Lower blood lactate and higher circulating natural killer cells at admission predict spontaneous survival in non-acetaminophen induced acute Liver failure

Background and AimsMassive cellular necrosis in ALF is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage. Our aim was to investigate specific innate immune cells or damage associated molecular patterns (DAMPs) relating to the final outcome of patient. MethodsIn fifty ALF patients and in fifteen age-matched healthy controls (HC), DAMPs were measured in plasma using ELISA. Phenotypic analysis of neutrophils, monocytes, natural killer (NK) and NKT cells was done by flow-cytometry and correlated with clinical and biochemical parameters. ResultsALF patients (aged 27{+/-}9 yr, 56% males, 78% viral etiology) had MELD of 31.5{+/-}8, jaundice to hepatic encephalopathy (HE) of 4.6{+/-}3.2 days, HE grade III-IV, 82% with cerebral edema, 38% met KCH criteria, 56% had suspected sepsis. Percentage of intermediate monocytes (CD14+CD16+) was increased (p 6.7%) at admission was a good predictor of survival. Non-survivors had higher levels of serum lactate (6.1 vs. 28, Odds ratio 2.23, CI 1.27-3.94) and granzymeB positive NK cells than survivors. Logistic regression model predicted the combination of lactate levels with NK cell percentage at admission for survival (AUROC of 0.94; sensitivity 95.8%, specificity of 78.5%). ConclusionCombination of NK cell frequency and lactate levels at admission can reliably predict survival of ALF patients. KEY POINTSO_LIALF is generally immune mediated and predominantly caused by viral infections or acetaminophen toxicity. C_LIO_LITherapeutic options are limited in ALF, important to know key immune players for their survival. C_LIO_LICD16+CD56+ NK cells were found to be higher in survivors than non survivors. C_LIO_LICombination of lactate levels with NK cell percentage at the time of admission can reliably predict the survival of ALF patients. C_LI