P667 Safety of anti-TNF treatment in liver transplant recipients – a meta-analysis
Bibliographic record
Abstract
Background: Primary Sclerosing Cholangitis (PSC) patients with refractory inflammatory bowel disease (IBD) after liver transplantation (LT) pose a dilemma for treating physicians, as little is known about the risk of serious infection when combining anti-TNF therapy with immunosuppression for prevention of rejection. Our aim was to investigate the infection risk in this patient group by systematic review and meta-analysis of the available data. Methods: A literature search was conducted for full papers and conference proceedings through September 2015 regarding liver transplant recipients and anti-TNF therapy. All studies were appraised using the adapted Newcastle-Ottawa Scale (NOS), which contains 9 criteria for cohort studies and is adapted to 6 criteria for case series and case reports. Two reviewers (MWvM and PWJM) independently extracted study and control-patient data (age, duration of follow up, number of all infections, number of serious infections, time since transplant). As additional control population, PSC-IBD patients from the LUMC LT cohort were used. Poisson regression was used to compare serious infections (according to ICH-definition) per patient year follow up between the anti-TNF and control group, correcting for mean time since transplant. Results: Initially, 465 articles and abstracts were identified, of which 8 were included. These 8 studies contained 53 post-LT patients on anti-TNF therapy and 23 post-LT control patients not on anti-TNF therapy. None of the studies scored less than 75% of the NOS quality criteria. From the LUMC LT cohort, 41 PSC-patients with PSC-IBD but without anti-TNF therapy were included as control population. Serious infection rates differed from 0 to 0.38 serious infections per patient year in the anti-TNF therapy group, and 0.04 to 0.24 in the control group. The overall infection rate for TNF-exposed patients was 0.12, compared to 0.15 in the control patients, resulting in a rate ratio of 0.80 (95% CI: 0.17–3.97, p=0.80). Age at time of transplant was not associated with the rate ratio for serious infections, whereas the time since transplantation was. Although correcting for time since transplant causes the infection rates in the anti-TNF-group to be higher than in the control group (0.13 vs 0.12 serious infections per patient year) the rate ratio remained non-significant (1.1, p=0.82). Conclusions: No significant increase in the serious infection rate was observed in LT-recipients with PSC-IBD during exposure to anti-TNF therapy. However, the wide confidence intervals of these results show that more data is needed to provide a definitive conclusion on the safety of anti-TNF therapy in these patients.
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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 | 0.015 | 0.025 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.012 | 0.047 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".