Rationale and Objectives
Fatty liver disease is a common clinical entity in hepatology practice. This study evaluates the prevalence and reproducibility of computed tomography (CT) measures for diagnosis of fatty liver and compares commonly used CT criteria for the diagnosis of liver fat.
Materials and Methods
The study includes 6814 asymptomatic participants from a population-based sample. The ratio of liver-to-spleen (L/S) Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used for diagnosing and assessing the severity of liver fat content. Participants with heavy alcohol intake (>7 drinks/week for women and >14 drinks/week for men) were excluded. Final analysis was performed on participants where images of both liver and spleen were available on the scans.
Results
The overall prevalence of fatty liver (4175 subjects included in final analysis) was 17.2% (using L/S ratio <1.0), with 6.3% (with <40 HU cutoff) of the population having moderate to severe steatosis (>30% liver fat content). The prevalence was high in participants with dyslipidemia (70.4%), hypertension (56.8%), and obesity (53%). Diabetic patients had 24.1% prevalence of fatty liver. The prevalence provided by L/S ratio <1.0 (17.2%) was comparable to prevalence provided by <51 HU (17.3%), whereas prevalence obtained by <40 HU (6.3%) cutoff corresponded to L/S ratio of <0.8 (6.5%). The measurements of liver and spleen HU attenuations were highly reproducible (0.96, 0.99 and 0.99, 0.99 for intra- and inter-reader variability, respectively) in a sample of 100 scans.
Conclusion
Fatty liver can be reliably diagnosed using nonenhanced CT scans.
Fatty liver is hepatic manifestation of a number of medical conditions and medication use . With the increasing epidemic of obesity in the United States and worldwide, fatty liver is increasingly being diagnosed . One special category is nonalcoholic fatty liver disease (NAFLD), which represents the accumulation of triglyceride droplets in the hepatocytes in the absence of significant alcohol intake. NAFLD encompasses a spectrum of clinical entities that includes simple steatosis that may progress to steatohepatitis . All of these entities include an accumulation of fat in the hepatic parenchyma . NAFLD with steatosis alone is a relatively inconsequential clinical entity; however, its clinical significance is increased by its association with cardiovascular disease . Nonalcoholic steatohepatitis (NASH) is a subtype of NAFLD characterized by hepatocytes ballooning and necrosis with or without Mallory’s hyaline and fibrosis on histological analysis that carries the risk of progressive liver disease and cirrhosis . The diagnosis of NAFLD is associated with shorter survival than expected for a general population of the same age and gender . NAFLD has been shown to be associated with insulin resistance and is considered a part of the metabolic syndrome . Studies are also looking at the association of NAFLD with inflammatory markers and subclinical atherosclerosis, evaluating its associations beyond the liver .
Population-based studies have shown varying prevalence of NAFLD ranging from 3% to 46% based on varying diagnostic modalities used and the patient population characteristics . Imaging studies such as computed tomography (CT), magnetic resonance imaging, and ultrasonography can show characteristic features of fatty liver but the ultimate diagnosis requires liver biopsy . Liver biopsy shows the presence of fatty changes along with any associated inflammation and fibrosis. It is an invasive procedure with its associated complications sometimes requiring hospitalization and significant bleeding. It may not be a suitable test to determine the presence of a widely prevalent condition in an asymptomatic population. CT scans have proven to be useful in diagnosing the presence and quantifying the severity of liver fat noninvasively. The Hounsfield unit (HU) attenuation of liver on CT scans is usually higher than the spleen; when this ratio is reversed, this can be used to diagnose the presence of liver fat . Liver-to-spleen ratio (L/S) <1.0 can be used effectively to diagnose the presence of liver fat . Studies have also shown liver HU attenuation <40 HU to reliably represent >30% of liver fat content . The current study looks at the prevalence and reproducibility of measurement of liver fat content using nonenhanced CT scans in a large well-validated population based cohort of asymptomatic participants using previously published criteria for liver fat measurement . We will also compare commonly used criteria mentioned (L/S ratio and liver HU attenuation) in the literature for the diagnosis of NAFLD.
Materials and methods
Study Population
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Image Acquisition
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Liver Fat Measurement
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Statistical Analysis
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Results
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Table 1
Characteristics of the Population Based on L/S Ratio <1.0 and Liver Attenuation <40 HU Cutoffs
L/S <1.0
n = 718 L/S ≥1.0
n = 3416P Value HU <40
n = 262 HU ≥40
n = 3886P Value Age, years 63 ± 10 61 ± 10 <.001 63 ± 10 60 ± 9 <.001 Men, n (%) 1522 (44.6) 334 (45.6) .60 1736 (44.7) 120 (45.8) .72 Height, kg 165.8 ± 10.0 164.9 ± 10.3 .03 165.7 ± 10.0 165.1 ± 10.1 .35 Weight, cm 77.3 ± 16.5 84.9 ± 17.5 <.001 78.0 ± 16.7 88.6 ± 18.2 <.001 BMI, kg/m 2 28.0 ± 5.2 31.1 ± 5.6 <.001 28.3 ± 5.2 32.4 ± 5.7 <.001 BMI >30, n (%) 388 (53%) 1004 (29.4%) <.001 166 (63.4%) 1226 (31.5) <.001 Waist-hip ratio 0.9 ± 0.1 1.0 ± 0.1 <.001 0.9 ± 0.1 1.0 ± 0.1 <.001 Smoker, n (%) 398 (11.7) 78 (10.7) .12 448 (11.6) 28 (10.7) .14 Family income ($25,000/year), n (%) 1202 (35.2) 261 (35.7) .81 1376 (35.4) 87 (33.2) .47 Education less than high school, n (%) 611 (17.9) 183 (25.0) <.001 732 (18.8) 62 (23.7) .06 LDL, mg/dL 117.9 ± 31.2 115.3 ± 31.0 .04 117.5 ± 31.2 116.0 ± 30.2 .45 HDL, mg/dL 51.7 ± 14.9 44.8 ± 12.0 <.001 50.9 ± 14.7 43.6 ± 10.6 <.001 TG, mg/dL 122.3 ± 70.0 178.9 ± 153.6 <.001 128.0 ± 83.3 196.4 ± 173.6 <.001 Hypertension, n (%) 408 (56.8) 1690 (49.0) <.001 153 (58.4) 1945 (49.8) .007 Diabetic, n (%) 173 (24.1) 442 (12.8) <.001 64 (24.4) 551 (14.1) <.001 Dyslipidemia 531 (70.4) 2008 (58.2) <.001 204 (77.9) 2335 (59.8) <.001
BMI, body mass index; HDL, high-density cholesterol; HU, Hounsfield unit; LDL, low-density cholesterol; L/S, liver/spleen ratio; TG, triglycerides.
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Table 2
Overall Prevalence of Fatty Liver Using Different Cutoffs for Liver Attenuation Values and L/S Ratios
HU L/S Ratio_n_ Prevalence, %n Prevalence, % HU <51 721 17.3 L/S <1.0 718 17.2 HU <50 642 15.4 HU <49 588 14.1 HU <48 545 13.1 HU <47 509 12.2 HU <46 463 11.1 HU <45 435 10.4 L/S <0.9 446 10.7 HU <44 394 9.5 HU <43 360 8.6 HU <42 327 7.8 HU <41 290 7.0 HU <40 262 6.3 L/S <0.8 270 6.5
HU, Hounsfield unit; L/S, liver/spleen ratio.
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Discussion
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Limitations
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Conclusion
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Acknowledgments
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References
1. Nonalcoholic fatty liver disease. In: Fauci AS, Braunwald E, Kasper DL, et al, editors. Harrison’s Principles of Internal Medicine, 17th ed. USA: McGraw-Hill Companies Inc; 2008. p.1982–1983.
2. Wanless I.R., Lentz J.S.: Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 1990; 12: pp. 1106-1110.
3. Adler M., Schaffner F.: Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 1979; 67: pp. 811-816.
4. Nasrallah S.M., Wills C.E., Galambos J.T.: Hepatic morphology in obesity. Dig Dis Sci 1981; 26: pp. 325-327.
5. Clain D.J., Lefkowitch J.H.: Fatty liver disease in morbid obesity. Gastroenterol Clin North Am 1987; 16: pp. 239-252.
6. Dixon J.B., Bhathal P.S., O’Brien P.E.: Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001; 121: pp. 91-100.
7. Adams L.A., Lymp J.F., St Sauver J., et. al.: The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129: pp. 113-121.
8. Ekstedt M., Franzen L.E., Mathiesen U.L., et. al.: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: pp. 865-873.
9. Younossi Z.M., Gramlich T., Liu Y.C., et. al.: Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations. Mod Pathol 1998; 11: pp. 560-565.
10. Hamaguchi M., Kojima T., Takeda N., et. al.: Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007; 13: pp. 1579-1584.
11. Targher G., Day C.P., Bonora E.: Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363: pp. 1341-1350.
12. Matteoni C.A., Younossi Z.M., Gramlich T., et. al.: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116: pp. 1413-1419.
13. Powell E.E., Cooksley W.G., Hanson R., et. al.: The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990; 11: pp. 74-80.
14. Goto T., Onuma T., Takebe K., et. al.: The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects. Int J Obes Relat Metab Disord 1995; 19: pp. 841-845.
15. Zelber-Sagi S., Nitzan-Kaluski D., Halpern Z., et. al.: Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver Int 2006; 26: pp. 856-863.
16. Lucero D., Zago V., Lopez G.I., et. al.: Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome. Clin Chim Acta 2011; 412: pp. 143-147.
17. Crum-Cianflone N., Krause D., Wessman D., et. al.: Fatty liver disease is associated with underlying cardiovascular disease in HIV-infected persons(*). HIV Med 2011; 12: pp. 463-471.
18. Targher G., Arcaro G.: Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007; 191: pp. 235-240.
19. Browning J.D., Szczepaniak L.S., Dobbins R., et. al.: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: pp. 1387-1395.
20. Bedogni G., Miglioli L., Masutti F., et. al.: Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysus nutrition and liver study. Hepatology 2005; 42: pp. 44-52.
21. Nomura H., Kashiwagi S., Hayashi J., et. al.: Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med 1988; 27: pp. 142-149.
22. Clark J.M., Brancati F.L., Diehl A.M.: The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003; 98: pp. 960-967.
23. Jimba S., Nakagami T., Takahashi M., et. al.: Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med 2005; 22: pp. 1141-1145.
24. Boyce C.J., Pickhardt P.J., Kim D.H., et. al.: Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. AJR Am J Roentgenol 2010; 194: pp. 623-628.
25. Lee S.S., Park S.H., Kim H.J., et. al.: Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 2010; 52: pp. 579-585.
26. Piekarski J., Goldberg H.I., Royal S.A., et. al.: Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology 1980; 137: pp. 727-729.
27. Bydder G.M., Chapman R.W., Harry D., et. al.: Computed tomography attenuation values in fatty liver. J Comput Tomogr 1981; 5: pp. 33-35.
28. Kawata R., Sakata K., Kunieda T., et. al.: Quantitative evaluation of fatty liver by computed tomography in rabbits. AJR Am J Roentgenol 1984; 142: pp. 741-746.
29. Kodama Y., Ng C.S., Wu T.T., et. al.: Comparison of CT methods for determining the fat content of the liver. AJR Am J Roentgenol 2007; 188: pp. 1307-1312.
30. Park S.H., Kim P.N., Kim K.W., et. al.: Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology 2006; 239: pp. 105-112.
31. Bild D.E., Bluemke D.A., Burke G.L., et. al.: Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol 2002; 156: pp. 871-881.
32. Carr J.J., Nelson J.C., Wong N.D., et. al.: Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study. Radiology 2005; 234: pp. 35-43.
33. Becker U., Deis A., Sorensen T.I., et. al.: Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology 1996; 23: pp. 1025-1029.
34. Coates R.A., Halliday M.L., Rankin J.G., et. al.: Risk of fatty infiltration or cirrhosis of the liver in relation to ethanol consumption: a case-control study. Clin Invest Med 1986; 9: pp. 26-32.
35. Longo R., Ricci C., Masutti F., et. al.: Fatty infiltration of the liver. Quantification by 1H localized magnetic resonance spectroscopy and comparison with computed tomography. Invest Radiol 1993; 28: pp. 297-302.
36. Pamilo M., Sotaniemi E.A., Suramo I., et. al.: Evaluation of liver steatotic and fibrous content by computerized tomography and ultrasound. Scand J Gastroenterol 1983; 18: pp. 743-747.
37. Johnston R.J., Stamm E.R., Lewin J.M., et. al.: Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations of liver-minus-spleen attenuation difference measurements. Abdom Imaging 1998; 23: pp. 409-415.
38. Iwasaki M., Takada Y., Hayashi M., et. al.: Noninvasive evaluation of graft steatosis in living donor liver transplantation. Transplantation 2004; 78: pp. 1501-1505.
39. Speliotes E.K., Massaro J.M., Hoffmann U., et. al.: Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study. J Gastroenterol Hepatol 2008; 23: pp. 894-899.
40. Davidson L.E., Kuk J.L., Church T.S., et. al.: Protocol for measurement of liver fat by computed tomography. J Appl Physiol 2006; 100: pp. 864-868.