Immunosuppressive regimens for adult liver transplant recipients in real-life practice: consensus recommendations from an Italian Working Group

Abstract

It is a well-recognized fact that implementing new guidelines in clinical practice may be difficult; therefore the Italian Society for Organ and Tissue Transplantation (SITO) set out to define practical immunosuppression tools for the management of liver transplantation patients. In 2017, an Italian Working Group of liver transplant experts and hepatologists issued a set of consensus statements along with evidence-based recommendations on the use of everolimus after liver transplantation. This article presents the evidence- and consensus-based algorithms developed within the Italian Working Group, which are aimed towards guiding clinicians in the selection of immunosuppressive regimens for the management of adult liver transplant recipients in real-life practice. The liver transplant recipient population, typically managed in clinical practice, was divided into the following categories: (1) standard patients; (2) critically ill patients; (3) patients with a specific etiology; (4) patients with hepatocellular carcinoma; (5) and patients with de novo malignancies. The algorithms are divided into two parts, according to the time from transplantation (0–3 months and > 3 months) and are discussed here along with relevant supporting literature, when available. Ultimately, it is hoped that the evidence- and consensus-based algorithms developed within the Italian Working Group, and presented here, contribute to simplify, personalize, and optimize immunosuppression of liver transplantation recipients in clinical practice.

Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation

“…Moreover, in clinical practice, side effects profile and comorbidities including kidney dysfunction must also be considered in the choice of the optimal immunosuppression strategy for a specific patient. However, while waiting for further well-designed multicenter studies delineating the use of mTOR inhibitors, an attempt in implementing strategies to reduce CNIs in order to limit the impact of their exposure on cancer recurrence is reasonable [ 124 ].…”

Foremost Concepts in Mechanisms of De Novo Post-Liver Transplantation Malignancy

“…In standard patients after LT, the first choice of IS, based on CNI, is often TAC, whereas cyclosporine could be optional [30]. The immunosuppressive mechanism of TAC is described in detail below (Figure 1).…”

“…A plethora of studies report the adverse effects associated with prolonged usage of CNI. Hence, strategies to reduce these adverse effects, including dose reduction or switching to another IS class, should be kept in mind by clinicians [30].…”

“…Most of the IS guidelines recommend MMF as IS combined with another IS class, such as CNI or mTOR inhibitors. The IS regimens containing MMF allow a reduction in CNI-induced renal toxicity through maintaining the dosages of CNI [30]. Initially, MMF was used as an antineoplastic agent because of its ability to inhibit some tumor cell lines' proliferation [49].…”

Tolerance and minimization of immunosuppressive therapy after liver transplantation

“…Представленные алгоритмы позволяют минимизировать риски нежелательных явлений и токсичности иммуносупрессантов (рис. 3, 4) [22]. Эти рекомендации согласуются и с приведенными выше экспериментальными данными о рациональных схемах иммуносупрессии, основанных на влиянии известных препаратов на фиброгенез в печени.…”