Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre- and post-transplant: A multi-system challenge

Abstract

Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease worldwide, and the fastest growing indication for liver transplantation in the United States. NASH is now the leading etiology for liver transplantation in women, the second leading indication for men, and the most common cause amongst recipients aged 65 years and older. Patients with end-stage liver disease related to NASH represent a unique and challenging patient population due the high incidence of associated comorbid diseases, including obesity, type 2 diabetes (T2D), and hypertension. These challenges manifest in the pre-liver transplantation period with increased waitlist times and waitlist mortality. Furthermore, these patients carry considerable risk of morbidity and mortality both before after liver transplantation, with high rates of T2D, cardiovascular disease, chronic kidney disease, poor nutrition, and disease recurrence. Successful transplantation for these patients requires identification and management of their comorbidities in the face of liver failure. Multidisciplinary evaluations include a thorough pre-transplant workup with a complete cardiac evaluation, control of diabetes, nutritional support, and even, potentially, consultation with a bariatric surgeon. This article provides a comprehensive review of the conditions and challenges facing patients with NASH cirrhosis undergoing liver transplantation and provides recommendations for evaluation and management to optimize them before liver transplantation to produce successful outcomes.

How best to combine liver transplantation and bariatric surgery?—Results from a global, web‐based survey

“…These answers reflect the current understanding that patients with end‐stage liver disease related to NASH and obesity are recognized as a specifically challenging patient population with higher risk for complications. Such candidates benefit from a multidisciplinary pretransplant assessment with thorough cardiovascular and metabolic workup and optimization of all comorbidities 46–49 . Despite the robust evidence for the effect of MBS on weight loss and the reduction of comorbidities, only a small fraction of the participants in our study considers a bariatric intervention (including endoscopic intervention) as part of the preparation programme for a LT. With the increasing proportion of patients undergoing LT for NASH cirrhosis, multidisciplinary evaluations of transplant candidates are increasingly integrated as essential part of the prelisting assessment to discuss treatment and workup modalities.…”

Sterile inflammation in liver transplantation

“…This is caused by persisting metabolic syndrome in these patients; liver transplantation treats their life-threatening symptoms, but does not reverse the etiology of the disease ( 105 ). The immune systems of these patients are still primed for chronic hepatic inflammation and buildup of fibrotic tissue in the implanted liver ( 106 ).…”

“…However, patients with metabolic syndrome that develop NASH severe enough to necessitate liver transplantation often develop de-novo NASH in the new liver (104). This is caused by persisting metabolic syndrome in these patients; liver transplantation treats their life-threatening symptoms, but does not reverse the etiology of the disease (105). The immune systems of these patients are still primed for chronic hepatic inflammation and buildup of fibrotic tissue in the implanted liver (106).…”

Understanding the Burden of Nonalcoholic Fatty Liver Disease: Time for Action

“…In addition, people with NASH are at higher risk for developing post-transplant diabetes, chronic kidney disease, myocardial infarction, and recurrence of NAFLD. Therefore, an extensive work-up that includes cardiology, bariatric surgery, nephrology, and nutrition consultations is needed, and strict follow-up post-transplant, with an emphasis on diet and exercise, is required, with close monitoring for post-transplant immunosuppression ( 31 ).…”

“…In fact, NASH is the top indication for women, individuals >55 years of age, and those with diabetes (28)(29)(30). Nevertheless, individuals with NAFLD/NASH have added challenges both pre-and post-transplantation given their high rate of comorbidities (e.g., obesity, diabetes, and hypertension), which not only extends their waitlist time, but also increases waitlist mortality (31). In addition, people with NASH are at higher risk for developing post-transplant diabetes, chronic kidney disease, myocardial infarction, and recurrence of NAFLD.…”