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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed in patients having undergone liver transplantation (LTx). These alterations are probably multifactorial in origin, and cluster to generate a metabolic syndrome (MS), increasing the risk of cardiovascular events. We assessed the prevalence of MS (National Cholesterol Education Program-Adult Treatment Panel III criteria) in 296 LTx patients in the course of regular follow-up, at least 6 months after transplantation (median, 38 months). Several pre-LTx and post-LTx data were collected to identify the factors associated with the presence of MS. In a subset of 99 patients, insulin resistance was measured by the homeostasis model assessment. High blood pressure was present in 53% of cases, hyperlipidemia in 51%, high glucose in 37%, and enlarged waist circumference in 32%. Overall, MS (defined as 3 or more of the above features) was present in 44.5% of cases. Insulin resistance (homeostasis model assessment > 2.7) was observed in 41% of cases. Hypertension and hyperlipidemia were more frequent in subjects on cyclosporine than in tacrolimus-treated cases, whereas the type of immunosuppressive drug had no effect on the prevalence of diabetes, enlarged waist, and MS. In a logistic regression analysis, only pre-LTx body mass index (odds ratio, 1.20), body mass index increase (odds ratio, 1.18), and pre-LTx diabetes (odds ratio, 2.36) predicted MS; age, gender, etiology of liver disease, time from LTx, type of immunosuppressive drug, and previous hepatocellular carcinoma were removed from the model. Disorders related to MS are frequent in LTx patients, and are related to both pre-LTx conditions and to weight gain. Weight control is mandatory in LTx patients to prevent risk factors of premature atherosclerosis. Liver Transpl 14: 1648–1654, 2008. © 2008 AASLD.

The survival and quality of life of patients after liver transplantation (LTx) has markedly improved during the last decades, but the survival curve has now flattened.1 The return to normal daily life and home and working activities, together with normalization of the hypermetabolic state of advanced liver failure2 and free food intake, are accompanied by a progressive weight gain.3 In turn, this heralds the development of hypertension, changes in blood lipid profile with hyperlipidemia, and altered glucose regulation.4, 5 The origin of these alterations, apparently related to insulin resistance (IR) and characterizing the metabolic syndrome (MS), is under debate.

In a very few cases, the occurrence of posttransplantation diabetes mellitus (PTDM) or full-blown posttransplantation metabolic syndrome (PTMS) might be the effect of recurrent liver disease, caused by etiologic factors also involved in the original liver cell failure,6 via nonalcoholic steatohepatitis (NASH) and cryptogenic cirrhosis,7 and encouraged by unhealthy lifestyles. In the vast majority of cases PTDM and PTMS might be lifestyle-related and induced by post-LTx immunosuppression.8 In keeping with this hypothesis and the metabolic effects of calcineurin inhibitors,9 these features appear independently of etiology (viral, cholestatic, autoimmune, secondary to iron or copper overload, as well as cryptogenic cirrhosis) and even in subjects submitted to LTx for noncirrhotic liver disease.

Whatever the origin, the presence of the PTMS has been associated with an increased prevalence of cardiovascular disorders, which becomes a prevailing cause of morbidity/mortality in long-term LTx survivors in many outcome studies10 and represents a relevant clinical issue,11 also favoring graft loss.12

However, only a few studies have systematically reported data on the markers of MS before and after transplantation in large LTx series, and on risk factors for the development of metabolic alterations. We carried out a cross-sectional study in a large cohort of patients having received transplants, including a systematic analysis of their pre-LTx clinical and biochemical condition, to verify the relative role of immunosuppression, etiology, and underlying metabolic factors in the development of PTMS.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patients

During the period of May 1, 2004 to December 21, 2006, we retrospectively analyzed the data of 296 consecutive patients (196 males, 100 females) who had received a liver transplant from a cadaver donor 6 or more months earlier, in the Transplant Unit of the S. Orsola-Malpighi Hospital, and seen as outpatients during regular follow-up visits. The standard immunosuppressive therapy consisted of a calcineurin inhibitor. All patients had a piggy-back allograft implantation and received identical intraoperative and postoperative care. Nearly all subjects received a calcineurin inhibitor drug (191 cyclosporine, 105 tacrolimus), associated with tapered corticosteroids. A small group of subjects on sirolimus (4 subjects) was not considered.

The majority of cases (over 40%) had undergone transplantation because of liver failure caused by the hepatitis C virus (HCV); over 20% had hepatitis B virus (HBV)-related liver disease; and another 20% had liver failure caused by a variety of genetic or biliary conditions, and were merged into a miscellaneous group for statistical analyses (Table 1). This group also included 25 cases with biliary cirrhosis (either primary biliary cirrhosis or primary sclerosing cholangitis) and 10 cases with cryptogenic cirrhosis, potentially an expression of advanced nonalcoholic fatty liver disease. The data for these subgroups will be presented in the details whenever relevant.

Table 1. Clinical and Laboratory Data of the Subjects Enrolled in the Study
 All (n = 296)Cyclosporine-Treated (n = 191)Tacrolimus-Treated (n = 105)P
  • NOTE: Data are reported as the mean (standard deviation), median (interquartile range), or percent prevalence (95% CI) of the observed condition.

  • Abbreviations: F, female; HCC, hepatocellular carcinoma; M, male.

  • *

    Data were available for 107 cyclosporine-treated and 62 tacrolimus-treated cases.

  • Data were available for 59 cyclosporine-treated and 40 tacrolimus-treated cases.

  • Data were available for 85 cyclosporine-treated and 48 tacrolimus-treated cases.

Age (years)56 (13)57 (13)55 (13)0.070
Gender (M/F)196/100133/5863/420.094
Time from LTx (months)38 (55)51 (65)26 (31)<0.001
Etiology of liver disease   0.506
 Alcohol-related (%)14.4 (10.7–18.7)15.8 (11.1–21.4)12.5 (7.1–19.7) 
 HBV-related (%)22.5 (18.0–27.4)23.2 (17.5–29.4)21.2 (14.0–29.4) 
 HCV-related (%)43.0 (37.3–48.5)43.2 (36.1–50.0)41.3 (31.9–50.5) 
 Miscellaneous (%)20.1 (15.8–24.9)17.9 (12.9–23.7)25.0 (17.3–33.6) 
Previous HCC (%)19.1 (14.9–23.8)21.6 (16.1–27.7)11.5 (6.4–18.5)0.047
Current alcohol drinkers (%)*1.3 (0.4–3.2)2.1 (0.7–4.9)0.172
Current smokers (%)23.8 (17.8–30.4)23.4 (16.0–31.7)21.0 (12.1–31.7)0.719
Diabetes (%)37.8 (32.3–43.3)34.2 (27.6–40.9)44.2 (34.6–53.3)0.117
Pre-LTx diabetes (%)9.8 (6.8–13.5)11.1 (7.1–16.0)7.7 (3.6–16.9)0.472
Post-LTx diabetes (%)29.4 (24.3–34.6)25.3 (19.4–31.6)36.5 (27.5–45.6)0.058
HOMA (%)3.09 [2.30]2.74 [1.91]3.61 [2.73]0.104
HOMA > 2.7 (%)41.4 (31.5–51.3)37.3 (24.6–50.0)47.5 (31.3–63.7)0.311
BMI (kg/m2)25.9 [4.1]26.4 [4.0]24.9 [4.2]0.003
BMI at 20 years old (kg/m2)23.3 [4.0]23.3 [4.1]23.0 [3.4]0.577
Pre-LTx BMI (kg/m2)24.7 [3.6]25.2 [3.6]23.9 [3.5]0.005
Pre-LTx weight class, normal/overweight/obesity (%)42/43/1537/45/1851/41/80.015
BMI at 20 years old > 30 kg/m2 (%)8.1 (4.3–13.5)7.1 (2.9–13.8)8.3 (2.7–18.2)0.789
Dyslipidemia50.7 (44.8–56.2)56.8 (49.5–63.4)37.5 (28.4–46.6)0.003
High waist circumference (M: >102 cm; F: >88) (%)32.4 (27.2–37.8)36.3 (29.6–43.1)26.9 (18.9–35.6)0.132
High blood pressure (≥130/85 mm Hg) (%)52.7 (46.8–58.2)58.9 (51.6–65.4)41.2 (31.7–50.4)0.005
High blood glucose (≥100 mg/dL) (%)59.8 (54.0–65.1)57.9 (50.5–64.4)62.7 (52.6–71.1)0.408
High triglycerides (≥150 mg/dL) (%)36.8 (31.4–42.3)40.5 (33.5–47.4)29.4 (21.0–38.4)0.060
Low HDL–cholesterol (M: <40 mg/dL; F: <50) (%)50.0 (44.2–55.5)50.5 (43.2–57.3)49.0 (39.1–58.1)0.902
Number of MS criteria   0.241
 0–2 (%)55.4 (49.5–60.8)52.1 (44.8–58.8)60.8 (50.6–69.2) 
 3 (%)26.0 (21.2–31.1)26.3 (20.3–32.7)25.5 (17.6–34.2) 
 4–5 (%)18.6 (14.4–23.2)21.6 (16.1–27.7)13.7 (8.0–21.2) 

In a few cases, liver disease had a multifactorial origin. Four cases in which HCV was associated with excessive alcohol drinking were included in the HCV group, and similarly, six cases with HBV and excessive alcohol drinking were included in the HBV group, given that in all cases stopping alcohol abuse was a prerequisite for entering the LTx waiting list. Finally, 14 cases with combined HBV and HCV infection were included in the HCV group, given that the metabolic impact of HCV infection is much higher than that ascribed to HBV.

After LTx, methylprednisolone had been gradually tapered down and usually discontinued after 6 months. Only 9 subjects, having undergone transplantation for liver disease of autoimmune origin or with other clinical markers of autoimmune disorders, were continuing methylprednisolone at low doses (2.5 to 5 mg/day) at the time of the study.

During a preplanned outpatient follow-up visit at the Liver Transplantation Center of Azienda Policlinico S. Orsola-Malpighi, consecutive patients had an extended clinical examination, including anthropometric assessment and registration of height and weight.

Patients were also interviewed about their weight history, including weight at the age of 20 years and details of pre-LTx body weight, and weight at time of inclusion on the transplantation list (registered in the database), to define the time of onset of weight changes and/or overweight. We also recorded from the database pre-LTx data, including etiology of liver disease, presence/absence of hepatocellular carcinoma, and pre-LTx diabetes mellitus. Finally, all subjects had a thorough assessment of clinical and biochemical data reflecting the features of the MS. All these data are reported in Table 1.

Anthropometric Assessment

Waist circumference was measured at the umbilicus with the patient standing, as an index of central fat accumulation. Body mass index (BMI) was calculated as the ratio between patient weight (in kilograms) and the square of patient height (in meters).

Laboratory Assays

Fasting venous blood samples were collected and assayed for lipid profile (total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides), glucose, and creatinine on the same day of blood sampling. In an unselected, consecutive group of 99 subjects, insulin was also measured in aliquots of serum frozen at −80°C with an electrochemoluminescence immunoassay (ECLIA; Insulin Elecsys Roche Diagnostics), with an analytical sensitivity of 0.2 mU/L.

Insulin Sensitivity and IR

An estimate of IR was calculated using homeostasis model assessment (HOMA) according to the formula: HOMA-IR = fasting insulin (mU/mL) × fasting glucose (mmol/L), divided by 22.5.13 The cutoff for the diagnosis of IR was set at a value of 2.7, which was previously determined in our laboratory.14

Assessment of the MS

We investigated the presence of PTMS according to the proposal of the National Cholesterol Education Program Adult Treatment Panel III (ATPIII),15 which was revised in accordance with the new standard of normal fasting glucose.16 According to this proposal, the presence of MS may be diagnosed in subjects having at least 3 of the following 5 criteria: (1) waist circumference >102 cm in men and >88 cm in women; (2) blood glucose ≥100 mg/dL (5.6 mmol/L) or treated for diabetes; (3) triglycerides ≥150 mg/dL (1.7 mmol/L) or treated with fibrates; (4) HDL-cholesterol <40 mg/dL (1.0 mmol/L) in males and <50 mg/dL (1.3 mmol/L) in females; and (5) blood pressure ≥130/85 mm Hg or treated for hypertension.

Statistical Analysis

Clinical and laboratory data were entered into an electronic spreadsheet. Statistical analysis was performed with the statistical package SPSS for Windows version 8.0 (SPSS Inc., Chicago, IL). Data in the text and in tables are presented as means ± standard deviation or as prevalence [95% confidence intervals (CIs)]. Differences among the groups were checked for significance by means of analysis of variance or Mann-Whitney U test. The chi-square test, or Fischer's exact test when necessary, were used to test for significance of the prevalence of clinical, laboratory, and instrumental abnormalities. Possible correlations among variables were tested for significance with multiple regression or stepwise logistic regression analysis. In the assessment of factors associated with PTMS, the following variables were tested: age, etiology, gender, time from LTx, pre-LTx diabetes, pre-LTx BMI, 20-year BMI, and type of immunosuppression. P values < 0.05 (2-tailed analyses) were considered statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The final data set included 296 LTx subjects (196 males and 100 females), aged 18 to 77 years (median, 56); their pertinent data are reported in Table 1. The large majority of cases had undergone transplantation for cirrhosis of viral etiology (HBV, HCV, or combined) from 7 months to over 17 years before the study.

The median age was different according to the etiology of liver disease (Kruskal-Wallis test: 29.14; P < 0.001). High blood pressure was present in 156 subjects (52.7%), hyperlipidemia in 150 (50.7%), diabetes in 112 (37.8%), and enlarged waist circumference in 96 (32.4%). Finally, 170 cases (57.4%) were overweight or obese at the time of survey.

The ATPIII diagnostic criteria of MS were fulfilled in 132 subjects (Table 1). Elevated BMI and hypertension were significantly more frequent in LTx subjects on cyclosporine as an immunosuppressive drug, whereas the overall prevalence of diabetes was nonsignificantly lower. However, the development of diabetes after LTx was more common in subjects on tacrolimus.

No significant differences were observed in the prevalence of PTMS in relation to immunosuppressive treatment (cyclosporine: 47.6%; tacrolimus: 39.0%; P = 0.193).

No differences in the prevalence of PTMS (χ2 = 1.73; P = 0.631) and its individual features were observed in relation to the etiology of liver disease, with the notable exception of high blood glucose levels, which were more common in subjects with cirrhosis of alcoholic origin (χ2 = 9.94; P = 0.019) (Table 2). However, the prevalence of diabetes (χ2 = 6.55; P = 0.088) and the time of diabetes onset in cases with PTDM (χ2 = 10.31; P = 0.112) were also similar between groups. Subjects with PTMS were not older than subjects without MS (Mann-Whitney U test: P = 0.361). Subjects belonging to the miscellaneous etiology group were moderately younger. This group was very heterogeneous, and subjects with biliary cirrhosis were characterized by the lower prevalence of pre-LTx diabetes mellitus (DM) (3.8%) among groups. The prevalence of diabetes in cryptogenic cirrhosis was only 10%.

Table 2. Age, Time Since Transplantation, and Prevalence of the Metabolic Syndrome and Its Individual Features in Relation to the Etiology of Liver Disease
 Alcoholic (n = 43)HBV-Related (n = 67)HCV-Related (n = 126)Others (n = 60)P
Age (years)53.7 ± 7.852.5 ± 8.357.5 ± 7.848.7 ± 13.6<0.001
Time from LTx (months)43.0 ± 38.050.6 ± 37.446.0 ± 36.261.4 ± 50.00.423
Enlarged waist (%)41.9 (27.4–55.6)32.8 (22.1–44.0)29.4 (21.8–37.4)31.7 (20.6–43.4)0.339
High glucose (%)69.8 (53.7–80.5)47.8 (35.6–58.8)66.7 (57.6–73.9)51.7 (38.5–63.0)0.019
High blood pressure (%)55.8 (40.0–68.5)53.7 (41.2–54.4)54.0 (44.9–62.0)46.7 (33.9–58.3)0.764
High triglycerides (%)39.5 (25.4–53.3)34.3 (23.4–45.5)34.1 (26.1–42.4)43.3 (30.8–55.1)0.615
Low HDL–cholesterol (%)51.2 (35.7–64.3)58.2 (45.5–68.6)50.8 (41.8–59.0)38.3 (26.4–50.2)0.163
Metabolic syndrome (%)51.2 (35.7–64.3)44.8 (32.8–55.9)45.2 (36.4–53.5)38.3 (26.4–50.2)0.631

With very few exceptions (9 cases), the subjects who were overweight or obese in the pre-LTx phase were also overweight or obese in the post-LTx assessment, but 68 more cases who had normal BMI before LTx became overweight in the post-LTx phase (Table 3), with no differences in relation to etiology of liver disease. Obesity (BMI ≥30 kg/m2) was present in 43 cases (15%). In addition, diabetes, which was rare in the pre-LTx phase, increased by 300% in the post-LTx survey, particularly in subjects with liver disease of alcoholic and HCV etiology. Only 4 cases with pre-LTx diabetes had normal glucose regulation in the post-LTx survey (Table 4).

Table 3. Prevalence of Overweight/Obese Patients According to the Etiology of Liver Disease
GroupPre-LTxPost-LTxPre-LTx/Post-LTx ChangesPre-LTx/ Post-LTx Difference, P
Normal Weight (n = 185)Overweight/ Obese (n = 111)Normal Weight (n = 126)Overweight/ Obese (n = 170)Became Overweight/ Obese (n = 68)*Regressed to Normal Weight (n = 9)
  • NOTE: Data are reported as the number (percent prevalence) of observed disorders.

  • *

    Data are expressed as the percentage of pre-LTx normal weight.

  • Data are expressed as the percentage of pre-LTx overweight/obesity.

All cases (n = 296) (%)185 (62.5)111 (37.5)126 (42.6)170 (57.4)68 (36.8)9 (8.1)< 0.001
Alcohol (n = 43) (%)25 (58.1)18 (41.9)15 (34.9)28 (65.1)11 (44.0)1 (5.6)0.051
HBV (n = 67) (%)39 (58.2)28 (41.8)25 (37.3)42 (62.7)14 (35.9)00.025
HCV (n = 126) (%)75 (59.5)51 (40.5)48 (38.1)78 (61.9)33 (44.0)6 (11.8)0.001
Other (n = 60) (%)46 (76.7)14 (23.3)38 (63.3)22 (36.7)10 (21.7)2 (14.3)0.163
P across groupsChi-square = 6.489; P = 0.090Chi-square = 13.401; P = 0.003Chi-square = 2.414; P = 0.491Chi-square = 3.484; P = 0.323 
Table 4. Prevalence of Diabetes in Relation to the Etiology of Liver Disease
GroupPre-LTxPost-LTxPre/Post-LTx ChangesPre/Post Difference, P
No Diabetes (n = 267)Diabetes (n = 29)No Diabetes (n = 184)Diabetes (n = 112)Developed Diabetes (n = 87)*Regressed to No Diabetes (n = 4)
  • NOTE: Data are reported as the number (percent prevalence) of observed disorders.

  • *

    Data are expressed as the percentage of pre-LTx no diabetes.

  • Data are expressed as the percentage of pre-LTx diabetes.

All cases (n = 296) (%)267 (90.2)29 (9.8)184 (62.2)112 (37.8)87 (32.5)4 (14.3)<0.001
Alcohol (n = 43) (%)36 (83.7)7 (16.3)23 (53.5)20 (46.5)14 (38.9)1 (14.3)0.005
HBV (n = 67) (%)60 (89.6)7 (10.4)46 (68.7)21 (31.3)15 (25.0)1 (14.3)0.006
HCV (n = 126 (%)114 (90.5)12 (9.5)73 (57.9)53 (42.1)43 (34.1)2 (18.2)<0.001
Other (n = 60) (%)57 (95.0)3 (5.0)42 (70.0)18 (30.0)15 (25.0)0<0.001
P across groups =Chi-square = 3.649; P = 0.302Chi-square = 5.101; P = 0.165Chi-square = 5.092; P = 0.532 

In a forward-looking logistic regression to define the variable/variables independently associated with PTMS, the model identified pre-LTx BMI [odds ratio (OR), 1.20; 95% CI, 1.12-1.30; P < 0.001], changes in BMI (OR, 1.18; 95% CI, 1.09-1.30; P < 0.001), and the presence of pre-LTx diabetes (OR, 2.36; 95% CI, 1.01-5.56; P = 0.048) as the sole significant variables. Age, gender, etiology of liver disease, time from LTx, type of immunosuppressive drug, and previous hepatocellular carcinoma were rejected from the model.

Fasting insulin was available in 99 cases. IR, as assessed by HOMA, was observed in 41 subjects (41.4%), with no differences in relation to the type of immunosuppressive drug.

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The clinical and biochemical features of MS are highly prevalent in LTx patients, independently of etiology of pre-LTx liver disease and type of immunosuppressive treatment. The metabolic changes associated with MS and IR promote the development of atherosclerosis and represent risk factors for premature coronary heart disease, which was not present before LTx, and an early recognition of MS is important for the prevention of cardiovascular events.

The prevalence of posttransplantation MS is a matter of concern in the transplantation area: the presence of MS is one more risk factor to be considered in the pretransplantation workup,11 but after transplantation the risk appears to be particularly elevated, particularly in subjects having undergone transplantation for HCV-related disease,17, 18 increasing the risk by a factor of 2 or more.19

The relationship between HCV infection and IR/diabetes is well-known in liver disease patients,20 and has been related to different mechanism(s) involving either a direct effect of the virus on insulin signaling21 or simply favoring the phenotypic expression of classical diabetes risk factors.22 Whatever the mechanism, the presence of PTDM remains a negative prognostic factor in the long term,23 although it is respondent to oral hypoglycemic agents.4 It has also been demonstrated that PTMS and nonalcoholic fatty liver disease in HCV patients is associated with a high risk of fibrosis progression.24 By contrast, the prevalence of PTMS was very low in cirrhosis of biliary origin, in keeping with the late involvement of hepatocytes, which are directly responsible for glucose metabolism.

The prevalence of PTMS was ascertained in the well-accepted revision of the ATPIII criteria.16 More recently, the International Diabetes Federation proposed a different classification having visceral obesity as a pivotal feature.25 Using these criteria, the prevalence of PTMS did not change remarkably (43.9% in the whole sample versus 44.5% by ATPIII criteria). These figures are definitely higher compared to reports in the Italian population in the age range between 45 and 65 years (around 30%-35%),26 and is definitely surprising considering that the prevalence is expected to be extremely low in the pre-LTx period. Data were not available for defining pre-LTx MS in our population, and any inference is subject to criticism.27 However, the figure should be very low, considering the hypotension due to vasodilation and the low lipid levels of advanced liver failure.

PTDM and PTMS were significantly associated with classical pre-LTx risk factors, namely diabetes and BMI, but no association was found with the type of immunosuppression. The glucocorticoid-sparing action of calcineurin inhibitors was originally welcomed in the hope to reduce the risk of diabetes, but soon it became evident that both cyclosporine and tacrolimus had a diabetogenic activity, impairing insulin sensitivity.28 Only later was it shown that calcineurin inhibitors also reduce insulin secretion,29 and that tacrolimus was more diabetogenic than cyclosporine,30, 31 mainly in the early post-LTx phase,32 because of its multiple sites of action.33 However, after controlling for time from liver transplantation, the type of immunosuppression did not qualify as prognostic factor for PTDM or PTMS. Once DM is established in the pretransplantation period, LTx does not always produce a complete clinical regression. Tueche34 reported a de novo incidence of DM in 26/108 (24%) transplant patients at 6 months, whereas only 8/35 (23%) were cured of their pre-LTx DM. Similarly, in our long-term analysis, we found that LTx cured pre-LTx DM in only 14% of cases, in keeping with an established b-cell defect,2 and PTDM developed in 32.5% of cases. This highlights the need for careful surveillance and comprehensive nutritional education to prevent DM and DM complications in the early and late post-LTx phase.

From a clinical perspective, the presence of PTMS is associated with an increased risk of major vascular events in the LTx population.5 Bianchi et al.35 reported an association between high levels of homocysteine and arterial events in LTx patients, but their potential negative effect in subjects with MS is doubtful.36–39 However, in LTx the actual risk of cardiovascular events should be lower than in the general population, considering the a priori exclusion from transplant procedures of all cases at high vascular risk.

In our series, very few subjects had undergone LTx because of metabolic liver disease progressing to end-stage cryptogenic cirrhosis, in contrast with series reported in other countries.40 Only 10 cases in the miscellaneous group could be ascribed to this etiology, and the prevalence of PTDM and MS in this cohort was low (3 cases for both; 30%), but in 1 case diabetes was already present before transplantation. Patients undergoing LTx for cirrhosis resulting from NASH may have poorer outcomes, despite careful selection of candidates. It is very likely that many potential LTx candidates with NASH are excluded from surgery due to comorbid conditions related to MS, thus explaining their low prevalence in countries with a high prevalence of viral and alcoholic disease.41 Their clinical outcomes appear to be similar to those observed in other patient groups42 or even better.43

This study has limitations. The retrospective collection of a few data may have introduced a recall bias, but most data were recorded in the original database, and pre-LTx weight or the presence of diseases could easily be remembered. With this caveat, we conclude that the risk factors of PTMS include pre-LTx conditions, as well as post-LTx weight gain and post-LTx obesity; the latter was reported to account for both cardiovascular risk and risk of graft loss in different settings.3, 5, 12, 44 Behavioral treatment toward a healthy lifestyle and preventing obesity is mandatory to reduce the burden of cardiovascular events in LTx patients, and there is now evidence that this is feasible and effective.45 This retrospective analysis is the basis for follow-up and intervention in our post-LTx population.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES