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1.
Medicine (Baltimore) ; 98(37): e17094, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517833

RESUMO

BACKGROUND: Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treatment have not been well characterized. We are aiming to determine the patient characteristics, disease prevalence, and treatment outcomes from published articles of patients with HIV and AIH. METHOD: A systematic search of PubMed, Web of Science, and Google Scholar through February 20, 2019 identified 15 studies that reported the outcomes of AIH in patients with HIV. Because of the small sample sizes and skewed distributions, resampling tests of mean differences using permutation distributions (MAXn = 10,000 permutations) were utilized; analyses were performed using R (v. 3.5.1). Categorical differences were calculated using Fisher exact test for odds ratio = 1 (equal odds), and Cramer V was calculated for effect size; analyses were completed in SPSS (v. 25). RESULTS: By reviewing 15 studies reporting a total of 35 patients with AIH and HIV, male patients were found to have significantly higher aspartate transaminase and alanine transaminase levels at time of diagnosis. No other significant findings identified. The CD4 count and viral load did not show significant correlation with AIH diagnosis or its prognosis. All patients but one who presented with severe immune deficiency and responded to highly active anti-retroviral therapy received immunosuppressive treatment without side effects and achieved remission except 2 lost to follow-up and 3 expired. CONCLUSION: Although rare, but AIH can develop in patients with HIV and physicians should consider it in the differential diagnosis for HIV patients presented with abnormal liver function tests, especially after excluding hepatitis C virus and drug-induced liver injury.Patients with immune deficiency disorders who present with AIH can be treated safely with steroid either as monotherapy or in combination with another immune suppressant therapy.


Assuntos
Infecções por HIV/complicações , Hepatite Autoimune/complicações , Adulto , Alanina Transaminase/análise , Alanina Transaminase/sangue , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepatite Autoimune/sangue , Hepatite Autoimune/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
2.
Arq Gastroenterol ; 56(2): 146-150, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460577

RESUMO

BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.


Assuntos
Colangite/genética , Cadeias HLA-DRB1/genética , Hepatite Autoimune/genética , Doenças do Tecido Conjuntivo Indiferenciado/genética , Adolescente , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo Genético , Adulto Jovem
3.
Arq Gastroenterol ; 56(2): 232-241, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31460591

RESUMO

New data concerning the management of autoimmune liver diseases have emerged since the last single-topic meeting sponsored by the Brazilian Society of Hepatology to draw recommendations about the diagnosis and treatment of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap syndromes of AIH, PBC and PSC and specific complications and topics concerning AIH and cholestatic liver diseases. This manuscript updates those previous recommendations according to the best evidence available in the literature up to now. The same panel of experts that took part in the first consensus document reviewed all recommendations, which were subsequently scrutinized by all members of the Brazilian Society of Hepatology using a web-based approach. The new recommendations are presented herein.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Hepatopatias/diagnóstico , Hepatopatias/terapia , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/terapia , Gerenciamento Clínico , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/terapia , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/terapia , Sociedades Médicas
4.
Medicine (Baltimore) ; 98(35): e16924, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464928

RESUMO

Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients.We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups.Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 ±â€Š4.9 ng/mL vs 8.9 ±â€Š3.0 ng/mL, P < .001) or healthy controls (13.8 ±â€Š4.9 ng/mL vs 5.0 ±â€Š1.3 ng/mL, P < .001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 ±â€Š4.9 ng/mL vs 8.3 ±â€Š3.8 ng/mL, P < .001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels.Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Biomarcadores/sangue , Proteínas de Transporte/sangue , Galectinas/sangue , Glicoproteínas/sangue , Hepatite Autoimune/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/metabolismo , Hepatite Autoimune/sangue , Humanos , Japão , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Esteroides/administração & dosagem , Esteroides/farmacologia , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
5.
Zhonghua Gan Zang Bing Za Zhi ; 27(5): 376-380, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31177663

RESUMO

Objective: To explore the clinicopathological features of anti-mitochondrial antibody (AMA) negative and positive patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome (PBC-AIH OS). Methods: Seventy-four cases diagnosed as PBC-AIH OS from June 2017 to April 2018 were enrolled in this study. Among them, forty cases were AMA negative (negative group) and thirty-four cases were AMA positive (positive group). The clinical manifestations, serum biochemical indexes, immunological indexes and histological data of the negative group were compared with the positive group. Mann-Whitney U test and theχ (2)test were used for statistical analysis. Results: There was no significant difference in sex, age, clinical manifestations and major liver function indexes (ALT, AST, ALP, GGT, TB, DB) between the negative group and positive group (P> 0.05). The level of IgM in the negative group (1.68 ± 0.87) was significantly lower than positive group (3.77 ± 2.88)(P< 0.05). The positive rates of antinuclear antibodies (ANA) and gp-210 antibodies was lower than positive group (P< 0.05). There were no significant differences in the stages of inflammation and fibrosis between the two groups (P> 0.05), and the bile duct injury was more significant in the negative than positive group (P< 0.05). Conclusion: The serum IgM level of AMA-negative PBC-AIH OS is low, and immunological antibody is often negative, which makes bile duct injury apparent in liver histology. A liver biopsy should be carried out as soon as possible for early diagnosis and treatment.


Assuntos
Colangite , Hepatite Autoimune , Cirrose Hepática Biliar , Doenças do Tecido Conjuntivo Indiferenciado , Autoanticorpos , Humanos
6.
World J Gastroenterol ; 25(15): 1899-1906, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057303

RESUMO

BACKGROUND: Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT). CASE SUMMARY: The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE. CONCLUSION: This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.


Assuntos
Doenças do Colo/diagnóstico , Infecções por Citomegalovirus/complicações , Gastroenterite/complicações , Perfuração Intestinal/diagnóstico , Transplante de Fígado/efeitos adversos , Antígenos Virais/sangue , Antígenos Virais/imunologia , Colo/diagnóstico por imagem , Colo/virologia , Doenças do Colo/etiologia , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Endoscopia Gastrointestinal , Feminino , Gastroenterite/sangue , Gastroenterite/imunologia , Gastroenterite/virologia , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Hepatite Autoimune/cirurgia , Humanos , Perfuração Intestinal/etiologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
7.
Zhonghua Nei Ke Za Zhi ; 58(5): 366-371, 2019 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-31060145

RESUMO

Objective: To analyze the chorological changes of diagnosis in patients with autoimmune liver disease (AILD) and related factors for early diagnosis. Methods: A total of 581 patients with age ranged from 16 to 81 were retrospectively analyzed, who were admitted to Tianjin Medical University General Hospital with AILD during January 2000 to December 2017. Age at diagnosis, diagnostic method and cirrhosis at diagnosis were compared in different groups according to admission period as 2000-2005, 2006-2011, 2012-2017. Results: The diagnostic rate of AILD showed an upward trend during the past near two decades. The proportion of AILD patients diagnosed via health examination was increasing year by year mainly by elevated transaminases (P<0.001). The mean age at diagnosis in our AILD patients were younger at present, especially in men (P=0.044). The proportion of cirrhosis at diagnosis was gradually reduced in three different periods respectively [77.78%(21/27), 41.58% (79/190), 25.00%(91/364), P<0.001], which were coincident in patients with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (P<0.001). The shrinking trend of cirrhosis at diagnosis was significantly correlated with the increasing application of health examination (r=-0.549, P<0.001). Conclusions: Extensive application of health examination expands the diagnostic rate of AILD. During the past 18 years, more young patients are diagnosed with AILD. The proportion of severe cases such as cirrhosis at diagnosis is decreasing. Screening of immunological examinations in patients with abnormal transaminases is needed and critical to the early diagnosis of asymptomatic AILD.


Assuntos
Hepatite Autoimune/diagnóstico , Cirrose Hepática Biliar , Cirrose Hepática , Hepatopatias , Humanos , Masculino , Estudos Retrospectivos
8.
Ter Arkh ; 91(2): 9-15, 2019 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-31094167

RESUMO

The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.


Assuntos
Colangite Esclerosante , Hepatite Autoimune , Adulto , Colangite Esclerosante/diagnóstico , Consenso , Humanos
9.
Ter Arkh ; 91(1): 89-94, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090378

RESUMO

Clinical features of overlap autoimmune hepatitis/primary biliary cholangitis and morphological-proved sarcoid lesions (lungs, lymph nodes, skin) were performed. Data of long-term clinical observation presented in comparison with the results of laboratory datas, instrumental and morphological studies of liver tissue, lungs, skin. The modern aspects of pathogenesis of association autoimmune and granulomatous diseases arediscussed on the example of clinical cases of combination of cholestatic variants of autoimmune hepatitis and generalized sarcoidosis. Keywords: sarcoidosis, autoimmune hepatitis, primary biliary cholangitis, primary biliary cholangitis-autoimmune hepatitis-overlap, extrahepatic manifestations.


Assuntos
Colangite/diagnóstico , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/diagnóstico , Sarcoidose/complicações , Humanos , Hepatopatias , Sarcoidose/diagnóstico
10.
BMJ Case Rep ; 12(3)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30898957

RESUMO

Rhabdomyolysis is a serious and life-threatening condition which has many established causes including endocrine disturbances. Of those, thyroid, adrenal and pituitary deficiencies are the most commonly seen. Most cases of rhabdomyolysis with adrenal insufficiency that have been reported have been primary. Here, we report an encounter with a patient who presented with her second case of severe rhabdomyolysis in the setting of secondary adrenal insufficiency. The cause for corticotropic suppression was most likely autoimmune hypophysitis given the presence of other autoimmune comorbidities including a new diagnosis of autoimmune hepatitis. In addition to her case, we present a brief review of the literature pertaining to cases of rhabdomyolysis attributed to adrenal insufficiency.


Assuntos
Insuficiência Adrenal/complicações , Hepatite Autoimune/complicações , Rabdomiólise/complicações , Creatina Quinase/sangue , Diagnóstico Diferencial , Feminino , Humanos , Hidrocortisona/sangue , Pessoa de Meia-Idade , Rabdomiólise/sangue
12.
Biomed Res Int ; 2019: 7604939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834274

RESUMO

Background: In inflammatory bowel disease (IBD) patients there are reports of the occurrence of hepatobiliary manifestations, so the aim of this study was to evaluate the hepatobiliary manifestations in patients with Crohn's disease (CD) and ulcerative colitis (UC) from an IBD reference center. Methods: Cross-sectional study in an IBD reference center, with interviews and review of medical charts, between July 2015 and August 2016. A questionnaire addressing epidemiological and clinical characteristics was used. Results: We interviewed 306 patients, and the majority had UC (53.9%) and were female (61.8%). Hepatobiliary manifestations were observed in 60 (19.6%) patients with IBD. In the greater part of the patients (56.7%) hepatobiliary disorders were detected after the diagnosis of IBD. In UC (18.2%) patients, the hepatobiliary disorders identified were 11 (6.7%) non-alcoholic fatty liver disease, 9 (5.5%) cholelithiasis, 6 (3.6%) primary sclerosing cholangitis (PSC), 3 (1.8%) hepatotoxicity associated with azathioprine, 1 (0.6%) hepatitis B, and 1 (0.6%) hepatic fibrosis. In CD (21.3%) patients, 11 (7.8%) had cholelithiasis, 11 (7.8%) non-alcoholic fatty liver disease, 4 (2.8%) PSC, 3 (2.1%) hepatotoxicity, 1 (0.7%) hepatitis B, (0.7%) hepatitis C, 1 (0.7%) alcoholic liver disease, and 1 (0.7%) autoimmune hepatitis (AIH). There was one case of PSC/AIH overlap syndrome. Conclusion: The frequency of hepatobiliary disorders was similar in both forms of IBD in patients evaluated. The most common nonspecific hepatobiliary manifestations in IBD patients were non-alcoholic liver disease and cholelithiasis. The most common specific hepatobiliary disorder was PSC in patients with extensive UC or ileocolonic CD involvement; this was seen more frequently in male patients.


Assuntos
Eliminação Hepatobiliar , Doenças Inflamatórias Intestinais/diagnóstico , Fígado/fisiopatologia , Adulto , Azatioprina/efeitos adversos , Colelitíase/diagnóstico , Colelitíase/fisiopatologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Estudos Transversais , Feminino , Hepatite B/diagnóstico , Hepatite B/fisiopatologia , Hepatite C/diagnóstico , Hepatite C/fisiopatologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/classificação , Doenças Inflamatórias Intestinais/fisiopatologia , Hepatopatias/classificação , Hepatopatias/patologia , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Adulto Jovem
13.
Med Mycol J ; 60(1): 17-21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814466

RESUMO

A 66-year-old woman with diabetes who was treated with prednisolone (15 mg/day) for autoimmune hepatitis developed multiple erythematous nodules with retention of purulent fluid on her lower right limb. Candida albicans was cultured from the nodules. She was started on oral fluconazole, and the lesions subsided. However, multiple dark-red abscesses and indurations newly appeared on the left crus. Histopathological examination showed numerous branched hyphae, and tissue culture yielded a Rhizopus microsporus-related fungus. She was treated with liposomal amphotericin B combined with drainage and debridement. However, she died because of poor control of the infection and hepatic disorder.


Assuntos
Abscesso/microbiologia , Dermatomicoses/microbiologia , Hospedeiro Imunocomprometido , Mucormicose/microbiologia , Rhizopus/isolamento & purificação , Rhizopus/patogenicidade , Abscesso/terapia , Idoso , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Desbridamento , Dermatomicoses/terapia , Drenagem , Evolução Fatal , Feminino , Hepatite Autoimune/tratamento farmacológico , Humanos , Mucormicose/terapia , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico
14.
Int Immunopharmacol ; 69: 184-193, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30735937

RESUMO

T cell-dependent liver injury is an important reason for the massive hepatic damage and cirrhosis. So far it is unclear whether the development of the disease could be efficiently suppressed by anti-inflammatory cytokine that modulates innate immune cells. Here we report that anti-inflammatory cytokine IL-37 could efficiently suppress the sustained hepatic expression of IFN-γ and TNF-α, two critical cytokines for inducing hepatocyte apoptosis and liver fibrosis in T cell-dependent liver injury. IL-37 could directly suppress IFN-γ/TLR4 ligand-induced M1 activation of macrophages, thus reducing the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-12. Moreover, IL-37 attenuated Th1 response in vivo and increased the expression of Th2 cytokines IL-4 and IL-13, which in turn promoted M2 activation of macrophages in the liver. The increase of M2 activation not only further reduced TNF-α, IL-1ß and IL-12 expression, but also increased IL-10 and IL-1Ra expression in macrophages, thus more efficiently suppressing the hepatic IFN-γ expression. By suppressing IFN-γ/TNF-α expression, IL-37 suppressed the up-regulation and activation of MLKL that drives hepatocellular necrosis in T cell-dependent liver damage. Accordingly, IL-37 efficiently reduced liver injury and hepatic inflammation after the repeated ConA challenge and the induction of autoimmune hepatitis, and also suppressed hepatic fibrosis resulting from the sustained liver damage. This study showed that the direct and indirect effect of IL-37 on macrophages could reduce the hepatic TNF-α expression, and also modulate IL-1ß/IL-12 and IL-10/IL-1Ra expression to suppress the hepatic IFN-γ expression, thus suppressing the development of T cell-dependent liver injury such as autoimmune hepatitis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Hepatócitos/fisiologia , Interleucina-1/uso terapêutico , Macrófagos/fisiologia , Linfócitos T/imunologia , Animais , Células Cultivadas , Concanavalina A , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Imunossupressão , Interferon gama/metabolismo , Camundongos , Receptores de Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Z Gastroenterol ; 57(1): 74-86, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30641606

RESUMO

The success of immune modulation by checkpoint blockade approaches is currently transforming oncology, with high and long-lasting tumor responses in patients with advanced disease across many cancer entities. Rooted in the reinvigoration of adaptive antitumor immune responses through disinhibition of negative feedback pathways, these approaches are particularly effective in patients with significant preexisting T cell responses in tumors with high neoantigen load. While promising data is starting to emerge from clinical trials in liver cancer patients, the underlying immunobiology remains poorly understood. In this review, we discuss the immunological mechanisms underlying the success of current checkpoint blockade therapies and the implications for hepatology including management of immune-related hepatitis. Checkpoint blockade therapy provides novel therapeutic options for difficult-to-treat liver cancers but also novel clinical challenges for hepatologists facing immune-related adverse events.


Assuntos
Imunoterapia , Neoplasias Hepáticas/terapia , Antígeno B7-H1 , Antígeno CTLA-4 , Gastroenterologia , Hepatite Autoimune , Humanos , Receptor de Morte Celular Programada 1
16.
Zhonghua Gan Zang Bing Za Zhi ; 27(1): 14-17, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30685918

RESUMO

Autoimmune liver disease is a group of hepatobiliary injuries mediated by abnormal immunity. It mainly includes autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. Recently, an advancement of diagnostic technology has improved the detection and treatment of autoimmune hepatitis. However, it is easy to be confused with other liver diseases. Thus, the standardization of diagnosis and treatment of autoimmune liver diseases has become a main concern. Moreover, new progress has been made in basic research and clinical treatment of autoimmune liver diseases since 2018. In this review, we have introduced the latest research advances for the diagnosis and treatment of autoimmune liver diseases.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Pesquisa Biomédica/tendências , Hepatopatias/diagnóstico , Hepatopatias/terapia , Colangite Esclerosante , Hepatite Autoimune , Humanos , Cirrose Hepática Biliar
17.
Scand J Gastroenterol ; 54(1): 76-80, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30650311

RESUMO

BACKGROUND: There is paucity of data on alternative drug therapies for patients with autoimmune hepatitis (AIH). Tacrolimus (TAC) is a promising salvage agent. We present a review of TAC therapy in AIH patients. METHODS: A search for studies with keywords 'autoimmune hepatitis' and 'tacrolimus' was performed. Reviews, studies of AIH post-transplant and AIH in children were excluded. Diagnosis of AIH was based on criteria established by the International Autoimmune Hepatitis Group. Complete biochemical response was defined as normalisation of aspartate aminotransferase (AST <45) and alanine aminotransferase (ALT <50). No biochemical response was defined as failure to return to normalisation at the end of follow-up. Demographic information and details of pre- and post-treatment liver biopsy were collected. RESULTS: Seven articles achieved the inclusion criteria and reported data for a total of 162 adult patients. The majority of studies reported average ages approximately 35 years old. Treatment duration ranged from 1 to 136 months. Indications for therapy were mostly AIH refractory to steroid treatment or inability to tolerate standard steroid treatment. Eighty-three patients (51.2%) were reported to have pre-therapy liver biopsy. Of 49 patients for whom stage was reported, 6 patients were stage 1, 16 were stage 2, 14 were stage 3 and 13 were stage 4. Of 40 patients for whom grade was reported, 1 patient was grade 0, 3 were grade 1, 9 were grade 2, 14 were grade 3 and 13 were grade 4. Dosing regimens were between 1 and 8 mg/day. Target trough TAC serum concentrations ranged from 0.5 to 10.7 ng/mL TAC was discontinued in 28 (17.3%) patients for various reasons. Renal function remained stable in most patients. One hundred and twenty-one patients (74.7%) demonstrated complete biochemical response to treatment. Post-therapy liver biopsy was obtained for 30 (18.5%) patients, and 25 (15.4%) of these patients were noted to have histological remission according to the grade of inflammation or stage of fibrosis. CONCLUSION: TAC is relatively effective in the treatment of AIH refractory to traditional therapy. It appears that liver function can be enhanced at a minimal cost to renal function. Key Points There is a cohort of patients with autoimmune hepatitis (AIH) who do not respond to standard therapy. Alternative treatment options for these patients have been explored, but outcomes have not been comprehensively examined. We report the use and efficacy of tacrolimus (TAC) in patients with AIH. We found that TAC can be safely and effectively used in patients with AIH with minimal side effects. TAC can be a potential treatment option for patients with AIH refractory to standard therapy.


Assuntos
Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Fígado/patologia , Tacrolimo/uso terapêutico , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Humanos , Resultado do Tratamento
18.
Pediatr Radiol ; 49(3): 332-341, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30607435

RESUMO

BACKGROUND: Primary sclerosing cholangitis, autoimmune hepatitis and autoimmune sclerosing cholangitis are forms of chronic, progressive autoimmune liver disease (AILD) that can affect the pediatric population. OBJECTIVE: To determine whether quantitative MRI- and laboratory-based biomarkers are associated with conventional imaging findings of portal hypertension (radiologic portal hypertension) in children and young adults with AILD. MATERIALS AND METHODS: Forty-four patients with AILD enrolled in an institutional registry underwent a research abdominal MRI examination at 1.5 tesla (T). Five quantitative MRI techniques were performed: liver MR elastography, spleen MR elastography, liver iron-corrected T1 mapping, liver T2 mapping, and liver diffusion-weighted imaging (DWI, quantified as apparent diffusion coefficients). Two anatomical sequences were used to document splenomegaly, varices and ascites. We calculated aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores - laboratory-based biomarkers of liver fibrosis. We used receiver operating characteristic (ROC) curve analyses to establish the diagnostic performance of quantitative MRI and laboratory biomarkers for indicating the presence of radiologic portal hypertension. RESULTS: Twenty-three (52%) patients were male; mean age was 15.2±4.0 years. Thirteen (30%) patients had radiologic portal hypertension. Liver and spleen stiffness demonstrated the greatest diagnostic performance for indicating the presence of portal hypertension (area-under-the-ROC-curve [AUROC]=0.98 and 0.96, respectively). The APRI and FIB-4 scores also demonstrated good diagnostic performance (AUROC=0.87 and 0.88, respectively). CONCLUSION: MRI-derived measures of liver and spleen stiffness as well as laboratory-based APRI and FIB-4 scores are highly associated with imaging findings of portal hypertension in children and young adults with AILD and thus might be useful for predicting portal hypertension impending onset and directing personalized patient management.


Assuntos
Colangite Esclerosante/diagnóstico por imagem , Hepatite Autoimune/diagnóstico por imagem , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/imunologia , Imagem por Ressonância Magnética/métodos , Adolescente , Aspartato Aminotransferases/análise , Biomarcadores/análise , Criança , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Valor Preditivo dos Testes , Sistema de Registros , Adulto Jovem
19.
Zhonghua Er Ke Za Zhi ; 57(1): 40-45, 2019 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-30630230

RESUMO

Objective: To review and analyze the clinical and pathological data of children with autoimmune hepatitis (AIH). Methods: Medical records of 46 patients hospitalized in Pediatric Liver Diseases Treatment and Research Center, Fifth Medical Center, General Hospital of People's Liberation Army(PLA) from April 2012 to April 2018 were extracted. Medical data included type of AIH, clinical manifestations, biochemical parameters, liver biopsy results, and outcomes of treatment were analyzed retrospectively. Among 46 children, 19 were males and 27 were females. The age of onset was 10.1(1.4-18.0) years old. Chi-Square test, Rank sum test or t test were used for inter-group comparison. Results: There were 32 (70%)AIH-I cases and 14 (30%)AIH-Ⅱ cases (χ(2)=12.565, P=0.000). Among the 46 patients, there were 5 modes of onest: 17 cases (37%) had acute viral hepatitis-like presentation, 2 cases (4%) had fulminant hepatic failure, 9 cases (20%) had insidious onset, 5 cases (11%) showed cirrhosis and portal hypertension, and 13 cases (28%) were incidentally found to be due to elevated hepatic aminotransferases. Comorbidities including primary sclerotic cholangitis (n=3), primary biliary cholangitis (n=1), systemic lupus erythematosus (n=1) and inflammatory bowel disease (n=2), were all seen in AIH-Ⅰ cases. The elevated biochemical parameters of these patients were as follows: alanine aminotransferase (n=46), aspartate transminase (n=46), total bilirubin (n=35) γ-glutamyl transpeptadase (n=39), γ-globulin (n=32) and IgG (n=33). The γ-globulin and IgG levels were significantly higher in AIH-Ⅰ patients than those with AIH-Ⅱ((32±9)% vs. (23±8)%, t=3.217, P=0.002,(27±10) vs. (18±8)g/L, t=3.193, P=0.003, respectively). Thirty-nine patients received liver biopsy, among whom 22 (56%) with inflammation grade (G)≥3, 26(67%) with fibrosis stage (S) ≥3, and 7 with hepatic cirrhosis (S4) according to pathological analysis. Typical histopathological changes of AIH included: 36 cases of interfacial hepatitis (92%), 23 cases of lymphocyte/plasma cell infiltration (59%), 3 cases of rosette (8%). Forty patients received prednisolone monotherapy or combined with azathioprine after diagnosis. Complete remission was seen in 29 (72%) patients, partial remission in 10 (25%) patients and no response in 1 (3%) patient. Among complete remission patients, 15 (52%) had relapse in the process of prednisolone reduction. Repeated liver biopsy performed in 8 patients after treatment showed that hepatic inflammation and fibrosis were both improved in 6 patients, only inflammation was alleviated without fibrosis improvement in 1 patient, and neither inflammation nor fibrosis was improved in 1 case. The length of follow-up was 3.3 (0.3-10.5) years, and none of the 39 prednisolone-responded cases discontinued treatment successfully. Adverse effect of long-term prednisolone therapy included bilateral cataract (n=6), spinal fracture accompanied with delayed bone age development (n=1). Conclusions: AIH-Ⅰ is more common than AIH-Ⅱ in children, with diverse clinical characteristics. Most cases have progressive liver inflammation and fibrosis when diagnosed. Prednisolone monotherapy or combined with azathioprine could achieve both biochemical and pathological improvement, but relapse is inevitable during drug tapering, hence long-term treatment is essential.


Assuntos
Glucocorticoides , Hepatite Autoimune , Prednisolona , Adolescente , Criança , Feminino , Glucocorticoides/uso terapêutico , Hepatite Autoimune/complicações , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/patologia , Humanos , Cirrose Hepática , Masculino , Prednisolona/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
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