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1.
Cancer Treat Rev ; 100: 102296, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34571378

RESUMO

BACKGROUND: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.


Assuntos
Sobreviventes de Câncer , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Neoplasias/terapia , Lesões por Radiação/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Humanos , Programas de Rastreamento/métodos , Neoplasias/mortalidade , Lesões por Radiação/etiologia
2.
Curr Opin Pulm Med ; 27(6): 593-599, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482340

RESUMO

PURPOSE OF REVIEW: Liver disease (CFLD) as a complication of cystic fibrosis is recognized as a more severe disease phenotype in both children and adults. We review recent advances in understanding the disease mechanism and consider the implications of new strategies for the diagnosis and management of cystic fibrosis in those with evidence of clinically significant liver disease. RECENT FINDINGS: Evidence suggests that the prevalence of CFLD has not declined with the introduction of newborn screening. Furthermore, children with CFLD, who have been diagnosed with cystic fibrosis following newborn screening continue to have a much higher mortality rate compared with those with no liver disease. There is further data suggesting noncirrhotic obliterative portal venopathy as the predominant pathological mechanism in the majority of children and young adults receiving a liver transplantation. Little progress has been made in developing an accurate noninvasive test for early diagnosis or monitoring disease progression in CFLD. The benefit of new modulator therapies is not well understood in those with established CFLD, whereas the risk of hepatotoxicity as a complication of treatment must be carefully monitored. SUMMARY: Better understanding of the pathophysiology of CFLD would allow a standardized approach to diagnosis, with the potential to improve outcomes for those with CFLD.


Assuntos
Fibrose Cística , Hepatopatias , Transplante de Fígado , Fibrose Cística/complicações , Fibrose Cística/terapia , Progressão da Doença , Humanos , Cirrose Hepática , Hepatopatias/etiologia , Fenótipo
3.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 721-724, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517449

RESUMO

Liver disease-associated infection is a common condition in clinic. The existence of underlying liver disease increases the morbidity, mortality, and other adverse consequences of various infections, which in turn aggravates the liver disease-associated infections progression. Therefore, liver disease and infection should be emphasized in the clinical management. The assessment of liver disease includes its etiology, severity level, and complications, while the assessment of infectious diseases emphasizes its etiology and lesion location. Timely elimination of pathogens and complications is the treatment aspect of liver disease, whereas empiric pathogenic therapy is the treatment aspect of infection. The use of anti-infective drugs with a high risk of liver damage should be avoided when the pathogen is determined, and the target should be treated as soon as possible.


Assuntos
Hepatopatias , Humanos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Hepatopatias/terapia , Fatores de Risco
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 740-742, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517453

RESUMO

Inherited metabolic liver disease is a wide-range of diseases that cause abnormal metabolism, resulting from genetic defects. Notably, some inherited metabolic liver diseases are closely associated to infection on account of specific substances abnormal metabolism or key enzyme activities deficiency. Therefore, understanding the inherited metabolic liver disease-associated infection would be helpful to clinical practice and improve patient prognosis.


Assuntos
Hepatopatias , Doenças Metabólicas , Erros Inatos do Metabolismo , Humanos , Hepatopatias/etiologia
5.
Cancer Sci ; 112(11): 4433-4443, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34533882

RESUMO

Gut microbiota and the mammalian host share a symbiotic relationship, in which the host provides a suitable ecosystem for the gut bacteria to digest indigestible nutrients and produce useful metabolites. Although gut microbiota primarily reside in and influence the intestine, they also regulate liver function via absorption and subsequent transfer of microbial components and metabolites through the portal vein to the liver. Due to this transfer, the liver may be continuously exposed to gut-derived metabolites and components. For example, short-chain fatty acids (SCFA) produced by gut microbiota, through the fermentation of dietary fiber, can suppress inflammation via regulatory T cell induction through SCFA-induced epigenetic mechanisms. Additionally, secondary bile acids (BA), such as deoxycholic acid, produced by gut bacteria through the 7α-dehydroxylation of primary BAs, are thought to induce DNA damage and contribute to the remodeling of tumor microenvironments. Other substances that are also thought to influence liver function include lipopolysaccharides (components of the outer membrane of gram-negative bacteria) and lipoteichoic acid (cell wall component of Gram-positive bacteria), which are ligands of innate immune receptors, Toll-like receptor-4, and Toll-like receptor-2, respectively, through which inflammatory signaling is elicited. In this review, we focus on the role of gut microbiota in the liver microenvironment, describing the anatomy of the gut-liver axis, the role of gut microbial metabolites, and the relationships that exist between gut microbiota and liver diseases, including liver cancer.


Assuntos
Carcinoma Hepatocelular/etiologia , Microbioma Gastrointestinal/fisiologia , Neoplasias Hepáticas/etiologia , Fígado/fisiologia , Microambiente Tumoral/fisiologia , Ácidos e Sais Biliares/metabolismo , Senescência Celular/fisiologia , Colina/metabolismo , Dano ao DNA , Etanol/metabolismo , Ácidos Graxos Voláteis/metabolismo , Bactérias Gram-Positivas/metabolismo , Hepatite Alcoólica/etiologia , Humanos , Lipopolissacarídeos/metabolismo , Fígado/anatomia & histologia , Fígado/metabolismo , Hepatopatias/etiologia , Neoplasias Hepáticas/microbiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Simbiose , Ácidos Teicoicos/metabolismo
6.
PLoS One ; 16(9): e0257805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570814

RESUMO

BACKGROUND: Leptospirosis, a global zoonotic infectious disease, has various clinical manifestations ranging from mild self-limiting illness to life-threatening with multi-organ damage, including liver involvement. This study was aimed at identifying circulating microRNAs (miRNAs) as novel biomarkers for predicting severe liver involvement in patients with leptospirosis. METHODS: In a discovery set, 12 serum samples of patients with anicteric and icteric leptospirosis at initial clinical presentation were used for miRNA profiling by a NanoString nCounter miRNA assay. In a validated cohort, top candidate miRNAs were selected and further tested by qRT-PCR in serum samples of 81 and 16 individuals with anicteric and icteric leptospirosis, respectively. RESULTS: The discovery set identified 38 significantly differential expression miRNAs between the two groups. Among these, miR-601 and miR-630 were selected as the top two candidates significantly up-regulated expressed in the icteric group. The enriched KEGG pathway showed that these miRNAs were mainly involved in immune responses and inflammation. In the validated cohort, miR-601 and miR-630 levels were significantly higher in the icteric group compared with the anicteric group. Additionally, these two miRNAs displayed good predictors of subsequent acute liver failure with a high sensitivity of 100%. On regression analysis, elevated miR-601 and miR-630 expression were also predictive of multi-organ failures and poor overall survival. CONCLUSION: Our data indicated that miRNA expression profiles were significantly differentiated between the icteric and anicteric groups. Serum miR-601 and miR-630 at presentation could potentially serve as promising biomarkers for predicting subsequent acute liver failure and overall survival in patients with leptospirosis.


Assuntos
MicroRNA Circulante/sangue , Leptospirose/complicações , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Leptospirose/sangue , Leptospirose/genética , Hepatopatias/genética , Masculino , Redes e Vias Metabólicas , MicroRNAs/sangue , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida
7.
Front Immunol ; 12: 691766, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456908

RESUMO

About 250 million people worldwide are chronically infected with Hepatitis B virus (HBV), contributing to a large burden on public health. Despite the existence of vaccines and antiviral drugs to prevent infection and suppress viral replication respectively, chronic hepatitis B (CHB) cure remains a remote treatment goal. The viral persistence caused by HBV is account for the chronic infection which increases the risk for developing liver cirrhosis and hepatocellular carcinoma (HCC). HBV virion utilizes various strategies to escape surveillance of host immune system therefore enhancing its replication, while the precise mechanisms involved remain elusive. Accumulating evidence suggests that the proteins encoded by HBV (hepatitis B surface antigen, hepatitis B core antigen, hepatitis B envelope antigen, HBx and polymerase) play an important role in viral persistence and liver pathogenesis. This review summarizes the major findings in functions of HBV encoding proteins, illustrating how these proteins affect hepatocytes and the immune system, which may open new venues for CHB therapies.


Assuntos
Antígenos da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Proteínas Virais/imunologia , Animais , DNA Polimerase Dirigida por DNA/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Humanos , Fígado/patologia , Hepatopatias/etiologia
8.
Ann Palliat Med ; 10(9): 9342-9353, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412498

RESUMO

BACKGROUND: Chronic liver diseases (CLD), including cirrhosis and non-cirrhotic liver diseases, are globally widespread and create a serious disease burden. Platelet count is a clinically accessible and affordable prognostic indicator of liver disease. We investigated the relationship between platelet count and 90-day prognosis in patients with acute-on-chronic liver diseases (AoCLD). METHODS: A total of 3,970 patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study, which included two prospective multi-center cohorts, were included in the study. We grouped the patients according to the platelet count and analyzed the 90-day adverse outcome (death or liver transplantation). RESULTS: In the final analysis, 3,939 patients with AoCLD were included, of whom 2,802 had definite liver cirrhosis. The cumulative incidence of 90-day adverse outcomes in patients increased with the change of platelet group (log-rank P<0.001). From univariate and multivariate analyses, platelet count was inversely associated with the incidence of 90-day adverse outcomes in patients (P for trend <0.001). The group with platelet count <20×109/L had the highest risk (odds ratio, 3.15; 95% confidence interval, 1.59-6.25), with 21 (36.8%) of these patients having adverse outcomes within 90 days. The risk of a 90-day adverse outcome in patients increased by 5% for every 10×109/L decrease in platelet count below 210×109/L. CONCLUSIONS: Lower platelet count was associated with a higher incidence of 90-day adverse outcomes in patients with AoCLD. Even within the normal platelet count range, the risk of a 90-day adverse outcome in patients increased with decreases in platelet count. TRIAL REGISTRATION: NCT02457637, NCT03641872.


Assuntos
Hepatopatias , Transplante de Fígado , Humanos , Hepatopatias/etiologia , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos
9.
BMC Pediatr ; 21(1): 361, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433432

RESUMO

BACKGROUND: Thyroid hormones modulate hepatic function through regulation of basal metabolic rate in addition; the liver metabolizes the thyroid hormones and regulates their endocrine effects. OBJECTIVES: To assess thyroid functions in children with acute and chronic liver diseases. METHODS: 85 studied children were divided into 4 groups; group 1 (20 children) with acute hepatitis (AH), group 2 (20 children) chronic liver disease1 (CLD1; relatively preserved liver functions including Child-Pugh stage A), group 3 (20 children) chronic liver disease2 (CLD2; includes Child-Pugh stage B or C), group 4 (25 children) controls. All groups were subjected to detailed history, physical examination, Complete blood count, liver, renal function tests, viral markers, and thyroid functions (FT3, FT4, TSH). RESULTS: Free T3 levels were lower in children with AH, CLD1 and CLD2. There was significant increase in TSH serum levels in CLD2.In acute hepatitis a negative correlation between serum free T4 and AST (r = -0.991), positive correlation between serum TSH and AST, VLDL, and cholesterol levels (r= 0.503, 0.533 and 0.498). A positive correlation between free T3 levels and prothrombin concentration (r= 0.991). Negative correlations between free T3 levels and PT, serum bilirubin and LDL serum levels in children with CLD2 (r= -0.992) (r= -0.902) and (r= -0.946) CONCLUSION: Acute and chronic liver diseases affect thyroid function in children and is correlated with the disease severity.


Assuntos
Hepatopatias , Glândula Tireoide , Humanos , Hepatopatias/etiologia , Testes de Função Hepática , Testes de Função Tireóidea , Glândula Tireoide/diagnóstico por imagem , Tireotropina , Tiroxina , Tri-Iodotironina
12.
Avian Dis ; 65(2): 269-280, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34412458

RESUMO

Hemorrhagic hepatopathy is a syndrome reported in layer pullets resulting in mortality and lesions including hepatic, splenic, and intestinal necrosis; hepatic and splenic enlargement; hemorrhages; amyloidosis of the muscle, spleen, and liver; accumulation of noncoagulated hemorrhagic fluid in the coelom; and frequently, granulomatous myositis at bacterin injection sites. The syndrome is characterized in the literature in table egg layer pullets and is thought to be associated with the administration of bacterin vaccines, namely, frequently Salmonella enterica subsp. enterica bacterins. Hemorrhagic hepatopathy is recognized by industry veterinarians as also occurring infrequently in broiler breeder pullets in the United States. As the condition is likely due to an inflammatory process in response to bacterial lipopolysaccharide inoculation, it is important to characterize both the pathologic changes and predisposing factors for the condition in broiler breeds, which are immunologically different from table egg layer breeds. In this study, we characterize the gross and microscopic lesions observed in a series of diagnostic laboratory cases of hemorrhagic hepatopathy in broiler breeder pullets and suggest a possible pathophysiology for the condition. Additionally, we report results from a case survey of the United States broiler industry that suggest that the condition is due to a reaction to bacterin vaccination and that certain bacterin products may predispose pullet flocks to develop the condition. Although further research is indicated, these findings establish hemorrhagic hepatopathy as a pathologic condition of broiler breeder pullets and may aid in the diagnosis and prevention of the syndrome.


Assuntos
Galinhas , Hepatopatias/veterinária , Doenças das Aves Domésticas/patologia , Amiloidose/veterinária , Animais , Autopsia/veterinária , Feminino , Hemorragia , Incidência , Intestinos/patologia , Fígado/patologia , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Hepatopatias/patologia , Doenças Musculares/epidemiologia , Doenças Musculares/etiologia , Doenças Musculares/patologia , Doenças Musculares/veterinária , Necrose , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/etiologia , Estudos Retrospectivos , Baço/patologia , Inquéritos e Questionários , Síndrome , Vacinação/efeitos adversos , Vacinação/veterinária
13.
Cells ; 10(8)2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34440614

RESUMO

Recent studies on liver disease burden worldwide estimated that cirrhosis is the 11th most common cause of death globally, and there is a great need for new therapies to limit the progression of liver injuries in the early stages. Cholestasis is caused by accumulation of hydrophobic bile acids (BA) in the liver due to dysfunctional BA efflux or bile flow into the gall bladder. Therefore, strategies to increase detoxification of hydrophobic BA and downregulate genes involved in BA production are largely investigated. Farnesoid X receptor (FXR) has a central role in BA homeostasis and recent publications revealed that changes in autophagy due to BA-induced reactive oxygen species and increased anti-oxidant response via nuclear factor E2-related factor 2 (NRF2), result in dysregulation of FXR signaling. Several mechanistic studies have identified new dysfunctions of the cholestatic liver at cellular and molecular level, opening new venues for developing more performant therapies.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colestase/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Colestase/complicações , Colestase/diagnóstico , Colestase/metabolismo , Fármacos Gastrointestinais/efeitos adversos , Humanos , Ligantes , Fígado/metabolismo , Fígado/patologia , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Hepatopatias/metabolismo , Terapia de Alvo Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais
14.
Medicine (Baltimore) ; 100(30): e26719, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397705

RESUMO

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


Assuntos
Aspartato Aminotransferases/sangue , COVID-19/complicações , L-Lactato Desidrogenase/sangue , Hepatopatias/etiologia , Adulto , COVID-19/sangue , Feminino , Ferritinas/sangue , Humanos , Contagem de Leucócitos , Hepatopatias/sangue , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Singapura
15.
J Med Case Rep ; 15(1): 421, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34340688

RESUMO

BACKGROUND: Polycystic liver disease is a clinical feature of autosomal dominant polycystic kidney disease, and it can sometimes cause health damage more serious than polycystic kidney. Dialysis therapy can be used for renal failure, but liver transplantation is the only method available for liver failure. Thus, giant and multiple hepatic cysts may affect mortality. However, liver transplantation is not indicated in many cases because of the preserved liver function. CASE PRESENTATION: A 54-year-old Japanese woman with polycystic liver disease was transferred back to our hospital for abdominal pain caused by liver cyst infection with abdominal wall herniation. She had been diagnosed with polycystic liver disease associated with sporadic autosomal dominant polycystic kidney disease 25 years earlier. Although she had several surgical interventions to reduce her liver volume, including right hepatic lobectomy and fenestration for liver cysts in another hospital, she needed further repair of the recurrent incisional herniation with patch graft surgery using fascia lata to cover the herniation site. However, new herniation sites reemerged in the fragile abdominal wall area around the patch, and therefore, she reduced the recurrent abdominal wall herniation by herself. Recurrent intestinal obstructions were luckily released by fasting with decompression treatment via nasogastric tube insertion, but multiple skin ulcers around the enlarged hernia sac gradually developed, and ascites was extremely difficult to control with any medication. At final admission, her abdominal wall was even more prominent, causing shortness of breath, and it spontaneously ruptured many times, which was accompanied by discharge of around 5 liters of ascites each time. She died from sepsis caused by drug-resistant Enterococcus. CONCLUSIONS: We report a case of autosomal dominant polycystic kidney disease with ruptured abdominal wall resulting from a hepatic cyst enlargement despite multiple laparotomy operations. Throughout the entire disease course, her liver volume increased rapidly, and her quality of life was severely impaired, but she could not undergo liver transplantation after readmission to our hospital. We will discuss the therapeutic strategy for this patient, including the timing and indication for liver transplantation.


Assuntos
Parede Abdominal , Cistos , Hepatopatias , Rim Policístico Autossômico Dominante , Cistos/complicações , Cistos/diagnóstico por imagem , Cistos/cirurgia , Feminino , Humanos , Hepatopatias/etiologia , Hepatopatias/cirurgia , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/complicações , Qualidade de Vida
16.
Curr Opin Pediatr ; 33(5): 521-529, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261897

RESUMO

PURPOSE OF REVIEW: Liver test abnormalities in children with inflammatory bowel disease (IBD) are usually insidious in onset. By the time that symptoms referable to liver disease have appeared, the liver injury may be well advanced. It is, therefore, important that children with an incidental finding of abnormal liver tests are investigated in an appropriate and timely manner. RECENT FINDINGS: The most prevalent cause of liver test elevations in paediatric IBD is immune-related liver disease, including primary sclerosing cholangitis, autoimmune sclerosing cholangitis, and autoimmune hepatitis. Although less common, drugs used in the treatment of IBD can also cause liver injury. The diagnosis of drug-induced liver injury relies largely on excluding other causes of liver injury, such as viral hepatitis, nonalcoholic fatty liver disease, and biliary and vascular complications. SUMMARY: This review highlights an avenue to a step-wise approach for investigating children with IBD and silent liver test elevations. Central to the timing of diagnostic actions is grading the severity of liver test elevations.


Assuntos
Colangite Esclerosante , Hepatite Autoimune , Doenças Inflamatórias Intestinais , Hepatopatias , Criança , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Hepatopatias/diagnóstico , Hepatopatias/etiologia
17.
Semin Immunopathol ; 43(4): 577-590, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236487

RESUMO

Bile acids and their signaling pathways are increasingly recognized as potential therapeutic targets for cholestatic and metabolic liver diseases. This review summarizes new insights in bile acid physiology, focusing on regulatory roles of bile acids in the control of immune regulation and on effects of pharmacological modulators of bile acid signaling pathways in human liver disease. Recent mouse studies have highlighted the importance of the interactions between bile acids and gut microbiome. Interfering with microbiome composition may be beneficial for cholestatic and metabolic liver diseases by modulating formation of secondary bile acids, as different bile acid species have different signaling functions. Bile acid receptors such as FXR, VDR, and TGR5 are expressed in a variety of cells involved in innate as well as adaptive immunity, and specific microbial bile acid metabolites positively modulate immune responses of the host. Identification of Cyp2c70 as the enzyme responsible for the generation of hydrophilic mouse/rat-specific muricholic acids has allowed the generation of murine models with a human-like bile acid composition. These novel mouse models will aid to accelerate translational research on the (patho)physiological roles of bile acids in human liver diseases .


Assuntos
Microbioma Gastrointestinal , Hepatopatias , Animais , Ácidos e Sais Biliares , Humanos , Fígado , Hepatopatias/etiologia , Camundongos , Ratos , Transdução de Sinais
19.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202537

RESUMO

The liver is an organ with impressive regenerative potential and has been shown to heal sizable portions after their removal. However, certain diseases can overstimulate its potential to self-heal and cause excessive cellular matrix and collagen buildup. Decompensation of liver fibrosis leads to cirrhosis, a buildup of fibrotic ECM that impedes the liver's ability to efficiently exchange fluid. This review summarizes the complex immunological activities in different liver diseases, and how failure to maintain liver homeostasis leads to progressive fibrotic tissue development. We also discuss a variety of pathologies that lead to liver cirrhosis, such as alcoholic liver disease and chronic hepatitis B virus (HBV). Mesenchymal stem cells are widely studied for their potential in tissue replacement and engineering. Herein, we discuss the potential of MSCs to regulate immune response and alter the disease state. Substantial efforts have been performed in preclinical animal testing, showing promising results following inhibition of host immunity. Finally, we outline the current state of clinical trials with mesenchymal stem cells and other cellular and non-cellular therapies as they relate to the detection and treatment of liver cirrhosis.


Assuntos
Suscetibilidade a Doenças , Hepatopatias/etiologia , Hepatopatias/metabolismo , Animais , Biomarcadores , Terapia Combinada , Gerenciamento Clínico , Progressão da Doença , Suscetibilidade a Doenças/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hepatopatias/diagnóstico , Hepatopatias/terapia , Pesquisa Médica Translacional
20.
Life Sci ; 282: 119807, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34245771

RESUMO

AIM: This study was designed to investigate the changes of liver injury and Nrf2 signaling pathway in the process of sepsis. We also aimed to examine the role of Nrf2 in resisting oxidative stress and relieving inflammation in sepsis-induced hepatic injury. MAIN METHODS: By operating cecal ligation and puncture (CLP) on Nrf2-/- mice and wild type mice, a sepsis-induced hepatic injury model was established. We compared and contrasted the wild type mice with the Nrf2-/- mice during sepsis-induced hepatic injury, and evaluated the liver damage by biochemical analyses and staining hematoxylin-eosin (HE). Western blot or real-time PCR was performed to detect Nrf2 and its regulated genes NQO-1, GCLM and HO-1. Additionally, we detected the expressions and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), IL-1ß and anti-inflammatory cytokines IL-10. We assessed the oxidative stress through the levels of MDA and NO. KEY FINDINGS: The results showed that Nrf2 expressions at mRNA and protein levels were increased 1 day after CLP, namely the early stage of sepsis. Compared with wild type mice after CLP, Nrf2-/- mice showed more severe liver injury, accompanied by higher expression of inflammatory cytokines and oxidative stress. Notably, Nrf2-regulated genes GCLM and NQO-1, were strongly downregulated in Nrf2-/- mice. SIGNIFICANCE: Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress to alleviate sepsis-induced hepatic injury, mainly through regulating GCLM and NQO-1 in the early stage after CLP.


Assuntos
Regulação da Expressão Gênica , Hepatopatias/prevenção & controle , Fígado , Fator 2 Relacionado a NF-E2/biossíntese , Estresse Oxidativo , Sepse/metabolismo , Animais , Fígado/lesões , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/genética , Hepatopatias/metabolismo , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Sepse/complicações , Sepse/genética
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