Pretransplant diabetes mellitus predicts worse outcomes of liver transplantation: evidence from meta-analysis

Li, P.; Fan, Huifeng; He, Qiang

doi:10.1007/s40618-017-0721-z

Cited by 14 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Diabetes mellitus may be evident in up to 30 % of patients with liver cirrhosis [34]. In further studies, the prevalence of pretransplant diabetes mellitus ranges between 15 % and 26 % [35]. In our patient cohort, pretransplant diabetes was found in 23.1 % of patients.…”

Section: Discussionmentioning

confidence: 50%

“…A recently publishes meta-analysis of Li et al indicated patients with pretransplant diabetes mellitus to be at higher risk for graft loss. Hyperglycemia associated systemic inflammation has been discussed to be an important underlying mechanism [35]. However, recurrence of fatty liver diseases and nonalcoholic steatohepatitis in diabetic patients after LT may also play an important role [36].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Risk factors for allograft failure in liver transplant recipients

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Risk factors for allograft failure in liver transplant recipients

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Diabetes is a global epidemic, and up to 25% of liver transplant patients have pre-existing diabetes mellitus ( 3 ). Pretransplant diabetes is a predictor of poor outcome following liver transplantation ( 4 ). One recent study reported that patients with diabetes have a higher risk of liver graft rejection ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia Aggravates Hepatic Ischemia and Reperfusion Injury by Inhibiting Liver-Resident Macrophage M2 Polarization via C/EBP Homologous Protein-Mediated Endoplasmic Reticulum Stress

et al. 2017

View full text Add to dashboard Cite

Aggravated liver ischemia and reperfusion (IR) injury has been observed in hyperglycemic hosts, but its underlying mechanism remains undefined. Liver-resident macrophages (Kupffer cells, KCs) and endoplasmic reticulum (ER) stress play crucial roles in the pathogenesis of liver IR injury. In this study, we evaluated the role of ER stress in regulating KC activation and liver IR injury in a streptozotocin-induced hyperglycemic/diabetic mouse model. Compared to the control group (CON group), hyperglycemic mice exhibited a significant increase in liver injury and intrahepatic inflammation following IR. KCs obtained from hyperglycemic mice secreted higher levels of the pro-inflammatory factors TNF-α and IL-6, while they secreted significantly lower levels of the anti-inflammatory factor IL-10. Furthermore, enhanced ER stress was revealed by increased C/EBP homologous protein (CHOP) activation in both IR-stressed livers and KCs from hyperglycemic mice. Specific CHOP knockdown in KCs by siRNA resulted in a slight decrease in TNF-α and IL-6 secretion but dramatically enhanced anti-inflammatory IL-10 secretion in the hyperglycemic group, while no significant changes in cytokine production were observed in the CON group. We also analyzed the role of hyperglycemia in macrophage M1/M2 polarization. Interestingly, we found that hyperglycemia inhibited IL-10-secreting M2-like macrophage polarization, as revealed by decreased Arg1 and Mrc1 gene induction accompanied by a decrease in STAT3 and STAT6 signaling pathway activation. CHOP knockdown restored Arg1 and Mrc1 gene induction, STAT3 and STAT6 activation, and most importantly, IL-10 secretion in hyperglycemic KCs. Finally, in vivo CHOP knockdown in KCs enhanced intrahepatic anti-inflammatory IL-10 gene induction and protected the liver against IR injury in hyperglycemic mice but had no significant effects in control mice. Our results demonstrate that hyperglycemia induces hyper-inflammatory activation of KCs during liver IR injury. Thus, hyperglycemia-induced CHOP over-activation inhibits IL-10-secreting M2-like macrophage polarization by liver-resident macrophages, thereby leading to excessive inflammation and the exacerbation of liver IR injury in diabetic/hyperglycemic hosts. This study provides novel mechanistic insight into macrophage inflammatory activation under hyperglycemic conditions during liver IR.

show abstract

“…Additionally, diabetes mellitus was, among others, a risk factor for intracardiac and pulmonary thromboembolism leading to liver recipient death within 24 h after OLT in multivariable regression analysis [14]. Meta-analysis of the results of OLT in 15 768 diabetic recipients and 60 176 non-diabetic OLT patients clearly showed that preexisting diabetes increased the risk of death after surgery by 40%, as well as increasing graft loss, with a hazard ratio (HR) of 1.28 [15]. Of note, patients with sustained post-transplant diabetes had significantly increased risk of major cardiovascular events after OLT, with HR 1.95, and cumulative risk of 13% and 27% at 5 and 10 years after OLT, respectively [16].…”

Section: Discussionmentioning

confidence: 99%

Renaissance of Modified Charlson Comorbidity Index in Prediction of Short- and Long-Term Survival After Liver Transplantation?

et al. 2019

View full text Add to dashboard Cite

Background Orthotopic liver transplantation (OLT) is the standard of care for end-stage liver disease. The Charlson Comorbidity Index (CCI) was originally created to assess the survival rate of patients with chronic diseases, although it was modified and adopted in OLT recipients as CCI-OLT. Material/Methods In total of 248 consecutive liver transplant recipients with viral cirrhosis in 98 (39.5%) patients were included. CCI-OLT was calculated assigning a weight of 3 to chronic obstructive pulmonary disease; weight of 2 to coronary artery disease, connective tissue disease, and renal insufficiency; and a weight of 1 to diabetes mellitus. Results CCI-OLT was significantly correlated with recipient age (p<0.001; R=0.333) and was a significant risk factor for early post-transplant mortality (p=0.004). The presence of diabetes mellitus significantly increased the odds of early mortality (p=0.010). The optimal cut-off for CCI-OLT in prediction of mortality during the first 90 days after transplantation was ≥1, with an AUROC of 0.780 (95% CI: 0.670–0.891; p<0.001). Increasing CCI-OLT was a significant risk factor for worse 5-year post-transplant survival (p=0.001), along with coronary artery disease (p=0.008) and diabetes mellitus (p=0.021). The optimal cut-off for prediction of 5-year mortality for CCI-OLT was ≥1, with the AUROC of 0.638 (95% CI: 0.544–0.733; p=0.004). Conclusions CCI-OLT is a useful tool for measuring the effect of pretransplant comorbidities and to stratify the effect of risk on both short- and long-term outcomes after OLT. Recipient age and diabetes strongly affected short-term survival after OLT, and metabolic and vascular complications were the leading causes of death at 5 years after OLT.

show abstract

Pretransplant diabetes mellitus predicts worse outcomes of liver transplantation: evidence from meta-analysis

Abstract: Preexisting DM predicts worse patient and graft survivals of LT. Concomitant HCV infection would further deteriorate this unfavorable impact. Given the high heterogeneities and the insufficient evidences, more studies are still warranted to support these observations.

Cited by 14 publications

References 26 publications

Risk factors for allograft failure in liver transplant recipients

Risk factors for allograft failure in liver transplant recipients

Hyperglycemia Aggravates Hepatic Ischemia and Reperfusion Injury by Inhibiting Liver-Resident Macrophage M2 Polarization via C/EBP Homologous Protein-Mediated Endoplasmic Reticulum Stress

Renaissance of Modified Charlson Comorbidity Index in Prediction of Short- and Long-Term Survival After Liver Transplantation?

Contact Info

Product

Resources

About