WASHINGTON — While the frequency of non-alcoholic steatohepatitis as an indicator for liver transplantation has increased, death from graft failure posttransplant related to NASH recurrence is less common than from cardiovascular complications and renal insufficiency, according to a presenter at Emerging Trends in Non-Alcoholic Fatty Liver Disease.
“In long-term studies, the highest frequency of graft loss related to recurrence of NASH appears to be around 5%. This is in stark contrast with hepatitis C ... with a 3rd of patients with HCV dying, requiring retransplantation or having cirrhosis due to recurrence of HCV within 5 years,” Michael R. Charlton, MD, of the department of medicine at the University of Chicago, said during his presentation. “Knowing that NASH itself is not an important cause of transplant graft failure and death, those other causes we looked at earlier — cardiovascular disease, neoplasia, renal insufficiency — these are much more common causes of death following liver transplantation, particularly in patients with fatty liver disease.”
Charlton’s presentation reviewed studies and reports from several databases, such as the Center for Disease Prevention and Control and the United Network for Organ Sharing, to analyze the frequency of different causes of liver graft failure and patient death following liver transplantation and the impact of immunosuppression courses.
In one prospective study of 800 patients, while the frequency of cause of death in posttransplant patients was initially similar, at 12 years the more frequent causes were HCV, malignancy, infection and cardiovascular disease. The most frequent cause in the long term was renal failure. Hypertension and diabetes were strong predictors for long term renal insufficiency as the cause of death. Several other studies reflected this frequency of cardiovascular and renal insufficiency as the leading cause of death.
Charlton’s presentation turned to discuss the impact of immunosuppression on different aspects of fatty liver disease. Both tacrolimus and cyclosporine, according to Charlton, were found to impair data cell function and decrease insulin secretion, enhancing insulin sensitivity. Calcineurin inhibitors increase systematic vascular resistance. And many immunosuppression therapies led to weight gain. Bariatric surgery for liver transplantation patients has important implications for management of immunosuppression posttransplantation, according to Charlton.
“There is no evidence for an accelerated course of NASH posttransplantation, [though] the school is still out a little bit on this. The impact of immunosuppression is generally not clear, but steroids should certainly be tapered early, and a minimalistic approach should be favored. The impact of immunosuppression on posttransplant metabolic syndrome is, however, evolving and current evidence all points to minimization being the prudent strategy, particularly for calcineurin inhibitors. Corticosteroids contribute to posttransplant metabolic syndrome and are not necessary beyond a short term; patients should be off of these by 6 months, unless they have some specific reason to continue, for example recurrence of autoimmune disease. The impact of mTOR inhibitors is complex; they are dyslipidemic but they have a low cardiovascular event rate and a lower transplant weight gain.” – by Talitha Bennett
Charlton MR. NASH and Liver Transplantation. Presented at: Emerging Trends in Non-Alcoholic Fatty Liver Disease; March 18-19, 2017; Washington.
Disclosure: Charlton reports receiving grant or research support from AbbVie, Gilead Sciences, Intercept, Janssen, Merck and Novartis as well as consulting for Gilead Sciences.