OP31 Can liver biopsy guide the management of deranged liver function tests in liver transplant recipients receiving Kaftrio?

Introduction

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a life-changing treatment for people with cystic fibrosis (CF). Its use in liver transplant recipients needs to be carefully assessed due to possible worsening of liver function tests (LFTs) and interactions with immunosuppressive treatment. We report our initial experience of ELX/TEZ/IVA in liver transplant recipients.

Methods

A retrospective review of clinical, biochemical, and histological data for adult liver transplant recipients receiving ELX/TEZ/IVA treatment was undertaken. All were attending the Leeds adult regional CF Centre and under regular review by the joint liver and CF multidisciplinary team.

Results

Four post liver transplant recipients (3 Male F/F, 1 female F/MF, age 18–45 y, median baseline FEV1 51.5 [31–72]%) had been started on ELX/TEZ/IVA. Median time from transplant was 6.5 [2–12] years. Treatment resulted in improved FEV1 (relative increase 22 (10–30)%), reduction in IV antibiotics requirement and sweat chloride concentration (median drop 50 (20–71) mmol/l) in all subjects. One subject (F, 42y) had no liver-related side effects and did not require tacrolimus dose adjustment. All male patients experienced increase in LFTs (max ALT 108–180 iU/L, max bilirubin 30–57 umol/L) within the first two months of treatment and underwent liver biopsy. In two cases, histopathology revealed unremarkable liver parenchyma and absence of drug-induced liver injury or rejection. In the third case, peri-venulitis, marked inflammation and mild fibrosis were identified and thought to reflect worsening features of a previously identified immuno-mediated pathology, requiring temporarily suspension of ELX/TEZ/IVA and augmented immunosuppression. The latter subject is now back on treatment and remains stable.

Conclusion

In our small cohort, ELX/TEZ/IVA caused acute derangement in LFTs in liver transplant recipients. Liver biopsy, reassuringly, showed no features of drug-induced liver injury.