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1.
J Immunol Res ; 2021: 5529784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926704

RESUMO

Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-ß, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-ß, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases.


Assuntos
Arginina Vasopressina/deficiência , Cirrose Hepática/patologia , Falência Hepática/imunologia , Hipófise/metabolismo , Receptores de Vasopressinas/metabolismo , Animais , Arginina Vasopressina/sangue , Modelos Animais de Doenças , Humanos , Hipofisectomia , Cirrose Hepática/sangue , Cirrose Hepática/imunologia , Falência Hepática/sangue , Falência Hepática/patologia , Masculino , Hipófise/cirurgia , Derivação Portocava Cirúrgica , Ratos , Ratos Wistar , Transdução de Sinais/imunologia
2.
Front Immunol ; 12: 661182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868313

RESUMO

Chronic liver injury results in immune-driven progressive fibrosis, with risk of cirrhosis development and impact on morbidity and mortality. Persistent liver cell damage and death causes immune cell activation and inflammation. Patients with advanced cirrhosis additionally experience pathological bacterial translocation, exposure to microbial products and chronic engagement of the immune system. Bacterial infections have a high incidence in cirrhosis, with spontaneous bacterial peritonitis being the most common, while the subsequent systemic inflammation, organ failure and immune dysregulation increase the mortality risk. Tissue-resident and recruited macrophages play a central part in the development of inflammation and fibrosis progression. In the liver, adipose tissue, peritoneum and intestines, diverse macrophage populations exhibit great phenotypic and functional plasticity determined by their ontogeny, epigenetic programming and local microenvironment. These changes can, at different times, promote or ameliorate disease states and therefore represent potential targets for macrophage-directed therapies. In this review, we discuss the evidence for macrophage phenotypic and functional alterations in tissue compartments during the development and progression of chronic liver failure in different aetiologies and highlight the potential of macrophage modulation as a therapeutic strategy for liver disease.


Assuntos
Doença Hepática Terminal/imunologia , Falência Hepática/etiologia , Falência Hepática/imunologia , Fígado/imunologia , Macrófagos/imunologia , Animais , Terapia Baseada em Transplante de Células e Tecidos , Doença Crônica , Doença Hepática Terminal/terapia , Humanos , Inflamação/patologia , Contagem de Leucócitos , Fígado/patologia , Falência Hepática/terapia , Macrófagos/classificação , Camundongos
3.
Int J Med Sci ; 18(5): 1104-1113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33526969

RESUMO

Ischemia-reperfusion injury refers to organ damage caused by the previous insufficient supply of oxygen and nutrients and the involvement of metabolic by-products after blood flow is restored. Liver ischemia-reperfusion injury (IRI) has become a hot research in recent years, because it occurs in many clinical scenarios. After the introduction of liver transplantation and vascular control techniques in liver surgery, liver ischemia-reperfusion injury is considered to be an important factor affecting postoperative mortality and morbidity. As the largest immune organ in the human body, liver contain a lot of immune cells such as resident macrophages (Kupffer cells), dendritic cells, natural killer cells, and natural killer T cells which play a key role in ischemia-reperfusion injury. Among those, macrophage-mediated excessive inflammatory response is considered to be an important factor in liver ischemia-reperfusion injury. The prominent feature of liver injury is an increase in the number of macrophages in liver due to the infiltration of blood monocytes and differentiation into monocyte-derived macrophages. Liver macrophages can be divided into M1 macrophages which can promote inflammation progress and M2 macrophages that inhibit inflammation progress according to their different phenotypes and functions. Both of them can regulate liver aseptic inflammation, and play an important role in triggering, maintaining, and improving liver ischemia-reperfusion injury. This review summarizes studies of macrophage polarization on liver ischemia-reperfusion injury in recent years, to provide potential ideas for translation application in future clinical management.


Assuntos
Falência Hepática/imunologia , Fígado/patologia , Macrófagos/imunologia , Complicações Pós-Operatórias/imunologia , Traumatismo por Reperfusão/imunologia , Animais , Modelos Animais de Doenças , Hepatectomia/efeitos adversos , Humanos , Fígado/citologia , Fígado/imunologia , Fígado/cirurgia , Falência Hepática/patologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/patologia , Traumatismo por Reperfusão/patologia , Ressuscitação/efeitos adversos , Ressuscitação/métodos , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia
4.
Minerva Med ; 111(5): 491-497, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32567820

RESUMO

BACKGROUND: The objective of this study was to explore the clinical effect of immunoglobulin test in patients with chronic hepatitis B. METHODS: Fifty patients with chronic hepatitis B, 50 patients with liver failure and 50 patients with cirrhosis were selected from the Third People's Hospital of Baoji as experimental groups, and 50 healthy people as the control group. The immunoglobulin M (IgM), IgG and IgA levels in serum of the patients were tested by immunoturbidimetry before and after targeted treatment. RESULTS: Before treatment, the level of Ig in patients with hepatitis B, liver failure and cirrhosis were significantly higher than those in normal people; the level of Ig in patients with hepatitis B were significantly lower than those in patients with liver failure and cirrhosis, and the level of Ig in patients in different groups increased significantly as the disease developed. After treatment, the level of Ig in patients in different groups decreased significantly; patients in the experimental group who had good treatment result had significant decrease of Ig level, while patients in the experimental group who had aggravated disease condition had significant increase of Ig level. CONCLUSIONS: Detection of serum Ig level in patients with chronic hepatitis B can effectively help determine the condition of patients before and after treatment, so as to formulate appropriate treatment plan.


Assuntos
Hepatite B Crônica/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunoturbidimetria/métodos , Cirrose Hepática/imunologia , Falência Hepática/imunologia , Adulto , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Falência Hepática/sangue , Falência Hepática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
5.
Yonsei Med J ; 61(1): 100-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31887806

RESUMO

To evaluate the pathophysiology of autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.


Assuntos
Hepatite A/complicações , Hepatite Autoimune/etiologia , Hepatite Autoimune/imunologia , Inflamação/patologia , Falência Hepática/etiologia , Falência Hepática/imunologia , Linfócitos T Reguladores/imunologia , Idoso , Feminino , Hepatite A/imunologia , Hepatite A/fisiopatologia , Hepatite Autoimune/fisiopatologia , Humanos , Fígado/patologia , Fígado/fisiopatologia , Falência Hepática/patologia , Falência Hepática/fisiopatologia , Testes de Função Hepática
6.
Transfus Apher Sci ; 58(4): 472-474, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31303512

RESUMO

Mogamulizumab (Mog), a humanized anti-CCR4 antibody, provides an important treatment option for relapsed/refractory adult T cell leukemia/lymphoma. However, administration of Mog before allogenic hematopoietic stem cell transplantation has been reported to be a risk factor for severe acute graft-versus-host disease (GVHD). The etiological hypothesis is Mogamulizumab may eradicate CCR4-positive regulatory T cells (Tregs). Theoretically, Treg homeostasis and course of GVHD can be affected by plasma exchange (PE) with decreasing plasma Mog concentration. Here, we present a case of severe acute GVHD after pretransplantation Mog, in which PE was performed for liver failure. As a result, plasma Mog concentration was decreased but it did not lead to the prompt elevation of Treg levels in peripheral blood and clinical responses of GVHD were limited to partial remission. Our case suggests that recovery of donor-derived Treg in the acute phase after HSCT is multifactorial and the single procedure of PE-based Mog depletion does not necessarily warrant the quick restoration of Treg homeostasis.


Assuntos
Anticorpos Monoclonais Humanizados , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Troca Plasmática , Linfócitos T Reguladores/imunologia , Doença Aguda , Aloenxertos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Feminino , Doença Enxerto-Hospedeiro/induzido quimicamente , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Falência Hepática/imunologia , Falência Hepática/terapia , Pessoa de Meia-Idade
7.
Dig Dis Sci ; 64(10): 2867-2877, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31049763

RESUMO

BACKGROUND: Probiotic use to prevent gastrointestinal infections in critical care has shown great promise in recent clinical trials. Although well-documented benefits of probiotic use in intestinal disorders, the potential for probiotic treatment to ameliorate liver injury and hypoxic hepatitis following sepsis has not been well explored. METHODS: In order to evaluate, if Lactobacillus rhamnosus GG (LGG) treatment in septic rats will protect against liver injury, this study used 20-22-week-old Sprague-Dawley rats which were subjected to cecal ligation and puncture to establish sepsis model and examine mRNA and protein levels of IL-1ß, NLRP3, IL-6, TNF-a, VEGF, MCP1, NF-kB and HIF-1α in the liver via real-time PCR, Elisa and Western blot. RESULTS: This study showed that LGG treatment significantly ameliorated liver injury following experimental infection and sepsis. Liver mRNA and protein levels of IL-1ß, NLRP3, IL-6, TNF-a, VEGF, MCP1, NF-kB and HIF-1α were significantly reduced in rats receiving LGG. CONCLUSIONS: Thus, our study demonstrated that LGG treatment can reduce liver injury following experimental infection and sepsis and is associated with improved hypoxic hepatitis. Probiotic therapy may be a promising intervention to ameliorate clinical liver injury and hypoxic hepatitis following systemic infection and sepsis.


Assuntos
Hepatite , Lacticaseibacillus rhamnosus , Falência Hepática , Probióticos/farmacologia , Sepse , Animais , Hepatite/etiologia , Hepatite/imunologia , Hepatite/prevenção & controle , Interleucina-1beta/metabolismo , Fígado/metabolismo , Fígado/patologia , Falência Hepática/etiologia , Falência Hepática/imunologia , Falência Hepática/prevenção & controle , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Sepse/complicações , Sepse/terapia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
8.
J Surg Res ; 236: 311-318, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694771

RESUMO

BACKGROUND: Despite melatonin treatment diminishes inflammatory mediator production and improves organ injury after acute pancreatitis (AP), the mechanisms remain unknown. This study explores whether melatonin improves liver damage after AP through protein kinase B (Akt)-dependent peroxisome proliferator activated receptor (PPAR)-γ pathway. METHODS: Male Sprague-Dawley rats were subjected to cerulein-induced AP. Animals were treated with vehicle, melatonin, and melatonin plus phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin 1 h following the onset of AP. Various indicators and targeted proteins were checked at 8 h in the sham and AP groups. RESULTS: At 8 h after AP, serum alanine aminotransferase/aspartate aminotransferase levels, histopathology score of hepatic injury, liver myeloperoxidase activity, and proinflammatory cytokine production were significantly increased and liver tissue adenosine triphosphate concentration was lower compared with shams. AP resulted in a marked decrease in liver Akt phosphorylation and PPAR-γ expression in comparison with the shams (relative density, 0.442 ± 0.037 versus. 1.098 ± 0.069 and 0.390 ± 0.041 versus ± 1.080 0.063, respectively). Melatonin normalized AP-induced reduction in liver tissue Akt activation (1.098 ± 0.054) and PPAR-γ expression (1.145 ± 0.083) as well as attenuated the increase in liver injury markers and proinflammatory mediator levels, which was abolished by coadministration of wortmannin. CONCLUSIONS: Collectively, our findings suggest that melatonin improves AP-induced liver damage in rats, at least in part, via Akt-dependent PPAR-γ pathway.


Assuntos
Falência Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Melatonina/administração & dosagem , Pancreatite/complicações , Transdução de Sinais/efeitos dos fármacos , Administração Intravenosa , Animais , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Fígado/imunologia , Fígado/patologia , Falência Hepática/diagnóstico , Falência Hepática/imunologia , Testes de Função Hepática , Masculino , PPAR gama/imunologia , PPAR gama/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/imunologia , Fosforilação/efeitos dos fármacos , Fosforilação/imunologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/imunologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/imunologia , Resultado do Tratamento , Wortmanina/administração & dosagem
9.
Crit Rev Immunol ; 39(4): 289-311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32421970

RESUMO

Liver failure is a clinical syndrome with many causes, a complicated pathogenesis, diverse clinical manifestations, and very high mortality. No effective treatment is yet available. Main pathological processes of liver failure include direct damage to parenchymal and nonparenchymal liver cells that might be caused by viruses or drugs, immune-mediated indirect damage, inflammation, and ischemia-hypoxia injury that further strengthen liver damage and lead to endotoxemia. Among these causes, viral or bacterial components (called pathogen-associated and damage-associated molecular patterns) are released during tissue damage and cell death and may be recognized by pattern recognition receptors (PRRs) to induce secretion of inflammatory cytokines and chemokines and activate immune cells. This process is an important mechanism that underlies the progression of liver failure. Research concerning the roles of PRR signaling pathways in liver failure is expected to result in development of immunomodulatory drugs to target specific disease stages, immune cells, and signal transduction molecules. This article briefly introduces the research status of six main PRRs (Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, retinoic-acid-inducible gene I-like receptors, cytosolic DNA sensors, C-type lectin receptors, and inflammasomes) in acute liver failure and acute-on-chronic liver failure and explores further research directions.


Assuntos
Inflamassomos/metabolismo , Falência Hepática/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Animais , Humanos , Imunidade Inata , Inflamação , Falência Hepática/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Transdução de Sinais , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
10.
J Autoimmun ; 95: 69-76, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30344030

RESUMO

Autoimmune hepatitis (AIH) is a rare, chronic disease that affects both adults and children, including infants. The disease is probably triggered by environmental factors in genetically predisposed individuals. The clinical presentation ranges from asymptomatic patients or patients with non-specific symptoms, such as fatigue, to fulminant liver failure, many children presenting with symptoms indistinguishable from those of acute hepatitis. Raised transaminase and immunoglobulin G (IgG) levels, in association with circulating autoantibodies, guide towards the diagnosis. The histological hallmark is interface hepatitis, which however is non-specific and may be absent. There are no bile duct changes on cholangiography. Presence of anti-nuclear antibody (ANA) and/or anti-smooth muscle antibody (SMA) is characteristic for type 1 AIH, whereas presence of anti-liver kidney microsomal type 1 (LKM1) antibody and/or anti-liver cytosol type 1 (LC1) antibody defines type 2 AIH. The latter accounts for about one third of the juvenile AIH cases, presents more acutely than type 1 AIH and is very rare in adults. Immunosuppressive therapy, based on steroids and azathioprine, is required, and in the vast majority of patients leads to clinical and biochemical remission, defined as absence of symptoms, normal transaminase and IgG levels, and negative or low-titer autoantibodies. In patients intolerant or non-responder to standard therapy, a number of second line drugs have been employed with variable results. For the rare cases who progress to end-stage liver disease, liver transplantation is life-saving, but recurrence of the disease is possible. A better understanding of the underlying pathogenic mechanisms will help to develop new, more effective and less toxic therapies, and to tailor treatment regimens to the individual patient.


Assuntos
Autoanticorpos/sangue , Colangite Esclerosante/imunologia , Hepatite Autoimune/imunologia , Falência Hepática/imunologia , Transplante de Fígado , Adolescente , Adulto , Azatioprina/uso terapêutico , Criança , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/patologia , Colangite Esclerosante/terapia , Gerenciamento Clínico , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/patologia , Hepatite Autoimune/terapia , Humanos , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Falência Hepática/diagnóstico , Falência Hepática/patologia , Falência Hepática/terapia , Recidiva , Esteroides/uso terapêutico , Transaminases/sangue
11.
Front Immunol ; 9: 2948, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619308

RESUMO

Acute and acute-on-chronic liver failure (ALF and ACLF), though distinct clinical entities, are considered syndromes of innate immune dysfunction. Patients with ALF and ACLF display evidence of a pro-inflammatory state with local liver inflammation, features of systemic inflammatory response syndrome (SIRS) and vascular endothelial dysfunction that drive progression to multi-organ failure. In an apparent paradox, these patients are concurrently immunosuppressed, exhibiting acquired immune defects that render them highly susceptible to infections. This paradigm of tissue injury succeeded by immunosuppression is seen in other inflammatory conditions such as sepsis, which share poor outcomes and infective complications that account for high morbidity and mortality. Monocyte and macrophage dysfunction are central to disease progression of ALF and ACLF. Activation of liver-resident macrophages (Kupffer cells) by pathogen and damage associated molecular patterns leads to the recruitment of innate effector cells to the injured liver. Early monocyte infiltration may contribute to local tissue destruction during the propagation phase and results in secretion of pro-inflammatory cytokines that drive SIRS. In the hepatic microenvironment, recruited monocytes mature into macrophages following local reprogramming so as to promote resolution responses in a drive to maintain tissue integrity. Intra-hepatic events may affect circulating monocytes through spill over of soluble mediators and exposure to apoptotic cell debris during passage through the liver. Hence, peripheral monocytes show numerous acquired defects in acute liver failure syndromes that impair their anti-microbial programmes and contribute to enhanced susceptibility to sepsis. This review will highlight the cellular and molecular mechanisms by which monocytes and macrophages contribute to the pathophysiology of ALF and ACLF, considering both hepatic inflammation and systemic immunosuppression. We identify areas for further research and potential targets for immune-based therapies to treat these devastating conditions.


Assuntos
Insuficiência Hepática Crônica Agudizada/imunologia , Falência Hepática/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Doença Aguda , Insuficiência Hepática Crônica Agudizada/patologia , Hepatite/imunologia , Hepatite/patologia , Humanos , Falência Hepática/patologia , Modelos Imunológicos , Sepse/imunologia , Sepse/patologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/patologia
12.
World J Gastroenterol ; 23(35): 6540-6545, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-29085203

RESUMO

We report the first case of a patient with hepatitis C virus (HCV) infection and idiopathic thrombocytopenic purpura (ITP), who later developed acquired amegakaryocytic thrombocytopenia (AAMT), with autoantibodies to the thrombopoietin (TPO) receptor (c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.


Assuntos
Autoanticorpos/sangue , Doenças da Medula Óssea/diagnóstico , Hepatite C Crônica/imunologia , Falência Hepática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica/diagnóstico , Autoanticorpos/imunologia , Medula Óssea/patologia , Células da Medula Óssea/patologia , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/patologia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Fígado/imunologia , Fígado/patologia , Falência Hepática/etiologia , Falência Hepática/imunologia , Falência Hepática/patologia , Megacariócitos/patologia , Pessoa de Meia-Idade , Púrpura Trombocitopênica/sangue , Púrpura Trombocitopênica/imunologia , Púrpura Trombocitopênica/patologia , Púrpura Trombocitopênica Idiopática/sangue , Receptores de Trombopoetina/imunologia , Trombopoetina/metabolismo
13.
Ann Transplant ; 22: 156-165, 2017 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-28336908

RESUMO

BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. RESULTS Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. CONCLUSIONS Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.


Assuntos
Quimerismo , Antígenos HLA/imunologia , Hepatite C/imunologia , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Adulto , Autoanticorpos , Linfócitos B/imunologia , Feminino , Citometria de Fluxo , Humanos , Falência Hepática/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva
14.
World J Gastroenterol ; 23(5): 776-791, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28223722

RESUMO

Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress.


Assuntos
Anticorpos/sangue , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Hepatopatias/complicações , Hepatopatias/imunologia , Doença Celíaca/imunologia , Colangite Esclerosante/complicações , Colangite Esclerosante/imunologia , Dieta Livre de Glúten , Glutens/efeitos adversos , Glutens/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Hepatite C/complicações , Hepatite C/imunologia , Hepatite Autoimune/complicações , Hepatite Autoimune/imunologia , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/imunologia , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/imunologia , Falência Hepática/complicações , Falência Hepática/imunologia , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/imunologia
15.
World J Gastroenterol ; 22(34): 7676-91, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27678350

RESUMO

Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as "operational tolerance". However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.


Assuntos
Falência Hepática/imunologia , Falência Hepática/cirurgia , Transplante de Fígado , Tolerância ao Transplante , Animais , Biomarcadores/metabolismo , Biomarcadores Tumorais/imunologia , Células Dendríticas/citologia , Homeostase , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Células Matadoras Naturais/citologia , Macrófagos/citologia , Macrófagos/imunologia , Sirolimo/uso terapêutico , Linfócitos T Reguladores/citologia
16.
Transplant Proc ; 48(4): 1119-22, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320570

RESUMO

BACKGROUND: Complete immune tolerance is the chief goal in organ transplantation. This study aimed to evaluate patients who successfully withdrew from immunosuppressive (IS) agents after living donor liver transplantation (LDLT). MATERIALS AND METHODS: A retrospective review of all adult LDLT from July 1999 to March 2012 was conducted. In patients who acquired immune tolerance after LDLT, their background and the course of surgical procedures were evaluated. RESULTS: Of a total of 101 adult LDLT patients, 8 patients were completely free of IS agents. Six of these patients (75%) were female, and the median age at the time of transplantation was 56 years (range, 31-66 years). The primary disease causing liver failure was type C liver cirrhosis (50%), fulminant hepatitis (25%), type B liver cirrhosis (12%), and alcoholic liver cirrhosis (12%). The median Child-Pugh score and MELD score were 13 points (range, 8-15 points) and 19 points (range, 10-18 points), respectively. The living related donor was the recipient's child (75%), sibling (12%), or parent (12%). ABO compatibility was identical in 62%, compatible in 25%, and incompatible in 12%. CONCLUSIONS: In this study, we evaluated the adult patients who successfully withdrew from IS agents after LDLT. In most cases, it took more than 5 years to reduce IS agents. Because monitoring of the serum transaminase level is not adequate to detect chronic liver fibrosis in immune tolerance cases, further study is required to find appropriate protocols for reducing IS agent use after LDLT.


Assuntos
Falência Hepática/imunologia , Falência Hepática/cirurgia , Transplante de Fígado , Tolerância ao Transplante , Adulto , Idoso , Esquema de Medicação , Feminino , Humanos , Imunossupressores/uso terapêutico , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Innate Immun ; 22(4): 274-83, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26993088

RESUMO

Endotoxins are the major components of the outer membrane of most Gram-negative bacteria and are one of the main targets in inflammatory diseases. The presence of endotoxins in blood can provoke septic shock in case of pronounced immune response. Here we show in vitro inactivation of endotoxins by polymyxin B (PMB). The inflammatory activity of the LPS-PMB complex in blood was examined in vitro in freshly drawn blood samples. Plasma protein binding of PMB was determined by ultracentrifugation using membranes with different molecular cut-offs, and PMB clearance during dialysis was calculated after in vitro experiments using the AV1000S filter. The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion. According to in vitro measurements, the appropriate plasma level of PMB for LPS inactivation is between 100 and 200 ng/ml. Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model. Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.


Assuntos
Antibacterianos/metabolismo , Células Sanguíneas/imunologia , Endotoxinas/metabolismo , Infecções por Bactérias Gram-Negativas/imunologia , Falência Hepática/prevenção & controle , Polimixina B/metabolismo , Sepse/prevenção & controle , Antibacterianos/uso terapêutico , Terapia Biológica/tendências , Células Cultivadas , Citocinas/sangue , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/terapia , Humanos , Mediadores da Inflamação/sangue , Falência Hepática/etiologia , Falência Hepática/imunologia , Polimixina B/uso terapêutico , Ligação Proteica , Diálise Renal/métodos , Sepse/etiologia , Sepse/imunologia
19.
Yonsei Med J ; 57(3): 652-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26996565

RESUMO

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.


Assuntos
Citocinas/sangue , Vírus da Hepatite A/genética , Vírus da Hepatite B/genética , Falência Hepática/patologia , Linfócitos T Citotóxicos/metabolismo , Doença Aguda , Adulto , Alanina Transaminase/sangue , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Proteína Ligante Fas/sangue , Feminino , Hepatite A/sangue , Hepatite A/virologia , Vírus da Hepatite A/imunologia , Hepatite B/sangue , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Interleucinas/sangue , Falência Hepática/imunologia , Falência Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/imunologia , Interleucina 22
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