Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can present with drug-induced liver injury (DILI), often mimicking acute liver failure and delaying diagnosis. Therapeutic options are limited in patients with severe hepatic dysfunction. Objectives To describe the clinical features, treatment, and outcomes of three adult patients presenting with DILI-mimicking HLH and evaluate the effectiveness of low-dose ruxolitinib combined with corticosteroids. Methods Three patients with DILI-like hepatic injury and secondary HLH were retrospectively analyzed. All patients exhibited severe hyperbilirubinemia and cytopenias refractory to conventional supportive therapy. Low-dose ruxolitinib plus corticosteroids were administered. Laboratory, imaging, genetic, and histopathological data were reviewed. Results All patients responded rapidly to the combination therapy, with progressive normalization of bilirubin and inflammatory markers. Transient declines in blood counts occurred but resolved without intervention. Genetic testing revealed heterozygous variants in immune-regulatory genes (NLRP3, DOCK8, MYO5A, PLCG2) classified as variants of uncertain significance, suggesting a potential predisposing role. No significant adverse events related to ruxolitinib were observed. Conclusions HLH can initially present as severe DILI, posing diagnostic challenges. Short-course, low-dose ruxolitinib combined with corticosteroids is a safe and effective treatment in patients with hepatic-predominant HLH. Early recognition and timely immunomodulatory therapy may improve outcomes in this life-threatening but treatable condition.
Dai et al. (Thu,) studied this question.