A6 HIGH SERUM IGG4 IS ASSOCIATED WITH A SHORTER TIME TO CIRRHOSIS DEVELOPMENT, HEPATIC DECOMPENSATION, AND LIVER TRANSPLANTATION IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS
Bibliographic record
Abstract
Primary sclerosing cholangitis (PSC) is an immune-mediated biliary disorder of unknown etiology for which there is no effective treatment. Eventually all PSC patients progress to end-stage liver disease and require liver transplantation (LT). The purpose of this study is to better prognosticate the development of complications related to portal hypertension and the requirement for LT in PSC patients based on IgG4 levels. We evaluated 121 PSC patients seen at the University of Alberta Hospital between 2002 and 2017. Patients with a radiologic and/or histologic diagnosis of PSC with at least one IgG4 level were included and categorized as high IgG4 group >70 mg/dL or normal IgG4 group ≤70 mg/dL (this IgG4 cut-off value was the best discriminant for LT-free survival in a previous study). The presence of cirrhosis was defined by imaging studies, Fibroscan, or biopsy. Decompensation date was recorded as the first episode of variceal bleeding, ascites, or hepatic encephalopathy. Data is reported as a mean ± standard error for continuous variables and as a percentage for categorical variables. Time to cirrhosis, portal hypertensive complications, and LT-free survival were calculated by Kaplan-Meier methods and compared by the Log Rank (Mantel-Cox) test. Factors associated with LT-free survival were analyzed by Cox regression univariate and multivariable analyses. 121 patients were followed over a period of 7.4 ± 5 years (1–25 years). 78 patients (65%) were male, and the mean age at diagnosis of PSC was 35 ± 16 years. IBD was present in 85 patients (70%) including 59 ulcerative colitis patients, 22 Crohn’s disease patients, and 4 type unclassified. High IgG4 levels were found in 41 patients (155 ± 74 mg/dL), and normal IgG4 levels were found in 80 patients (30 ± 19 mg/dL), with a mean number of IgG4 determinations of 2.7 ± 0.2. Patients with high IgG4 levels had higher ALP levels (428 ± 49 vs. 279 ± 33 U/L, p=0.01), higher INR (1.2 ± 0.4 vs. 1.0 ± 0.2, p=0.05), lower albumin levels (36 ± 1 vs. 40 ± 1 g/L, p=0.01), higher PSC Mayo scores (0.64 ± 0.3 vs. 0.12 ± 0.2, p=0.04), and higher MELD scores (11 ± 1 vs. 9 ± 1, p=0.007). Furthermore, patients with high IgG4 levels had a shorter time to cirrhosis development (9 ± 1 vs. 13 ± 1 years, p=0.04) and decompensation (11 ± 1 vs. 20 ± 1 years, p=0.05). Lastly, LT-free survival was shorter in patients with high IgG4 levels (10 ± 1 vs. 18 ± 2 years, p<0.001, Figure 1). Patients with high IgG4 had an increased risk for LT (HR 3.8, 95% 1.38–12.87, p=0.03), after controlling for age at diagnosis and MELD score. PSC patients with high IgG4 levels have more aggressive disease, reflected by higher ALP levels, MELD scores, and PSC Mayo scores, as well as a shorter time to cirrhosis development, decompensation, and liver transplantation. Figure 1 None
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".