Alcohol and Alcoholism Advance Access published online on February 29, 2008
Alcohol and Alcoholism, doi:10.1093/alcalc/agn011
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Prognostic Value of Nutritional Status in Alcoholics, Assessed by Double-Energy X-Ray Absorptiometry
Servicios de Medicina Interna and Medicina Nuclear, Hospital Universitario de Canarias (HUC), Universidad de La Laguna, Tenerife, Canary Islands 38320, Spain
* Author to whom correspondence should be addressed: Servicio de Medicina Interna, Hospital Universitario de Canarias (HUC), Universidad de La Laguna, Tenerife, Canary Islands 38320 Spain. Tel.: 34 922 678640; Fax: 34 922 319279; E-mail: egonrey{at}ull.es
Received 22 February 2007; first review notified 21 November 2007; ; accepted 13 December 2007
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objectives: This study was performed in order to assess nutritional status of 77 alcoholic patients. Methods: Patients underwent a total body double-energy X-ray absorptiometry (DEXA) analysis, with estimation of lean and fat mass at different parts of the body. Results: Lean mass, but not fat mass, was significantly reduced among alcoholics, compared to 31 age-matched controls, especially at right arm, legs, and total body. Lean mass at both arms was significantly related to liver function parameters (albumin, prothrombin activity, bilirubin) and, inversely, with ethanol consumption. The 24 patients who died during a follow-up period of 88 months showed less lean mass at both arms, trunk, and left leg, and also less fat at the left arm, than survivors. When right and left arm lean mass were classified in quartiles, Kaplan–Meier curves showed significant differences between dead and survivors. Left arm lean mass was the parameter which was independently related to mortality when encephalopathy was not included in a stepwise Cox regression analysis, but was displaced by this last parameter when it was also introduced in the analysis. Conclusion: lean mass is reduced in alcoholics, is related to liver function derangement and ethanol consumption, and is related to mortality.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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A normal nutritional status reflects an imbalance between nutrient intake and energy expenditure, maintained over relatively long periods of time. Assessment of nutritional status includes assessment of lean mass, fat mass and visceral proteins. Lean mass and fat mass can be easily estimated by anthropometry, double-energy X-ray absorptiometry (DEXA) (Lohman, 1996
), or bioimpedance, whereas serum proteins, such as albumin, prealbumin, or transferrin, among others, may serve to assess visceral compartment. Nutritional status is a very important predictor of mortality. Body mass index (BMI) is related to mortality, a relation that fits into a J-shaped curve; a relation also exists between lean mass and mortality, and between fat amount and mortality.
Alcoholics usually showed altered nutritional status, partly because of the calorie-wasting effect of ethanol itself (Lands and Zakhari, 1991), partly because of the irregular style of life of alcoholics, partly because of the nutritional impairment produced by the accompanying disease, such as cirrhosis, cancer, pancreatitis or infection (Morgan, 1982; Simko et al. 1982; Romero et al., 1994; Seitz et al., 2005). Several studies have pointed out the clinical significance of deranged nutritional status in alcoholics, especially in those affected by chronic liver disease (Merli et al., 1996; Addolorato et al., 1998; Stickel et al., 2003; Halsted, 2004; Leevy and Moroianu, 2005). In a previous study on 108 alcoholics we have shown that impaired nutritional status is present in alcoholics, and may result from irregular food intake, which is dependent on break of social links and familial support (Santolaria et al., 2000). However, the prognostic value of the compartmental assessment of fat or lean mass in different parts of the body (arms, legs, trunk) in alcoholics is less well studied. This constitutes the aim of our study.
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PATIENTS AND METHODS |
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Patients and controls
We included 77 male alcoholic patients consecutively admitted to our hospitalization unit. All of them were heavy drinkers of more than 150 g ethanol/day for prolonged (>5 years) time periods. The control group was composed of 31 healthy sanitary workers, drinkers of less than 10 g ethanol/day. Some clinical and biochemical parameters of patients and controls are shown in Table 1.
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After they had given written informed consent, all the patients and controls underwent an assessment of lean mass and fat mass by double-energy X-ray absorptiometry (DEXA), recording both parameters at trunk, right and left arms, right and left legs, and total lean and fat mass.
We recorded the presence or absence of ascites, encephalopathy, and withdrawal syndrome at admission, and determined serum free cortisol bilirubin, prothrombin activity and serum albumin, mean corpuscular volume (MCV) and serum 
-glutamyl transpeptidase (GGT), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT), by routine laboratory techniques. We also determined serum IGF-1 (chemiluminescent assay; DPC, Los Angeles, CA, USA), estradiol (competitive immunoassay; DPC, Los Angeles, CA, USA), and serum free testosterone (radioimmunoanalysis; DPC, Los Angeles, CA, USA),
The study protocol was approved by the local ethics committee of our Hospital and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.
Patients were followed up for a mean time of 74.1 ± 25.1 months (median = 88 months, range = 4–88 months). During this period, 24 patients died.
Statistics
We compared mean values of lean mass and fat mass assessed at different parts of the body between patients and controls, and between survivors and nonsurvivors by means of Student's t-test.
We further classified fat and lean mass parameters in quartiles, and compared survival using Kaplan–Meier curves and log-rank and Breslow tests. In addition, with those parameters that showed significant differences between survivors and nonsurvivors, we performed a stepwise Cox regression analysis, (1) introducing all the parameters and (2) excluding parameters such as encephalopathy, suggestive of severe liver failure.
All the tests performed were two-tailed. Statistical Package for Social Sciences (SPSS, Chicago, Illinois) was used for statistical analysis.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients showed less lean mass than controls at any level studied (Table 2). Differences were especially significant at left arm, and, especially, at both legs.
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There were close relationships between lean mass and liver function (Table 3). On the contrary, no relation was observed between fat parameters and any of ethanol-consumption-related parameters or liver function parameters, except for an inverse relation between total fat and daily ethanol consumption (r = –0.26, P = 0.024).
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Right arm lean mass was significantly related to IGF-1 (r = 0.29, P = 0.03). Also, a direct relationship was observed between cortisol and left arm lean mass (r = 0.34, P < = 0.005). Serum estradiol was significantly related to total lean mass (r = 0.30, P = 0.04), trunk lean mass (r = 0.33, P = 0.026), left leg lean mass (r = 0.43, P = 0.003), left arm fat (r = 0.38, P = 0.008), right arm fat (r = 0.45, P = 0.001), and trunk fat (r = 0.32, P = 0.029).
Significant differences were observed between survivors and nonsurvivors regarding lean mass (Table 4). When right arm lean mass was classified into quartiles, Kaplan–Meier survival curves showed significant differences among all the intervals analyzed (Fig. 1), differences that were also significant when left arm lean mass was classified into quartiles, especially when the first quartile was compared with the fourth one (Fig. 2).
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Cox regression model including all the parameters analyzed (encephalopathy, ascites, bilirubin, prothrombin, albumin, ASAT, ALAT, age, lean and fat mass at each arm, each leg, trunk, and total, mean daily ethanol consumption, years of ethanol consumption, and BMI) showed that encephalopathy was the first one which was independently related to mortality, followed by BMI (Table 5); but when encephalopathy was removed, right arm lean mass displaced BMI (Table 6).
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When patients with ascites and without ascites were compared (Table 7) we observed a trend to higher lean mass values at legs and trunk, but lower values at both arms. We therefore calculated the index (lean mass at trunk + lean mass at legs)/total lean mass, which is clearly different in patients with ascites (0.8271 ± 0.0218) and without ascites (0.8092 ± 0.0187, t = 3.21, P = 0.002), and which also yields prognostic value, being lower ion survivors (0.8086 ± 0.0177) than in nonsurvivors (0.8191 ± 0.0249, t = 2.04, P = 0.046).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In this study we clearly show that reduced lean mass is an adverse prognostic factor in chronic alcoholics. Impaired nutritional status profoundly affects immune response (Cunningham-Rundles, 1982
), synthesis of acute phase reactants (Jennings et al., 1992), and antioxidative capacity (Belmonte et al., 2007). Therefore, it is not surprising that mortality is increased in malnourished individuals. In our study, the results are especially striking regarding lean mass at both arms—especially the left arm. The importance of muscle mass in survival has been stressed by Mendenhall et al. (1995), who found that handgrip strength and creatinine excretion—both parameters related to muscle mass—were related to survival in patients with acute alcoholic hepatitis. On the contrary, results regarding trunk lean mass are not statistically significant when patients are compared with controls. As we pointed out in a previous study (Santolaria et al., 2000), lean mass at both legs and trunk not only reflects true lean mass, but also edema and ascites (Madden and Morgan, 1997). This fact may explain the lack of relationships between low values of legs and trunk lean mass and mortality. Therefore we compared these parameters between patients with ascites and patients without ascites. A trend to higher values in ascites patients was observed in lean mass at lower legs and trunk. The confounding effect of fluid retention may also explain why BMI was displaced by right arm lean mass in survival analysis using Cox's regression model. This result is similar to that reported by Kato et al. (2003) in hemodialysis patients, among whom BMI was also displaced by DEXA parameters in survival analysis.
Interestingly, although fat parameters lack prognostic significance, and did not show any relation to biochemical parameters of liver dysfunction, fat amount was higher in patients with ascites, The explanation for this finding is not fully understood, but the term "obese-type malnutrition" has been coined to describe this situation (Lautz et al., 1992).
This study stresses the paramount importance of the nutritional parameters in survival assessment. Indeed, right arm lean mass was the first parameter that entered a logistic regression analysis when criteria such as prothrombin, albumin, bilirubin, ascites, daily ethanol consumption, BMI, or age, were introduced in a stepwise multivariate analysis. Only when encephalopathy was also introduced, nutritional parameters were displaced in prognostic value. This result suggests that, in absence of an advanced liver disease, nutritional status is the major factor influencing the outcome of chronic alcoholics. In this study we do not analyze the causes of impaired nutrition in alcoholics, but, as commented before, there are several mechanisms involved. In addition to concurrent diseases, which may impair nutritional status, such as chronic pancreatitis, several studies support the observation that disruption of social and familial links underlies nutritional impairment of alcoholic patients. In fact, Nicolas et al. (1993) found that impaired nutritional status was related to organic complications rather than to ethanol itself in 250 alcoholics with stable social status and familial support. On the contrary, inveterate, lone, alcoholics become progressively isolated from the social environment, usually eat in bars or taverns, and food consumption becomes irregular and insufficient (Santolaria and González-Reimers, 2004). Empty calories due to ethanol consumption complicate this scenario, especially considering that MEOS system is activated in chronic alcoholics (Lieber, 1980).
Thus, we conclude that the DEXA-assessed nutritional status is impaired in chronic alcoholics, especially regarding lean mass, which is significantly reduced compared to age-matched controls. Reduced lean mass is related to increased mortality, especially when assessed at upper extremities; ascites and/or edema may obscure the significance of lean mass assessment at lower legs and trunk, as well as BMI. Therefore, results regarding lean mass at lower extremities and trunk should be cautiously interpreted in chronic alcoholics, especially with coexisting liver disease.
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