Outcomes in patients with diabetes 10 years after liver transplantation

Ramos-Prol, Agustín; Hervás‐Marín, David; GarcÍa‐castell, Alia; Merino-Torres, Juan Francisco

doi:10.1111/1753-0407.12520

Cited by 10 publications

(11 citation statements)

References 39 publications

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“…In addition, we noted no impact of BMI on both all‐cause mortality and cardiovascular‐related mortality when BMI <30 and BMI ≥30 were compared. The presence of type 2 diabetes has been associated with an increased risk of adverse post‐transplant outcomes in an earlier study using the SRTR (The Scientific Registry of Transplant Recipients) data . Another study using UNOS data noted obesity alone was not associated with lower post‐transplant survival.…”

Section: Discussionmentioning

confidence: 99%

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Cardiovascular mortality among liver transplant recipients with nonalcoholic steatohepatitis in the United States-a retrospective study

et al. 2017

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Nonalcoholic steatohepatitis (NASH) has become an increasingly important indication for liver transplantation (LT), and there has been a particular concern of excessive cardiovascular-related mortality in this group. Using the United Network for Organ Sharing-Standard Transplant Analysis and Research (UNOS STAR) dataset, we reviewed data on 56,995 adult transplants (January 2002 through June 2013). A total of 3,170 NASH liver-only recipients were identified and were matched with 3,012 non-NASH HCV+ and 3,159 non-NASH HCV- controls [matched 1:1 based on gender, age at LT (±3 years), and MELD score (±3)]. Cox regression analysis revealed significantly lower hazard of all-cause (HR 0.669; P < 0.0001) and cardiovascular-related mortality (HR 0.648; P < 0.0001) in the NASH compared to the non-NASH group after adjusting for diabetes, BMI, and race. Relative to the non-NASH HCV-positive group, NASH group has lower hazard of all-cause (HR 0.539; P < 0.0001) and cardiovascular-related mortality (HR 0.491; P < 0001). A lower hazard of all-cause mortality (HR 0.844; P = 0.0094) was also observed in NASH patients compared to non-NASH HCV-negative group, but cardiovascular mortality was similar (HR 0.892; P = 0.3276). LT recipients with NASH have either lower or similar risk of all-cause and cardiovascular-related mortality compared to its non-NASH counterparts after adjusting for diabetes, BMI, and race.

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Section: Discussionmentioning

confidence: 99%

“…The impact of DM on long‐term survival of the transplant recipients has been reported . Diabetes has been associated with a higher risk of liver graft rejection and cardiovascular events . Despite evidence for such association with diabetes, a recent study has also reported no impact of diabetes on the post‐transplant outcome .…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular mortality among liver transplant recipients with nonalcoholic steatohepatitis in the United States-a retrospective study

et al. 2017

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“…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 ). Diabetes mellitus is also a major risk factor involved in ischemic diseases affecting multiple organs, including the heart ( 6 ), brain ( 7 ), kidney ( 8 ), and liver ( 9 , 10 ).…”

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

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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.

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“…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]. Ramos-Prol et al reported a trend for higher mortality in liver graft recipients with diabetes, showing to the need for more rigorous pretransplant evaluation and closer monitoring after OLT in order to reduce associated complications in diabetics [17]. Additionally, transplanted patients with hepatitis B-related hepatocellular carcinoma and diabetes mellitus had decreased survival and poor OLT outcomes at 1, 3, and 5 years after the procedure [18].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Outcomes in patients with diabetes 10 years after liver transplantation

Cited by 10 publications

References 39 publications

Cardiovascular mortality among liver transplant recipients with nonalcoholic steatohepatitis in the United States-a retrospective study

Cardiovascular mortality among liver transplant recipients with nonalcoholic steatohepatitis in the United States-a retrospective study

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?

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