Serum autotaxin is associated with significant impairment of health related quality of life, biochemical and clinical and parameters in patients with PBC
Bibliographic record
Abstract
Background & Aims: Autotaxin (ATX) is involved in the synthesis of lysophoshatidic acid (LPA), a robust neuronal activator. Both parameters were recently linked to pruritus in cholestasis (Hepatology 2012;56:1391 – 1400), and it was hypothesized that ATX inhibitors could be useful for the treatment of cholestatic itch. The potential association between ATX and other relevant factors related to chronic cholestatic conditions has not been studied yet. Methods: We recruited a cohort of 116 patients with primary biliary cirrhosis (PBC; M/F-9/107; mean age 58 ± 12 years). A total of 52 patients presented with cirrhosis on histology or imaging. The PBC-40, PBC-27 and SF-36 questionnaires were used to assess health related quality of life (HRQoL). Total fasting serum bile salts (BS) and 27 BS metabolites were analyzed in 47 patients. ATX activity was quantified enzymatically. Results: Serum ATX activity showed a significant correlation with pruritus assessed with the itch-specific domains of PBC-40 and PBC-27 questionnaires (r = 0.31; p = 0.001). It also correlated with serum AST (r = 0.23; p = 0.02) and ALP activities (r = 0.32; p = 0.0007). ATX was significantly increased in patients with cirrhosis (11.6 ± 3.5 nmol/mL*min vs. 9.3 ± 4.7 nmol/mL*min; p = 0.004) and correlated with the Mayo risk score (r = 0.45; p = 0.004). It also correlated with total fasting serum BS concentrations (r = 0.49; p = 0.0005) and in multivariate analysis, glycine conjugates of lithocholate (LCA-Gly) and cholate (CA-Gly) were independent variables related to ATX levels. In terms of HRQoL, serum ATX levels were associated with fatigue (r = 0.22; p = 0.02) in PBC-40 as well as fatigue (r = 0.22; p = 0.02), cognitive (r = 0.21; p = 0.03) and emotional (r = 0.20; p = 0.03) domains of the PBC-27 questionnaire. No correlations were oberved with generic SF-36 domains, except for physical functioning (r = 0.20; p = 0.03). Conclusions: In patients with PBC, serum ATX is not only associated with increased pruritus but may also be involved in impairment of further aspects related to patients' quality of life and liver dysfunction. Thus, ATX inhibitors could be of potential benefit not only in the treatment of pruritus but also other incapacitating cholestasis-related symptoms.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".