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

Background and Aims Massive 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. Methods In 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. Results ALF 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<0.01) and non-classical monocytes (CD14-CD16+) was decreased in ALF compared to HC. CD16+CD56+ NK cells in total lymphocytes was significantly lower in ALF patients compared to HC, but was higher in survivors {9.28% (0.5-20.3)} than non-survivors {5.1% (0.2-10.6)} (p<0.001). Higher percentage of circulating NK cells (>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%). Conclusion Combination of NK cell frequency and lactate levels at admission can reliably predict survival of ALF patients. KEY POINTS ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NA ### Funding Statement The study was supported by Intramural funding to SKS and NTP. TA was supported by post-doctoral fellowship provided by Department of Biotechnology, India as a part of Extramural funding provided to SKS. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval statement: All investigations was performed in accordance with the declaration of Helsinki. The protocol was approved by the institutional review board and ethics committee and approved the prospective collection of blood samples. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes yes