Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study

Abstract

Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long-term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow-up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal-related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre-LT diabetes, post-LT diabetes, post-LT hypertension, post-LT renal insufficiency, retransplantation >1 year, pre-LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post-LT diabetes, hypertension and renal insufficiency were significant risk factors for liver-related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre-LT hypertension and post-LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post-LT factors including diabetes, hypertension and renal insufficiency may impact long-term mortality.

Figure 1. Kaplan-Meier Mortality Curve

The probability of death after liver transplant exhibited a trimodal pattern, with the greatest risk during the first 6 months post transplant, decreasing and remaining stable for 8 years post-LT, and increasing thereafter.

Figure 2

A. Causes Death Overall, N=327. B. Non-Hepatic Causes of Deaths, N=207. CV=Cardiovascular.

Figure 3. Cause Specific Probability of Death Over Time (by Primary cause)

Infection is the leading cause of death over the first 3 years, with majority occurring in the first 6 months. Liver related causes of death are the most common cause of death thereafter and overall, with increased frequency after 8 years. Renal related deaths increase in probability after 8 years of followup, with a sharp rise after 10 years. Cardiovascular deaths are under-reported – see text (10 deaths had major contributing cardiovascular cause not captured in graph).