Assessing Hepatomegaly

Rationale and Objectives

The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing hepatomegaly.

Materials and Methods

Livers were automatically segmented from 148 abdominal contrast-enhanced computed tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by visual inspection and/or linear liver height by radiologists). Quantified liver volumes were compared to manual measurements using volume overlap and error. Liver volumes were normalized to body surface area, from which hepatomegaly nomograms were defined (H scores) by analyzing the distribution of liver sizes in the healthy population. H scores were validated against consensus reports. The performance of radiologists in diagnosing hepatomegaly was retrospectively evaluated.

Results

The automated segmentation of livers was robust, with volume overlap and error of 96.2% and 2.2%, respectively. There were no significant differences ( P > .10) between manual and automated segmentation for either the normal or the hepatomegaly subgroup. The average volumes of normal and enlarged livers were 1.51 ± 0.25 and 2.32 ± 0.75 L, respectively. One-way analysis of variance found that body surface area ( P = .004) and gender ( P = .02), but not age, significantly affected normal liver volume. No significant effects were observed for two-way and three-way interactions among the three variables ( P > .18). H-score cutoffs of 0.92 and 1.08 L/m 2 were used to define mild and massive hepatomegaly (95% confidence interval, ±0.02 L/m 2 ). Using the H score as the reference standard, the sensitivity of radiologists in detecting all, mild, and massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity, respectively. Radiologists disagreed on 20.9% of the diagnosed cases ( n = 31). The area under the receiver-operating characteristic curve of the H-score criterion for hepatomegaly detection was 0.98.

Conclusions

Nomograms for the identification and grading of hepatomegaly from automatic volumetric liver assessment normalized to body surface area (H scores) are introduced. H scores match well with clinical interpretations for hepatomegaly and may improve hepatomegaly detection compared with height measurements or visual inspection, commonly used in current clinical practice.

Hepatomegaly is an abnormal enlargement of liver size and is inherently defined by a volumetric change. Patient size has been reported to correlate with the volume of the liver . To date, there are no defined volumetric liver nomograms to detect hepatomegaly.

Hepatic size has been an important biomarker for assessing disorders and surgical planning . Predictably, hepatic size estimates by physicians using palpation and percussion are approximate and adequate for diagnosing only cases of massive hepatomegaly . Blendis et al found that only half of enlarged livers detected by plain radiography were also identified by physical examination, while approximately half of normal livers were diagnosed as enlarged.

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Materials and methods

Study Patients and CT Imaging

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Segmentation

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Definition of Hepatomegaly and Nomograms

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Performance of Radiologists Relative to the Hepatomegaly Nomogram

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Statistical Analysis

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Results

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Table 1

Average Automated Liver Volumes and Heights

Cases Mean ± Standard Deviation Normal volume (L) ( n = 74) 1.52 ± 0.26 Normal volume/BSA (L/m 2 ) ( n = 74) 0.81 ± 0.11 Normal MHL height (cm) ( n = 74) 12.86 ± 2.21 Enlarged volume (L) ( n = 43) 2.57 ± 0.76 Enlarged volume/BSA (L/m 2 ) ( n = 43) 1.45 ± 0.40 Enlarged MHL height (cm) ( n = 43) 19.32 ± 3.64 Hepatectomy volume (L) ( n = 23) 1.56 ± 0.40

BSA, body surface area; MHL, midhepatic line.

Average volumes, volumes normalized to BSA, and heights at the MHL for normal and enlarged livers. Only average volumes are reported for partial hepatectomy cases, because of the frequent inability to calculate the MHL height and extraneous relationship to body size after surgery.

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Table 2

Correlations between Liver Volume and Height and Patient BSA and Age

Cases/Correlation Factor Correlation ( P value) Normal volume ( n = 74)/BSA 0.60 (<.001) Normal volume ( n = 74)/age 0.01 (.90) Enlarged volume ( n = 43)/BSA 0.41 (.005) Enlarged volume ( n = 43)/age 0.38 (.01) Normal MHL height ( n = 74)/BSA −0.02 (.80) Normal MHL height ( n = 74)/age −0.33 (.003) Enlarged MHL height ( n = 43)/BSA 0.08 (.50) Enlarged MHL height ( n = 43)/age 0.18 (.20)

BSA, body surface area; MHL, midhepatic line.

Correlation coefficients (and associated P values) are presented between volume and MHL height measurements and patient BSA and age for normal and enlarged livers.

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Table 3

Retrospective Sensitivity and Specificity of Radiologists and Liver MHL Height to Detect Hepatomegaly

Criterion ( n = 148) Sensitivity/Specificity (%) Mild Hepatomegaly Massive Hepatomegaly All Hepatomegaly Radiologists 56.7/90.1100.0 /90.184.4 /90.1 MHL height 40.0/88.7 85.1/88.7 67.5/88.7

MHL, midhepatic line.

The H score was used as the reference standard with cutoffs of 0.92 and 1.08 L/m 2 to identify mild and massive hepatomegaly. The radiologic reports were used to compute the sensitivity and specificity of the radiologists. A cutoff of 15.5 cm was used to identify hepatomegaly using liver MHL height. Significant differences ( P < .007, shown in italics) were noted between the sensitivity of the radiologist and the sensitivity of the liver MHL height criterion for the detection of massive and all cases of hepatomegaly.

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Discussion

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Table 4

Review of Average Volumes for Normal and Diseased Livers

Study Patient Livers Sex Number of Cases Mean Volume (L) Modality Andersen et al Normal Male 7 1.60 CT Kwo et al Normal Male 10 1.54 ± 0.08 CT Sandrasegaran et al Normal Male 8 1.67 CT Andersen et al Normal Female 16 1.34 CT Kwo et al Normal Female 10 1.48 ± 0.06 CT Sandrasegaran et al Normal Female 11 1.52 CT Farraher et al Normal Male/female 18 1.66 ± 0.35 MRI Henderson et al Normal Male/female 11 1.45 ± 0.17 CT Kardel et al Normal Male/female 20 1.61 ± 0.19 Ultrasound Mazonakis et al Normal Male/female 27 1.47 ± 0.23 MRI Stapakis et al Normal Male/female 22 1.32 ± 0.42 CT Farraher et al Diseased Male/female 9 1.99 ± 0.52 MRI Henderson et al Diseased Male/female 12 1.64 ± 0.7 CT Mazonakis et al Diseased Male/female 11 1.94 ± 0.19 MRI Van Thiel et al Diseased Male/female 99 1.78 ± 0.09 CT

CT, computed tomography; MRI, magnetic resonance imaging.

Table 1 reports the average volumes of normal and diseased livers in our study.

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Table 5

Correlations between Liver Volume and Patient Data

Study Body Surface Area Weight Height Age This study Yes Yes Yes Yes Andersen et al – Yes No No Boyd – – – Yes Calloway et al – – – Yes Hauksen et al Yes Yes Yes – Kardel et al – Yes – – Kratzer et al – Yes Yes Yes Leung et al Yes Yes No – McNeal et al – Yes – – Raeth et al Yes Yes Yes – Urata et al Yes – – – Wynne et al Yes – – Yes Zoli et al Yes Yes – –

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Acknowledgments

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Appendix A

STARD Flowchart for Hepatomegaly Study

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BSA, body surface area; CRIS, clinical research information system; CT, computed tomography; NIH, National Institutes of Health; PACS, picture archiving and communication system; RIS, radiology information system; SD, standard deviation; STARD, Standards for the Reporting of Diagnostic Accuracy Studies.

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Appendix B

Clinical Diagnoses of the Hepatomegaly Data

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Liver Disorder Number of Cases Acute myeloid leukemia 2 Adult T-cell leukemia/lymphoma 1 Alveolar soft part sarcoma 1 Aplastic anemia 2 Appendiceal cancer 1 Autoimmune lymphoproliferative syndrome type 12 1 B-cell chronic lymphocytic leukemia 1 Chronic granulomatous disease 7 Chronic myelogenous (or myeloid) leukemia 2 Colon cancer with liver metastases 1 Cutaneous T-cell lymphoma 1 Dermatomyositis lipodystrophy 1 Desmoplastic small round cell tumor 1 D-MAC/myelodysplastic syndromes 1 Follicular lymphoma 1 Hepatitis C 1 Hepatosplenic T-cell lymphoma 1 Hereditary papillary renal carcinoma type I 1 Histoplasmosis (Darling’s disease) 1 HIV 1 HIV with MAC 2 HIV/hepatic steatosis 1 HIV/KS/multicentric Castleman’s disease 1 HIV/primary effusion lymphoma/multicentric Castleman’s disease/KS 1 HIV with Burkitt’s non-Hodgkin’s lymphoma 1 HIV/lymphoma 1 Hypertriglyceridemia/pancreatitis 1 Hypertension 1 KS 2 Large granular lymphocytic leukemia 2 Lymphoma 3 Mantle cell lymphoma 1 Mastocytosis 2 Melanoma 4 Mesothelioma 1 Multicentric Castleman’s disease 3 MAC 1 Mycobacterium avium intracellulare 1 No diagnosis 3 Nontuberculous mycobacteria 1 Ocular melanoma with liver metastases 3 Peritoneal mesothelioma 1 Prostate carcinoma 2 Pure red cell aplasia 1 Systemic lupus erythematosus 1 Thalassemia 1 Total 71

HIV, human immunodeficiency virus; KS, Kaposi’s sarcoma; MAC, mycobacterium avium complex.

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References

1. Andersen V., Sonne J., Sletting S., et. al.: The volume of the liver in patients correlates to body weight and alcohol consumption. Alcohol Alcohol 2000; 35: pp. 531-532.
2. Leung N.W., Farrant P., Peters T.J.: Liver volume measurement by ultrasonography in normal subjects and alcoholic patients. J Hepatol 1986; 2: pp. 157-164.
3. Wynne H.A., Cope L.H., Mutch E., et. al.: The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1989; 9: pp. 297-301.
4. Zoli M., Cordiani M.R., Marchesini G., et. al.: Prognostic indicators in compensated cirrhosis. Am J Gastroenterol 1991; 86: pp. 1508-1513.
5. Ellert J., Kreel L.: The role of computed tomography in the initial staging and subsequent management of the lymphomas. J Comput Assist Tomogr 1980; 4: pp. 368-391.
6. Elstein D., Hadas-Halpern I., Azuri Y., et. al.: Accuracy of ultrasonography in assessing spleen and liver size in patients with Gaucher disease: comparison to computed tomographic measurements. J Ultrasound Med 1997; 16: pp. 209-211.
7. Gosink B.B., Leymaster C.E.: Ultrasonic determination of hepatomegaly. J Clin Ultrasound 1981; 9: pp. 37-44.
8. Kawasaki S., Makuuchi M., Matsunami H., et. al.: Preoperative measurement of segmental liver volume of donors for living related liver transplantation. Hepatology 1993; 18: pp. 1115-1120.
9. Okamoto E., Kyo A., Yamanaka N., et. al.: Prediction of the safe limits of hepatectomy by combined volumetric and functional measurements in patients with impaired hepatic function. Surgery 1984; 95: pp. 586-592.
10. Sekiyama K., Yoshiba M., Inoue K., et. al.: Prognostic value of hepatic volumetry in fulminant hepatic failure. Dig Dis Sci 1994; 39: pp. 240-244.
11. Soyer P., Roche A., Elias D., et. al.: Hepatic metastases from colorectal cancer: influence of hepatic volumetric analysis on surgical decision making. Radiology 1992; 184: pp. 695-697.
12. Tsushima Y., Endo K.: Spleen enlargement in patients with nonalcoholic fatty liver: correlation between degree of fatty infiltration in liver and size of spleen. Dig Dis Sci 2000; 45: pp. 196-200.
13. Van Thiel D.H., Hagler N.G., Schade R.R., et. al.: In vivo hepatic volume determination using sonography and computed tomography. Validation and a comparison of the two techniques. Gastroenterology 1985; 88: pp. 1812-1817.
14. Broering D.C., Sterneck M., Rogiers X.: Living donor liver transplantation. J Hepatol 2003; 38: pp. S119-S135.
15. Chen Y.S., Cheng Y.F., De Villa V.H., et. al.: Evaluation of living liver donors. Transplantation 2003; 75: pp. S16-S19.
16. Hermoye L., Laamari-Azjal I., Cao Z., et. al.: Liver segmentation in living liver transplant donors: comparison of semiautomatic and manual methods. Radiology 2005; 234: pp. 171-178.
17. Kasai H., Makuuchi M., Kawasaki S., et. al.: Intraoperative color Doppler ultrasonography for partial-liver transplantation from the living donor in pediatric patients. Transplantation 1992; 54: pp. 173-175.
18. Sugarbaker P.H.: Surgical decision making for large bowel cancer metastatic to the liver. Radiology 1990; 174: pp. 621-626.
19. Delp M.H., Manning R.T.: Examination of the abdomen and gastrointestinal and hepatobiliary disorders.Major’s physical diagnosis.1981.Lippincott Williams & WilkinsPhiladelphia, PA:
20. Sherlock S.: Disease of the liver and biliary system1981.Blackwell ScientificBoston
21. Blendis L.M., McNeilly W.J., Sheppard L., et. al.: Observer variation in the clinical and radiological assessment of hepatosplenomegaly. Br Med J 1970; 1: pp. 727-730.
22. Castell D.O., O’Brien D.K., Myench H., et. al.: Estimation of liver size by percussion in normal individuals. Ann Intern Med 1969; 70: pp. 1183-1189.
23. Meyhoff H.H., Roder O., Andersen B.: Palpatory estimation of liver size. Within- and between-observer variation. Acta Chir Scand 1979; 145: pp. 479-481.
24. Riemenschneider P.A., Whalen J.P.: Relative accuracy of estimation of enlargement of liver and spleen by radiologic and clinical methods. Am J Roentgenol Radium Ther Nucl Med 1965; 94: pp. 462-468.
25. Cheng Y.F., Chen C.L., Huang T.L., et. al.: Single imaging modality evaluation of living donors in liver transplantation: magnetic resonance imaging. Transplantation 2001; 72: pp. 1527-1533.
26. Schroeder T., Nadalin S., Stattaus J., et. al.: Potential living liver donors: evaluation with an all-in-one protocol with multi-detector row CT. Radiology 2002; 224: pp. 586-591.
27. Heymsfield S.B., Fulenwider T., Nordlinger B., et. al.: Accurate measurement of liver, kidney, and spleen volume and mass by computerized axial tomography. Ann Intern Med 1979; 90: pp. 185-187.
28. Raeth U., Johnson P.J., Williams R.: Ultrasound determination of liver size and assessment of patients with malignant liver disease. Liver 1984; 4: pp. 287-293.
29. Rasmussen S.N.: Liver volume determination by ultrasonic scanning. Br J Radiol 1972; 45: pp. 579-585.
30. Mazonakis M., Damilakis J., Maris T., et. al.: Comparison of two volumetric techniques for estimating liver volume using magnetic resonance imaging. J Magn Reson Imaging 2002; 15: pp. 557-563.
31. McAfee J.G., Ause R.G., Wagner H.N.: Diagnostic value of scintillation scanning of the liver. Arch Intern Med 1965; 116: pp. 95-110.
32. Gillard J.H., Patel M.C., Abrahams P.H., et. al.: Riedel’s lobe of the liver: fact or fiction?. Clin Anat 1998; 11: pp. 47-49.
33. Kudo M.: Riedel’s lobe of the liver and its clinical implication. Int Med 2000; 39: pp. 87-88.
34. Baum S., Locko R.C., Davignon M.B.: Functional-anatomy and radionuclide imaging—Riedels lobe of the liver. Anat Clin 1982; 4: pp. 121-123.
35. Sham R., Sain A., Silver L.: Hypertrophic Riedel’s lobe of the liver. Clin Nucl Med 1978; 3: pp. 79-81.
36. Aussilhou B., Douflé G., Hubert C., et. al.: Extended liver resection for polycystic liver disease can challenge lver transplantation. Ann Surg 2010; 252: pp. 735-743.
37. Schnelldorfer T., Torres V.E., Zakaria S., et. al.: Polycystic liver disease. Ann Surg 2009; 250: pp. 112-118.
38. Rosenfield A.T., Schneider P.B.: Rapid evaluation of hepatic size on radioisotope scan. J Nucl Med 1974; 15: pp. 237-240.
39. Hausken T., Leotta D.F., Helton S., et. al.: Estimation of the human liver volume and configuration using three-dimensional ultrasonography: effect of a high-caloric liquid meal. Ultrasound Med Biol 1998; 24: pp. 1357-1367.
40. Urata K., Kawasaki S., Matsunami H., et. al.: Calculation of child and adult standard liver volume for liver transplantation. Hepatology 1995; 21: pp. 1317-1321.
41. Sandrasegaran K., Kwo P.W., DiGirolamo D., et. al.: Measurement of liver volume using spiral CT and the curved line and cubic spline algorithms: reproducibility and interobserver variation. Abdom Imaging 1999; 24: pp. 61-65.
42. Linguraru M.G., Sandberg J.K., Li Z., et. al.: Automated segmentation and quantification of liver and spleen from CT images using normalized probabilistic atlases and enhancement estimation. Med Phys 2010; 37: pp. 771-783.
43. Goshima S., Kanematsu M., Nishibori H., et. al.: Multi-detector row CT of the kidney: optimizing scan delays for bolus tracking techniques of arterial, corticomedullary, and nephrographic phases. Eur J Radiol 2007; 63: pp. 420-426.
44. Pickhardt P.J., Choi J.R., Hwang I., et. al.: Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003; 349: pp. 2191-2200.
45. Link T.M., Koppers B.B., Licht T., et. al.: In vitro and in vivo spiral CT to determine bone mineral density: initial experience in patients at risk for osteoporosis. Radiology 2004; 231: pp. 805-811.
46. Engelke K., Adams J.E., Armbrecht G., et. al.: Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD official positions. J Clin Densitom Assess Skel Health 2008; 11: pp. 123-162.
47. Bland J.M., Altman D.G.: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: pp. 307-310.
48. Kardel T., Holm H.H., Rasmussen S.N., et. al.: Ultrasonic determination of liver and spleen volumes. Scand J Clin Lab Invest 1971; 27: pp. 123-128.
49. Kwo P.Y., Ramchandani V.A., O’Connor S., et. al.: Gender differences in alcohol metabolism: relationship to liver volume and effect of adjusting for body mass. Gastroenterology 1998; 115: pp. 1552-1557.
50. Farraher S.W., Jara H., Chang K.J., et. al.: Liver and spleen volumetry with quantitative MR imaging and dual-space clustering segmentation. Radiology 2005; 237: pp. 322-328.
51. Henderson J.M., Heymsfield S.B., Horowitz J., et. al.: Measurement of liver and spleen volume by computed tomography. Assessment of reproducibility and changes found following a selective distal splenorenal shunt. Radiology 1981; 141: pp. 525-527.
52. Stapakis J., Stamm E., Townsend R., et. al.: Liver volume assessment by conventional vs. helical CT. Abdom Imaging 1995; 20: pp. 209-210.
53. Kratzer W., Fritz V., Mason R.A., et. al.: Factors affecting liver size: a sonographic survey of 2080 subjects. J Ultrasound Med 2003; 22: pp. 1155-1161.
54. Boyd E.: Normal variability in weight of the adult human liver and spleen. Arch Pathol 1933; 16: pp. 350-372.
55. Calloway N.O., Foley C.F., Lagerbloom P.: Uncertainties in geriatric data. II. Organ size. J Am Geriatr Soc 1965; 13: pp. 20-28.
56. McNeal G.R., Maynard W.H., Branch R.A., et. al.: Liver volume measurements and three-dimensional display from MR images. Radiology 1988; 169: pp. 851-854.
57. Niederau C., Sonnenberg A.: Liver size evaluated by ultrasound: ROC curves for hepatitis and alcoholism. Radiology 1984; 153: pp. 503-505.
58. Kornasiewicz O., Dudek K., Bugajski M., et. al.: Choice of transplantation techniques and indications for liver transplantation in polycystic liver disease in patients with no signs of end-stage liver disease. Transplantation Proceedings 2008; 40: pp. 1536-1538.

Assessing Hepatomegaly

Rationale and Objectives

Materials and Methods

Results

Conclusions

Materials and methods

Study Patients and CT Imaging

Segmentation

Definition of Hepatomegaly and Nomograms

Performance of Radiologists Relative to the Hepatomegaly Nomogram

Statistical Analysis

Results

Discussion

Acknowledgments

Appendix A

STARD Flowchart for Hepatomegaly Study

Appendix B

Clinical Diagnoses of the Hepatomegaly Data

References

Further Reading

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