scholarly journals Histological activity despite normal ALT and IgG serum levels in patients with autoimmune hepatitis and cirrhosis

JHEP Reports ◽  
2021 ◽  
pp. 100321
Author(s):  
Alena Laschtowitz ◽  
Kalliopi Zachou ◽  
Vasiliki Lygoura ◽  
Simon Pape ◽  
Finn Derben ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Magdalena Świderska ◽  
Jerzy Jaroszewicz ◽  
Anna Parfieniuk-Kowerda ◽  
Magdalena Rogalska-Płońska ◽  
Agnieszka Stawicka ◽  
...  

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P<0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ma Liang ◽  
Zhang Liwen ◽  
Zhuang Yun ◽  
Ding Yanbo ◽  
Chen Jianping

This study is aimed at examining the potential role of regulatory T- (Treg-) Th1-Th17-Th22 cells in the pathogenic process of autoimmune hepatitis (AIH). The numbers of Foxp3+Tregs and Th1, Th17, and Th22 cells were measured in 32 AIH patients using flow cytometry. Moreover, a murine model of experimental autoimmune hepatitis (EAH) was also established and used to investigate the function of Treg-Th1-Th17-Th22 cells in disease progression. AIH patients undergoing an active state had significantly decreased numbers of CD3+CD4+CD25+Foxp3+Tregs and increased numbers of CD3+CD4+CD25−Foxp3+T, CD3+CD4+IFN-γ+Th1, CD3+CD4+IL-17+Th17, and CD3+CD4+IL-2+Th22 cells as well as higher levels of Th1/Th17/Th22-type cytokines compared to AIH patients in remission and HC. Additionally, the numbers of CD3+CD4+CD25+Foxp3+Tregs were negatively correlated with the numbers of Th1-Th17-Th22 cells. Also, the serum levels of IL-17A and IL-22 were correlated positively with liver injury (ALT/AST), whereas the serum levels of IL-10 were correlated negatively with hypergammaglobulinaemia (IgG, IgM) in AIH patients. Interestingly, the percentages of spleen Tregs, expression of Foxp3 mRNA, and liver IL-10 levels decreased, whereas the percentages of spleen Th1-Th17-Th22 cells, expression of T-bet/AHR/RORγt mRNA, and liver IFN-γ, IL-17, and IL-22 levels increased in the murine model of EAH. Our findings demonstrated that an imbalance between Tregs and Th1-Th17-Th22 cells might contribute to the pathogenic process of AIH.


2009 ◽  
Vol 131 ◽  
pp. S143-S144
Author(s):  
Krzysztof Gutkowski ◽  
Teresa Kacperek-Hartleb ◽  
Maciej Kajor ◽  
Wlodzimierz Mazur ◽  
Grzegorz Boryczka ◽  
...  

2019 ◽  
Vol 29 (4) ◽  
pp. 635-637
Author(s):  
Tomoki Nishimura ◽  
Hiroaki Tsunezuka ◽  
Naoko Miyata ◽  
Masayoshi Inoue

Abstract Autoimmune diseases associated with thymoma are well known, with myasthenia gravis being the most common, while autoimmune hepatitis (AIH) is extremely rare. The case of a 63-year-old woman with AIH that developed during preoperative chemotherapy for invasive type B2 thymoma is presented. Liver dysfunction was improved by steroid treatment using oral prednisolone, 30 mg daily, followed by tapering. The patient underwent a macroscopic complete resection including dissemination, and no evidence of recurrence has been seen for 13 months. Although the serum levels of anti-acetylcholine receptor antibody were elevated, no symptoms of myasthenia gravis appeared during the clinical course. This is a rare case of non-myasthenic thymoma complicated with AIH. AIH should be carefully considered in thymoma patients with liver dysfunction, since multidisciplinary treatment is required for invasive thymoma.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Rui Wu ◽  
Yan Liu ◽  
Ruyu Yan ◽  
Xiaoyu Liu ◽  
Liang Duan

Abstract Background Autoimmune hepatitis (AIH) is a liver disease characterized by the autoimmune-induced injury of hepatocytes which can lead to cirrhosis and hepatic failure. The diagnosis and disease management of AIH patients remain challenging due to the diversity of clinical phenotypes and the presence of confounders such as alcohol and viruses. Recently, EN-RAGE and sRAGEs have been implicated in inflammatory-immune response. Nonetheless, their natural behaviour and relationship to disease activity as well as clinical predictive values in AIH development or therapy-induced remission have not been reported. Methods Sixty-seven AIH patients and thirty gender- and age-matched healthy controls (HC) were enrolled. The serum concentrations of EN-RAGE, sRAGE and their ratio (EN-RAGE/sRAGE) in these subjects were measured by ELISA. Besides, the correlations of three parameters with clinical features and therapeutic response were analyzed, respectively. Furthermore, their potential predictive values for monitoring the AIH progression and therapeutic response were also evaluated. Results Higher serum EN-RAGE, lower sRAGE and higher EN-RAGE/sRAGE value were observed in AIH patients. EN-RAGE and sRAGE as well as EN-RAGE/sRAGE were correlated with liver necroinflammation parameters, cirrhosis occurrence and therapeutic response. In addition, we identified that EN-RAGE/sRAGE, EN-RAGE and sRAGE had valuable predicting power for AIH patients, AIH patients with normal ALT and cirrhosis incidence, respectively. More importantly, EN-RAGE/sRAGE also exerted predicting power for the remission in AIH patients. Conclusions AIH patients rendered distinct patterns of serum EN-RAGE, sRAGE or EN-RAGE/sRAGE compared to healthy controls. Moreover, these three parameters exhibited potentials as novel biomarkers for AIH diagnosis and prognosis evaluation.


1998 ◽  
Vol 28 (5) ◽  
pp. 803-811 ◽  
Author(s):  
Elke M. Bayer ◽  
Wolfgang Herr ◽  
Stephan Kanzler ◽  
Christine Waldmann ◽  
Karl-Hermann Meyer Zum Büschenfelde ◽  
...  

1990 ◽  
Vol 104 (3) ◽  
pp. 511-518 ◽  
Author(s):  
M. Rapicetta ◽  
V. Di Nardo ◽  
C. Rozera ◽  
G. Marinucci ◽  
D. Francisci ◽  
...  

SUMMARYA population of 488 HBsAg carrier individuals, from central Italy, classified on the basis of biochemical, clinical and histological parameters, was analysed for the presence of HBV-DNA in serum and its relationship with HBeAg/anti-HBe markers. The prevalence of HBV-DNA was 32·8% in chronic patients with biopsy-proven liver disease, and 20 and 4·3% respectively in asymptomatic carriers with and without altered ALT levels. The values in chronic patients were correlated with the histological activity.Concordance of HBV-DNA presence and HBeAg positivity was observed in only 61·4% of cases. However HBV-DNA prevalence in sera of anti-HBe positive individuals was very low in asymptomatic carriers with normal ALT levels (2·5%). Higher values were observed in anti-HBe positive chronic patients (15·8%) and in carriers occasionally found with changes in ALT without any other clinical sign of illness (16·7%). These data would indicate that HBV-DNA is the serological marker which is most closely related to liver disease.


2009 ◽  
Vol 46 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Margareth L. G. Saron ◽  
Helena T. Godoy ◽  
Gabriel Hessel

CONTEXT: Chronic liver disease may induce to malabsorption of lipids and fat-soluble vitamins, leading to injury of nutritional status. OBJECTIVES: To evaluate the nutritional status of pediatric-age patients with autoimmune hepatitis and biliary atresia related to serum levels of vitamins A, D and E and the disease severity. METHODS: This controlled transverse study, evaluated the patients with autoimmune hepatitis and biliary atresia and a reference group paired by sex and age. The patients underwent anthropometric evaluation, alimentary inquiry and determination of serum levels of vitamins A, D and E by high performance liquid chromatography. The Mann-Whitney test, Spearman correlation coefficients and variance analysis (ANOVA) were utilized for data treatment, regarding significant difference if P<0.05. RESULTS: The highest nutritional deficit was observed in patients with biliary atresia, mainly with cholestasis. The serum levels of vitamins A and E for the reference group changed as a function of age. The serum levels of vitamins A, D and E were higher in reference group than in patients with biliary atresia and autoimmune hepatitis together or separately. There were not difference in the serum levels of vitamins A, D and E between biliary atresia groups with cholestasis and without cholestasis. It was verified correlation between weight/age, triceps skinfold thickness, subscapular skinfold thickness, midarm circumference, midarm fat area values and vitamin A serum levels, as well as between all anthropometric indicators and vitamin E in patients with autoimmune hepatitis and biliary atresia. CONCLUSION: The patients with biliary atresia and cholestasis presented the highest nutritional injury. The patients with biliary atresia and autoimmune hepatitis presented lower serum levels of vitamins A, D and E that in control group. There is a directly proportional correlation between vitamin serum levels, mainly vitamin E, and all anthropometric variables of biliary atresia and autoimmune hepatitis groups.


2005 ◽  
Vol 18 (3) ◽  
pp. 603-607 ◽  
Author(s):  
M. Montalto ◽  
L. Santoro ◽  
M. Vastola ◽  
V. Curigliano ◽  
R. Ricci ◽  
...  

Carbohydrate 19-9 antigen (CA 19–9) is considered a specific marker of pancreatobiliary adenocarcinomas, but slight increase of its levels can be found in several non malignant diseases of the liver, such as autoimmune hepatitis. We describe a case of marked CA 19-9 elevation (up to 898.0 U/ml) in a patient with autoimmune hepatitis. Laboratory and instrumental examinations excluded malignant diseases. Immunohistochemical analysis for CA 19-9 and MIB-1, performed on liver biopsy, showed reactivity in inflammatory areas, in particular in bile ductule cells and hepatocytes in ductular metaplasia, suggesting that these cells could be involved in CA 19-9 serum levels increase. After steroids, the clinical picture improved and all the laboratory parameters normalised.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satoru Hagiwara ◽  
Tomohiro Watanabe ◽  
Masatoshi Kudo ◽  
Kosuke Minaga ◽  
Yoriaki Komeda ◽  
...  

AbstractImmune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs.


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