Serum interleukin­17 levels predict inflammatory activity in patients with autoimmune hepatitis.

INTRODUCTION    The etiology of autoimmune hepatitis (AIH) is unclear, with molecular mimicry between host and viral/drug antigens being the most plausible mechanism initiating the immune cascade that induces hepatocyte injury. Finding a serologic parameter that closely relates to the liver histology would be beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES    We studied serum interleukin (IL)-17 levels and IL­17 activators (IL­6 and transforming growth factor ß1 [TGF-ß1]) in treatment-naive and immunosuppressed patients with AIH. We also analyzed the relationships between these cytokines and histological inflammation scores. PATIENTS AND METHODS    A total of 44 patients with confirmed AIH were enrolled to the study (22 treatment-naive patients and 22 patients in clinical remission after at least 3 years of immunosuppression). Liver biopsies were performed, and the histological grading of inflammatory activity was performed by a single pathologist. The control group comprised 30 healthy age- and sex­matched subjects. Serum IL­17, IL­6, and TGF­ß1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS    Serum IL­17, IL­6, and TGF­ß1 levels were higher in treatment-naive patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively). In treatment-naive patients, serum IL­17 negatively correlated with hepatic inflammation (r = -0.63, P = 0.01). A reduced serum IL­17 concentration correlated with an increased TGF­ß1 concentration in patients in clinical remission (r = -0.51, P = 0.03). CONCLUSIONS    Serum IL­17 levels may be a useful parameter for assessing disease activity in patients with AIH.

Laboratory-based scoring system for prediction of hepatic inflammatory activity in patients with autoimmune hepatitis.

BACKGROUND & AIMS: In autoimmune hepatitis (AIH), inflammation is closely related to fibrosis. Although transaminase levels are commonly used to assess hepatic inflammation, they may not relate directly to the histology. We developed a noninvasive diagnostic score as an alternative to liver biopsy to help optimize treatment for AIH and monitor disease progress. METHODS: Eighty-two participants with type 1 AIH who had undergone liver biopsy were included (44 in training and 38 in validation sets). Liver histology was assessed according to the histologic activity index (HAI; score 0-18) and Ishak's histologic fibrosis index (HFI; score 0-6). High inflammation was defined as HAI>4, and advanced fibrosis was defined as HFI>2. Routine laboratory test findings and stepwise linear regression were used to develop the best models predicting HAI and HFI. The best cut-off value to predict high inflammation and advanced fibrosis for these formulas was then calculated based on receiver-operating characteristic analysis. RESULTS: The cut-off value for a model predicting high inflammation was ≥3.57 (AUROC = 0.93; 95% CI: 0.86-1.00), with 100% sensitivity and 85% specificity. High inflammation was confirmed with an 81% positive predictive value and excluded with a 100% negative predictive value. In the validation set, the sensitivity, specificity, positive predictive value and negative predictive values were 100, 56, 88 and 100% respectively. The diagnostic yield of the fibrosis score was unsatisfactory. CONCLUSIONS: The noninvasive inflammatory score based on four routine laboratory parameters discriminated patients with and without significant hepatic inflammation and may facilitate follow-up of type 1 AIH patients.

[Serum level of TNF-alpha receptor type II better correlates with severity of Crohn's disease than other cytokines and conventional clinical activity indicators]. / Surowicze stezenie receptora typu II dla TNF-alpha wykazuje lepsza korelacje z ciezkoscia choroby Lesniowskiego-Crohna niz inne cytokiny i konwencjonalne wskazniki aktywnosci choroby.

UNLABELLED: Crohn's disease activity index (CDAI) and serum C-reactive protein (CRP) levels are not prefect indicators of Crohn's disease severity. Magnetic resonance enteroclysis (MRE) is a method allowing simultaneous assessment of lesions involving an entire intestinal wall as well as intra- and extraintestinal spaces. This method, however, is not appropriate for monitoring the course of disease and therapeutic effects. THE AIM OF THE STUDY: To evaluate which of the extensive panel of pro- and anti- inflammatory cytokines correlates with an actual severity of CD assessed by MRE. MATERIAL AND METHODS. 57 patients with endoscopically diagnosed ileocecal form of CD (28 women, age 29 + 11 yrs, range 18-62 yrs) hospitalized in 2007-2008. The mean CDAI was 293 + 119 points, range 18-503 points and serum CRP level was 17.5 + 31 mg/l, range 0.1-122 mg/l. MRE was performed in each patient not later than 3 days after entry to the study. The summarized score was calculated using standardized protocol, assessing the intestine wall thickness and length of its involvement (ileocecal region), pattern of mural contrast enhancement, presence of fistulas or other extraintestinal lesions and enlargement of mesenteric lymph nodes. At admission the blood was taken to measure following cytokines: IL-la, IL-1 receptor antagonist, IL-6, soluble IL-6 receptor, TNF-alpha, TNF-alpha type II receptor and IL-10. RESULTS: In Spearman's correlation test the MRE score showed the strongest relationship with serum level of TNF-alpha type II receptor (r = 0.52, p < 0.001), correlating less significantly with IL-6 level (r = 0.37, p < 0.01) and CDAI (r = 0.40, p < 0.001). CONCLUSION: TNFalpha receptor type II shows better correlation with the severity of ileocecal CD (assessed by MRE) than CDAI or serum levels of other cytokines and CRP.

The dynamics of the oxidant-antioxidant balance in the early phase of human acute biliary pancreatitis.

BACKGROUND/AIM: Reactive oxygen species play an important role in the pathogenesis of acute pancreatitis (AP) in animal models. Data on the oxidant-antioxidant balance in humans are scanty. The present study was undertaken to evaluate the dynamics of changes in the oxidant-antioxidant balance in the early phase of human AP. METHODS: 74 consecutive patients with acute biliary pancreatitis (16 with severe, 58 with mild pancreatitis), treated endoscopically, were included in the study. Serum concentrations of sulfhydryl groups (SH; main nonenzymatic antioxidant; 73 patients) and thiobarbituric acid reactive substances (TBARS; markers of reactive oxygen species-mediated tissue damage; 56 patients) were determined on admission and on each of 10 successive days. The analysis comprised the comparison of results in patients with mild and severe outcome of pancreatitis. RESULTS: Serum SH dropped by 27%, reaching the trough level on day 4 of hospitalization, whereas serum TBARS rose by 28%, reaching a peak 1 day later. Neither SH nor TBARS returned to initial values at the end of observation. The most dynamic changes in both SH and TBARS concentrations occurred in the first 3 days of hospitalization. The changes were significantly greater in patients with complicated pancreatitis in comparison to patients with mild disease, and were most pronounced in patients who developed infected pancreatic necrosis and who subsequently died. CONCLUSIONS: The oxidant-antioxidant balance changes rapidly in the early phase of human AP, confirming the role of oxidative stress in the pathogenesis of AP. The degree of changes correlates with the clinical severity of pancreatitis.