Intra-Abdominal Fat Better Predictor of Liver Injury

Increased trunk fat on dual-energy x-ray absorptiometry was independently associated with elevated serum alanine aminotransferase levels, a measure of liver injury—more so than was extremity fat, body mass index, or waist circumference, according to an analysis of the National Health and Nutrition Examination Survey.

The findings “support the hypothesis that liver injury can be induced by metabolically active intra-abdominal fat,” wrote Dr. Constance E. Ruhl and Dr. James E. Everhart, noting that “obesity is an important risk factor for liver injury.”

Dr. Ruhl of Social & Scientific Systems Inc., a research support company, and Dr. Everhart of the National Institute of Diabetes and Digestive and Kidney Diseases studied data from patients in the National Health and Nutrition Examination Survey (NHANES). Pregnant women and survey participants who were positive for serum hepatitis B surface antigen or were positive or indeterminate for hepatitis C antibody were excluded, as were patients whose hepatitis status could not be determined. Patients were aged 20 years and older.

In all, 11,821 participants (5,918 men and 5,903 women) who participated in NHANES between 1999 and 2004 were ultimately included in the analysis. Study participants had dual-energy x-ray absorptiometry (DXA) measurements to determine trunk fat, trunk lean mass, extremity fat, and extremity lean mass, and were then divided into quintiles within each category. Missing DXA measurements were imputed by the National Center for Health Statistics. Serum alanine aminotransferase (ALT) levels, a marker of liver damage, were considered elevated above 44 U/L in men and above 31 U/L in women.

“The prevalence of elevated ALT was 11.1% among men and 10.1% among women,” wrote the authors.

Among men, each step up in trunk fat quintile conferred a 1.7 increased odds ratio for elevated ALT (P less than .001). In women, each step up in trunk fat quintile was associated with a 1.4 increased OR (P less than .001). The results were adjusted for ethnicity, age, glucose status, serum total cholesterol, cigarette smoking, and alcohol consumption.

In contrast, having an increased amount of extremity fat actually was protective against elevated ALT. Among men, every increased quintile conferred a 0.87 OR of elevated ALT (P = .002), and for women, each increasing quintile conferred a 0.86 OR (P = .001).

Trunk lean mass and extremity lean mass, however, showed no significant relationship with ALT level.

“Having established that elevated ALT was most strongly associated with trunk fat, we considered its effect on the association of BMI and waist circumference with elevated ALT,” wrote the authors. “When trunk fat, BMI, and waist circumference were included together in multivariate-adjusted models, higher trunk fat remained independently associated with elevated ALT among both men [P = .002] and women [P = .011], but BMI and waist circumference were not.”

Regarding the “unexpected” finding that extremity fat was protective against elevated ALT, the researchers postulated that the “uptake and storage of free fatty acids by femoral adipose tissue could lead to protection of other organs such as the liver from exposure to fatty acids and ectopic fat deposition.”

The authors conceded several limitations to their study. First, DXA measurements of abdominal fat are not as accurate as CT or MRI, although the technology “is still considered a relatively accurate and precise method to estimate body fat and lean soft tissue mass components.” Second, the use of ALT levels alone as a marker of liver damage cannot be entirely accurate. “Inevitably, participants were included in the elevated ALT group who would not have been had repeat ALT measurements been available.”

Dr. Ruhl and Dr. Everhart reported having no conflicts of interest. The study was supported by NIDDK.

Trunk fat, as measured by DXA (right image), was significantly associated with elevated ALT levels.

Source ©2008 Elsevier, Inc.

Increased trunk fat on dual-energy x-ray absorptiometry was independently associated with elevated serum alanine aminotransferase levels, a measure of liver injury—more so than was extremity fat, body mass index, or waist circumference, according to an analysis of the National Health and Nutrition Examination Survey.

The findings “support the hypothesis that liver injury can be induced by metabolically active intra-abdominal fat,” wrote Dr. Constance E. Ruhl and Dr. James E. Everhart, noting that “obesity is an important risk factor for liver injury.”

Dr. Ruhl of Social & Scientific Systems Inc., a research support company, and Dr. Everhart of the National Institute of Diabetes and Digestive and Kidney Diseases studied data from patients in the National Health and Nutrition Examination Survey (NHANES). Pregnant women and survey participants who were positive for serum hepatitis B surface antigen or were positive or indeterminate for hepatitis C antibody were excluded, as were patients whose hepatitis status could not be determined. Patients were aged 20 years and older.

In all, 11,821 participants (5,918 men and 5,903 women) who participated in NHANES between 1999 and 2004 were ultimately included in the analysis. Study participants had dual-energy x-ray absorptiometry (DXA) measurements to determine trunk fat, trunk lean mass, extremity fat, and extremity lean mass, and were then divided into quintiles within each category. Missing DXA measurements were imputed by the National Center for Health Statistics. Serum alanine aminotransferase (ALT) levels, a marker of liver damage, were considered elevated above 44 U/L in men and above 31 U/L in women.

“The prevalence of elevated ALT was 11.1% among men and 10.1% among women,” wrote the authors.

Among men, each step up in trunk fat quintile conferred a 1.7 increased odds ratio for elevated ALT (P less than .001). In women, each step up in trunk fat quintile was associated with a 1.4 increased OR (P less than .001). The results were adjusted for ethnicity, age, glucose status, serum total cholesterol, cigarette smoking, and alcohol consumption.

In contrast, having an increased amount of extremity fat actually was protective against elevated ALT. Among men, every increased quintile conferred a 0.87 OR of elevated ALT (P = .002), and for women, each increasing quintile conferred a 0.86 OR (P = .001).

Trunk lean mass and extremity lean mass, however, showed no significant relationship with ALT level.

“Having established that elevated ALT was most strongly associated with trunk fat, we considered its effect on the association of BMI and waist circumference with elevated ALT,” wrote the authors. “When trunk fat, BMI, and waist circumference were included together in multivariate-adjusted models, higher trunk fat remained independently associated with elevated ALT among both men [P = .002] and women [P = .011], but BMI and waist circumference were not.”

Regarding the “unexpected” finding that extremity fat was protective against elevated ALT, the researchers postulated that the “uptake and storage of free fatty acids by femoral adipose tissue could lead to protection of other organs such as the liver from exposure to fatty acids and ectopic fat deposition.”

The authors conceded several limitations to their study. First, DXA measurements of abdominal fat are not as accurate as CT or MRI, although the technology “is still considered a relatively accurate and precise method to estimate body fat and lean soft tissue mass components.” Second, the use of ALT levels alone as a marker of liver damage cannot be entirely accurate. “Inevitably, participants were included in the elevated ALT group who would not have been had repeat ALT measurements been available.”

Dr. Ruhl and Dr. Everhart reported having no conflicts of interest. The study was supported by NIDDK.

Trunk fat, as measured by DXA (right image), was significantly associated with elevated ALT levels.

Source ©2008 Elsevier, Inc.

Increased trunk fat on dual-energy x-ray absorptiometry was independently associated with elevated serum alanine aminotransferase levels, a measure of liver injury—more so than was extremity fat, body mass index, or waist circumference, according to an analysis of the National Health and Nutrition Examination Survey.

The findings “support the hypothesis that liver injury can be induced by metabolically active intra-abdominal fat,” wrote Dr. Constance E. Ruhl and Dr. James E. Everhart, noting that “obesity is an important risk factor for liver injury.”

Dr. Ruhl of Social & Scientific Systems Inc., a research support company, and Dr. Everhart of the National Institute of Diabetes and Digestive and Kidney Diseases studied data from patients in the National Health and Nutrition Examination Survey (NHANES). Pregnant women and survey participants who were positive for serum hepatitis B surface antigen or were positive or indeterminate for hepatitis C antibody were excluded, as were patients whose hepatitis status could not be determined. Patients were aged 20 years and older.

In all, 11,821 participants (5,918 men and 5,903 women) who participated in NHANES between 1999 and 2004 were ultimately included in the analysis. Study participants had dual-energy x-ray absorptiometry (DXA) measurements to determine trunk fat, trunk lean mass, extremity fat, and extremity lean mass, and were then divided into quintiles within each category. Missing DXA measurements were imputed by the National Center for Health Statistics. Serum alanine aminotransferase (ALT) levels, a marker of liver damage, were considered elevated above 44 U/L in men and above 31 U/L in women.

“The prevalence of elevated ALT was 11.1% among men and 10.1% among women,” wrote the authors.

Among men, each step up in trunk fat quintile conferred a 1.7 increased odds ratio for elevated ALT (P less than .001). In women, each step up in trunk fat quintile was associated with a 1.4 increased OR (P less than .001). The results were adjusted for ethnicity, age, glucose status, serum total cholesterol, cigarette smoking, and alcohol consumption.

In contrast, having an increased amount of extremity fat actually was protective against elevated ALT. Among men, every increased quintile conferred a 0.87 OR of elevated ALT (P = .002), and for women, each increasing quintile conferred a 0.86 OR (P = .001).

Trunk lean mass and extremity lean mass, however, showed no significant relationship with ALT level.

“Having established that elevated ALT was most strongly associated with trunk fat, we considered its effect on the association of BMI and waist circumference with elevated ALT,” wrote the authors. “When trunk fat, BMI, and waist circumference were included together in multivariate-adjusted models, higher trunk fat remained independently associated with elevated ALT among both men [P = .002] and women [P = .011], but BMI and waist circumference were not.”

Regarding the “unexpected” finding that extremity fat was protective against elevated ALT, the researchers postulated that the “uptake and storage of free fatty acids by femoral adipose tissue could lead to protection of other organs such as the liver from exposure to fatty acids and ectopic fat deposition.”

The authors conceded several limitations to their study. First, DXA measurements of abdominal fat are not as accurate as CT or MRI, although the technology “is still considered a relatively accurate and precise method to estimate body fat and lean soft tissue mass components.” Second, the use of ALT levels alone as a marker of liver damage cannot be entirely accurate. “Inevitably, participants were included in the elevated ALT group who would not have been had repeat ALT measurements been available.”

Dr. Ruhl and Dr. Everhart reported having no conflicts of interest. The study was supported by NIDDK.

Trunk fat, as measured by DXA (right image), was significantly associated with elevated ALT levels.

Source ©2008 Elsevier, Inc.