Liver transplantation in patients with alcohol and other substance use disorders

In this article we tackle the controversial subject of alcohol and other substance use following liver transplantation (LT). Most of the literature on and importance of this topic pertains not to recreational use of alcohol or substances but to patients who have alcohol or substance use disorders (AUDs/SUDs). To understand these behaviors after such a lifesaving and resource-intensive procedure as LT necessitates an understanding of these disorders as chronic medical diseases. It also requires an awareness that management of these disorders begins before transplant, so we will briefly touch on considerations to prepare patients for the transplantation. Additionally, we review not only the rates of alcohol and substance use post-LT but strategies clinicians could adopt to identify and manage these events post-LT. Thus, we will summarize approaches for monitoring use and a range of therapeutic treatment options, including pharmacotherapy, to employ once use is discovered. While clinical gastroenterologists may be the primary clinicians responsible for the care of LT recipients, we emphasize a multidisciplinary team approach which, especially for the behavioral health components of the treatment, is likely to be the most successful. This article concludes with a summary of recommendations for clinicians working with these patients and possible future directions for both clinical care and research. While the bulk of the literature is on LT in the context of AUD, we review the smaller body of literature available on non-alcohol substance use.

Converging lines of evidence point to a significant role of neuroinflammation in a host of psychiatric conditions, including alcohol use disorder, TBI, and PTSD. A complex interaction of both peripheral and central signaling underlies processes involved in neuroinflammation. Calcineurin is a molecule that sits at the nexus of these processes and has been clearly linked to a number of psychiatric disorders including alcohol use disorder (AUD). Like its role in regulating peripheral immune cells, calcineurin (CN) plays an integral role in processes regulating neuroimmune function and neuroinflammatory processes. Targeting CN or elements of its signaling pathways at critical points may aid in the functional recovery from neuroinflammatory related disorders. In this review we will highlight the role of neuroinflammation and calcineurin signaling in AUD, TBI and stress-induced disorders and discuss recent findings demonstrating a therapeutic effect of immunosuppressant-induced calcineurin inhibition in a pre-clinical model of binge alcohol drinking.

End-stage alcoholic liver disease is a recognised indication for liver transplantation but some questions on the matter remain open. It is difficult to quantify alcohol consumption, and a single definition of post-transplant relapse is lacking. Moreover, there are no internationally accepted criteria for the selection of candidates for liver transplantation and the eligibility parameters for these patients are controversial. Additional clinical and psychological evaluations are necessary in this setting, especially to establish the risk of alcohol relapse. Nevertheless, patient and graft survival rates after liver transplantation in alcoholic liver disease are comparable to those after transplant for other aetiologies, alcohol consumption relapse being one of the most important problems in the post-transplant phase.

In conclusion, alcohol-related liver disease is a good indication for liver transplantation. The main future goals are to formulate a well-defined pre-transplant approach and a single definition of alcohol relapse and to improve prevention strategies.

As long-term graft survival and mortality after liver transplantation improve, recognition that allografts may be affected by the same disease process that resulted in the failure of the liver is of both clinical and academic importance. Recipients need to be counseled about recurrence and potential impact on graft function and graft survival; clinicians need to be aware of the potential of recurrence to interpret the clinical, laboratory, radiologic, and histologic findings and alter management. Understanding which conditions recur in the allograft and factors associated with recurrence may shed light on pathogenesis. This article discusses the recurrence of nonviral diseases after liver transplantation, diagnosis, and management.