Impact of comorbidities on mortality after liver transplantation varies with time

Last Updated: 2015-05-28

By Will Boggs MD

NEW YORK (Reuters Health) - Different comorbidities come to play at different times after liver transplantation to influence mortality, with some making no contribution to mortality, researchers from the UK report.

"The effects of comorbidities change over time," Dr. Chutwichai Tovikkai, from the Royal College of Surgeons of England, London, and the University of Cambridge, told Reuters Health by email. "Therefore, clinicians should focus on a particular comorbidity during the particular time period after transplantation."

"For example," he said, "cardiac failure had a strong impact only in the short term (within 90 days); thus, patients with this comorbidity should have intensive post-transplant care during this period. Whereas patients with atherosclerotic cardiovascular comorbidities had an impact in all time periods, but stronger in the long term (5 to 10 years), so a long-term follow-up plan for these patients should include surveillance for complications of these comorbid diseases."

Comorbidity is an important determinant of outcomes in medical and surgical patients, but the reported impact of comorbidities on liver transplantation outcomes varies widely.

Dr. Tovikkai's team used linked clinical and administrative data from 3837 adult patients to investigate the impact of comorbidities on mortality in three time periods after liver transplantation: first 90 days, 90 days to 5 years, and 5 to 10 years.

Overall, 45.1% of patients had at least one comorbidity. Diabetes was most common, followed by chronic pulmonary disease and chronic renal disease.

Cardiovascular disease was associated with significantly increased mortality risk in all three time periods, with the highest risk coming at the 5-year mark, according to the May 14 BMJ online report.

Congestive cardiac failure increased the 90-day mortality risk about three-fold, but this excess risk was not seen beyond the first period.

Non-hepatic malignancy was associated with an increased risk in all three time periods, but only the 1.9-fold increased risk in the first 90 days was statistically significant.

The researchers observed nonsignificant trends toward increased mortality in the first 90 days in patients with chronic renal disease and beyond five years in patients with dementia.

"We were surprised that diabetes, chronic pulmonary disease, and chronic renal disease were not found to be risk factors for post-transplant mortality," Dr. Tovikkai said. The outcomes of these patients after liver transplantation were not different from those without, if they did not have other cardiovascular comorbidities."

"Patients with underlying cardiovascular disease, heart failure, and previous non-hepatic malignancy had a higher risk after liver transplantation, so clinicians should thoroughly investigate these patients during the pre-transplant evaluation process to screen for complications of these comorbidities, and optimize them before transplant, where possible," Dr. Tovikkai concluded. "However, the decision whether or not to undergo liver transplantation cannot be concluded from our study. It still should be based on clinical decisions of the transplant team, taking account of other information besides comorbidities alone."

Dr. David A. Goldberg, from Perelman School of Medicine at the University of Pennsylvania, Philadelphia, who has published extensively on liver transplantation outcomes, told Reuters Health by email, "I am not surprised that pre-transplant cardiovascular disease and congestive heart failure were associated with an increased risk of 90-day mortality, but the presence of a non-hepatic malignancy was surprising, and difficult to explain. Typically we think of early post-transplant mortalities being related to perioperative complications, infections, or cardiac events, and not malignancies."

"These data highlight that despite the rigorous pre-transplant cardiac testing that these patients undergo, there still remains a substantial risk of mortality from cardiovascular disease," Dr. Goldberg said. "Future work is needed to refine our pre-transplant cardiac testing, and to potentially identify better tests or biomarkers of adverse post-transplant events."

"Unfortunately there is a scarcity of transplantable livers, so transplant physicians must be responsible stewards of this scarce resource when deciding who to transplant," Dr. Goldberg added. "We are forced to triage these very sick patients, and identify those in the greatest need, who we would accept to have acceptable post-transplant survival. Thus, comorbidities that might specifically compromise the survival of the patient and the graft must be factored into our decision making."

Dr. Lisa B. VanWagner, Advanced/Transplant Hepatology Fellow at Feinberg School of Medicine, Northwestern University, Chicago, told Reuters Health by email, "I am surprised that renal disease did not have more of an impact on mortality, given the large body of research that demonstrates that it is a leading cause of mortality, which is why creatinine is part of the model for end-stage liver disease score. I suspect that the discrepant finding is due to the way in which the authors coded renal disease (ignored creatinine) and that they excluded multi-organ transplants (e.g., liver-kidney recipients)."

"I think this study provides an excellent base for future work that focuses on improved management of cardiovascular disease specifically post transplant," Dr. VanWagner said. "We spend a lot of time focusing on liver-specific comorbidities and complications, and chronic disease conditions often get overlooked. We have precedence for improving management of certain conditions such as diabetes. This article highlights opportunities for patient-specific interventions specifically surrounding cardiovascular disease and heart failure management."

The authors reported no funding or competing interests.

SOURCE: http://bit.ly/1Br6KYn

BMJ 2015.