Graft injury and neutrophil lymphocyte ratio predicts the severity and survival due to COVID 19 among liver transplant recipients - Multicentre results from apcolis-lt study

ABSTRACT

Background: Liver Transplant recipients have an increased susceptibility to SARS CoV2 infection with a possible more severe disease course. There is paucity of data of SARSCoV2 infection in this cohort from Asia. We report on the data of an on-going APCOLIS-1 (APASL Liver Injury Spectrum, APCOLIS) registry with the aim to define the profile, risk factors for severity and predictors of survival among the liver transplant recipients. Methods: In a multinational study, data was recorded between April 2020 to May 2021 across 13 countries in Asia. The data was compiled on a survey monkey under the APASL COVID-19 study task force [NCT04345640]. We performed multivariate logistic regression to identify independent predictors of severity and all cause mortality among the liver transplant (LT) recipients suffering from COVID-19. Results: Altogether, 130 LT recipients were enrolled [mean age 53 ± 12 years, median post-transplant period, 54 months (range 2-77 months)]. Majority (92, 71% ) of the patients had undergone live-donor transplant. Severe COVID was seen in 21/130 (16%) and 17/130 (13%) required ICU care. COVID related organ failures (OF) were seen in 17 patients (13%), predominantly as respiratory (16/21, 76.2%) followed by renal (9/21, 42.8%) and circulatory (5/21, 23.8%) with ventilatory requirement in 12/21 (57.1%) of the severe cases. Among the baseline parameters age [HR=1.08, 95CI 1.01-1.16, p=0.03], presentation with dyspnea [HR=6.34, 95CI 1.78-22.9, p=0.004] and Neutrophil to Lymphocyte ratio (NLR) [HR=1.08, 95CI 1.01-1.17, p=0.04] independently predicted a severe course of the COVID-19 among LT recipients. The baseline NLR of 8.47 ± 1.45 peaked to 17.94 ± 3.68 in median of 15 days (range 1-37) among severe cases [p<0.001] indicating rapid progression of disease. Age above 55 years increased the disease severity with AUROC of 0.78, sensitivity of 72.7% and specificity of 74.8%. Time from LT, immunosuppression dosage or presence of co-morbidities did not influence the outcome. Graft dysfunction was seen in 21/130 (16%);predominantly as acute cellular rejection in 13/130 (10%) and graft failure 7/130 (5%). The all cause mortality was 8% (11/130). Among non-survivors, the baseline NLR of 4.88 ± 1.63 increased to a peak value of 25.14 ± 5.49 [p<0.001] i.e 5 folds. The baseline NLR [HR=1.17, 95CI 1.03-1.34, p=0.02], development of graft injury [HR=27.21, 95CI 2.55-290., p=0.006] and COVID related OF [ HR=21.87, 95CI 2.39-203.85, p=0.007] independently predicted mortality due to SARSCoV2 infection. Conclusion: COVID-19 infection precipitates a severe disease course in one fifth of the liver transplant recipients, leading to graft dysfunction and early mortality. LT recipients above 55 years of age, presenting with dyspnea and high NLR need to be specifically watched for a progressive disease course. Dynamic NLR determination can help in early stratification and referral to a specialized liver unit to improve outcomes.