Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS

Abstract

Background: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown.

Methods: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis.

Results: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004).

Conclusions: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.

Keywords: Covid-19; critically ill patients; liver; lung transplantation; secondary sclerosing cholangitis.

Figure 1

Liver serum biochemistry A – at time of listing B – highest value between onset and transplantation C – at time of transplantation * (p ≤ 0.05); ** (p ≤ 0.01); *** (p ≤ 0.001); (Abbreviations: ALAT, Alanine aminotransferase; ALP, Alkaline phosphatase; ASAT, Aspartate aminotransferase; GGT, Gamma-glutamyltransferase; TBi, Total bilirubin; SSC, Secondary sclerosing cholangitis).

Figure 2

ROC curves for GGT at time of listing and for highest GGT between onset and transplantation (Abbreviations: AUC, Area under the curve; GGT, Gamma-glutamyltransferase).

Figure 3

Kaplan-Meier survival with 95% confidence intervals (Abbreviations: AUC, Area under the curve; GGT, Gamma-glutamyltransferase; SSC, Secondary sclerosing cholangitis;).