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1.
Turk J Gastroenterol ; 35(3): 232-238, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-39115109

RESUMEN

The thiopurine drugs-azathioprine and mercaptopurine-are purine antimetabolites used for the treatment of autoimmune hepatitis. These drugs undergo metabolism through genetically determined pathways, which influences their effectiveness and toxicity. There is scarce information regarding the clinical effects of measuring drug metabolites in these patients. The goal of the study is to test the clinical significance of measuring thiopurine metabolites in patients unsuccessfully treated with thiopurines. Clinical and laboratory data collected for patients who were treated for autoimmune hepatitis between 2015 and 2018, and did not achieve full remission under thiopurine therapy and had thiopurine metabolite levels measured due to lack of response and suspicious side effects were chosen. We compared clinical and laboratory data before and after the therapy change. The study included 25 tests of thiopurine metabolites in 21 patients. Six tests had therapeutic levels. Three tests showed high levels leading to lowering the drug dose. In 11 cases, levels of 6-thioguanine nucleotide were low; the dose was not changed in 3 of these, and the dose was increased in the remaining 8. Shunting was observed in 5 cases, 2 of which were mild and the dose was not changed. In the remaining 3, the dose was decreased, and allopurinol was added. Significant improvements in liver enzymes were observed following dose adjustments. We showed that, in cases of suboptimal response to thiopurine treatment, measuring thiopurine metabolites had an important role in optimizing therapy. In most patients, changing the dose led to a significant improvement with no need to switch to secondline therapies.


Asunto(s)
Azatioprina , Hepatitis Autoinmune , Inmunosupresores , Mercaptopurina , Humanos , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/metabolismo , Hepatitis Autoinmune/sangre , Femenino , Masculino , Mercaptopurina/análogos & derivados , Mercaptopurina/uso terapéutico , Mercaptopurina/metabolismo , Mercaptopurina/sangre , Persona de Mediana Edad , Azatioprina/uso terapéutico , Adulto , Inmunosupresores/uso terapéutico , Anciano , Resultado del Tratamiento , Nucleótidos de Guanina/sangre , Estudios Retrospectivos , Monitoreo de Drogas/métodos , Tionucleótidos/sangre
2.
PLoS One ; 19(8): e0307285, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39163317

RESUMEN

BACKGROUND/AIMS: Autoimmune hepatitis (AIH) is characterized by the presence of auto-antibodies and high blood immunoglobulin G (IgG) levels. In this study, the line immunoassay (LIA) was designed to assess various autoantibodies. METHODS: In total, 1371 patients who underwent autoimmune liver disease antibody testing between July 2019 and November 2022 were enrolled. Autoantibodies including antinuclear antibody (ANA) and anti-mitochondrial antibody (AMA) were tested, and clinical data were collected. Statistical analyses were performed by categorizing the data based on diagnosis and IgG quantification separately. A scoring system was applied to identify individuals with AIH. Patients were also classified into the AIH and non-AIH groups. RESULTS: The positivity rate for ANA was 80.2% in the AIH group. The IgG-high group had a high likelihood of the presence of detectable autoantibodies, with anti-Ro-52 being the most frequently detected antibody using LIA. The "Consider AIH" and "AMA" groups had 3-4 times more patients in the IgG-high group than in the "Not Considered" group. CONCLUSIONS: Among autoantibodies, the prevalence of ANA was the highest. As per LIA results, anti-Ro-52 was the most prevalent. AIH cannot be diagnosed based on IgG levels alone and must be distinguished via autoantibody testing. Therefore, extensive testing, including autoantibodies, IgG, ANA, and liver enzyme levels, will help accurately diagnose AIH.


Asunto(s)
Anticuerpos Antinucleares , Autoanticuerpos , Hepatitis Autoinmune , Inmunoglobulina G , Humanos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Adulto , Anciano
3.
Hepatol Int ; 18(4): 1214-1226, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38976227

RESUMEN

OBJECTIVE: The detection of autoantibodies is essential to diagnose autoimmune hepatitis (AIH). Particularly in children, specificity of autoantibodies decreases due to lower titers being diagnostic and being present not only in AIH but also in other liver diseases. Recently, quantification of polyreactive IgG (pIgG) for detection of adult AIH showed the highest overall accuracy compared to antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), anti-liver kidney microsomal antibodies (anti-LKM) and anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP). We aimed to evaluate the diagnostic value of pIgG for pediatric AIH. DESIGN: pIgG, quantified using HIP1R/BSA coated ELISA, and immunofluorescence on rodent tissue sections were performed centrally. The diagnostic fidelity to diagnose AIH was compared to conventional autoantibodies of AIH in training and validation cohorts from a retrospective, European multi-center cohort from nine centers from eight European countries composed of existing biorepositories from expert centers (n = 285). RESULTS: IgG from pediatric AIH patients exhibited increased polyreactivity to multiple protein and non-protein substrates compared to non-AIH liver diseases and healthy children. pIgG had an AUC of 0.900 to distinguish AIH from non-AIH liver diseases. pIgG had a 31-73% higher specificity than ANA and anti-SMA and comparable sensitivity that was 6-20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM. pIgG had a 21-34% higher accuracy than conventional autoantibodies, was positive in 43-75% of children with AIH and normal IgG and independent from treatment response. CONCLUSION: Detecting pIgG improves the diagnostic evaluation of pediatric AIH compared to conventional autoantibodies, primarily owing to higher accuracy and specificity.


Asunto(s)
Autoanticuerpos , Hepatitis Autoinmune , Inmunoglobulina G , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/sangre , Humanos , Niño , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Femenino , Adolescente , Estudios Retrospectivos , Preescolar , Sensibilidad y Especificidad , Ensayo de Inmunoadsorción Enzimática/métodos , Animales
4.
Clin Exp Immunol ; 217(3): 233-239, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-38902849

RESUMEN

Smooth muscle antibodies (SMA) with anti-microfilament actin (MF-SMA) specificity are regarded as highly specific markers of type 1 autoimmune hepatitis (AIH-1) but their recognition relying on immunofluorescence of vessel, glomeruli, and tubules (SMA-VGT pattern) in rodent kidney tissue, is restricted by operator-dependent interpretation. A gold standard method for their identification is not available. We assessed and compared the diagnostic accuracy for AIH-1 of an embryonal aorta vascular smooth muscle (VSM) cell line-based assay with those of the rodent tissue-based assay for the detection of MF-SMA pattern in AIH-1 patients and controls. Sera from 138 AIH-1 patients and 295 controls (105 primary biliary cholangitis, 40 primary sclerosing cholangitis, 50 chronic viral hepatitis, 20 alcohol-related liver disease, 40 steatotic liver disease, and 40 healthy controls) were assayed for MF-SMA and SMA-VGT using VSM-based and rodent tissue-based assays, respectively. MF-SMA and SMA-VGT were found in 96 (70%) and 87 (63%) AIH-1 patients, and 2 controls (P < 0.0001). Compared with SMA-VGT, MF-SMA showed similar specificity (99%), higher sensitivity (70% vs 63%, P = ns) and likelihood ratio for a positive test (70 vs 65). Nine (7%) AIH-1 patients were MF-SMA positive despite being SMA-VGT negative. Overall agreement between SMA-VGT and MF-SMA was 87% (kappa coefficient 0.870, [0.789-0.952]). MF-SMA were associated with higher serum γ-globulin [26 (12-55) vs 20 g/l (13-34), P < 0.005] and immunoglobulin G (IgG) levels [3155 (1296-7344) vs 2050 mg/dl (1377-3357), P < 0.002]. The easily recognizable IFL MF-SMA pattern on VSM cells strongly correlated with SMA-VGT and has an equally high specificity for AIH-1. Confirmation of these results in other laboratories would support the clinical application of the VSM cell-based assay for reliable detection of AIH-specific SMA.


Asunto(s)
Actinas , Autoanticuerpos , Hepatitis Autoinmune , Músculo Liso Vascular , Humanos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/sangre , Actinas/inmunología , Actinas/metabolismo , Masculino , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Músculo Liso Vascular/inmunología , Persona de Mediana Edad , Adulto , Femenino , Animales , Anciano , Sensibilidad y Especificidad , Línea Celular , Miocitos del Músculo Liso/inmunología , Miocitos del Músculo Liso/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Ratas , Citoesqueleto de Actina/inmunología , Adolescente , Biomarcadores/sangre , Adulto Joven
5.
J Immunoassay Immunochem ; 45(3): 210-232, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38808600

RESUMEN

BACKGROUND: Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). OBJECTIVE: Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. PATIENTS AND METHODS: Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients' data was studied. Patients follow up to assess treatment response. RESULTS: Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. CONCLUSION: High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.


Asunto(s)
Hepatitis Autoinmune , Leptina , Polimorfismo Genético , Humanos , Leptina/sangre , Leptina/genética , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/sangre , Niño , Femenino , Masculino , Preescolar , Adolescente , Genotipo
6.
Autoimmunity ; 57(1): 2356089, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38770919

RESUMEN

Autoimmune hepatitis (AIH) is a chronic, inflammatory liver disease of unknown aetiology which requires lifelong immunosuppression. Most therapeutic and outcome studies of AIH have been conducted predominantly in Caucasian (European Ancestry, EA) cohorts, with the exclusion of African American (AA) patients due to inadequate sample size. It is known that AA patients have a severe phenotype of autoimmune diseases and demonstrate a poor response to conventional medical therapy. Understanding cellular and molecular pathways which determine AIH severity and progression in AA patients is likely to lead to the discovery of novel, personalised and better tolerated therapies. The aim of the study is to determine the distinct effector B cell phenotypes which contribute to disease severity and progression of AIH in AA children as compared to their EA cohorts. PBMCs were isolated from blood samples collected from patients visiting Children's Healthcare of Atlanta (CHOA) and were grouped into AA, (n = 12), EA, (n = 11) and controls (n = 12) and were processed for flow cytometry. Markers of B cell development, maturation and activation were assessed namely CD19, CD21, IgD, CD27, CD38, CD11c, CD24, CD138. AA children with AIH demonstrated an expansion of CD19 + ve, Activated Naïve (aN), (CD19+ IgD-/CD27- Double Negative (DN2) ([CD19+/IgD-/CD27++CD38++) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD+CD27+ (USM) B cells were significantly contracted in AA patients with AIH. B cell phenotyping reveals a distinct profile in AA AIH patients with a major skewing towards the expansion of effector pathways which have been previously characterised in severe SLE in AA patients. These results suggest that the quantification and therapeutic target of B cell pathway could contribute substantially to the clinical approach to AIH especially in the AA population.


Asunto(s)
Linfocitos B , Hepatitis Autoinmune , Inmunoglobulina D , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral , Humanos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/patología , Hepatitis Autoinmune/diagnóstico , Inmunoglobulina D/inmunología , Inmunoglobulina D/metabolismo , Niño , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Masculino , Femenino , Adolescente , Linfocitos B/inmunología , Linfocitos B/metabolismo , Preescolar , Inmunofenotipificación , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Edad de Inicio , Biomarcadores
7.
J Transl Med ; 22(1): 456, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745252

RESUMEN

BACKGROUND: Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases. METHODS: In this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases. RESULTS: Glycan traits bisection (OR: 3.78 [1.88-9.35], p-value: 5.88 × 10- 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75-5.16], p-value: 1.63 × 10- 3), IgG1 galactosylation (OR: 0.35 [0.2-0.58], p-value: 3.47 × 10- 5) and hybrid type glycans (OR: 2.73 [1.67-4.89], p-value: 2.31 × 10- 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity. CONCLUSIONS: Compared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.


Asunto(s)
Hepatitis Autoinmune , Polisacáridos , Humanos , Hepatitis Autoinmune/sangre , Femenino , Masculino , Polisacáridos/sangre , Polisacáridos/metabolismo , Persona de Mediana Edad , Glicosilación , Estudios de Casos y Controles , Inmunoglobulina G/sangre , Hepatopatías/sangre , Adulto , Estudios Transversales , Anciano
8.
Am J Physiol Gastrointest Liver Physiol ; 326(6): G736-G746, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38625142

RESUMEN

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.


Asunto(s)
Glucemia , Hepatitis Autoinmune , Resistencia a la Insulina , Insulina , Humanos , Femenino , Masculino , Persona de Mediana Edad , Glucemia/metabolismo , Estudios Transversales , Adulto , Insulina/sangre , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/metabolismo , Hepatitis Autoinmune/complicaciones , Péptido 1 Similar al Glucagón/sangre , Péptido 1 Similar al Glucagón/metabolismo , Hígado Graso/metabolismo , Hígado Graso/sangre , Polipéptido Inhibidor Gástrico/sangre , Polipéptido Inhibidor Gástrico/metabolismo , Anciano , Prueba de Tolerancia a la Glucosa , Colangitis Esclerosante/sangre , Colangitis Esclerosante/metabolismo , Colangitis Esclerosante/complicaciones , Glucagón/sangre , Glucagón/metabolismo , Cirrosis Hepática Biliar/sangre , Cirrosis Hepática Biliar/metabolismo , Cirrosis Hepática Biliar/complicaciones , Péptido C/sangre
9.
J Gastroenterol ; 59(7): 598-608, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38625546

RESUMEN

BACKGROUND: The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology. METHODS: We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation. RESULTS: In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001). CONCLUSIONS: The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage.


Asunto(s)
Cirrosis Hepática , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antígenos de Neoplasias/sangre , Adulto , Glicoproteínas de Membrana/sangre , Progresión de la Enfermedad , Glicosilación , Biomarcadores/sangre , Enfermedad del Hígado Graso no Alcohólico/patología , Hepatitis Autoinmune/patología , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/diagnóstico , Hepatitis Viral Humana/patología , Hepatitis Viral Humana/complicaciones , Inflamación/patología , Enfermedad Crónica
10.
Pol Arch Intern Med ; 134(5)2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38655875

RESUMEN

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic, progressive liver disease that, in most cases, may require lifelong immunosuppression. Hepatitis E virus (HEV) is a leading cause of acute, typically self­limited hepatitis worldwide, although immunocompromised patients may develop chronic hepatitis. OBJECTIVES: We aimed to evaluate the impact of HEV seropositivity on the clinical course of AIH. PATIENTS AND METHODS: The study involved a group of 374 adult patients with AIH (68% women; median [interquartile range] age, 34 [18-83] years; 38% with liver cirrhosis). Serum HEV immunoglobulin (Ig) G and IgM antibodies were measured by enzyme­linked immunosorbent assay, liver fibrosis was assessed by liver stiffness measurement (LSM), and liver cirrhosis was confirmed with liver histology or LSM. RESULTS: Fifty­five patients (15%) with AIH were HEV IgG­positive. These patients were older (P <0.001), had higher body mass index, and higher value of LSM (both P <0.05). In a multivariable model including the levels of alanine aminotransferase and IgG, the HEV seropositive status was associated with an increased risk of advanced liver fibrosis with odds ratio of 3.69 (95% CI, 1.26-10.77; P = 0.02), as reflected by liver stiffness equal to or above 10.5 kPa. HEV IgG seropositivity was, however, not linked with the type of treatment or worse AIH outcome. Seroprevalence of HEV in the patients with AIH was lower than in the general population of Polish blood donors (43%). CONCLUSIONS: Patients with AIH and HEV IgG­positive status seem to be at risk of more advanced liver fibrosis. However, the overall seroprevalence of HEV IgG is lower in patients with AIH than in blood donors in Poland.


Asunto(s)
Hepatitis E , Hepatitis Autoinmune , Humanos , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/sangre , Hepatitis E/complicaciones , Hepatitis E/epidemiología , Femenino , Adulto , Masculino , Persona de Mediana Edad , Anciano , Adulto Joven , Cirrosis Hepática/etiología , Anciano de 80 o más Años , Adolescente , Inmunoglobulina G/sangre , Virus de la Hepatitis E/inmunología , Hígado/patología , Hígado/diagnóstico por imagen
11.
Immun Inflamm Dis ; 12(4): e1258, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38652023

RESUMEN

OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD. METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367. RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC. CONCLUSION: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.


Asunto(s)
Homocisteína , Humanos , Homocisteína/sangre , Vitaminas/sangre , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/inmunología , Estudios de Casos y Controles , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología
12.
Clin Chim Acta ; 559: 119682, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38643819

RESUMEN

BACKGROUND: Human epididymis protein 4 (HE4) has been identified as a biomarker for renal fibrosis. This study aimed to evaluate the role of HE4 in the diagnosis and determination of disease severity and hepatic fibrosis in autoimmune hepatitis (AIH). METHODS: Serum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th-75th percentile). RESULTS: Serum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15-139.08) vs 73.50 (59.88-82.00) vs 48.75 (43.38-52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child-Pugh class C patients compared with Child-Pugh class B patients and Child-Pugh class A patients [106.50 (83.46-151.25) vs 110.00 (73.83-166.75) vs 77.03 (72.35-83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412-54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146-0.946). CONCLUSIONS: Serum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.


Asunto(s)
Biomarcadores , Hepatitis Autoinmune , Cirrosis Hepática , Índice de Severidad de la Enfermedad , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Biomarcadores/sangre , Masculino , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/análisis , Femenino , Persona de Mediana Edad , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/complicaciones , Adulto
13.
J Hepatol ; 81(2): 227-237, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38527524

RESUMEN

BACKGROUND & AIMS: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH. METHODS: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. RESULTS: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. CONCLUSION: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. IMPACT AND IMPLICATIONS: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects.


Asunto(s)
Alanina Transaminasa , Hepatitis Autoinmune , Humanos , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/mortalidad , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Canadá/epidemiología , Adulto , Alanina Transaminasa/sangre , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Estudios de Cohortes , Resultado del Tratamiento , Pronóstico , Bilirrubina/sangre , Estudios de Seguimiento , Modelos de Riesgos Proporcionales , Inmunoglobulina G/sangre
14.
Ann Hepatol ; 29(4): 101497, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38460715

RESUMEN

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.


Asunto(s)
Hepatitis Autoinmune , Inmunosupresores , Humanos , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/mortalidad , Hepatitis Autoinmune/patología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Pronóstico , Brasil/epidemiología , Resultado del Tratamiento , Trasplante de Hígado , Cirrosis Hepática/mortalidad , Recurrencia , Aspartato Aminotransferasas/sangre , Alanina Transaminasa/sangre , Inducción de Remisión , Biomarcadores/sangre , Adulto Joven , Ascitis/etiología , Anciano
15.
Hepatology ; 80(2): 266-277, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38305739

RESUMEN

BACKGROUND AND AIMS: Metabolomics is used to predict, diagnose, and monitor metabolic disorders but altered metabolomic signatures have also been reported in diverse diseases, including autoimmune disorders. However, the metabolomic profile in autoimmune hepatitis (AIH) has not been investigated in depth. Therefore, we investigated the metabolomic signature of AIH and its significance as a diagnostic and pathogenetic tool. APPROACH AND RESULTS: Metabolites in plasma samples from 50 patients with AIH at diagnosis, 43 healthy controls, 72 patients with primary biliary cholangitis (PBC), 26 patients with metabolic dysfunction-associated liver disease, and 101 patients with chronic viral hepatitis were determined by 1 H NMR (nuclear magnetic resonance) spectroscopy. Fifty-two metabolites were quantified, and metabolic pathway analysis was performed. Multivariate analysis revealed that AIH could be differentiated from healthy controls and each of the disease controls ( p <0.001). Fifteen metabolites differentiated AIH from disease controls (PBC+chronic viral hepatitis+metabolic dysfunction-associated liver disease) (95% sensitivity and 92% specificity). Ten distinct metabolic pathways were altered in AIH compared to disease controls. The metabolic pathway of branched-chain amino acids (lower valine, leucine, and isoleucine levels and their catabolic intermediates in PBC), methionine (lower methionine, 2-aminobutyrate, and 2-hydroxybutyrate levels in PBC), alanine-aspartate-glutamate (lower metabolites in PBC), and that of metabolites associated with gut microbiota (lower choline, betaine, and dimethylamine levels in PBC) were significantly different between AIH and PBC ( p <0.01). CONCLUSIONS: 1 H NMR spectroscopy could be a promising novel tool to diagnose and study AIH pathogenesis as there is no need for much sample handling, is highly reproducible with high sensitivity and specificity, and low cost.


Asunto(s)
Hepatitis Autoinmune , Metabolómica , Humanos , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Metabolómica/métodos , Adulto , Espectroscopía de Resonancia Magnética/métodos , Anciano , Estudios de Casos y Controles
16.
Med Mol Morphol ; 57(2): 110-123, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38340154

RESUMEN

Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.


Asunto(s)
Hepatitis Autoinmune , Leucocitos Mononucleares , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Humanos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/patología , Hepatitis Autoinmune/sangre , Análisis de la Célula Individual/métodos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Transcriptoma , Femenino , Masculino , Perfilación de la Expresión Génica , Adulto , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/metabolismo
17.
Ann Hepatol ; 29(3): 101287, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38266674

RESUMEN

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.


Asunto(s)
Hepatitis Autoinmune , Cirrosis Hepática , Nomogramas , Valor Predictivo de las Pruebas , Curva ROC , Humanos , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/diagnóstico , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/sangre , Femenino , Masculino , Persona de Mediana Edad , Adulto , Recuento de Plaquetas , Modelos Logísticos , Factores de Riesgo , Reproducibilidad de los Resultados , China/epidemiología , Técnicas de Apoyo para la Decisión , Área Bajo la Curva , Factores de Edad , Biomarcadores/sangre , Estudios Retrospectivos , Adulto Joven , Pueblo Asiatico , Anciano , Pueblos del Este de Asia
18.
Rev. méd. Chile ; 151(4): 461-468, abr. 2023. ilus, tab
Artículo en Español | LILACS | ID: biblio-1560202

RESUMEN

INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. Methods: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Autoanticuerpos/sangre , Immunoblotting/métodos , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/sangre , Hepatopatías/diagnóstico , Hepatopatías/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/sangre , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/sangre
19.
Rev Med Chil ; 151(4): 461-468, 2023 Apr.
Artículo en Español | MEDLINE | ID: mdl-38687521

RESUMEN

INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. METHODS: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.


Asunto(s)
Autoanticuerpos , Hepatitis Autoinmune , Immunoblotting , Hepatopatías , Humanos , Femenino , Autoanticuerpos/sangre , Masculino , Persona de Mediana Edad , Adulto , Anciano , Adolescente , Adulto Joven , Immunoblotting/métodos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/sangre , Hepatopatías/inmunología , Hepatopatías/diagnóstico , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/sangre
20.
Arch Toxicol ; 96(10): 2785-2797, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35763063

RESUMEN

Occupational exposure to trichloroethylene (TCE) causes a systemic skin disorder with hepatitis known as TCE hypersensitivity syndrome (TCE-HS). Human Leukocyte Antigen (HLA)-B*13:01 is its susceptibility factor; however, the immunological pathogenesis of TCE-HS remains unknown. We herein examined the hypothesis that autoantibodies to CYP2E1 are primarily involved in TCE-HS. A case-control study of 80 TCE-HS patients, 186 TCE-tolerant controls (TCE-TC), and 71 TCE-nonexposed controls (TCE-nonEC) was conducted to measure their serum anti-CYP2E1 antibody (IgG) levels. The effects of TCE exposure indices, such as 8-h time-weighted-average (TWA) airborne concentrations, urinary metabolite concentrations, and TCE usage duration; sex; smoking and drinking habits; and alanine aminotransferase (ALT) levels on the antibody levels were also analyzed in the two control groups. There were significant differences in anti-CYP2E1 antibody levels among the three groups: TCE-TC > TCE-HS patients > TCE-nonEC. Antibody levels were not different between HLA-B*13:01 carriers and noncarriers in TCE-HS patients and TCE-TC. The serum CYP2E1 measurement suggested increased immunocomplex levels only in patients with TCE-HS. Multiple regression analysis for the two control groups showed that the antibody levels were significantly higher by the TCE exposure. Women had higher antibody levels than men; however, smoking, drinking, and ALT levels did not affect the anti-CYP2E1 antibody levels. Anti-CYP2E1 antibodies were elevated at concentrations lower than the TWA concentration of 2.5 ppm for TCE exposure. Since HLA-B*13:01 polymorphism was not involved in the autoantibody levels, the possible mechanism underlying the pathogenesis of TCE-HS is that TCE exposure induces anti-CYP2E1 autoantibody production, and HLA-B*13:01 is involved in the development of TCE-HS.


Asunto(s)
Citocromo P-450 CYP2E1 , Síndrome de Hipersensibilidad a Medicamentos , Exposición Profesional , Tricloroetileno , Autoanticuerpos/sangre , Autoanticuerpos/genética , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Citocromo P-450 CYP2E1/sangre , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/inmunología , Síndrome de Hipersensibilidad a Medicamentos/sangre , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Femenino , Antígenos HLA-B/sangre , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Masculino , Exposición Profesional/efectos adversos , Polimorfismo Genético , Tricloroetileno/inmunología , Tricloroetileno/toxicidad
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