Background: Despite advancements in immunosuppressive therapies, rejection remains a significant challenge post-liver transplantation. Current diagnostic methods for rejection, such as liver biopsy, are invasive and may not capture rejection episodes in a timely manner. The emergence of circulating biomarkers, particularly donor-derived cell-free DNA (ddcfDNA), presents a promising non-invasive approach for rejection diagnosis and therapeutic monitoring. This case report explores the feasibility and potential benefits of ddcfDNA measurement into clinical practice for liver transplant recipients.
Methods: A 45-year-old male patient, about 200 days after deceased-donor liver transplantation for alcoholic liver cirrhosis, visited our hospital for regular follow-up. His liver function has been well maintained during the post-transplant follow-up, but on this day, his total bilirubin level was elevated to 3.02 mg/dL aspartate transaminase (AST) was 469 U/L alanine transaminase (ALT) was 779 U/L and he complained of itching sensation. The tacrolimus level was 11.3 ng/mL, however, the patient reported that he had skipped his immunosuppressant medication while traveling the week before.
Result: The patient was hospitalized with suspected acute rejection, and a liver biopsy was performed to confirm diagnosis and the first serum ddcfDNA sample was collected. We check absolute number of ddcfDNA copies per mL of plasma and fraction of ddcfDNA (ddcfDNA%) and the result was 39.1%. Patient was diagnosed with T-cell mediated rejection, steroid pulse therapy was initiated with an intravenous methylprednisolone dose of 500 mg/day administered for 3 days and then tapered by half every day to 60 mg/day. After that, patient discharged with oral methylprednisolone initiated at 32 mg/day, tapered to 4–8 mg/day within 1–2 weeks. On discharge day, the total bilirubin level was 1.69 mg/dL, AST was 51 U/L, ALT was 164 U/L, and the patient was discharged without any symptoms. And second serum ddcfDNA sample was collected at patient discharge day, the result was 9.01%, a decrease from the time of admission.
Conclusions: ddcfDNA serves as a sensitive biomarker for detecting graft injuries in liver transplant recipients. Further large‐scale research, which should ideally include protocol biopsies, will be needed to establish the practical value of ddcfDNA measurements in the management of liver transplant recipients.