Liver stiffness measurement in the early post-liver transplant phase predicts acute allograft rejection

Introduction

Acute allograft rejection (ACR) continues to be a significant complication following liver transplantation (LT). Currently, diagnosis depends on laboratory tests and histopathological criteria, which do not always enable prompt diagnosis and early treatment initiation. Liver stiffness measurement (LSM) is known to be an accurate method for estimating liver fibrosis; however, many other conditions have been shown to impact it, including necro-inflammatory liver damage. Thus, the inflammatory process related to ACR could also impact on LSM.The present study aims to explore the potential prognostic role of LSM in predicting the development of ACR after LT.

Methods

This study included all adult consecutive patients who underwent orthotopic LT between 1 September 2021 and 31 December 2023 at Policlinico Universitario A. Gemelli, IRCCS. We excluded patients who underwent LT for acute liver failure and patients who develop an early vascular or surgical complication. During the first 14 days after LT, complete blood counts and liver function tests were performed daily. Diagnosis of ACR was based on validated histological criteria (Banff RAI). LSM was performed on post-operative day (POD) 1st, 3rd, and 7th with Fibroscan (Echosense, France) after a fasting period of at least 6 hours.

Results

Seventy patients were enrolled. The analysis involved 65 patients, as 5 patients met exclusion criteria. The median age was 62 years (IQR 56-66), and 80% of the patients were male. Fifteen patients (23%) developed ACR within the first 4 weeks after LT (median at 9 POD - IQR 7-10). At POD 1, LSM was not significantly different between patients who developed ACR and those who did not (15.0 [IQR 10.5–21.7] vs 17.7 kPa [IQR 12.3–22.4], respectively). AST and bilirubin levels, but not eosinophil count, on POD 3 and 7 were significantly higher in patients who were subsequently diagnosed with ACR compared to those who did not develop ACR. During the first week post-transplant, patients who developed ACR showed a progressive worsening of LSM, which was significantly different compared to patients who did not on POD 3 (19.2 [IQR 14.7–27.8] vs 13.7 [IQR 9.9–18.9], p<0.01, respectively) and POD 7 (26.6 [IQR 19.7–31.6] vs 10.5 [IQR 8.8–14.9], p<0.01, respectively). Consequently, the relative change over time in LSM was significantly different between patients who developed ACR and those who did not (delta% LSM POD3–1: 28.8% [IQR 1.4–63.1] vs -15.1% [IQR -30.3 to -5.8], p<0.01; delta% LSM POD7–1: 53.7% [IQR 10.9–101.1] vs -25.2% [IQR -48.1 to -15.8], p<0.01).At logistic regression analysis delta% LSM POD3–1 and delta% LSM POD7–1 were significantly associated with ACR development independently from delta% AST and delta%eosinophil count at same timepoints (OR 1.06; CI 1.03-1.10; p<0.01 and OR 1.07; CI 1.03-1.12; p<0.01, respectively).

Conclusions

We observed that the development of ACR is often preceded by an increase in LSM values compared to those measured immediately post-transplant, possibly indicating the progressive onset of the intrahepatic inflammatory response. Notably, the increase in LSM in patients who will develop ACR occurs earlier than other signs traditionally considered suggestive of ACR, such as increased bilirubin, AST, and eosinophils count. Therefore, LSM in the early post-transplant setting could serve as an additional tool for enabling earlier diagnosis of ACR and, consequently, earlier treatment.