SynthesisFrontiers in immunology2025
Global assessment of hepatic safety in novel immunotherapies: a systematic review and meta-analysis.
Synthesis in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Ablation-immunotherapy synergy in cancer: mechanisms of the abscopal effect, emerging clinical applications, and translational roadmaps for next-generation onco-immunology.Medical oncology (Northwood, London, England) · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: This study explored whether integrating innovative immunotherapies targeting costimulatory or co-inhibitory pathways beyond standard PD-1, PD-L1, and CTLA-4 treatments affects hepatic adverse events. We further analyzed liver-related side effects in patients with cancer receiving these novel therapies alone or in combination with others. Methods: Clinical studies on immunotherapies targeting molecules such as LAG-3, TIGIT, TIM-3, VISTA, CD47, ICOS, CD40, and B7-H3 were retrieved from PubMed, Embase, Cochrane Library, and Web of Science. Data from eligible studies that reported liver-related adverse events until May 2024 were included. Results: This analysis included 63 studies involving 7,327 patients. Among these, randomized controlled trials demonstrated that adding LAG-3 or TIGIT inhibitors to established therapies did not increase the risk of elevated hepatic enzyme levels or hepatitis. CD27-CD70-targeted monotherapy showed a strong association with elevated transaminase levels. Dual therapies combining 4-1BB agonists with PD-1/PD-L1 inhibitors resulted in >15% all-grade transaminase elevation, whereas CD40 agonists paired with immunotherapy resulted in >4% high-grade elevations. Immunotherapy-chemotherapy combinations showed high transaminase elevation rates. Overall, the incidence of elevated liver enzyme levels was similar between the single-agent and dual immunotherapy groups. The addition of chemotherapy or targeted therapy to single-agent immunotherapy increases the incidence of adverse events associated with elevated liver enzyme levels. The incidence of liver enzyme adverse events continued to increase with the addition of immunotherapy to the combination regimens. Cholestatic enzyme elevations were prominent in CD27-CD70 monotherapy and CD40 agonist combinations. Conclusions: This meta-analysis suggests adding LAG-3 or TIGIT inhibitors to existing therapies may not significantly increase hepatic toxicity. It reviewed adverse events from novel immunotherapies alone or combined with PD-1/PD-L1/CTLA-4 inhibitors, targeted agents, or chemotherapy. These findings have important clinical implications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.