Incidence, mortality, and risk factors of immunotherapy-associated hepatotoxicity: A nationwide hospitalization analysis

Background and aims Anti-neoplastic immunotherapy has revolutionized cancer management;however,its safety profile with respect to liver-related injury remains largely unexplored.Herein,we analyzed a United States national database to determine the incidence,mortality,and predictors of hepatotoxicity in the setting of anti-neoplastic immunotherapy.Methods This was a nationwide retrospective study of hospital encounters from 2011 to 2014 using the National Inpatient Sample(NIS)database.We utilized the International Classification of Diseases,Ninth Revision(ICD-9)coding system to identify all adult patients who underwent anti-neoplastic immunotherapy during hospitalization.The primary outcome was the incidence of hepatotoxicity during the same hospitalization.Secondary outcomes included in-hospital mortality as well as socioeconomic and ethno-racial predictors of hepatotoxicity.Analyses were performed using IBM SPSS Statistics 23.0.Results The sample included 3002 patients who underwent inpatient anti-neoplastic immunotherapy.The incidence of hepatotoxicity was 10.1%,which was significantly higher as compared to a matched inpatient population(adjusted odds ratio(aOR)4.93,95%confidence interval(CI):3.80–6.40,P=0.001).No significant mortality difference was seen in those that developed hepatotoxicity compared to those who did not(aOR 0.47,95%CI:0.03–8.03,P=0.612).Age under 60(aOR 1.56,95%CI:1.23–1.78,P=0.050)and white race(aOR 1.85,95%CI:1.35–2.04,P<0.010)were independent risk factors for developing immunotherapy-associated hepatotoxicity.Conclusions In this large,nationwide database analysis,we found that anti-neoplastic immunotherapy was associated with a nearly five-fold risk of in-hospital hepatotoxicity as compared to a matched inpatient population,though without an associated mortality difference.Additionally,younger age and white race were identified as predictors of immunotherapy-associated hepatotoxicity.Heightened vigilance and prospective investigation of the risk factors and liver-related adverse effects of anti-neoplastic immunotherapy are warranted.