DOP39 Safety of combination biologic and anti-rejection therapy post-liver transplantation in patients with inflammatory bowel disease: London Ontario experience
Bibliographic record
Abstract
Despite anti-rejection immunosuppressive therapies post-liver transplantation (LT), patients with concurrent inflammatory bowel disease (IBD) may have persistent bowel inflammation that requires addition of biologic therapy. The aim of this study was to evaluate the safety of combination biologic and anti-rejection therapy in IBD patients after LT. The LT Registry at London Health Sciences Centre (LHSC) was searched to identify all patients undergoing LT from 1985 to 2018. IBD patients initiated on biologic treatment post-LT, in addition to anti-rejection therapy, were eligible for inclusion. Medical chart review was conducted to extract safety outcomes, including rates of infections, malignancy, colectomy and death. Nineteen patients were included (78.9% male, mean age 46.0 years, 8 patients with ulcerative colitis), followed for a median duration of 19 months (IQR 5.8, 30.8). Indications for LT included: primary sclerosing cholangitis (PSC) (14/19, 73.7%), autoimmune hepatitis (AIH) (2/19, 10.5%), AIH-PSC overlap syndrome (2/19, 10.5%), and biliary atresia (1/19, 5.3%). Post-LT, six patients were treated with only TNF antagonists (infliximab in 5 patients, golimumab in 1 patient); eight patients with only anti-integrin therapies (vedolizumab in 7 patients, natalizumab in 1 patient); and five patients with sequential TNF antagonists followed by either ustekinumab (n = 2) or vedolizumab (n = 3). Six patients required long-term prednisone. The most commonly used anti-rejection therapies were tacrolimus and mycophenolate mofetil. Disease course was complicated by infections in nine patients (47.4%), most commonly Clostridium difficile colitis (4/19, 31.6%). One patient had recurrent C. difficile infection and one patient had CMV colitis and viremia. Other infections included cholangitis (n = 2), perianal abscess (n = 1), JC virus seroconversion but without progressive multifocal leukoencephalopathy (n = 1) and hospital-acquired pneumonia (n = 1). Two patients required colectomy for refractory colitis. One patient required re-transplantation due to PSC recurrence. No deaths or malignancies were reported although one patient developed low-grade colonic dysplasia. This is the largest reported case series from a single centre to date evaluating the safety of combination biologic therapy with anti-rejection regimens in IBD patients post-LT. Whilst there appeared to be an increased risk of enteric infections, especially C. difficile, there were no life-threatening infections reported. Active screening for enteric infections should be pursued in these patients presenting with increased IBD 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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".