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Risk factors for loss of lean body mass after liver transplantation
Appl. Radiat. lsot. Vol. 49. No. 5/6, pp. 663-664, 1998
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Pergamon PII: S0969-8043(97)00088-2
.~ 1998 ElsevierScienceLtd. All rights reserved Printed in Great Britain 0969-8043/98 $19.00+ 0.00
Risk Factors for Loss of Lean Body Mass after Liver Transplantation S. H . H U S S A I N 1 . 1 , S. S O O l, S. P. S T E W A R T 2, B. O L D R O Y D 2, F. R O M A N 2, M. A. S M I T H 2, J. G. O ' G R A D Y ~ a n d M . S. L O S O W S K Y I ~Departments of Medicine and Hepatology, St James' University Hospital, Leeds, U.K. and 2Centre for Bone and Body Composition Research, University of Leeds, Leeds, U.K.
Background:After liver transplantation
there is a fall in lean body mass. Aims: To determine the risk factors for this fall in lean body mass using univariate and subgroup analyses. PatientsandMethods:Dual energy X-ray absorptiometry was performed in 36 patients (12 with Child-Pugh Class A, 20 with Class B and 4 with Class C disease) before and up to 24 months after liver transplantation. Univariate and sub-group comparative analyses were performed to assess possible risk factors for the fall in lean body mass post-transplantation. Results: The pre-transplantation serum albumin inversely correlated with the fall lean body mass at 1 month (r=0.55; p < 0.009) and at 6-9 months (r=0.51; p<0.05) post-transplantation. A positive correlation between the fall in lean body mass and: (i) cumulative dose of steroids administered at 2-5 months (r = 0.57; p < 0.05) and (ii) length of hospital stay after transplantation (r = 0.52; p < 0.05) were also observed. Neither the severity or presence ofcholestatic liver disease pre-transplant, nor acute cellular rejection post-transplant were risk factors for a fall in lean mass. Discussion:A hypercatabolic state post-transplant (represented by low albumin pre-transplantation), immobility, lack of exercise and steroid induced catabolism of muscle may cause the observed fall in lean mass after liver transplantation. Earlier transplantation of patients with better nutritional status and the use of low dose steroid immunosuppressive regimens may prevent the observed fall in lean body mass after transplantation. © 1998 Elsevier Science Ltd. All rights reserved
Background
Patients and Methods
Orthotopic liver transplantation (OLT) is now established in the treatment of patients with end-stage chronic liver disease. These patients are often malnourished. Fortunately, after transplantation there is a progressive rise in total body weight. Using a variety of techniques such as dual emission X-ray absorptiometry (DEXA), total body potassium measurement, bioimpedance and skin fold anthropometry we have found that this increase in weight is secondary to an increase in body fat (Hussaini et al., 1995). However, paired D E X A studies before and after transplantation revealed a significant loss in lean body mass (Hussaini et al., 1995). The loss in lean mass occurred not only at 1 month, but also at 2-5 months and 6-9 months after transplantation, with no significant rise in lean weight thereafter for up to 24 months follow up (Hussaini et al., 1995). Thus the aim of the present study was to determine the risk factors for the fall in lean body mass after liver transplantation using univariate and subgroup analyses.
A total of 36 patients, 19 of whom were female, were studied before and after liver transplantation. The mean age of the group was 48 + 2 yr (range 24-69 yr). Nineteen patients had cholestatic liver disease, 13 with primary biliary cirrhosis, four with primary sclerosing cholangitis, and two with secondary biliary cirrhosis. The remaining 17 patients had alcohol related disease (n = 8), autoimmune chronic hepatitis (n = 4), cryptogenic cirrhosis (n = 2), neoplastic disease (n = 2) and hepatitis B cirrhosis (n = 1). The severity of chronic liver disease was classified according to the modified Child-Pugh system (Pugh et al., 1973). Twelve patients had mild (class A) and 20 had moderately severe (class B) chronic liver disease disease. Only four patients had severe disease (class C) or clinical ascites and fluid retention. Total body bone mineral content, fat and fat free mass were measured by D E X A using a Lunar DPX Bone Densitometer (Lunar Radiation Corporation, Madison, WI, USA). Analysis of the bone scans was made using the manufacturer's software (version 3.2). Lean mass was derived by subtracting bone mineral content from fat mass. Patients were assessed before transplantation, at 1 month, 2-5 months,
*To whom all correspondence should be addressed: Dr S. H. Hussaini, Department of Medicine, Level 7, Clinical Science Building, St James' University Hospital, Leeds LS9 7TF, U.K.
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S.H. Hussaini et al.
6-9 months, 12 months and 18-24 months after transplantation.
Statistical Analysis Univariate analyses (Spearman rank correlation, two-tailed test) were performed between the fall in lean body mass and the following parameters: (i) pre-transplant serum albumin; (ii) the cumulative dose of steroids after transplantation; and (iii) the length of hospital stay after transplantation. The fall in lean body mass was then compared in groups of patients stratified for sex, disease severity, disease type (cholestatitic vs non cholestatic) and the presence of acute cellular rejection. The statistical significance of differences between groups was tested with the non-parametric heteroscedastic 't test'. Excel software version 7.0 (Microsoft Corporation, 1 Microsoft Way, Redmond, WA 98052-6399, USA) was used to analyse data. P values of < 0.05 were considered to be statistically significant.
Results The pre-transplantation serum albumin inversely correlated with the fall in lean body mass, 1 month after transplantation (r = 0.55; P < 0.009). Although no similar relationship between pre-transplant albumin and fall in lean body mass between 2 and 5 months post OLT was observed, a weaker inverse correlation was seen at 6-9 months ( r = 0 . 5 1 ; P < 0.05). A stronger positive correlation between the fall in lean body mass and cumulative dose of steroids administered after transplantation was seen at 2 5 months (r = 0.57; P < 0.05), with a slightly weaker ( r = 0.52) but still significant ( P < 0.05) correlation between fall in lean body mass and length of hospital stay after transplantation. In the first month after transplantation, there was a greater fall in mean lean body mass in men compared to women (7.3 _+ 3.1 vs 2.0 _+ 0.8 kg) and in patients with severe compared to those with mild liver disease (5.5 + 2.0 vs 1.0 _+ 1.5 kg), although this difference was not statistically significant. However, at longer time periods after transplantation there was no marked difference in the fall in lean body mass between these two subgroups. Similarly no marked
difference in the fall of mean lean body mass after OLT was seen in patients with or without cholestatic liver disease or with or without acute rejection following transplantation.
Discussion The present study demonstrates that low serum albumin, high dose steroid immunosupression regimens and protracted hospitalisation following transplantation are all risk factors for a fall in lean body mass after liver transplantation. The fall in lean body mass may have represented a drop in total body water. Further analysis of total body potassium and total body water may clarify whether the fall in lean mass represents a true loss of muscle mass rather than water. A low pre-transplant serum albumin may not only represent poor hepatic synthetic function but also a hypercatabolic state which could account for the early fall in lean mass after transplantation. A long post-operative course after transplantation is often associated with immobility and a lack of exercise which could lead to the observed fall in body mass. Perhaps the most important factor in the fall in lean body mass was the dose of steroids administered. High dose corticosteroids favour the catabolism of muscle tissue to form adipose tissue (Rogers et al., 1981), which would therefore cause a fall in lean mass. In conclusion, we would propose that earlier transplantation of patients with better nutritional status and the use of low dose steroid immunosupressive regimens after transplantation may prevent the observed fall in lean body mass found in our study.
References Hussaini, S. H., Stewart, S. P., Roman, F., Oldroyd, B., Bramley, P., Simpson, M., Smith, M. A., O'Grady, J. and Losowsky, M. S. (1995) Nutritional status after orthotopic liver transplantation. Gut 37, AI4. Pugh, R. N., Murray-Lyon, I. M., Dawson, J. L., Pietroni, M. C. and Williams, R. (1973) Transection of the oesophagus for bleeding oesophageal varices. Brit. J. Surg. 60, 646-649. Rogers et al. (1981) A textbook of Clinical Pharmacology, ed. H.J. Rogers, R.G. Spector and J.R. Trounce, pp. 598-599. Hodder and Stoughton, London.
~
Pergamon PII: S0969-8043(97)00088-2
.~ 1998 ElsevierScienceLtd. All rights reserved Printed in Great Britain 0969-8043/98 $19.00+ 0.00
Risk Factors for Loss of Lean Body Mass after Liver Transplantation S. H . H U S S A I N 1 . 1 , S. S O O l, S. P. S T E W A R T 2, B. O L D R O Y D 2, F. R O M A N 2, M. A. S M I T H 2, J. G. O ' G R A D Y ~ a n d M . S. L O S O W S K Y I ~Departments of Medicine and Hepatology, St James' University Hospital, Leeds, U.K. and 2Centre for Bone and Body Composition Research, University of Leeds, Leeds, U.K.
Background:After liver transplantation
there is a fall in lean body mass. Aims: To determine the risk factors for this fall in lean body mass using univariate and subgroup analyses. PatientsandMethods:Dual energy X-ray absorptiometry was performed in 36 patients (12 with Child-Pugh Class A, 20 with Class B and 4 with Class C disease) before and up to 24 months after liver transplantation. Univariate and sub-group comparative analyses were performed to assess possible risk factors for the fall in lean body mass post-transplantation. Results: The pre-transplantation serum albumin inversely correlated with the fall lean body mass at 1 month (r=0.55; p < 0.009) and at 6-9 months (r=0.51; p<0.05) post-transplantation. A positive correlation between the fall in lean body mass and: (i) cumulative dose of steroids administered at 2-5 months (r = 0.57; p < 0.05) and (ii) length of hospital stay after transplantation (r = 0.52; p < 0.05) were also observed. Neither the severity or presence ofcholestatic liver disease pre-transplant, nor acute cellular rejection post-transplant were risk factors for a fall in lean mass. Discussion:A hypercatabolic state post-transplant (represented by low albumin pre-transplantation), immobility, lack of exercise and steroid induced catabolism of muscle may cause the observed fall in lean mass after liver transplantation. Earlier transplantation of patients with better nutritional status and the use of low dose steroid immunosuppressive regimens may prevent the observed fall in lean body mass after transplantation. © 1998 Elsevier Science Ltd. All rights reserved
Background
Patients and Methods
Orthotopic liver transplantation (OLT) is now established in the treatment of patients with end-stage chronic liver disease. These patients are often malnourished. Fortunately, after transplantation there is a progressive rise in total body weight. Using a variety of techniques such as dual emission X-ray absorptiometry (DEXA), total body potassium measurement, bioimpedance and skin fold anthropometry we have found that this increase in weight is secondary to an increase in body fat (Hussaini et al., 1995). However, paired D E X A studies before and after transplantation revealed a significant loss in lean body mass (Hussaini et al., 1995). The loss in lean mass occurred not only at 1 month, but also at 2-5 months and 6-9 months after transplantation, with no significant rise in lean weight thereafter for up to 24 months follow up (Hussaini et al., 1995). Thus the aim of the present study was to determine the risk factors for the fall in lean body mass after liver transplantation using univariate and subgroup analyses.
A total of 36 patients, 19 of whom were female, were studied before and after liver transplantation. The mean age of the group was 48 + 2 yr (range 24-69 yr). Nineteen patients had cholestatic liver disease, 13 with primary biliary cirrhosis, four with primary sclerosing cholangitis, and two with secondary biliary cirrhosis. The remaining 17 patients had alcohol related disease (n = 8), autoimmune chronic hepatitis (n = 4), cryptogenic cirrhosis (n = 2), neoplastic disease (n = 2) and hepatitis B cirrhosis (n = 1). The severity of chronic liver disease was classified according to the modified Child-Pugh system (Pugh et al., 1973). Twelve patients had mild (class A) and 20 had moderately severe (class B) chronic liver disease disease. Only four patients had severe disease (class C) or clinical ascites and fluid retention. Total body bone mineral content, fat and fat free mass were measured by D E X A using a Lunar DPX Bone Densitometer (Lunar Radiation Corporation, Madison, WI, USA). Analysis of the bone scans was made using the manufacturer's software (version 3.2). Lean mass was derived by subtracting bone mineral content from fat mass. Patients were assessed before transplantation, at 1 month, 2-5 months,
*To whom all correspondence should be addressed: Dr S. H. Hussaini, Department of Medicine, Level 7, Clinical Science Building, St James' University Hospital, Leeds LS9 7TF, U.K.
663
664
S.H. Hussaini et al.
6-9 months, 12 months and 18-24 months after transplantation.
Statistical Analysis Univariate analyses (Spearman rank correlation, two-tailed test) were performed between the fall in lean body mass and the following parameters: (i) pre-transplant serum albumin; (ii) the cumulative dose of steroids after transplantation; and (iii) the length of hospital stay after transplantation. The fall in lean body mass was then compared in groups of patients stratified for sex, disease severity, disease type (cholestatitic vs non cholestatic) and the presence of acute cellular rejection. The statistical significance of differences between groups was tested with the non-parametric heteroscedastic 't test'. Excel software version 7.0 (Microsoft Corporation, 1 Microsoft Way, Redmond, WA 98052-6399, USA) was used to analyse data. P values of < 0.05 were considered to be statistically significant.
Results The pre-transplantation serum albumin inversely correlated with the fall in lean body mass, 1 month after transplantation (r = 0.55; P < 0.009). Although no similar relationship between pre-transplant albumin and fall in lean body mass between 2 and 5 months post OLT was observed, a weaker inverse correlation was seen at 6-9 months ( r = 0 . 5 1 ; P < 0.05). A stronger positive correlation between the fall in lean body mass and cumulative dose of steroids administered after transplantation was seen at 2 5 months (r = 0.57; P < 0.05), with a slightly weaker ( r = 0.52) but still significant ( P < 0.05) correlation between fall in lean body mass and length of hospital stay after transplantation. In the first month after transplantation, there was a greater fall in mean lean body mass in men compared to women (7.3 _+ 3.1 vs 2.0 _+ 0.8 kg) and in patients with severe compared to those with mild liver disease (5.5 + 2.0 vs 1.0 _+ 1.5 kg), although this difference was not statistically significant. However, at longer time periods after transplantation there was no marked difference in the fall in lean body mass between these two subgroups. Similarly no marked
difference in the fall of mean lean body mass after OLT was seen in patients with or without cholestatic liver disease or with or without acute rejection following transplantation.
Discussion The present study demonstrates that low serum albumin, high dose steroid immunosupression regimens and protracted hospitalisation following transplantation are all risk factors for a fall in lean body mass after liver transplantation. The fall in lean body mass may have represented a drop in total body water. Further analysis of total body potassium and total body water may clarify whether the fall in lean mass represents a true loss of muscle mass rather than water. A low pre-transplant serum albumin may not only represent poor hepatic synthetic function but also a hypercatabolic state which could account for the early fall in lean mass after transplantation. A long post-operative course after transplantation is often associated with immobility and a lack of exercise which could lead to the observed fall in body mass. Perhaps the most important factor in the fall in lean body mass was the dose of steroids administered. High dose corticosteroids favour the catabolism of muscle tissue to form adipose tissue (Rogers et al., 1981), which would therefore cause a fall in lean mass. In conclusion, we would propose that earlier transplantation of patients with better nutritional status and the use of low dose steroid immunosupressive regimens after transplantation may prevent the observed fall in lean body mass found in our study.
References Hussaini, S. H., Stewart, S. P., Roman, F., Oldroyd, B., Bramley, P., Simpson, M., Smith, M. A., O'Grady, J. and Losowsky, M. S. (1995) Nutritional status after orthotopic liver transplantation. Gut 37, AI4. Pugh, R. N., Murray-Lyon, I. M., Dawson, J. L., Pietroni, M. C. and Williams, R. (1973) Transection of the oesophagus for bleeding oesophageal varices. Brit. J. Surg. 60, 646-649. Rogers et al. (1981) A textbook of Clinical Pharmacology, ed. H.J. Rogers, R.G. Spector and J.R. Trounce, pp. 598-599. Hodder and Stoughton, London.