Systematic review with meta‐analysis: de novo non‐alcoholic fatty liver disease in liver‐transplanted patients

Losurdo, Giuseppe; Castellaneta, Antonino; Rendina, Maria; Carparelli, Sonia; Leandro, Gioacchino; Leo, Alfredo Di

doi:10.1111/apt.14521

Cited by 48 publications

(46 citation statements)

References 62 publications

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“…Moreover, TAC could induce hepatic triglyceride accumulation via increasing SREBP1 expression. Clinical studies have shown a close association between TAC and posttransplant hepatic steatosis . The results provided direct evidence for the molecular mechanism of TAC‐related hepatic steatosis.…”

Section: Discussionmentioning

confidence: 64%

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The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

Ling

Huang

Han

et al. 2020

American Journal of Transplantation

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Tacrolimus (TAC), the mainstay of maintenance immunosuppressive agents, plays a crucial role in new‐onset diabetes after transplant (NODAT). Previous studies investigating the diabetogenic effects of TAC have focused on the β cells of islets. In this study, we found that TAC contributed to NODAT through directly affecting hepatic metabolic homeostasis. In mice, TAC‐induced hypoglycemia rather than hyperglycemia during starvation via suppressing gluconeogenetic genes, suggesting the limitation of fasting blood glucose in the diagnosis of NODAT. In addition, TAC caused hepatic insulin resistance and triglyceride accumulation through insulin receptor substrate (IRS)2/AKT and sterol regulatory element binding protein (SREBP1) signaling, respectively. Furthermore, we found a pivotal role of CREB‐regulated transcription coactivator 2 (CRTC2) in TAC‐induced metabolic disorders. The restoration of hepatic CRTC2 alleviated the metabolic disorders through its downstream molecules (eg, PCK1, IRS2, and SREBP1). Consistent with the findings from bench, low CRTC2 expression in graft hepatocytes was an independent risk factor for NODAT (odds ratio = 2.692, P = .023, n = 135). Integrating grafts’ CRTC2 score into the clinical model could significantly increase the predictive capacity (areas under the receiver operating characteristic curve: 0.71 vs 0.79, P = .048). Taken together, in addition to its impact on pancreatic cells, TAC induces “hematogenous diabetes” via CRTC2 signaling. Liver‐targeted management may be of help to prevent or heal TAC‐associated diabetes.

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Section: Discussionmentioning

confidence: 64%

“…Clinical studies have shown a close association between TAC and posttransplant hepatic steatosis. 27,28 The results provided direct evidence for the molecular mechanism of TAC-related hepatic steatosis.…”

Section: Discussionmentioning

confidence: 79%

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

Ling

Huang

Han

et al. 2020

American Journal of Transplantation

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“…Additionally, de novo NAFLD in LT patients not transplanted due to NASH is being increasingly observed. One systematic review reported a 26% pooled weighted prevalence of biopsy‐proven de novo NAFLD in a LT patient population . In a single‐center study of patients undergoing LT for NASH, Malik et al identified recurrent NAFLD, NASH, and stage 2 fibrosis in 70%, 25%, and 18% of patients, respectively, with a mean follow‐up time of 18 months .…”

Section: Methodsmentioning

confidence: 99%

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post–liver transplant patient

Winters

Mittal

Schiano

2019

Clinical Transplantation

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Liver biopsy is considered the gold standard method for diagnosing and staging liver disease, particularly in the post-liver transplant setting. Given the invasive nature of biopsy, alternate means for accurately assessing liver fibrosis and steatosis are preferred especially as the number of patients with fatty liver disease is increasing.Transient elastography has been validated as a useful tool for evaluation of liver fibrosis, as has controlled attenuation parameter index as a tool for assessing steatosis. It is a non-invasive, rapid, and highly reproducible approach to demonstrate the presence of fibrosis among non-transplant patients with chronic liver disease of various etiologies. However, it has not yet found wide acceptance in liver transplant recipients. There are few published studies evaluating the merits and applicability of transient elastography to assess allografts after liver transplantation. We review the published data on the use of transient elastography with concurrent controlled attenuation parameter in liver transplant recipients and recommend its greater use to follow allograft function over time.

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“…(1) A meta-analysis including 2166 patients showed a 26% pooled prevalence of de novo NAFLD in posttransplant patients. (2) The majority of studies have not shown a clear association between recurrent or de novo NAFLD/ NASH and survival; however, the quality of the evidence is low. (1) This bias toward a limited clinical importance may be related to the small number of patients or the short-term follow-up in the majority of studies.…”

Section: To the Editormentioning

confidence: 99%

“…Nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is very common in the posttransplant population, and the progression of fibrosis is accelerated in these patients as compared with NASH patients in the general population . A meta‐analysis including 2166 patients showed a 26% pooled prevalence of de novo NAFLD in posttransplant patients . The majority of studies have not shown a clear association between recurrent or de novo NAFLD/NASH and survival; however, the quality of the evidence is low .…”

mentioning

confidence: 99%

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

et al. 2019

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Systematic review with meta‐analysis: de novo non‐alcoholic fatty liver disease in liver‐transplanted patients

Cited by 48 publications

References 62 publications

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post–liver transplant patient

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

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