Gamma-Glutamyltransferase at the Time of Listing May Predict Irreversible Severe Cholangiopathy After Lung Transplantation for COVID19-ARDS

PURPOSE: Lung transplantation (LTx) can be considered for selected patients suffering from COVID19 ARDS or fibrosis. Besides the lung, the virus also affects the liver and cholangiopathy with progressive biliary liver failure has been described in a substantial rate of COVID19 ARDS survivors. Despite an increasing number of LTx performed worldwide for post-COVID19 ARDS, rates of cholangiopathic liver dysfunction and factors predicting this detrimental late complication are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS or post-COVID fibrosis in our institution between May 2020 and October 2021. Clinical parameters available at the time of listing were compared between LTx recipients who developed irreversible cholangiopathy leading to death or consideration for liver transplantation (‘cholangiopathy’ group) and patients who had no or only transient liver dysfunction (‘control’ group). Severe elevation of LFPs was defined as greater than 5 times the upper limit of normal (ULN) of bilirubin, ASAT, ALAT, GGT and AP, respectively. RESULTS: A total of 23 patients were included in the analysis. While 14 (60.9%) showed no or only transient liver dysfunction post-transplant, 9 (39.1%) developed persistent cholangiopathy after LTx. In 4 of these cases, this ultimately led to death, while 2 patients had to be put on the liver transplant wait list. Median time between COVID disease onset and Tx listing (p=0.603) was similar in both study groups. Recipient BMI, previous comorbidities and SOFA score at Tx listing were comparable. Levels of AP, ASAT, ALAT and bilirubin were similar in both groups, however, GGT at the time of listing seemed to predict a later development of cholangiopathy (median 510 vs 211.5 U/L; p=0.062). Moreover, patients with a GGT > 5xULN had a 12 times higher likelihood for the development of post-transplant cholangiopathy compared to those with lower GGT values (OR 95% CI: 0.010 - 0.590). CONCLUSION: Since severe cholangiopathy is associated with a high mortality after LTx, liver function should be thoroughly assessed in all post-COVID ARDS/fibrosis LTx candidates. In this preliminary observation, we found that GGT at the time of listing was the only parameter which appeared to predict this late complication. Further large-scale studies are required to confirm our findings.