Evaluation of risk factors for the development of cirrhosis in autoimmune hepatitis: Japanese NHO-AIH prospective study

Migita, Kiyoshi; Watanabe, Yukio; Jiuchi, Yuka; Nakamura, Yoko; Saito, Akira; Yagura, Michiyasu; Morimoto, Hideo; Shimada, Muneaki; Mita, Eiji; Hijioka, Taizo; Yamashita, Haruhiro; Takezaki, Eiichi; Muro, Toyokichi; Sakai, Hironori; Nakamuta, Makoto; Abiru, Seigo; Yano, Koji; Komori, Atsumasa; Yatsuhashi, Hiroshi; Nakamura, Minoru; Ishibashi, Hiromi

doi:10.1007/s00535-010-0337-y

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…[3] However, some AIH patients develop liver cirrhosis and liver failure at initial presentation. [4,5] Hepatic inflammation is regulated by the activities of immune cells including lymphocytes, Kupffer cells, hepatocytes, and hepatic stellate cells. [6] Serum cytokines/chemokines are thought to be linked to the pathogenesis of AIH by activating these hepatic immune cells.…”

Section: Introductionmentioning

confidence: 99%

Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis

et al. 2018

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Autoimmune hepatitis (AIH) is an autoimmune liver disease that is characterized by a progressive destruction of the liver parenchyma and the development of liver fibrosis. We aimed to examine the relationship between circulating cytokines/chemokines and the Mac-2 binding protein glycosylation isomer (M2BPGi) levels in Japanese patients with autoimmune hepatitis (AIH).We investigated the relationship between circulating cytokines/chemokines and M2BPGi levels in Japanese patients with AIH. Seventy-seven patients with well-documented AIH were enrolled in the National Hospital Organization (NHO)-AIH-liver-network database. We measured the serum levels of 20 cytokines in 31 selected AIH patients before and after steroid treatment using multisuspension cytokine array.Eleven cytokines and soluble adhesion molecules were increased in untreated AIH patients compared with treated AIH patients. Among these cytokines and soluble adhesion molecules, soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-γ-inducible protein 10 (IP-10) were most downregulated by steroid therapy in AIH patients. We measured serum sICAM-1 and IP-10 by ELISA and found the levels were significantly higher in AIH patients (n = 77) compared with chronic viral hepatitis C patients (n = 32). Furthermore, there was a positive correlation between sICAM-1 or IP-10 and alanine aminotransferase, total bilirubin, and circulating M2BPGi levels. M2BPGi levels were increased in AIH patients with high stages of liver fibrosis. Additionally, M2BPGi levels were correlated with the histological grade of inflammation in AIH. Circulating M2BPGi levels were significantly reduced by steroid treatment in AIH patients.sICAM-1 and IP-10 are useful markers to assess immune-mediated hepatitis activity in AIH and they correlate with circulating M2BPGi. Serum M2BPGi levels increased in untreated AIH patients with active hepatitis and were decreased by steroid therapy. M2BPGi reflects autoimmune-mediated hepatic inflammation as well as liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis

et al. 2018

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“…In addition, the age at the time of AIH diagnosis in the cirrhosis cases (60 years) was significantly higher than that in the non-cirrhosis cases. The period of onset for these cases is unknown; however, it has been reported that cirrhosis tends to develop in cases of onset at advanced ages (14). Miyake et al reported that the male-to-female ratio of cirrhosis cases is equal to that of non-cirrhosis cases of AIH (15); however, the male-to-female ratio of cirrhosis cases in the present study was 1:4.3, with the ratio of men being higher, although not significantly higher.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features of Cirrhosis in Japanese Patients with Type I Autoimmune Hepatitis

et al. 2012

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Objective Autoimmune hepatitis (AIH) is a chronic inflammatory disorder of unknown etiology that may proceed to cirrhosis, although some patients already have cirrhosis at the time of AIH diagnosis. The aim of this study was to clarify the clinical characteristics of AIH patients with cirrhosis in Japan. Methods Questionnaires were sent to liver specialists at four research facilities. Data for 250 patients diagnosed with AIH using the scoring system of the International Autoimmune Hepatitis Group (IAIHG) between 1975 and 2010 were collected and analyzed. Results The male-to-female ratio was 1:8.3 and the average patient age was 55.6 years. Liver cirrhosis was found in 51 AIH patients (20.4%). Of these, 43 patients (84.3%) had cirrhosis at presentation and eight patients (15.7%) developed cirrhosis during the follow-up period (average follow-up of 82.1 months). There were significant differences between the two groups with and without cirrhosis at presentation with regard to age and biochemical parameters at presentation. There were no significant differences in histology, with the exception of liver fibrosis. The overall 10-year probability of survival was 71.2% vs. 99.3% in the patients with and without cirrhosis (log-rank test, p<0.001). The relapse rate was significantly higher in the patients who developed cirrhosis during treatment than in those who did not develop cirrhosis during treatment (100% vs. 7.5%, p<0.001). Conclusion Since liver cirrhosis has already developed at presentation in many AIH patients with cirrhosis, it is important to diagnose the disease in the early stage and administer treatment rapidly with corticosteroids or immunosuppressants. In addition, a history of relapse is a risk factor for the development of cirrhosis in Japanese patients with AIH.

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“…Liver cirrhosis is sometimes complicated with AIH at diagnosis and influences its prognosis. AIH patients with cirrhosis had a worse survival 2 . The genetic and environmental factors are involved in the pathogenesis of AIH.…”

Section: Introductionmentioning

confidence: 94%

Role of deleterious single nucleotide variants in the coding regions of TNFAIP3 for Japanese autoimmune hepatitis with cirrhosis

Higuchi

Oka

Furukawa

et al. 2019

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Autoimmune hepatitis (AIH) is an autoimmune liver disease and cirrhosis is sometimes complicated with AIH at diagnosis, influencing its prognosis. TNFAIP3 gene encodes A20, an inhibitor of nuclear factor-κB pathway, and is a susceptibility gene for autoimmune diseases. We investigated deleterious variants in the coding regions of TNFAIP3 gene of Japanese AIH patients or those with cirrhosis. The deleterious variants in the coding regions of TNFAIP3 gene were analyzed by the cycle sequencing method and the frequencies of deleterious TNFAIP3 alleles of AIH or AIH with cirrhosis were compared with those of Japanese controls. The deleterious alleles in TNFAIP3 were not associated with AIH. A significant association was shown for the deleterious alleles in TNFAIP3 ( P = 0.0180, odds ratio (OR) 4.28, 95% confidence interval (CI) 1.53–11.95) with AIH with cirrhosis at presentation. The serum IgM levels in AIH patients with deleterious alleles in TNFAIP3 were tended to be lower than those without ( P = 0.0152, Q = 0.1216). The frequency of deleterious alleles in TNFAIP3 was higher in the AIH subset without the DRB1 risk alleles than that with ( P = 0.0052, OR 5.10, 95%CI 1.55–16.74). The deleterious alleles in TNFAIP3 were associated with AIH with cirrhosis.

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Evaluation of risk factors for the development of cirrhosis in autoimmune hepatitis: Japanese NHO-AIH prospective study

Cited by 16 publications

References 22 publications

Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis

Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis

Clinical Features of Cirrhosis in Japanese Patients with Type I Autoimmune Hepatitis

Role of deleterious single nucleotide variants in the coding regions of TNFAIP3 for Japanese autoimmune hepatitis with cirrhosis

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