Predictors of De Novo Nonalcoholic Fatty Liver Disease After Liver Transplantation and Associated Fibrosis

Abstract

Nonalcoholic fatty liver disease (NAFLD) can occur de novo in patients undergoing liver transplantation (LT) for indications other than NAFLD, and it has been increasingly recognized as a complication in the post‐LT setting. This study aims to better characterize de novo NAFLD after LT by identifying risk factors for its development, describing incidence and extent of fibrosis, assessing the diagnostic utility of noninvasive serum fibrosis algorithms, and comparing survival to those without NAFLD. This was a retrospective single‐center analysis of de novo NAFLD in a post‐LT cohort. Those whose primary indication for LT was nonalcoholic steatohepatitis (NASH) were excluded. Risk factors were analyzed by univariate and multivariate analyses. De novo NAFLD and fibrosis were assessed on posttransplant liver biopsies, and noninvasive fibrosis scores were calculated from concomitant blood tests. After applying the exclusion criteria, 430 for‐cause post‐LT biopsies were evaluated; 33.3% (n = 143) had evidence of de novo steatosis and/or NASH at a median of 3.0 years after transplant. On multivariate analysis, body mass index (BMI; odds ratio [OR], 1.12; P < 0.001), diabetes mellitus (OR, 3.01; P = 0.002), hepatitis C virus (OR, 4.61; P < 0.001), weight gain (OR, 1.03; P = 0.007), and sirolimus use (OR, 3.11; P = 0.02) were predictive of de novo NAFLD after LT. Significant fibrosis (≥F2) was present in almost 40% of the cohort. Noninvasive serum fibrosis scores were not useful diagnostic tests. There was no significant difference in the short‐term or longterm survival of patients who developed de novo NAFLD. In conclusion, diabetes, BMI, weight gain after LT, and sirolimus‐based immunosuppression, in keeping with insulin resistance, were the only modifiable factors associated with development of de novo NAFLD. A significant proportion of patients with de novo NAFLD had fibrosis and given the limited utility of noninvasive serum fibrosis algorithms, alternative noninvasive tools are required to screen for fibrosis in this population. There was no significant difference in the short‐term or longterm survival of patients who developed de novo NAFLD.

Multidisciplinary Approach for Liver Transplantation in Patients with Nonalcoholic Steatohepatitis: It Takes a Village

“…Galvin et al conducted a retrospective single-center analysis in LT recipients, separately identifying pretransplant recipient risk factors to include older age, male sex, and HCV as indications for transplantation. 110 Donor risk factors include older donor age and higher donor BMI (►Table 3). On multivariate analysis, BMI and tacrolimus were risk factors for the development of de novo post-LT NALFD.…”

“…On multivariate analysis, BMI and tacrolimus were risk factors for the development of de novo post-LT NALFD. 110 The use of donor livers with severe hepatic steatosis (>60%) is associated with primary graft nonfunction. The use of donor livers with moderate-to-severe hepatic steatosis (>30%) is associated with diminished outcomes including a significant decrease in 4-month graft survival (76 vs. 89%; p < 0.05) and in 2-year patient survival (77 vs. 91%; p < 0.05).…”

“…In a recent study, Galvin et al evaluated the diagnostic utility of noninvasive fibrosis scores such as FIB-4 and found limited utility of these scores in posttransplant NAFLD fibrosis evaluation. 110 Unfortunately, there are no studies to date that compare the accuracy of TE for the diagnosis of NAFLD and fibrosis assessment with that for liver biopsy. Additionally, it is important to underscore the limitations of TE and how it impacts clinical practice, including liver position in instances of hemidiaphragmatic elevation or geometric mismatch of graft and abdominal cavity, and the lack of established cutoff values for the prediction of fibrosis or cirrhosis in the post-LT setting.…”

Predictors of De Novo Nonalcoholic Fatty Liver Disease After Liver Transplantation and Associated Fibrosis

“…(4) In this context, Galvin et al tried to answer some of the remaining questions. (5) The authors studied 430 patients, including 143 (33.3.%) with de novo NAFLD. Significant fibrosis (≥F2) was present in almost 40% of the patients, while 51.8% had NASH, and >5% had cirrhosis.…”

“…In this context, Galvin et al tried to answer some of the remaining questions . The authors studied 430 patients, including 143 (33.3.%) with de novo NAFLD.…”