Hemophagocytic Lymphohistiocytosis in the Medical ICU: A Single-Institution Cohort Study on Acute Liver Failure and Mortality

Abstract

Objectives: Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammatory disorder that is associated with high morbidity and mortality in the ICU. It has also been associated with acute liver failure. Design: Retrospective observational study. Setting: Tertiary-care medical ICU. Patients: Thirty-one patients critically ill with hemophagocytic lymphohistiocytosis. Interventions: None. Measurements and Main Results: We performed a comprehensive review of critically ill hemophagocytic lymphohistiocytosis patients admitted to a tertiary-care medical ICU from January 2012 to December 2018. Most patients presented with constitutional symptoms and elevated liver enzymes and thrombocytopenia were common upon hospital admission. ICU admission laboratory and clinical variables were used to calculate Acute Physiology and Chronic Health Evaluation II, hemophagocytic syndrome diagnostic score, and model for end-stage liver disease. Mean age of the cohort was 48.1 years, and 45% were male. The mortality rate was 65% at 28 days and 77% at 1 year. About 28-day survivors were younger, had lower mean Acute Physiology and Chronic Health Evaluation II score (16.5 vs 23.0; p = 0.004), and higher mean hemophagocytic syndrome diagnostic score (249.1 vs 226.0; p = 0.032) compared with nonsurvivors. Survivors were less likely to receive mechanical ventilation, renal replacement therapy, or vasopressor support and were more likely to receive chemotherapy for hemophagocytic lymphohistiocytosis. In this ICU cohort, 29% were diagnosed with acute liver failure, of whom only 22% developed acute liver failure early during their hospital stay. Acute liver failure was associated with a higher model for end-stage liver disease score upon hospital admission. Available histology in those that developed acute liver failure showed massive hepatic necrosis, or histiocytic or lymphocytic infiltrates. Conclusions: Patients admitted to the ICU with hemophagocytic lymphohistiocytosis have a high mortality. Those who survived had lower Acute Physiology and Chronic Health Evaluation scores, had higher hemophagocytic syndrome diagnostic scores, are more likely to receive hemophagocytic lymphohistiocytosis specific chemotherapy, and are less likely to have organ failure. Hemophagocytic lymphohistiocytosis can be associated with acute liver failure especially when model for end-stage liver disease score is elevated upon admission.

Hemophagocytic Lymphohistiocytosis: A Practical Review for Liver Pathologists

“…The mortality rate of HLH is very high in both pediatric and adult groups. In one cohort, mortality reached as high as 65% at 28 days and 77% at 1 year 59 . Previous studies have recommended early diagnosis and treatment to improve survival outcomes and reduce complications in pediatric cohorts 32,34,60 .…”

“…In one cohort, mortality reached as high as 65% at 28 days and 77% at 1 year. 59 Previous studies have recommended early diagnosis and treatment to improve survival outcomes and reduce complications in pediatric cohorts. 32,34,60 Pediatric patients diagnosed with HLH in the setting of multisystem Langerhans cell histiocytosis had a statistically significant lower 5-year survival rate than those who did not have HLH (68.9% vs 97.1%).…”

Hemophagocytic Lymphohistiocytosis in Children

“…Наши данные совпадают с данными литературы [3,4,7,8], где указывается, что наиболее часто ГЛГ ассоциируется с вирусными инфекциями. При этом более 50% составляет герпесвирусная инфекция: как первичная, так и реактивация вирусом Эпштейна -Барр (у больной выявлены вирус Эпштейна -Барр и парвовирус В19).…”

“…ГЛГ может осложнить течение основного заболевания и в случае отсутствия своевременного лечения привести к смертельному исходу [4,5]. Различают первичный и вторичный ГЛГ [6][7][8]. Первичный ГЛГ -это результат мутации генов, кодирующих белки, играющих важную роль в регулировании цитотоксических лимфоцитов [7].…”

“…Первичный ГЛГ -это результат мутации генов, кодирующих белки, играющих важную роль в регулировании цитотоксических лимфоцитов [7]. Способствовать развитию вторичного ГЛГ могут вирусы (герпесвирусы, парвовирус В19, аденовирус, энтеровирусы, вирусы Коксаки, вирус гриппа А Н5N1), ГЛГ может также возникнуть при туберкулезе, брюшном тифе, болезни Лайма, бруцеллезе, пневмонии, риккетсиозе, паразитарных и грибковых инфекциях, злокачественных новообразованиях и аутоиммунных заболеваниях [3,8,9].…”