Risk factors for fractures following liver transplantation: a population-based cohort study

Ann Med. 2023 Dec;55(1):2230871. doi: 10.1080/07853890.2023.2230871.

Abstract

Background: Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant in a Taiwanese population.

Methods: We identified newly diagnosed liver transplant recipients from the National Health Insurance Research Database in Taiwan between 2003 and 2015. Risk factors of post-transplant fractures were analyzed using a Cox proportional hazards model.

Results: A total of 4821 patients underwent liver transplantation, of whom 419 (8.7%) had post-transplant fractures. Independent predictors of post-transplant fractures were age ≥65 years at transplantation (hazard ratio (HR): 1.566; 95% confidence interval (CI) 1.122-2.186), female sex (HR: 1.648; 95% CI 1.319-2.057), fractures within 1 year prior to transplant (HR: 3.664; 95% CI 2.503-5.364), hepatitis C carriers (HR: 1.594; 95% CI 1.289-1.970), alcoholism (HR: 1.557; 95% CI 1.087-2.230) and daily prednisolone dose >1.61-3.78 mg/day (HR: 1.354; 95% CI 1.005-1.824), >3.78-9.18 mg (HR: 4.182; 95% CI 3.155-5.544) and >9.18 mg (HR: 13.334; 95% CI 9.506-18.703). Post-transplant fractures were inversely correlated with tacrolimus (HR: 0.617; 95% CI 0.417-0.913) and sirolimus/everolimus (HR: 0.504; 95% CI 0.391-0.650) treatment.

Conclusions: The liver transplant recipients, and especially those who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were associated with an increased risk of post-transplant fractures. Conversely, the use of tacrolimus and sirolimus/everolimus was associated with a decreased risk of fractures.

Keywords: Fracture; glucocorticoid; hepatitis B; hepatitis C; immunosuppressant; liver transplantation.

Plain language summary

This study identified risk factors for fractures after liver transplant in a population-based study in an area with high prevalence of hepatitis B and hepatitis C.Recipients who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were independent risk factors for post-transplant fractures.Our findings highlight the importance of identifying individuals at high risk of fractures and concomitant tacrolimus and sirolimus/everolimus treatment to avoid the use of high-dose steroids and prevent post-transplant fractures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism* / complications
  • Alcoholism* / drug therapy
  • Cohort Studies
  • Everolimus
  • Female
  • Fractures, Bone* / epidemiology
  • Fractures, Bone* / etiology
  • Hepatitis C* / complications
  • Hepatitis C* / drug therapy
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Liver Transplantation* / adverse effects
  • Prednisolone
  • Proportional Hazards Models
  • Risk Factors
  • Sirolimus / adverse effects
  • Tacrolimus / therapeutic use

Substances

  • Tacrolimus
  • Everolimus
  • Sirolimus
  • Prednisolone
  • Immunosuppressive Agents

Grants and funding

This study was supported by a grant from Taipei Veterans General Hospital (V109C-164).