A Hepatic Impairment Index for Mortality Prediction in NK/T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

Background: Hepatic impairment is a severe complication in natural killer/T cell lymphoma with hemophagocytic lymphohistiocytosis (NK/T-HLH). Abnormal levels of liver enzymes, bilirubin or albumin serve as features of hepatic impairment，but its critical indicators correlated with prognosis in NK/T-HLH remains unclear. Patients and Methods: We conducted a retrospective study including 47 NK/T patients with and without HLH. Logistic regression and receiver-operating curve analyses were used to identify the most useful prognostic parameters of hepatic and to optimize laboratory cutoff values. Correlated factors of hepatic compromise was analyzed with Pearson's r-test. Results: The incidence of patients experiencing hepatic impairment was 100% among 17 NK/T with HLH (NK/T-HLH), notably higher than the 50% incidence of 30 without HLH (NK/T-NHLH). Among hepatic features, gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and direct bilirubin (DBIL) can serve as important predictive markers for mortality in NK/T patients. Integrating GGT, AST, and DBIL into a novel index that we termed the GSD index, which achieved an improved mortality predictive. The respective cut-off values for these three parameters were determined using ROC curves at GGT 181.8 U/L, AST 98.5 U/L, and DBIL 6.4 μmol/L. Moreover, patients with NK/T-HLH who fulfilled the GSD index criteria exhibited a significantly shorter median survival time compared to those who did not. Interferon-gamma (IFN-γ) is an important cytokine produced by immune cells that is often elevated in HLH patients. Our analysis revealed a significant and positive linear correlation between IFN-γ levels and the elevation of GGT, ALT, AST, and DBIL. Finally, we report two successful cases of NK/T-HLH patients with severe hepatic failure using a combination treatment of chemotherapy and emapalumab, a fully human anti-IFN-γ monoclonal antibody approved for treatment of patients with primary HLH. Conclusion: The GSD index is critical for predicting poor outcomes in NK/T-HLH patients with hepatic impairment. Emapalumab combined with chemotherapy may be an effective treatment for those with severe liver damage.