Assessment of Hemophagocytic Lympho-Histiocytosis (HLH) in the Setting of Adult Acute Liver Failure

Hemophagocytic lympho-histiocytosis (HLH) is a life-threatening disease, only occasionally presenting as acute liver failure (ALF) in adults. HLH is challenging to diagnose. We reviewed the ALF Study Group (ALFSG) registry for suspected HLH subjects, as well as 184 with other ALF etiologies for cases that might have been missed, assessing standard laboratory tests, as well as interleukin-18 (IL-18) and soluble interleukin-2 receptor (sIL-2r), to determine the diagnostic utility of these biomarkers. We also calculated standard diagnostic algorithms (H score, HLH-2004 diagnostic criteria) to assess their value. Within 3364 ALF subjects, only 14 were initially cited as HLH. Upon thorough review by an adjudication committee, 5/14 (35.7%) were considered definite, five probable, two possible, and two unlikely. Definite HLH patients had significantly higher ferritin (p = 0.047), IL-18 (p = 0.003) and s-IL2r (p = 0.005) levels, H scores (p < 0.001) and HLH scores (p < 0.001). Other etiologies (APAP, DILI and viral) showed lower IL-18 and sIL2r levels and scores, but overlapping ferritins. Several probable/possible HLH cases lacked complete data for scoring. No additional (missed) HLH cases were identified. HLH remains a rare cause of ALF. Biomarkers, particularly IL-18 and sIL-2r, appear of value. HLH and H scores were also helpful but limited when data was missing.