Posttransplant Metabolic Syndrome

Siddiqui, M. Shadab; Sterling, Richard K.

doi:https://doi.org/10.1155/2012/891516

International Journal of Hepatology

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Review Article | Open Access

Volume 2012 | Article ID 891516 | https://doi.org/10.1155/2012/891516

Posttransplant Metabolic Syndrome

M. Shadab Siddiqui¹and Richard K. Sterling^1,2

Academic Editor: Koichi Tsuneyama

Received24 Sept 2012

Accepted01 Nov 2012

Published27 Nov 2012

Abstract

Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44–58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients.

1. Introduction

Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. According to the Adult Treatment Panel III definition (Table 1), MS is defined as the presence of dyslipidemia, obesity, glucose intolerance, and hypertension [1].

Metabolic syndrome has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. According to the Framingham study, MS alone can predict at least 25% of all new onset cardiovascular disease. The Third National Health and Nutrition Examination Survey (NHANES) in 1999-2000 estimated the age-adjusted prevalence of MS in the adult US population to be 24% and is projected to increase further with the increasing prevalence of obesity and diabetes [2]. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD), cholelithiasis, polycystic ovary disease, and obstructive sleep apnea. The aim of this paper is to discuss the importance and impact of metabolic syndrome and its component in liver-transplant recipients. Although only evidence that pertains of liver transplantation will be discussed, similar metabolic complications have been observed in patients undergoing other solid organ transplants.

2. Nonalcoholic Fatty Liver Disease (NAFLD) and Metabolic Syndrome

NAFLD is considered to be the hepatic manifestation of MS and is defined as the presence of >5% deposition of triglycerides in the liver in the absence of significant alcohol consumption (<20–40 g/day for women and 40–80 g/day for men). Up to 90% of patients with NAFLD have at least 1 feature of the MS, with 33% having all components of the MS. The reported prevalence of NAFLD varies widely depending on the population studied and modality used to make the diagnosis but is estimated to be 6.3% to 33% in the general population. Nonalcoholic steatohepatitis (NASH), the most aggressive phenotype of NAFLD, is characterized by the presence of hepatocyte injury, cytologic ballooning, and inflammation and has an estimated prevalence of 3–5%. Unlike NAFLD, NASH is associated with a decreased patient survival compared to the general population due to the increased cardiovascular risk. Additionally, the presence of NASH is associated with the increased risk of progression to cirrhosis and a need for liver transplantation. A recent analysis of the Scientific Registry of Transplant Recipients (SRTRs) confirmed that the NASH as an indication for liver transplant increased over 7-fold from 2001 to 2009, while no other indication for liver transplantation increased over the same time period [3]. Already being the 3rd most common indication for liver transplant, it is poised to surpass HCV as the leading indication for liver transplant in the near future due to an unparalleled increase in features of MS.

3. Posttransplant Metabolic Syndrome (PTMS)

The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to be ascertained due to changes usually associated with end-stage liver disease. The low systemic vascular resistance and low lipid levels associated with chronic liver disease reduce the likelihood that patients with cirrhosis would meet ATP III criteria. Presence of ascites in cirrhotic patients can further confound the diagnosis of obesity thereby, making the diagnosis of MS in patients with cirrhosis difficult. However, there are data to suggest that the prevalence of MS in cirrhosis and end-stage liver disease likely varies with the etiology of liver disease and is likely higher in patients with cryptogenic or NASH cirrhosis [4].

Liver transplantation is an effective therapy for chronic end-stage liver disease. Improvement in surgical techniques, management of infectious complications, and immunosuppression have led to excellent long-term survival rates in liver-transplant recipients. Consequently, death related to metabolic consequences (cardiovascular disease and malignancies) is becoming increasingly important as hepatic etiologies of late post-liver-transplant death become less common.

The limited number of studies evaluating the incidence of PTMS in liver-transplant recipients has considerable variability in the reported data due to differing definitions of MS used [5]. Recent studies estimate the prevalence of PTMS to be 44–58% in liver-transplant recipients and is associated with increased cardiovascular mortality (Table 2) [6, 7]. The relative risk of cardiovascular death in liver-transplant recipients is 2.5 times that of the age- and sex-matched individuals (Figure 1) [8]. Additionally, the presence of PTMS has been associated with a rapid progression to fibrosis in individuals transplanted for HCV cirrhosis [9]. This risk is even greater (30% versus 8%, ) in individuals with PTMS compared to those without it [6]. Since PTMS can affect 1 out of 2 transplant recipients and can account for up to 42% cardiovascular disease related mortality, its impact on liver-transplant recipients is immense [8, 10, 11]. The main factors associated with PTMS are posttransplant diabetes, obesity, dyslipidemia, and hypertension (Table 2), which can result in posttransplant NAFLD.

4. Posttransplant Diabetes Mellitus (PTDM)

Up to 60–80% of patients with cirrhosis may have glucose intolerance and 20% may develop DM; it is due to profound peripheral resistance, decreased glycogen synthesis, and impaired glucose oxidation [12, 13]. Unfortunately, up to third of patients will remain diabetic after liver transplantation [14, 15]. Posttransplant diabetes mellitus confers a twofold increased risk of cardiovascular and liver related deaths in liver-transplant recipients [10]. Presence of diabetes can also have detrimental impact on graft survival. PTDM is associated with increased advanced graft fibrosis, late onset hepatic artery thrombosis, recurrent or de novo fatty liver disease, and acute and chronic rejection [14, 16–18]. Additionally, the mortality and morbidity in liver-transplant recipients is higher even when posttransplant diabetes is transient [17, 19].

Earlier studies in liver-transplant recipients reported the prevalence of PTDM 1 year after transplant from 13–27% using the fasting plasma glucose of 140 mg/dL as the diagnostic criteria [5, 17, 20, 21]. However, using the more recent diagnostic criteria of fasting plasma glucose of 126 mg/dL, Laryea et al. reported the prevalence of PTDM to be 61% [6]. In one study, 80% of new onset diabetes (NOD) occurred within the first month after liver transplant and only a small minority (12%) developed NOD after the 1st year after transplant [14].

Although limited by retrospective data and small cohorts, factors associated with PTDM include HCV and alcohol related cirrhosis as indications for transplant (), pretransplant DM (, ), male gender, HCV infection, and steroid use () [7, 16, 21, 22]. High doses of corticosteroids are an integral part of the early immunosuppressive regiments in many transplant centers. Corticosteroids lead to insulin resistance and diabetes by decreasing insulin production, increasing gluconeogenesis, and decreasing peripheral glucose utilization [23]. Decreasing the dose of prednisone from 10 mg to 5 mg per day reduced the prevalence of PTDM () [5]. Similarly, reducing the daily dose of prednisone from mg at 1 year to mg at 3 years leads to a 20% reduction in the prevalence of PTDM [20]. In a recent meta-analysis, the relative risk of diabetes (, ) was attenuated when corticosteroids were replaced by another immunosuppressive agent [24]. These effects appear to be transient as the prevalence of diabetes in post-liver-transplant recipients reverts to that of patients on steroid-free regiments once corticosteroids are discontinued [25].

Calcineurin inhibitors, cyclosporine (CsA) and Tacrolimus (FK506), are associated with an increased risk of PTDM, with the incidence possibly being higher with the use of Tacrolimus [7, 17, 21, 26]. The increased risk of posttransplant diabetes associated with Tacrolimus (RR 1.38, CI 1.01–1.86) use compared to CsA in liver transplant recipient was confirmed in a recent Cochrane review [27]. The calcineurin inhibitors exert their diabetogenic effects by inhibiting pancreatic β-cell ability and diminishing insulin synthesis and secretion [28]. Calcineurin inhibitors also reduce peripheral glucose utilization leading to peripheral insulin resistance.

Finally the data regarding the impact of Sirolimus, an mTOR inhibitor, on posttransplant diabetes is conflicting. Chronic mTOR inhibition has been associated with reduced pancreatic β-cell mass, reduced hepatic insulin clearance, and increased gluconeogenesis, thereby causing insulin resistance [29]. On the other hand, activation of the mTOR pathway via glucose leads to the inhibition of insulin receptor substrate-2 (IRS-2), increase β-cell apoptosis and insulin resistance [30]. Therefore, the impact of Sirolimus on PTDM remains unclear.

5. Posttransplant Obesity

Obesity (body mass index (BMI) kg/m²) is a common sequela of liver transplantation affecting 21–42% liver-transplant recipient [5, 31–33]. Risk factors for post-OLT obesity include donor BMI, absence of acute rejection, and steroid use [31]. Additionally, patients who are overweight or obese before transplant will likely remain overweight or obese after transplant. Furthermore, patients who were not obese at the time of transplant, 16% became obese at 1 year and 26% at 3 years [32].

Well-known side effect of corticosteroid use is weight gain and truncal obesity. Although corticosteroids have been traditionally associated with greater posttransplant weight gain, available literature suggests otherwise [32, 33]. This is likely due to a reduction in dosing and duration of steroid use as well as emergence of steroid-free or steroid-sparing immunosuppressive regiments. Cyclosporine compared to Tacrolimus was associated with an additional 2.3 kg gain 1 year after transplant [26]. However, these differences were not significant 3 years after transplant.

6. Posttransplant Dyslipidemia

Dyslipidemia is common after transplant affecting 45–69% of liver-transplant recipients [7, 19, 34–37]. One study reported the pretransplant prevalence of dyslipidemia rose from 8% to 66% after liver transplant in patients who were followed for over 14 months [35]. More specifically, prevalence of hypercholesterolemia and hypertriglyceridemia increased from 2.9% and 18.2% before transplant to 15.3% and 70% after transplant, respectively [38]. The prevalence of low HDL after transplantation is reported to be 48–52% [6, 39].

Risk factors of hypercholesterolemia in liver-transplant recipients include pretransplant hypercholesterolemia, cyclosporine, and corticosteroid use [35, 39]. Predictors of posttransplant hypertriglyceridemia include cirrhosis resulting from HCV, HBV, alcohol, cryptogenic cirrhosis and posttransplant renal insufficiency [35]. Although, long-term therapy with corticosteroids can result in dyslipidemia, it is unclear how corticosteroids impact long-term dyslipidemia in posttransplant population [40]. Corticosteroids can lead to dyslipidemia by increasing the hepatic production of lipids, increased production of very low-density lipoprotein (VLDL) cholesterol, and decreased hepatic LDL reuptake.

Although both calcineurin inhibitors are also associated with posttransplant dyslipidemia and the relationship between posttransplant dyslipidemia and cyclosporine is more robust. Cyclosporine inhibits hepatic bile acid 26-hydroxylase, which is thought to decrease reverse cholesterol transport or transport of cholesterol into bile and its subsequent elimination into the intestines [41]. Additionally, cyclosporine binds to LDL receptor and thereby decreases LDL-cholesterol uptake [15, 39]. Conversion from cyclosporine to Tacrolimus results in improvement in both serum cholesterol and triglyceride levels but has no impact on HDL cholesterol [42, 43].

Sirolimus is associated with posttransplant hypertriglyceridemia and elevated serum LDL cholesterol. Sirolimus alters the insulin-signaling pathway by increasing adipose tissue lipase activity, decreasing lipoprotein lipase activity which results in increased hepatic triglyceride synthesis, increased secretion of VLDL and thereby causing hypertriglyceridemia [44]. Additionally, cyclosporine and Sirolimus work synergistically to promote dyslipidemia and should be avoided in patients with underlying dyslipidemia [44, 45]. This synergistic effect is not seen with Sirolimus and Tacrolimus.

7. Posttransplant Hypertension

Since patients with cirrhosis, particularly decompensated cirrhosis, have decreased systemic vascular resistance, hypertension is only present in a small minority of patients before transplant but can affect 62–69% of liver-transplant recipients [5, 9, 45, 46]. Post-transplant hypertension may result from increased renal vasoconstriction and impaired sodium excretion induced by cyclosporine use and may occur less frequently with Tacrolimus use [23, 46]. Patients treated specifically with cyclosporine, the prevalence of hypertension was 58–82%, while the incidence of posttransplant hypertension was 31–38% in patients treated with Tacrolimus [26, 47, 48]. In animal models, cyclosporine generates interstitial fibrosis without any significant decrease in renal blood flow or structural arteriolar lesion, through early macrophage influx and increased TGF-β expression. Additionally, since cyclosporine-induced ischemia and tubulointerstitial injury can occur independently, preventing renal injury with CsA altogether could be difficult [49]. Data regarding the use of Sirolimus and posttransplant hypertension is still evolving and no definitive statements can be made.

8. Posttransplant Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease is closely associated with features of metabolic syndrome and likely represents the hepatic manifestation of the metabolic syndrome. De novo NALFD after transplant was initially reported in a retrospective study where 75% of patients transplanted for NASH had fatty infiltration of the graft and 38% developed NASH [50]. In patients transplanted for cryptogenic cirrhosis, time-dependent risk of developing allograft steatosis was 100% by five years [51]. Additionally, 25% of patients transplanted for alcoholic and cholestatic liver disease developed fatty liver disease. The risk of developing de novo NAFLD after liver transplant is associated with pretransplant obesity, a higher BMI at the time of the last biopsy, and a higher post-transplant BMI [52, 53]. Patients with greater than 10% increase in pretransplant BMI had a significantly higher risk of developing de novo NAFLD compared to those without weight gain. Unfortunately, the natural history of posttransplant de novo fatty liver disease is currently unknown but it is possible that post-transplant fatty liver disease contributes to the increased cardiovascular mortality since NAFLD is an independent risk factor CVD in noncirrhotic patients. Well-designed prospective trials are needed to confirm this assertion.

9. Conclusion

Metabolic syndrome and its components are common in liver-transplant recipients and associated with increased cardiovascular disease, fibrosis, de novo NAFLD after transplant (Figure 1), and decreased patient and graft survival. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with PTMS. In the interim, early recognition, prevention, and treatment of components of PTMS are vital in improving outcomes in liver-transplant recipients.

References

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, “Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III),” The Journal of the American Medical Association, vol. 285, no. 19, pp. 2486–2497, 2001.
View at: Google Scholar
E. S. Ford, W. H. Giles, and W. H. Dietz, “Prevalence of the metabolic syndrome among US adults: findings from the third national health and nutrition examination survey,” The Journal of the American Medical Association, vol. 287, no. 3, pp. 356–359, 2002.
View at: Google Scholar
M. R. Charlton, J. M. Burns, R. A. Pedersen, K. D. Watt, J. K. Heimbach, and R. A. Dierkhsing, “Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the united states,” Gastroenterology, vol. 141, no. 4, pp. 1249–1253, 2011.
View at: Publisher Site | Google Scholar
F. I. Tellez-Avila, F. Sanchez-Avila, M. García-Saenz-de-Sicilia et al., “Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis,” World Journal of Gastroenterology, vol. 14, no. 30, pp. 4771–4775, 2008.
View at: Publisher Site | Google Scholar
M. D. Stegall, G. Everson, G. Schroter, B. Bilir, F. Karrer, and I. Kam, “Metabolic complications after liver transplantation: diabetes, hypercholesterolemia, hypertension, and obesity,” Transplantation, vol. 60, no. 9, pp. 1057–1060, 1995.
View at: Google Scholar
M. Laryea, K. D. Watt, M. Molinari et al., “Metabolic syndrome in liver transplant recipients: prevalence and association with major vascular events,” Liver Transplantation, vol. 13, no. 8, pp. 1109–1114, 2007.
View at: Publisher Site | Google Scholar
G. Bianchi, G. Marchesini, R. Marzocchi, A. D. Pinna, and M. Zoli, “Metabolic syndrome in liver transplantation: relation to etiology and immunosuppression,” Liver Transplantation, vol. 14, no. 11, pp. 1645–1654, 2008.
View at: Publisher Site | Google Scholar
S. D. Johnston, J. K. Morris, R. Cramb, B. K. Gunson, and J. Neuberger, “Cardiovascular morbidity and mortality after orthotopic liver transplantation,” Transplantation, vol. 73, no. 6, pp. 901–906, 2002.
View at: Google Scholar
I. A. Hanouneh, A. E. Feldstein, A. J. McCullough et al., “The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation,” Liver Transplantation, vol. 14, no. 9, pp. 1287–1293, 2008.
View at: Publisher Site | Google Scholar
K. D. S. Watt, R. A. Pedersen, W. K. Kremers, J. K. Heimbach, and M. R. Charlton, “Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study,” American Journal of Transplantation, vol. 10, no. 6, pp. 1420–1427, 2010.
View at: Publisher Site | Google Scholar
D. P. Vogt, J. M. Henderson, W. D. Carey, and D. Barnes, “The long-term survival and causes of death in patients who survive at least 1 year after liver transplantation,” Surgery, vol. 132, no. 4, pp. 775–780, 2002.
View at: Publisher Site | Google Scholar
G. Perseghin, V. Mazzaferro, L. P. Sereni et al., “Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: effect of liver transplantation,” Hepatology, vol. 31, no. 3, pp. 694–703, 2000.
View at: Google Scholar
A. S. Petrides, C. Vogt, D. Schulze-Berge, D. Matthews, and G. Strohmeyer, “Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis,” Hepatology, vol. 19, no. 3, pp. 616–627, 1994.
View at: Google Scholar
J. I. Moon, R. Barbeito, R. N. Faradji, J. J. Gaynor, and A. G. Tzakis, “Negative impact of new-onset diabetes mellitus on patient and graft survival after liver transplantation: long-term follow up,” Transplantation, vol. 82, no. 12, pp. 1625–1628, 2006.
View at: Publisher Site | Google Scholar
A. Reuben, “Long-term management of the liver transplant patient: diabetes, hyperlipidemia, and obesity,” Liver Transplantation, vol. 7, no. 11, supplement 1, pp. S13–S21, 2001.
View at: Publisher Site | Google Scholar
S. Baid, A. B. Cosimi, M. L. Farrell et al., “Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal, relationship with hepatitis C virus allograft hepatitis, and impact on mortality,” Transplantation, vol. 72, no. 6, pp. 1066–1072, 2001.
View at: Google Scholar
P. R. John and P. J. Thuluvath, “Outcome of patients with new-onset diabetes mellitus after liver transplantation compared with those without diabetes mellitus,” Liver Transplantation, vol. 8, no. 8, pp. 708–713, 2002.
View at: Publisher Site | Google Scholar
B. J. Veldt, J. J. Poterucha, K. D. S. Watt et al., “Insulin resistance, serum adipokines and risk of fibrosis progression in patients transplanted for hepatitis C,” American Journal of Transplantation, vol. 9, no. 6, pp. 1406–1413, 2009.
View at: Publisher Site | Google Scholar
H. Y. Yoo and P. J. Thuluvath, “The effect of insulin-dependent diabetes mellitus on outcome of liver transplantation,” Transplantation, vol. 74, no. 7, pp. 1007–1012, 2002.
View at: Google Scholar
M. Navasa, J. Bustamante, C. Marroni et al., “Diabetes mellitus after liver transplantation: prevalence and predictive factors,” Journal of Hepatology, vol. 25, no. 1, pp. 64–71, 1996.
View at: Publisher Site | Google Scholar
S. G. Tueche, “Diabetes mellitus after liver transplant new etiologic clues and cornerstones for understanding,” Transplantation Proceedings, vol. 35, no. 4, pp. 1466–1468, 2003.
View at: Publisher Site | Google Scholar
K. C. Trail, T. M. McCashland, J. L. Larsen et al., “Morbidity in patients with posttransplant diabetes mellitus following orthotopic liver transplantation,” Liver Transplantation and Surgery, vol. 2, no. 4, pp. 276–283, 1996.
View at: Google Scholar
H. Schäcke, W. D. Döcke, and K. Asadullah, “Mechanisms involved in the side effects of glucocorticoids,” Pharmacology and Therapeutics, vol. 96, no. 1, pp. 23–43, 2002.
View at: Publisher Site | Google Scholar
D. L. Segev, S. M. Sozio, E. J. Shin et al., “Steroid avoidance in liver transplantation: meta-analysis and meta-regression of randomized trials,” Liver Transplantation, vol. 14, no. 4, pp. 512–525, 2008.
View at: Publisher Site | Google Scholar
N. Weiler, I. Thrun, M. Hoppe-Lotichius, T. Zimmermann, I. Kraemer, and G. Otto, “Early steroid-free immunosuppression with FK506 after liver transplantation: long-term results of a prospectively randomized double-blinded trial,” Transplantation, vol. 90, no. 12, pp. 1562–1566, 2010.
View at: Publisher Site | Google Scholar
V. J. Canzanello, L. Schwartz, S. J. Taler et al., “Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506),” Liver Transplantation and Surgery, vol. 3, no. 1, pp. 1–9, 1997.
View at: Google Scholar
E. M. Haddad, V. C. McAlister, E. Renouf, R. Malthaner, M. S. Kjaer, and L. L. Gluud, “Cyclosporin versus tacrolimus for liver transplanted patients,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD005161, 2006.
View at: Google Scholar
L. A. Øzbay, K. Smidt, D. M. Mortensen, J. Carstens, K. A. Jørgensen, and J. Rungby, “Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E β-cells,” British Journal of Pharmacology, vol. 162, no. 1, pp. 136–146, 2011.
View at: Publisher Site | Google Scholar
V. P. Houde, S. Brûlé, W. T. Festuccia et al., “Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue,” Diabetes, vol. 59, no. 6, pp. 1338–1348, 2010.
View at: Publisher Site | Google Scholar
I. Briaud, L. M. Dickson, M. K. Lingohr, J. F. McCuaig, J. C. Lawrence, and C. J. Rhodes, “Insulin receptor substrate-2 proteasomal degradation mediated by a mammalian target of rapamycin (mTOR)-induced negative feedback down-regulates protein kinase B-mediated signaling pathway in β-cells,” The Journal of Biological Chemistry, vol. 280, no. 3, pp. 2282–2293, 2005.
View at: Publisher Site | Google Scholar
J. E. Everhart, M. Lombardero, J. R. Lake, R. H. Wiesner, R. K. Zetterman, and J. H. Hoofnagle, “Weight change and obesity after liver transplantation: incidence and risk factors,” Liver Transplantation and Surgery, vol. 4, no. 4, pp. 285–296, 1998.
View at: Google Scholar
J. Richards, B. Gunson, J. Johnson, and J. Neuberger, “Weight gain and obesity after liver transplantation,” Transplant International, vol. 18, no. 4, pp. 461–466, 2005.
View at: Publisher Site | Google Scholar
M. Wawrzynowicz-Syczewska, E. Karpińska, K. Jurczyk, Ł. Laurans, and A. Bororń-Kaczmarska, “Risk factors and dynamics of weight gain in patients after liver transplantation,” Annals of Transplantation, vol. 14, no. 3, pp. 45–50, 2009.
View at: Google Scholar
S. Desai, J. C. Hong, and S. Saab, “Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management,” Liver International, vol. 30, no. 7, pp. 948–957, 2010.
View at: Publisher Site | Google Scholar
C. Gisbert, M. Prieto, M. Berenguer et al., “Hyperlipidemia in liver transplant recipients: prevalence and risk factors,” Liver Transplantation and Surgery, vol. 3, no. 4, pp. 416–442, 1997.
View at: Google Scholar
D. A. J. Neal, B. D. M. Tom, J. Luan et al., “Is there disparity between risk and incidence of cardiovascular disease after liver transplant?” Transplantation, vol. 77, no. 1, pp. 93–99, 2004.
View at: Publisher Site | Google Scholar
R. Pfitzmann, N. C. Nüssler, M. Hippler-Benscheidt, R. Neuhaus, and P. Neuhaus, “Long-term results after liver transplantation,” Transplant International, vol. 21, no. 3, pp. 234–246, 2008.
View at: Publisher Site | Google Scholar
S. M. Dehghani, S. A. R. Taghavi, A. Eshraghian et al., “Hyperlipidemia in Iranian liver transplant recipients: prevalence and risk factors,” Journal of Gastroenterology, vol. 42, no. 9, pp. 769–774, 2007.
View at: Publisher Site | Google Scholar
S. J. Munoz, R. O. Deems, M. J. Moritz, P. Martin, B. E. Jarrell, and W. C. Maddrey, “Hyperlipidemia and obesity after orthotopic liver transplantation,” Transplantation Proceedings, vol. 23, no. 1, part 2, pp. 1480–1483, 1991.
View at: Google Scholar
K. K. Lau, D. J. Tancredi, R. V. Perez, and L. Butani, “Unusual pattern of dyslipidemia in children receiving steroid minimization immunosuppression after renal transplantation,” Clinical Journal of the American Society of Nephrology, vol. 5, no. 8, pp. 1506–1512, 2010.
View at: Publisher Site | Google Scholar
C. V. Hulzebos, C. M. A. Bijleveld, F. Stellaard et al., “Cyclosporine A—induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation,” Liver Transplantation, vol. 10, no. 7, pp. 872–880, 2004.
View at: Publisher Site | Google Scholar
C. Manzarbeitia, D. J. Reich, K. D. Rothstein, L. E. Braitman, S. Levin, and S. J. Munoz, “Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients,” Liver Transplantation, vol. 7, no. 2, pp. 93–99, 2001.
View at: Publisher Site | Google Scholar
A. Roy, N. Kneteman, L. Lilly et al., “Tacrolimus as intervention in the treatment of hyperlipidemia after liver transplant,” Transplantation, vol. 82, no. 4, pp. 494–500, 2006.
View at: Publisher Site | Google Scholar
J. D. Morrisett, G. Abdel-Fattah, and B. D. Kahan, “Sirolimus changes lipid concentrations and lipoprotein metabolism in kidney transplant recipients,” Transplantation Proceedings, vol. 35, no. 3, supplement, pp. 143S–150S, 2003.
View at: Publisher Site | Google Scholar
J. F. Trotter, M. E. Wachs, T. E. Trouillot et al., “Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus,” Liver Transplantation, vol. 7, no. 5, pp. 401–408, 2001.
View at: Publisher Site | Google Scholar
V. J. Canzanello, S. C. Textor, S. J. Taler et al., “Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation,” Journal of the American Society of Nephrology, vol. 5, no. 11, pp. 1910–1917, 1995.
View at: Google Scholar
C. Fernández-Miranda, M. Sanz, A. dela Calle et al., “Cardiovascular risk factors in 116 patients 5 years or more after liver transplantation,” Transplant International, vol. 15, no. 11, pp. 556–562, 2002.
View at: Publisher Site | Google Scholar
J. M. Rabkin, H. R. Rosen, C. L. Corless, and A. J. Olyaei, “Tacrolimus is associated with a lower incidence of cardiovascular complications in liver transplant recipients,” Transplantation Proceedings, vol. 34, no. 5, pp. 1557–1558, 2002.
View at: Publisher Site | Google Scholar
J. M. Vieira Jr., I. L. Noronha, D. M. A. C. Malheiros, and E. A. Burdmann, “Cyclosporine-induced interstitial fibrosis and arteriolar TGF-β expression with preserved renal blood flow,” Transplantation, vol. 68, no. 11, pp. 1746–1753, 1999.
View at: Google Scholar
W. R. Kim, J. J. Poterucha, M. K. Porayko, E. R. Dickson, J. L. Steers, and R. H. Wiesner, “Recurrence of nonalcoholic steatohepatitis following liver transplantation,” Transplantation, vol. 62, no. 12, pp. 1802–1805, 1996.
View at: Publisher Site | Google Scholar
M. J. Contos, W. Cales, R. K. Sterling et al., “Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis,” Liver Transplantation, vol. 7, no. 4, pp. 363–373, 2001.
View at: Publisher Site | Google Scholar
L. G. Lim, C. L. Cheng, A. Wee et al., “Prevalence and clinical associations of posttransplant fatty liver disease,” Liver International, vol. 27, no. 1, pp. 76–80, 2007.
View at: Publisher Site | Google Scholar
S. Seo, K. Maganti, M. Khehra et al., “De novo nonalcoholic fatty liver disease after liver transplantation,” Liver Transplantation, vol. 13, no. 6, pp. 844–847, 2007.
View at: Publisher Site | Google Scholar

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Copyright © 2012 M. Shadab Siddiqui and Richard K. Sterling. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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