Skip to main content
Top
Published in: European Radiology 5/2012

01-05-2012 | Gastrointestinal

Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis

Authors: Perry J. Pickhardt, Seong Ho Park, Luke Hahn, Sung-Gyu Lee, Kyongtae T. Bae, Eun Sil Yu

Published in: European Radiology | Issue 5/2012

Login to get access

Abstract

Objectives

To determine a highly specific liver attenuation threshold at unenhanced CT for biopsy-proven moderate to severe hepatic steatosis (≥30% at histology).

Methods

315 asymptomatic adults (mean age ± SD, 31.5 ± 10.1 years; 207 men, 108 women) underwent same-day unenhanced liver CT and ultrasound-guided liver biopsy. Blinded to biopsy results, CT liver attenuation was measured using standard region-of-interest methodology. Multiple linear regression analysis was used to assess the relationship of CT liver attenuation with patient age, gender, BMI, CT system, and hepatic fat and iron content.

Results

Thirty-nine subjects had moderate to severe steatosis and 276 had mild or no steatosis. A liver attenuation threshold of 48 HU was 100% specific (276/276) for moderate to severe steatosis, with no false-positives. Sensitivity, PPV and NPV at this HU threshold was 53.8%, 100% and 93.9%. Hepatic fat content was the overwhelming determinant of liver attenuation values, but CT system (P < 0.001), and hepatic iron (P = 0.035) also had a statistically significant independent association.

Conclusions

Unenhanced CT liver attenuation alone is highly specific for moderate to severe hepatic steatosis, allowing for confident non-invasive identification of large retrospective/prospective cohorts for natural history evaluation of incidental non-alcoholic fatty liver disease. Low sensitivity, however, precludes effective population screening at this threshold.

Key Points

Unenhanced CT liver attenuation is highly specific for diagnosing moderate/severe hepatic steatosis.
Unenhanced CT can identify large cohorts for epidemiological studies of incidental steatosis.
Unenhanced CT is not, however, effective for population screening for hepatic steatosis.
Literature
1.
go back to reference Boyce CJ, Pickhardt PJ, Kim DH et al (2010) Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. AJR Am J Roentgenol 194:623–628PubMedCrossRef Boyce CJ, Pickhardt PJ, Kim DH et al (2010) Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. AJR Am J Roentgenol 194:623–628PubMedCrossRef
2.
go back to reference Browning JD, Szczepaniak LS, Dobbins R et al (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387–1395PubMedCrossRef Browning JD, Szczepaniak LS, Dobbins R et al (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387–1395PubMedCrossRef
3.
go back to reference Byron D, Minuk GY (1996) Clinical hepatology: profile of an urban, hospital-based practice. Hepatology 24:813–815PubMedCrossRef Byron D, Minuk GY (1996) Clinical hepatology: profile of an urban, hospital-based practice. Hepatology 24:813–815PubMedCrossRef
4.
go back to reference Clark JM, Brancati FL, Diehl AM (2003) The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 98:960–967PubMedCrossRef Clark JM, Brancati FL, Diehl AM (2003) The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 98:960–967PubMedCrossRef
5.
go back to reference Hilden M, Christoffersen P, Juhl E et al (1977) Liver histology in a ‘normal’ population–examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol 12:593–597PubMedCrossRef Hilden M, Christoffersen P, Juhl E et al (1977) Liver histology in a ‘normal’ population–examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol 12:593–597PubMedCrossRef
6.
go back to reference Kammen BF, Pacharn P, Thoeni RF et al (2001) Focal fatty infiltration of the liver: analysis of prevalence and CT findings in children and young adults. AJR Am J Roentgenol 177:1035–1039PubMed Kammen BF, Pacharn P, Thoeni RF et al (2001) Focal fatty infiltration of the liver: analysis of prevalence and CT findings in children and young adults. AJR Am J Roentgenol 177:1035–1039PubMed
7.
go back to reference Park SH, Jeon WK, Kim SH et al (2006) Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol 21:138–143PubMedCrossRef Park SH, Jeon WK, Kim SH et al (2006) Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol 21:138–143PubMedCrossRef
9.
go back to reference Dunn W, Xu R, Wingard DL et al (2008) Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol 103:2263–2271PubMedCrossRef Dunn W, Xu R, Wingard DL et al (2008) Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol 103:2263–2271PubMedCrossRef
10.
go back to reference Marchesini G, Bugianesi E, Forlani G et al (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917–923PubMedCrossRef Marchesini G, Bugianesi E, Forlani G et al (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917–923PubMedCrossRef
11.
go back to reference Ong JP, Pitts A, Younossi ZM (2008) Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 49:608–612PubMedCrossRef Ong JP, Pitts A, Younossi ZM (2008) Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 49:608–612PubMedCrossRef
12.
go back to reference Vuppalanchi R, Chalasani N (2009) Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology 49:306–317PubMedCrossRef Vuppalanchi R, Chalasani N (2009) Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology 49:306–317PubMedCrossRef
13.
go back to reference Brunt EM, Janney CG, Di Bisceglie AM et al (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474PubMedCrossRef Brunt EM, Janney CG, Di Bisceglie AM et al (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474PubMedCrossRef
14.
go back to reference Hourigan LF, Macdonald GA, Purdie D et al (1999) Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 29:1215–1219PubMedCrossRef Hourigan LF, Macdonald GA, Purdie D et al (1999) Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 29:1215–1219PubMedCrossRef
15.
go back to reference Kleiner DE, Brunt EM, Van Natta M et al (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321PubMedCrossRef Kleiner DE, Brunt EM, Van Natta M et al (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321PubMedCrossRef
16.
go back to reference Petta S, Camma C, Di Marco V et al (2011) Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int 31:507–515PubMedCrossRef Petta S, Camma C, Di Marco V et al (2011) Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int 31:507–515PubMedCrossRef
17.
go back to reference Selzner M, Clavien PA (2001) Fatty liver in liver transplantation and surgery. Semin Liver Dis 21:105–113PubMedCrossRef Selzner M, Clavien PA (2001) Fatty liver in liver transplantation and surgery. Semin Liver Dis 21:105–113PubMedCrossRef
18.
go back to reference Angulo P (2010) Long-term mortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology 51:373–375PubMedCrossRef Angulo P (2010) Long-term mortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology 51:373–375PubMedCrossRef
19.
go back to reference Angulo P (2011) Diagnosing steatohepatitis and predicting liver-related mortality in patients with NAFLD: two distinct concepts. Hepatology 53:1792–1794PubMedCrossRef Angulo P (2011) Diagnosing steatohepatitis and predicting liver-related mortality in patients with NAFLD: two distinct concepts. Hepatology 53:1792–1794PubMedCrossRef
20.
go back to reference Adams LA, Lymp JF, St Sauver J et al (2005) The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129:113–121PubMedCrossRef Adams LA, Lymp JF, St Sauver J et al (2005) The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129:113–121PubMedCrossRef
21.
go back to reference Dam-Larsen S, Franzmann M, Andersen IB et al (2004) Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut 53:750–755PubMedCrossRef Dam-Larsen S, Franzmann M, Andersen IB et al (2004) Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut 53:750–755PubMedCrossRef
22.
go back to reference Ekstedt M, Franzen LE, Mathiesen UL et al (2006) Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44:865–873PubMedCrossRef Ekstedt M, Franzen LE, Mathiesen UL et al (2006) Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44:865–873PubMedCrossRef
23.
go back to reference Teli MR, James OF, Burt AD, Bennett MK, Day CP (1995) The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 22:1714–1719PubMedCrossRef Teli MR, James OF, Burt AD, Bennett MK, Day CP (1995) The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 22:1714–1719PubMedCrossRef
24.
go back to reference McKimmie RL, Daniel KR, Carr JJ et al (2008) Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study. Am J Gastroenterol 103:3029–3035PubMedCrossRef McKimmie RL, Daniel KR, Carr JJ et al (2008) Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study. Am J Gastroenterol 103:3029–3035PubMedCrossRef
25.
go back to reference Chalasani N, Wilson L, Kleiner DE et al (2008) Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. J Hepatol 48:829–834PubMedCrossRef Chalasani N, Wilson L, Kleiner DE et al (2008) Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. J Hepatol 48:829–834PubMedCrossRef
26.
go back to reference Kodama Y, Ng CS, Wu TT et al (2007) Comparison of CT methods for determining the fat content of the liver. AJR Am J Roentgenol 188:1307–1312PubMedCrossRef Kodama Y, Ng CS, Wu TT et al (2007) Comparison of CT methods for determining the fat content of the liver. AJR Am J Roentgenol 188:1307–1312PubMedCrossRef
27.
go back to reference Lee SS, Park SH, Kim HJ et al (2010) Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 52:579–585PubMedCrossRef Lee SS, Park SH, Kim HJ et al (2010) Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 52:579–585PubMedCrossRef
28.
go back to reference Park SH, Kim PN, Kim KW et al (2006) Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology 239:105–112PubMedCrossRef Park SH, Kim PN, Kim KW et al (2006) Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology 239:105–112PubMedCrossRef
29.
go back to reference Park YS, Park SH, Lee SS et al (2011) Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT. Radiology 258:760–766PubMedCrossRef Park YS, Park SH, Lee SS et al (2011) Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT. Radiology 258:760–766PubMedCrossRef
30.
go back to reference Speliotes EK, Massaro JM, Hoffmann U et al (2008) Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study. J Gastroenterol Hepatol 23:894–899PubMedCrossRef Speliotes EK, Massaro JM, Hoffmann U et al (2008) Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study. J Gastroenterol Hepatol 23:894–899PubMedCrossRef
31.
go back to reference LeSage GD, Baldus WP, Fairbanks VF et al (1983) Hemochromatosis: genetic or alcohol-induced? Gastroenterology 84:1471–1477PubMed LeSage GD, Baldus WP, Fairbanks VF et al (1983) Hemochromatosis: genetic or alcohol-induced? Gastroenterology 84:1471–1477PubMed
32.
go back to reference Strauss S, Gavish E, Gottlieb P et al (2007) Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol 189:W320–323PubMedCrossRef Strauss S, Gavish E, Gottlieb P et al (2007) Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol 189:W320–323PubMedCrossRef
33.
go back to reference Guiu B, Loffroy R, Cercueil JP et al (2008) Multiecho MR imaging and proton MR spectroscopy for liver fat quantification. Radiology 249:1081PubMedCrossRef Guiu B, Loffroy R, Cercueil JP et al (2008) Multiecho MR imaging and proton MR spectroscopy for liver fat quantification. Radiology 249:1081PubMedCrossRef
34.
go back to reference Hines CD, Frydrychowicz A, Hamilton G et al (2011) T(1) independent, T(2) (*) corrected chemical shift based fat-water separation with multi-peak fat spectral modeling is an accurate and precise measure of hepatic steatosis. J Magn Reson Imaging 33:873–881PubMedCrossRef Hines CD, Frydrychowicz A, Hamilton G et al (2011) T(1) independent, T(2) (*) corrected chemical shift based fat-water separation with multi-peak fat spectral modeling is an accurate and precise measure of hepatic steatosis. J Magn Reson Imaging 33:873–881PubMedCrossRef
35.
go back to reference Meisamy S, Hines CD, Hamilton G et al (2011) Quantification of hepatic steatosis with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy. Radiology 258:767–775PubMedCrossRef Meisamy S, Hines CD, Hamilton G et al (2011) Quantification of hepatic steatosis with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy. Radiology 258:767–775PubMedCrossRef
36.
go back to reference Yokoo T, Bydder M, Hamilton G et al (2009) Nonalcoholic fatty liver disease: diagnostic and fat-grading accuracy of low-flip-angle multiecho gradient-recalled-echo MR imaging at 1.5 T. Radiology 251:67–76PubMedCrossRef Yokoo T, Bydder M, Hamilton G et al (2009) Nonalcoholic fatty liver disease: diagnostic and fat-grading accuracy of low-flip-angle multiecho gradient-recalled-echo MR imaging at 1.5 T. Radiology 251:67–76PubMedCrossRef
37.
go back to reference Fischer MA, Gnannt R, Raptis D et al (2011) Quantification of liver fat in the presence of iron and iodine: an ex-vivo dual-energy CT study. Invest Radiol 46:351–358PubMedCrossRef Fischer MA, Gnannt R, Raptis D et al (2011) Quantification of liver fat in the presence of iron and iodine: an ex-vivo dual-energy CT study. Invest Radiol 46:351–358PubMedCrossRef
38.
go back to reference Bydder GM, Kreel L, Chapman RW et al (1980) Accuracy of computed tomography in diagnosis of fatty liver. Br Med J 281:1042PubMedCrossRef Bydder GM, Kreel L, Chapman RW et al (1980) Accuracy of computed tomography in diagnosis of fatty liver. Br Med J 281:1042PubMedCrossRef
39.
go back to reference Piekarski J, Goldberg HI, Royal SA et al (1980) Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology 137:727–729PubMed Piekarski J, Goldberg HI, Royal SA et al (1980) Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology 137:727–729PubMed
40.
go back to reference Kim DY, Park SH, Lee SS et al (2010) Contrast-enhanced computed tomography for the diagnosis of fatty liver: prospective study with same-day biopsy used as the reference standard. Eur Radiol 20:359–366PubMedCrossRef Kim DY, Park SH, Lee SS et al (2010) Contrast-enhanced computed tomography for the diagnosis of fatty liver: prospective study with same-day biopsy used as the reference standard. Eur Radiol 20:359–366PubMedCrossRef
41.
go back to reference Lee SW, Park SH, Kim KW et al (2007) Unenhanced CT for assessment of macrovesicular hepatic steatosis in living liver donors: comparison of visual grading with liver attenuation index. Radiology 244:479–485PubMedCrossRef Lee SW, Park SH, Kim KW et al (2007) Unenhanced CT for assessment of macrovesicular hepatic steatosis in living liver donors: comparison of visual grading with liver attenuation index. Radiology 244:479–485PubMedCrossRef
42.
go back to reference Limanond P, Raman SS, Lassman C et al (2004) Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology 230:276–280PubMedCrossRef Limanond P, Raman SS, Lassman C et al (2004) Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology 230:276–280PubMedCrossRef
43.
go back to reference Oliva MR, Mortele KJ, Segatto E et al (2005) Computed tomography features of nonalcoholic steatohepatitis with histopathologic correlation. J Comput Assist Tomogr 30:37–43CrossRef Oliva MR, Mortele KJ, Segatto E et al (2005) Computed tomography features of nonalcoholic steatohepatitis with histopathologic correlation. J Comput Assist Tomogr 30:37–43CrossRef
44.
go back to reference Yoshimitsu K, Kuroda Y, Nakamuta M et al (2008) Noninvasive estimation of hepatic steatosis using plain CT vs. chemical-shift MR imaging: significance for living donors. J Magn Reson Imaging 28:678–684PubMedCrossRef Yoshimitsu K, Kuroda Y, Nakamuta M et al (2008) Noninvasive estimation of hepatic steatosis using plain CT vs. chemical-shift MR imaging: significance for living donors. J Magn Reson Imaging 28:678–684PubMedCrossRef
45.
go back to reference Birnbaum BA, Hindman N, Lee J et al (2007) Multi-detector row CT attenuation measurements: assessment of intra- and interscanner variability with an anthropomorphic body CT phantom. Radiology 242:109–119PubMedCrossRef Birnbaum BA, Hindman N, Lee J et al (2007) Multi-detector row CT attenuation measurements: assessment of intra- and interscanner variability with an anthropomorphic body CT phantom. Radiology 242:109–119PubMedCrossRef
46.
go back to reference Sande EP, Martinsen AC, Hole EO et al (2010) Interphantom and interscanner variations for Hounsfield units–establishment of reference values for HU in a commercial QA phantom. Phys Med Biol 55:5123–5135PubMedCrossRef Sande EP, Martinsen AC, Hole EO et al (2010) Interphantom and interscanner variations for Hounsfield units–establishment of reference values for HU in a commercial QA phantom. Phys Med Biol 55:5123–5135PubMedCrossRef
47.
go back to reference Cakir B, Kirbas I, Demirhan B et al (2009) Fulminant hepatic failure in children: etiology, histopathology and MDCT findings. Eur J Radiol 72:327–334PubMedCrossRef Cakir B, Kirbas I, Demirhan B et al (2009) Fulminant hepatic failure in children: etiology, histopathology and MDCT findings. Eur J Radiol 72:327–334PubMedCrossRef
48.
go back to reference Shakil AO, Jones BC, Lee RG et al (2000) Prognostic value of abdominal CT scanning and hepatic histopathology in patients with acute liver failure. Dig Dis Sci 45:334–339PubMedCrossRef Shakil AO, Jones BC, Lee RG et al (2000) Prognostic value of abdominal CT scanning and hepatic histopathology in patients with acute liver failure. Dig Dis Sci 45:334–339PubMedCrossRef
49.
go back to reference Saadeh S, Younossi ZM, Remer EM et al (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123:745–750PubMedCrossRef Saadeh S, Younossi ZM, Remer EM et al (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123:745–750PubMedCrossRef
Metadata
Title
Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis
Authors
Perry J. Pickhardt
Seong Ho Park
Luke Hahn
Sung-Gyu Lee
Kyongtae T. Bae
Eun Sil Yu
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
European Radiology / Issue 5/2012
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-011-2349-2

Other articles of this Issue 5/2012

European Radiology 5/2012 Go to the issue