Editorial: Redefining Safety in Post‐Liver Transplant IBD—Why Therapeutic Effectiveness Is the Ultimate Shield. Authors' Reply

We would like to thank Quraishi and Al-Bawardy for their comments [1] regarding our paper [2]. As they rightly point out, primary sclerosing cholangitis (PSC) is a known independent risk factor for the development of colorectal neoplasia in patients with inflammatory bowel disease (IBD) [3, 4]. This risk is not eradicated following liver transplantation [5]. In PSC, colorectal neoplasia (CRN) risk may be linked to the extent (i.e., the surface area involved), along with the duration and degree of colonic inflammation. Hence, reducing the extent, degree and duration of inflammation is thought to reduce the risk of CRN. Both biologic and small molecule therapies have previously been demonstrated to have efficacy in the control of IBD in patients with coexistent PSC and IBD [6, 7]. However, there is no evidence to indicate that any of the advanced therapies available for IBD mitigate the risk of CRN in PSC patients. While it appears that advanced therapies do reduce colitis in IBD-PSC, comparative data are difficult to obtain in the context of relatively small sample sizes, making therapeutic positioning challenging. In addition, mechanisms other than persistent colonic inflammation (such as altered bile acid or gut microbial composition) may contribute to CRN risk in PSC-IBD patients [5]. This implies that controlling CRN risk in these patients may not be as straightforward as solely controlling their IBD. Adding further to the complexity of therapeutic decision-making is the fact that post-liver transplant PSC-IBD patients must also contend with the risk of extra-colonic malignancy. There is an increased risk of de novo malignancy in liver transplant recipients, which has been attributed at least in part to the long-term immunosuppression required post-transplant [8]. Of note, malignancies such as post-transplant lymphoproliferative disorder are directly linked to the depth and duration of immunosuppression [9]. The impact that prolonged durations of combination biologic and transplant immunosuppression may have on such malignant complications remains unknown. We agree that controlling mucosal inflammation is paramount in PSC-IBD patients following liver transplantation and should remain our aspirational goal as IBD clinicians in line with STRIDE targets [10]. However, given the multifaceted oncologic risk that this population faces, this remains a complex area of decision-making that must be guided by collaborative multidisciplinary discussion with our transplant physician colleagues and ongoing research efforts including larger cohorts with longer periods of follow-up. The authors' declarations of personal and financial interests are unchanged from those in the original article [2]. Simone Chin: writing – original draft. Danny Con: writing – review and editing. Patrick Hilley: writing – review and editing. Crispin Corte: writing – review and editing. Ken Liu: writing – review and editing. Adam Testro: writing – review and editing. Peter De Cruz: writing – original draft, writing – review and editing. Matthew C. Choy: writing – review and editing. Ashish Srinivasan: writing – review and editing.