HCV Infection and Post-liver Transplant Diabetes
HCV Infection and Post-liver Transplant Diabetes
Background Hepatitis C virus (HCV) is associated with metabolic manifestations including insulin resistance and diabetes through various mechanisms. Whether HCV infection is associated with an increased risk of post-transplant diabetes in liver transplant recipients is unclear.
Aim To assess the association of HCV infection with post-transplant diabetes.
Methods All liver transplant recipients infected with hepatitis C (exposed) and hepatitis B (HBV) (controls) with post-transplant follow-up from the Scientific Registry of Transplant Recipients (2003–2012) were included.
Results A total of 17 121 HCV patients and 1450 HBV controls were included in this observational study. Subjects with HCV were more likely to be overweight and obese at transplant, but the rate of pre-transplant diabetes of 13.7% was similar to HBV (P > 0.05). Post-transplant, 32.5% of HCV patients and 27.5% of HBV patients had diabetes (P < 0.0001). This difference was observed starting as early as 6 months post-transplant: 22.5% HCV and 18.9% HBV (P= 0.0043). With longer follow-up, both the cumulative and incidental risks of developing post-transplant diabetes were consistently higher in HCV patients. In particular, by 5 years post-transplant, both the relative risk of having diabetes [1.18 (1.08–1.29), P = 0.0002] and the hazard ratio for time to developing diabetes [1.27 (1.15–1.41), P < 0.0001] were significantly higher in HCV patients compared to HBV patients. In multivariate analysis, after adjustment for confounders including the use of immunosuppressants, hepatitis C infection was independently associated with developing post-transplant diabetes: aHR = 1.55 (1.34–1.79), P < 0.0001.
Conclusion Hepatitis C infection is associated with a higher risk of post-transplant diabetes that persists up to 5 years post-transplant.
Over the past decades, a number of reports from both cohort and population-based studies have suggested an association between hepatitis C virus (HCV) infection and insulin resistance (IR) and type 2 diabetes (DM). HCV-induced diabetes mellitus is currently believed to be a result of insulin resistance in both hepatic and peripheral tissue. Of potential mechanisms behind this association, it has been demonstrated that secretion of tumour necrosis factor- promotes IR through its impact on the insulin signaling pathway. HCV core protein levels have also been linked with decreasing the expression of insulin receptor substrate (IRS)-1 and -2, and up-regulation of the degradation of IRS-1 and IRS-2, both leading to an increase in homoeostasis of model assessment (HOMA) scores and developing insulin resistance and type 2 diabetes. Furthermore, direct autoimmune destruction of pancreatic β-cells has also been suggested.
However, very few studies have investigated whether this association of IR/DM and HCV continues post-liver transplantation (LT) in HCV-positive patients. Current evidence suggests that there is an increased risk of development post-transplant DM in patients with HCV, especially in patients who had IR/DM prior to transplantation: more than 50% of such patients develop diabetes post-transplantation. However, questions still persist as to how strong this relationship is and also whether the extent of this association is influenced by diabetogenic immunosuppressive drugs such as tacrolimus. To assess this potential association, a large collection of liver transplant data to include clinical outcomes and extensive clinical data would be very useful.
Therefore, the aim of this study is to assess the incidence and independent risk factors for developing post-liver transplant DM in a cohort of HCV-infected patients.
Abstract and Introduction
Abstract
Background Hepatitis C virus (HCV) is associated with metabolic manifestations including insulin resistance and diabetes through various mechanisms. Whether HCV infection is associated with an increased risk of post-transplant diabetes in liver transplant recipients is unclear.
Aim To assess the association of HCV infection with post-transplant diabetes.
Methods All liver transplant recipients infected with hepatitis C (exposed) and hepatitis B (HBV) (controls) with post-transplant follow-up from the Scientific Registry of Transplant Recipients (2003–2012) were included.
Results A total of 17 121 HCV patients and 1450 HBV controls were included in this observational study. Subjects with HCV were more likely to be overweight and obese at transplant, but the rate of pre-transplant diabetes of 13.7% was similar to HBV (P > 0.05). Post-transplant, 32.5% of HCV patients and 27.5% of HBV patients had diabetes (P < 0.0001). This difference was observed starting as early as 6 months post-transplant: 22.5% HCV and 18.9% HBV (P= 0.0043). With longer follow-up, both the cumulative and incidental risks of developing post-transplant diabetes were consistently higher in HCV patients. In particular, by 5 years post-transplant, both the relative risk of having diabetes [1.18 (1.08–1.29), P = 0.0002] and the hazard ratio for time to developing diabetes [1.27 (1.15–1.41), P < 0.0001] were significantly higher in HCV patients compared to HBV patients. In multivariate analysis, after adjustment for confounders including the use of immunosuppressants, hepatitis C infection was independently associated with developing post-transplant diabetes: aHR = 1.55 (1.34–1.79), P < 0.0001.
Conclusion Hepatitis C infection is associated with a higher risk of post-transplant diabetes that persists up to 5 years post-transplant.
Introduction
Over the past decades, a number of reports from both cohort and population-based studies have suggested an association between hepatitis C virus (HCV) infection and insulin resistance (IR) and type 2 diabetes (DM). HCV-induced diabetes mellitus is currently believed to be a result of insulin resistance in both hepatic and peripheral tissue. Of potential mechanisms behind this association, it has been demonstrated that secretion of tumour necrosis factor- promotes IR through its impact on the insulin signaling pathway. HCV core protein levels have also been linked with decreasing the expression of insulin receptor substrate (IRS)-1 and -2, and up-regulation of the degradation of IRS-1 and IRS-2, both leading to an increase in homoeostasis of model assessment (HOMA) scores and developing insulin resistance and type 2 diabetes. Furthermore, direct autoimmune destruction of pancreatic β-cells has also been suggested.
However, very few studies have investigated whether this association of IR/DM and HCV continues post-liver transplantation (LT) in HCV-positive patients. Current evidence suggests that there is an increased risk of development post-transplant DM in patients with HCV, especially in patients who had IR/DM prior to transplantation: more than 50% of such patients develop diabetes post-transplantation. However, questions still persist as to how strong this relationship is and also whether the extent of this association is influenced by diabetogenic immunosuppressive drugs such as tacrolimus. To assess this potential association, a large collection of liver transplant data to include clinical outcomes and extensive clinical data would be very useful.
Therefore, the aim of this study is to assess the incidence and independent risk factors for developing post-liver transplant DM in a cohort of HCV-infected patients.
