Research Article
Risk factors for arterial hypertension after liver transplantation

https://doi.org/10.1016/j.jash.2018.01.002Get rights and content

Highlights

  • Cirrhotic patients treated with tacrolimus are less likely to develop transient hypertension.

  • Mammalian target of rapamycin inhibitors are related to a higher prevalence of new-onset sustained hypertension.

  • The development of steatosis in transplanted liver is related to sustained hypertension.

Abstract

Arterial hypertension represents a common complication of immunosuppressive therapy after liver transplantation (LT). The aim of the study is to evaluate the prevalence and risk factors associated with hypertension after LT. From a cohort of 323 cirrhotic patients who underwent LT from 2008 to 2012, 270 patients were retrospectively evaluated, whereas 53 (16.4%) patients deceased. Hypertension was defined as blood pressure ≥140/90 mm Hg in at least two visits and/or the need for antihypertensive therapy. The prevalence of hypertension was 15% before LT and significantly increased up to 53% after LT (P < .001). Mean follow-up was 43 ± 19 months. In normotensive (NT) subjects at baseline, 35.9% developed sustained hypertension after LT, whereas 15.2% developed transient hypertension within the first month after LT, and then returned NT. The development of sustained hypertension after LT was related to the mammalian target of rapamycin inhibitor treatment (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.26–13.48; P = .02), alcoholic cirrhosis before LT (OR, 3.38; 95% CI, 1.44–8.09; P = .005), and new-onset hepatic steatosis after LT (OR, 2.13; 95% CI, 1.10–4.11; P = .02). Tacrolimus, the etiology and severity of liver disease, and other immunosuppressive regimens were not related to the development of hypertension after LT. In our cohort, the prevalence of arterial hypertension has increased up to 53% after LT, and metabolic comorbidities and immunosuppressive treatment with mammalian target of rapamycin inhibitors are the risk factors for the development of hypertension after LT.

Introduction

In the last decades, the development of new surgical techniques and targeted immunosuppressive treatments has improved the outcome of cirrhotic patients undergoing liver transplantation (LT), with a reduction of intraoperative and perioperative mortalities, graft failure, and acute organ rejection. The overall survival of LT recipients is estimated to be 81%–97% at 1 year,1, 2 56%–80.6% at 5 years,3, 4 and 52%–72% at 10 years after LT.1, 5, 6 Nevertheless, metabolic comorbidities, including arterial hypertension, diabetes mellitus, and dyslipidemia, have increased in cirrhotic patients after LT,7, 8, 9, 10, 11 and new onset of cardiovascular (CV) events has significantly affected the overall prognosis of these patients. In North American populations, CV mortality ranges from 2% to 24% within the first year,6, 12, 13 from 7% to 16% after 5 years,3, 6, 14, 15 and 13% after 10 years from LT.16, 17 In this study, we have analyzed the prevalence of arterial hypertension before and after LT in patients recruited in the Liver Transplant Center of the University of Turin, in an effort to identify metabolic comorbidities and immunosuppressive therapies that may be related to new-onset hypertension after LT in previously normotensive (NT) patients.

Section snippets

Methods

This study is a retrospective evaluation of a consecutive series of 359 Caucasian cirrhotic patients who underwent LT at the Liver Transplant Center of the University of Turin, Italy from January 1, 2008 to December 1, 2012 and were followed up until January 1, 2015. The design of the study is summarized in Figure 1. Pediatric patients (younger than 18 years), intraoperative deaths, and patients without at least two follow-up visits (n = 36) were excluded, and 323 subjects were considered for

Baseline Evaluation

At baseline, 323 cirrhotic patients (24.1% females) were considered with a mean age at the transplantation of 53.4 ± 9.3 years and Child-Pugh and MELD scores of 10.9 ± 1.4 and 17.6 ± 7.6, respectively (Table 1). Hepatitis C virus (HCV) infection was the most frequent cause of cirrhosis in the global population; 11 patients underwent a second LT because of acute graft failure: six for graft hepatic artery thrombosis, two for biliary complications, two for HCV recurrence, and one for

Discussion

This study analyzed different BP patterns in LT recipients, considering the different timings of the onset of arterial hypertension and metabolic complications. In our cohort, the prevalence of arterial hypertension increased from 15.2% to 52.9% after LT in line with previously published studies8, 11, 21, 22, 23, 24, 25; we noted a high incidence of transient hypertension after LT (15.2%), a finding previously described in a small cohort of 32 subjects.22

Transient hypertension is related to

Conclusion

In NT LT recipients, the development of arterial hypertension after LT is a frequent finding; in a group of previously NT subjects, about 15% will develop a transient and 36% a sustained arterial hypertension.

The sustained arterial hypertension may be related to immunosuppressive regimen with mTORi, development of hepatic steatosis and alcoholic cirrhosis. Tacrolimus was not correlated with development of transient hypertension, suggesting a safe profile as first-line immunosuppressive

Acknowledgments

C.D.S. wrote the manuscript and was responsible for the analysis and interpretation of data with V.M.; V.B., E.N., E.M., and R.Y. were responsible for acquisition of data; A.M., E.V., and S.M. were responsible for the conception and design of the study; S.M. and A.M. drafted the article and revised it critically for important intellectual contents; and R.R., M.S., and F.V. gave the final approval of the version to be submitted.

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Grant support: This study did not receive grants or financial support.

Conflict of interest: None.

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