Adjuvant treatment with Capecitabine in patients who received orthotopic liver transplantation with incidental diagnosis of intrahepatic cholangiocarcinoma. Implications on DPYD polymorphisms assessment: report of two cases and review of the literature

In recent years, assessing dihydropyrimidine dehydrogenase (DPD) activity has become crucial for cancer patients undergoing 5-fluorouracil (5FU)-based chemotherapy due to the life-threatening toxicity associated with reduced DPD function. The methods for evaluating DPD activity have evolved, with the analysis of DPYD polymorphisms in blood samples becoming the preferred approach. As the indications for liver transplantation are increasing—particularly due to a rise in cases of cholangiocarcinoma (CCA) and non-resectable colorectal liver metastasis—more cancer patients with a history of liver transplantation may experience disease relapse. Furthermore, 5-fluorouracil chemotherapy is a standard treatment for both cancers. This growing need to evaluate DPD activity in transplanted livers arises because standard tests conducted on blood samples reflect the activity of native liver tissue and may produce misleading results. This paper presents two clinical cases from 2022 to 2023 involving patients who underwent successful liver transplants but were later diagnosed with intrahepatic CCA in the explanted liver. Both patients were subsequently prescribed capecitabine as adjuvant chemotherapy, making it essential to assess DPD activity in donor liver tissue to ensure safe treatment protocols. However, there are currently no established guidelines for this specific patient group. If we follow standard clinical practice, this critical analysis will be insufficient, as it only describes the DPD activity of the native liver. It is imperative to determine the DPD activity of the transplanted liver. In summary, this case report highlights the importance of managing this complex situation effectively