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 liverrelated 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.

Long-term Medical Management of the Liver Transplant Recipient: What the Primary Care Physician Needs to Know

“…[21][22][23][24][25] Both pre-and post-OLT diabetes are risk factors associated with higher mortality and morbidity in OLT recipients. 2,26 Post-OLT diabetes not only is associated with the usual microvascular and macrovascular complications but also has a significant impact …”

“…2 Risk factors for development of CKD include pretransplant factors, including preexisting CKD, advanced age, diabetes, hypertension, hepatitis C, and posttransplant factors, including early acute kidney injury, diabetes, and CNI use. 2,42,43 Duration and etiology of pretransplant renal failure, in particular, are important predictors of posttransplant CKD. Patients with pretransplant hepatorenal syndrome are expected to recover renal function owing to an absence of parenchymal renal disease.…”

“…36 Cardiovascular disease was noted to be the third most common cause of late mortality in LT recipients, accounting for 12% to 16% of patient deaths. 2 Risk-reduction strategies for all patients after OLT include healthy lifestyle changes and better control of hypertension, diabetes, and hyperlipidemia, as are also recommended for those in the general population; prophylactic low-dose aspirin may be beneficial, although adding aspirin has not been systematically studied in this population.…”

“…2 MEDICAL COMPLICATIONS AFTER LIVER TRANSPLANT After 1 year posttransplant, nonhepatic-related causes of death include malignancy (22%), cardiovascular disease (11%), infection (9%), and renal failure (6%), whereas liver allograft failure accounts for less than one-third of deaths ( Figure 1). 2 Metabolic syndrome is uncommon in patients with endstage liver disease before transplant (except in patients with nonalcoholic steatohepatitis [NASH]-related cirrhosis), but it increases dramatically after OLT, with 44% to 58% of patients affected (34% prevalence in nontransplant US adult population) and is associated with an important increase in cardiovascular morbidity. [3][4][5][6] Many centers defer the management of metabolic syndrome and medical complications to primary care physicians.…”

Investigation of PNPLA3 and IL28B Genotypes on Diabetes and Obesity After Liver Transplantation: Insight Into Mechanisms of Disease

“…Obesity, insulin resistance and/or diabetes are common metabolic complications in liver transplant recipients and risk factors for increased morbidity and mortality in longterm followup (1,2). Approximately 30-40% of liver transplant recipients have sustained diabetes beyond 6 months after transplant (2).…”