title: Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis.
abstract: OBJECTIVE
  Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors.
  
  
  METHODS
  PubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were randomized controlled trials of cancer patients treated with PD-1 inhibitors with adequate data on hepatic AEs.
  
  
  RESULTS
  A total of nine randomized controlled trials with a variety of solid tumors were eligible for the meta-analysis. The use of PD-1 inhibitors significantly increased the risk of developing all-grade hepatic AEs but not for high-grade hepatic AEs in comparison with chemotherapy or everolimus control. Additionally, the risk of all-grade and high-grade hepatic AEs with a nivolumab/ipilimumab combination was substantially higher than ipilimumab. No significant differences in the risk of all-grade and high-grade hepatic AEs were found between PD-1 inhibitors monotherapy and ipilimumab.
  
  
  CONCLUSIONS
  While the use of PD-1 inhibitors is associated with an increased risk of developing hepatic AEs in cancer patients, this is primarily for lower grade events.
authors.affiliation: Department of Radiation Oncology.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology.
authors.forename: Yuge
authors.initials: Y
authors.lastname: Ran
authors.affiliation: Department of Medical Oncology.
authors.forename: Kunjie
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology.
authors.forename: Yuanxue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, People's Republic of China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000068338:Everolimus / Q000494:pharmacology*; D006505:Hepatitis / Q000178:diet therapy / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D000074324:Ipilimumab; D009369:Neoplasms / Q000188:drug therapy*; D012306:Risk
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D000068338:Everolimus
keywords: PD-1 inhibitors; cancer; hepatic toxicities; meta-analysis