method for probing of disease progression. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for fibrosis staging. The current study evaluates the marker among healthy donors and hepatitis C (HCV) patients. 100 HCV subjects were evaluated by liver biopsy. These patients had varying fibrosis severity based on METAVIR scores. Healthy donors were confirmed based on normal liver functions tests. Comparisons of M2BPGi levels among different study groups were performed and the effectiveness was evaluated using receiver operating characteristics (ROC) curves. Using liver biopsy as the reference standard, median M2BPGi levels in HCV cases were 0.74, 1.38 and 2.88 COI for F0-1, F2 and > F3 cases respectively. In healthy donors, the baseline values ranged 0.1-0.24 COI and statistically lower than liver disease cases profiled using M2BPGi. ROC analysis demonstrated superior results for M2BPGi levels among diseased populations and healthy controls. AUROC was determined at 0.983. Comparing with other non-invasive tests, M2BPGi showed a positive linear trend that indicated a strong match to existing methodologies. M2BPGi addresses a critical need in the management of liver disease by providing straightforward means to probe fibrosis severity. In this study, we found significant differences between hepatitis C and healthy subjects and established the background level in healthy donors.


Assuntos
Hepatite C , Hepatopatias , Glicosilação , Hepatite C/diagnóstico , Humanos , Cirrose Hepática/patologia , Hepatopatias/diagnóstico , Glicoproteínas de Membrana/metabolismo
19.
J Healthc Eng ; 2022: 4584965, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480158

RESUMO

SARS-CoV-2 is a recently discovered virus that poses an urgent threat to global health. The disease caused by this virus is termed COVID-19. Death tolls in different countries remain to rise, leading to continuous social distancing and lockdowns. Patients of different ages are susceptible to severe disease, in particular those who have been admitted to an ICU. Machine learning (ML) predictive models based on medical data patterns are an emerging topic in areas such as the prediction of liver diseases. Prediction models that combine several variables or features to estimate the risk of people being infected or experiencing a poor outcome from infection could assist medical staff in the treatment of patients, especially those that develop organ failure such as that of the liver. In this paper, we propose a model called the detecting model for liver damage (DMLD) that predicts the risk of liver damage in COVID-19 ICU patients. The DMLD model applies machine learning algorithms in order to assess the risk of liver failure based on patient data. To assess the DMLD model, collected data were preprocessed and used as input for several classifiers. SVM, decision tree (DT), Naïve Bayes (NB), KNN, and ANN classifiers were tested for performance. SVM and DT performed the best in terms of predicting illness severity based on laboratory testing.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hepatopatias , Teorema de Bayes , Controle de Doenças Transmissíveis , Humanos , Unidades de Terapia Intensiva , SARS-CoV-2
20.
Stem Cell Res ; 61: 102763, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35395623

RESUMO

Research in the field of hepatology is limited by the incomplete recapitulation of all major aspects of human hepatic metabolism in most established models. This restricts our ability to study the molecular mechanisms underlying hepatic diseases, and it leads to inadequate assessment of toxicology during drug development, resulting in tremendous unnecessary costs for the pharma industry. Animal models differ in their metabolism compared to the human system, while primary human cells dedifferentiate rapidly and are not suitable for long-term culture and studies. To overcome these obstacles, several protocols for in vitro differentiation of pluripotent stem cells into hepatocyte like cells (HLCs) have been established. These cells are currently used for modeling inherited and acquired diseases, and to test for drug efficacy and toxicity. Unfortunately, HLCs lack maturity and resemble rather fetal than adult hepatocytes. Novel 3D-based models may overcome these drawbacks in the future. In this review, we critically analyse the most common differentiation protocols and their evolution. In addition, we introduce recently developed techniques for 3D differentiation. Finally, we discuss drawbacks, challenges, and advantages of the distinct systems for routine toxicity tests, disease modeling and future cell replacement therapies.


Assuntos
Hepatopatias , Células-Tronco Pluripotentes , Animais , Diferenciação Celular , Células Cultivadas , Hepatócitos/metabolismo , Hepatopatias/metabolismo , Células-Tronco Pluripotentes/metabolismo
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