Type 1 autoimmune hepatitis and adipokines: New markers for activity and disease progression?

Department of Internal Medicine, University of Turin, Turin, Italy.
Journal of Gastroenterology (Impact Factor: 4.52). 04/2009; 44(5):476-82. DOI: 10.1007/s00535-009-0023-0
Source: PubMed


Cytokines may play an important role as inflammatory factors in liver diseases. There is some evidence suggesting a link between adiponectin-biliary function and liver disease. The aim of this study was to clarify the behavior of adipokines in autoimmune hepatitis type 1.
We assessed the circulating levels of adiponectin, tumor necrosis factor-alpha, resistin and leptin in 42 patients with autoimmune hepatitis, comparing them with 42 healthy subjects who were matched for age and sex and with 31 patients with nonalcoholic steatohepatitis (NASH), evaluating the associations with markers of cytolysis, cholestasis, and histological severity.
Adiponectin and TNF-alpha values were higher in patients compared to controls. The patients showed significantly higher Homeostasis Model Assessment values, suggesting an increased insulin resistance and serum levels of adiponectin positively correlated with gamma-glutamyltranspeptidase and alkaline phosphatase values after a simple regression analysis. Serum levels of resistin positively correlated with elevated aminotransferases and bilirubin values, and serum levels of TNF-alpha positively correlated with elevated alanine-aminotransferase and resistin values. The concentration of adiponectin increased significantly with staging of the disease. Patients with NASH showed lower levels of adiponectin and higher levels of resistin than AIH patients and controls.
Patients with AIH showed significantly higher adiponectin concentrations than controls despite their higher HOMA-IR values. The significant correlation between adiponectin levels and serological features of cholestasis suggested an association with biliary function. Our results indicate that adiponectin may be a possible marker for disease progression in AIH.

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    • "Although resistin is secreted by human adipocytes, the most significant source appears to be blood mononuclear cells [3]. Plasma concentrations of adipokines have been investigated in patients with different liver disorders, that is, nonalcoholic fatty liver disease [4] [5] [6], type 1 autoimmune hepatitis [7], and viral hepatitis B [8] and C [9]. Alcoholic liver disease (ALD) is another one where adipokines may play pivotal role and represent a link between inflammation and metabolic state. "
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    ABSTRACT: Background and aims: There is growing evidence that white adipose tissue is an important contributor in the pathogenesis of alcoholic liver disease (ALD). We investigated serum concentrations of total adiponectin (Acrp30), leptin, and resistin in patients with chronic alcohol abuse and different grades of liver dysfunction, as well as ALD complications. Materials and methods: One hundred forty-seven consecutive inpatients with ALD were prospectively recruited. The evaluation of plasma adipokine levels was performed using immunoenzymatic ELISA tests. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Results: Acrp30 and resistin levels were significantly higher in patients with ALD than in controls. Lower leptin levels in females with ALD compared to controls, but no significant differences in leptin concentrations in males, were found. High serum Acrp30 level revealed an independent association with advanced liver dysfunction, as well as the development of ALD complications, that is, ascites and hepatic encephalopathy. Conclusion: Gender-related differences in serum leptin concentrations may influence the ALD course, different in females compared with males. Serum Acrp30 level may serve as a potential prognostic indicator for patients with ALD.
    Full-text · Article · Oct 2013 · Mediators of Inflammation
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    • "Furthermore, raised levels of resistin have been reported in patients with IBD, more specifically in CD and ulcerative colitis (UC) [18] [19] [20] [21]. Studies on autoimmune [22] and viral hepatitis [23] showed increased circulating levels of resistin in proportion to liver tissue damage assessed by aminotransferases [22], but not in relation to steatosis or stage of fibrosis [23]. One study on non-alcoholic fatty liver disease (NAFLD) has demonstrated a direct correlation between serum resistin levels and the severity of morphological changes in the liver [24]. "
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    ABSTRACT: Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohn's disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P < 0.001) and PSC (P < 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P < 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.
    Full-text · Article · Jun 2011 · Scandinavian Journal of Immunology
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    ABSTRACT: This study aimed to investigate the efficacy of ursodeoxycholic acid (UDCA) for Japanese patients with autoimmune hepatitis (AIH). One hundred forty-seven patients were investigated. As initial treatment, 25 patients received UDCA (300-600 mg/day) monotherapy (UDCA group), 40 received a combination of prednisolone (PSL) (≥20 mg/day) and UDCA (combination group), 68 received PSL monotherapy (PSL group), and 14 received other treatments. During the follow-up, in the UDCA group, PSL was added to 8 of 12 patients failing to achieve the normalization of serum transaminase levels with UDCA monotherapy. Cumulative incidence of the normalization of serum transaminase levels was 64% in the UDCA group, 95% in the combination group, and 94% in the PSL group (log-rank test, P = 0.0001). UDCA group required longest periods until the normalization of serum transaminase levels. Eleven patients, who achieved persistent normalization of serum transaminase levels with UDCA monotherapy, did not reach liver failure or develop hepatocellular carcinoma for 49.7 (range = 13.4-137.3) months. Meanwhile, during the taper of PSL, doses of PSL at the initial relapse were lower in patients treated with PSL and UDCA than in those treated with PSL monotherapy, and initial relapse occurred earlier in patients treated with PSL monotherapy. UDCA monotherapy is effective for some Japanese AIH patients; however, UDCA monotherapy for patients with either high-grade inflammatory activity or poor residual capacity of liver function is not recommended because they may reach liver failure before achievement of remission. Meanwhile, additional use of UDCA during the taper of corticosteroids may be effective for the prevention of early relapse.
    Full-text · Article · Oct 2009 · Hepatology International
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