AJCN Tufts Nutrition Symposium, Boston & Online Sept 2009
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American Journal of Clinical Nutrition, Vol. 69, No. 6, 1066-1068, June 1999
© 1999 American Society for Clinical Nutrition

Editorials

Effect of cirrhosis on energy expenditure1,2,3

Arthur J McCullough and Comasia Raguso

Cirrhosis is considered to be a catabolic disease associated with a high prevalence of protein-energy malnutrition (1). Increased energy expenditure (EE) has been proposed (1) and editorialized (2) to be of pathophysiologic importance in liver disease. As shown in Table 1Go, quantitative disturbances in EE in cirrhotic patients are variable. Most studies using indirect calorimetry to calculate EE have found no difference in absolute EE or EE corrected for body weight between cirrhotic and control subjects. However, 3 studies in Table 1Go showed an increased absolute EE; the first in patients with primary biliary cirrhosis (9), the second in children with portal hypertension (13), and the third in patients with postviral cirrhosis (14). Four of the studies (5, 6, 8, 10) in Table 1Go also showed increased EE when energy consumption was expressed per unit lean body mass (estimated from urinary creatinine excretion). In these latter studies, EE correlated directly with lean body mass but the pattern of EE was dependent on the type of liver disease. In primary biliary cirrhosis and alcoholic hepatitis, EE increased with worsening liver function (5, 9), whereas EE decreased with worsening liver function in patients with alcoholic cirrhosis (8). On the basis of the results of these studies and the assumption that urinary creatinine excretion reflects total lean body mass, cirrhotic patients may have increased resting EE, which in turn correlates with the severity of liver disease in a fashion dependent on the type of liver injury. However, there are inherent difficulties in the measurement of EE and the calculation of lean body mass from urinary creatinine excretion (15–17). These difficulties are compounded by differences among patient populations in sex, genetics, type and stage of liver disease, and variability of EE among different organs (17), especially in studies with small sample sizes such as those listed in Table 1Go.


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  		TABLE 1 Resting energy expenditure of cirrhotic patients compared with that of control subjects, as measured by indirect calorimetry1
 
In this issue of the Journal, Müller et al (18) report a carefully performed, large, prospective study that improves our understanding of EE in cirrhosis in 4 important ways. First and foremost, by comparing measured with calculated EE, these investigators described a spectrum of EE among cirrhotic patients. As shown in Table 2Go (18, 19, 20), EE is normal in most cirrhotic patients, whereas 16–34% are hypermetabolic. These observations were made possible by comparing the measured values of EE in cirrhotic patients with EE calculated from prediction equations derived from normal populations rather than from a control group in any individual study. Because these results are so dependent on the prediction equations, Müller et al are to be commended for studying such a large patient population and for using both the classic (21) and more recently developed prediction equations (22–25), which strengthen their conclusions. EE also differed between male and female patients, as was observed previously (13). The spectrum of EE in cirrhosis and its sex dependence may explain the conflicting results displayed in Table 1Go and are important factors to be considered in the design of future studies.


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  		TABLE 2 Percentages of cirrhotic patient populations in categories of resting energy expenditure (REE)1
 
The second important finding of this work was that hypermetabolism correlated with lean body mass rather than with the type (with the exception of primary biliary cirrhosis), duration, or severity of liver disease. These data suggest that hypermetabolism in cirrhosis cannot be accurately determined by clinical, laboratory, or histologic measures, but rather must be determined by the measurement of EE in comparison with EE determined with standard prediction formulas. They further suggest that hypermetabolism may be influenced to a great extent by extrahepatic factors, such as portal hypertension and portosystemic shunting. This concept is supported by evidence that hypermetabolism exists in patients with presinusoidal extrahepatic portal obstruction (13) and in patients who have received liver transplants (26, 27); both conditions are associated with normal liver function.

The third important finding was that plasma catecholamines were elevated only in the hypermetabolic patients, although no catecholamine data were supplied for the normometabolic patients (18). This observation is consistent with the previously described elevation of plasma catecholamines and activation of the sympathetic nervous system in cirrhosis (28, 29). Furthermore, propranolol administration diminished EE, heart rate, and lactate concentrations in both the normo- and hypermetabolic cirrhotic patients. Therefore, therapy intended to decrease EE in these patients may have clinical relevance. Two other studies showed that hypermetabolism may predict a poor clinical outcome in patients undergoing liver transplantation (26, 27), whereas another showed that nutritional status improved in cirrhotic patients when energy intake was increased relative to EE (30).

Fourth, the hypermetabolic patients in the study of Müller et al also had elevated EE despite a decrease in body potassium, a marker of body cell mass (BCM), while maintaining a normal muscle mass (based on the creatinine height index and anthropometry). This method for estimating BCM assumes that the ratio of potassium to nitrogen is normal, but this measurement has never been made in cirrhotic patients. Because it is well known that EE in different body tissues is unrelated to the mass of those tissues (31), it is possible that EE may be elevated nonuniformly in the tissues of cirrhotic patients.

Because the present study used a cross-sectional design, normative EE (based on values compared with results of predictive equations) may actually be abnormal in an individual patient and vice-versa. Furthermore, the prediction equations suggest that 10% of a normal population is hypermetabolic. It will be important to reevaluate these patients in a prospective study designed to determine whether hypermetabolism is a cause or a consequence of malnutrition (14, 30).

In summary, Müller et al have described a pathophysiologic abnormality of elevated EE that can be treated and that has a measurable endpoint (decreased EE) with potentially important clinical outcomes. They have also provided clinical investigators with new insights to investigate the causes and potential new therapies of hypermetabolism in these patients. EE may be controlled centrally (32, 33), so therapies such as transjugular intrahepatic portal systemic shunts may actually increase energy expenditure, whereas therapeutic agents other than ß-blockers may also have clinical value (34).

FOOTNOTES

See corresponding article on 1194.

1 From the Robert Schwartz Center of Metabolism and Nutrition and the Division of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University, Cleveland.

2 Supported in part by NIH grant AA 10445.

3 Address reprint requests to AJ McCullough, MetroHealth Medical Center, Division of Gastroenterology, 2500 MetroHealth Drive, Cleveland, OH 44109.

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