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Published in: Digestive Diseases and Sciences 7/2020

01-07-2020 | Computed Tomography | Original Article

Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients

Authors: Kung-Hao Liang, Peng Zhang, Chih-Lang Lin, Stewart C. Wang, Tsung-Hui Hu, Chau-Ting Yeh, Grace L. Su

Published in: Digestive Diseases and Sciences | Issue 7/2020

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Abstract

Background and Aims

Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients.

Methods

A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population.

Results

Of the 27 digitized features at the 12th thoracic vertebral level, six features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) were able to stratify patients into high- and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044, respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor.

Conclusion

Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.
Appendix
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Literature
1.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136:E359–E386.CrossRef Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136:E359–E386.CrossRef
2.
go back to reference Huang T-S, Lin C-L, Shyu Y-C, et al. Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: a population-based cohort study. Journal of Gastroenterology and Hepatology. 2017;32:1355–1362.CrossRef Huang T-S, Lin C-L, Shyu Y-C, et al. Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: a population-based cohort study. Journal of Gastroenterology and Hepatology. 2017;32:1355–1362.CrossRef
3.
go back to reference Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35–S50.CrossRef Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35–S50.CrossRef
4.
go back to reference Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236.CrossRef Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236.CrossRef
5.
go back to reference Liaw Y-F, Kao J-H, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–561.CrossRef Liaw Y-F, Kao J-H, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–561.CrossRef
6.
go back to reference Lok ASF. Hepatitis B: liver fibrosis and hepatocellular carcinoma. Gastroentérol Clin Biol. 2009;33:911–915.CrossRef Lok ASF. Hepatitis B: liver fibrosis and hepatocellular carcinoma. Gastroentérol Clin Biol. 2009;33:911–915.CrossRef
7.
go back to reference Yang H-I, Sherman M, Su J, et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol. 2010;28:2437–2444.CrossRef Yang H-I, Sherman M, Su J, et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol. 2010;28:2437–2444.CrossRef
8.
go back to reference Lee M-H, Yang H-I, Liu J, et al. Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles. Hepatology. 2013;58:546–554.CrossRef Lee M-H, Yang H-I, Liu J, et al. Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles. Hepatology. 2013;58:546–554.CrossRef
9.
go back to reference Yang H-I, Yuen M-F, Chan HL-Y, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12:568–574.CrossRef Yang H-I, Yuen M-F, Chan HL-Y, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12:568–574.CrossRef
10.
go back to reference Benjamin AJ, Buschmann MM, Schneider A, et al. Can comprehensive imaging analysis with analytic morphomics and geriatric assessment predict serious complications in patients undergoing pancreatic surgery? J Gastrointest Surg. 2017;21:1009–1016.CrossRef Benjamin AJ, Buschmann MM, Schneider A, et al. Can comprehensive imaging analysis with analytic morphomics and geriatric assessment predict serious complications in patients undergoing pancreatic surgery? J Gastrointest Surg. 2017;21:1009–1016.CrossRef
11.
go back to reference Crass RL, Ross BE, Derstine BA, et al. Measurement of skeletal muscle area improves estimation of aminoglycoside clearance across body size. Antimicrob Agents Chemother. 2018;62:e00441-18.CrossRef Crass RL, Ross BE, Derstine BA, et al. Measurement of skeletal muscle area improves estimation of aminoglycoside clearance across body size. Antimicrob Agents Chemother. 2018;62:e00441-18.CrossRef
12.
go back to reference Cron DC, Noon KA, Cote DR, et al. Using analytic morphomics to describe body composition associated with post-kidney transplantation diabetes mellitus. Clin Transplant. 2017;31:e13040.CrossRef Cron DC, Noon KA, Cote DR, et al. Using analytic morphomics to describe body composition associated with post-kidney transplantation diabetes mellitus. Clin Transplant. 2017;31:e13040.CrossRef
13.
go back to reference Derstine BA, Holcombe SA, Goulson RL, et al. quantifying sarcopenia reference values using lumbar and thoracic muscle areas in a healthy population. J Nutr Health Aging. 2018;22:180–185.CrossRef Derstine BA, Holcombe SA, Goulson RL, et al. quantifying sarcopenia reference values using lumbar and thoracic muscle areas in a healthy population. J Nutr Health Aging. 2018;22:180–185.CrossRef
14.
go back to reference Derstine BA, Holcombe SA, Ross BE, Wang NC, Su GL, Wang SC. Skeletal muscle cutoff values for sarcopenia diagnosis using T10 to L5 measurements in a healthy US population. Sci Rep. 2018;8:11369.CrossRef Derstine BA, Holcombe SA, Ross BE, Wang NC, Su GL, Wang SC. Skeletal muscle cutoff values for sarcopenia diagnosis using T10 to L5 measurements in a healthy US population. Sci Rep. 2018;8:11369.CrossRef
15.
go back to reference Harbaugh C, Henderson B, Zhang P, et al. The ‘cushion effect’ is not protective for children involved in motor vehicle crashes. J Am Coll Surg. 2017;225:e187–e188.CrossRef Harbaugh C, Henderson B, Zhang P, et al. The ‘cushion effect’ is not protective for children involved in motor vehicle crashes. J Am Coll Surg. 2017;225:e187–e188.CrossRef
16.
go back to reference Harbaugh CM, Zhang P, Henderson B, et al. Personalized medicine: enhancing our understanding of pediatric growth with analytic morphomics. J Pediatr Surg. 2017;52:837–842.CrossRef Harbaugh CM, Zhang P, Henderson B, et al. Personalized medicine: enhancing our understanding of pediatric growth with analytic morphomics. J Pediatr Surg. 2017;52:837–842.CrossRef
17.
go back to reference Harbaugh CM, Zhang P, Henderson B, et al. Evaluating the “cushion effect” among children in frontal motor vehicle crashes. J Pediatr Surg. 2018;53:1033–1036.CrossRef Harbaugh CM, Zhang P, Henderson B, et al. Evaluating the “cushion effect” among children in frontal motor vehicle crashes. J Pediatr Surg. 2018;53:1033–1036.CrossRef
18.
go back to reference Heckman KM, Otemuyiwa B, Chenevert TL, et al. Validation of a DIXON-based fat quantification technique for the measurement of visceral fat using a CT-based reference standard. Abdom Radiol. 2019;44:346–354.CrossRef Heckman KM, Otemuyiwa B, Chenevert TL, et al. Validation of a DIXON-based fat quantification technique for the measurement of visceral fat using a CT-based reference standard. Abdom Radiol. 2019;44:346–354.CrossRef
19.
go back to reference Holcombe SA, Hwang E, Derstine BA, Wang SC. Measuring rib cortical bone thickness and cross section from CT. Med Image Anal. 2018;49:27–34.CrossRef Holcombe SA, Hwang E, Derstine BA, Wang SC. Measuring rib cortical bone thickness and cross section from CT. Med Image Anal. 2018;49:27–34.CrossRef
20.
go back to reference Holcombe SA, Wang SC, Grotberg JB. The effect of age and demographics on rib shape. J Anat. 2017;231:229–247.CrossRef Holcombe SA, Wang SC, Grotberg JB. The effect of age and demographics on rib shape. J Anat. 2017;231:229–247.CrossRef
21.
go back to reference Lee C, Raymond E, Derstine BA, et al. Morphomic malnutrition score: a standardized screening tool for severe malnutrition in adults. J Parenter Enter Nutr. 2018;42:1263–1271.CrossRef Lee C, Raymond E, Derstine BA, et al. Morphomic malnutrition score: a standardized screening tool for severe malnutrition in adults. J Parenter Enter Nutr. 2018;42:1263–1271.CrossRef
22.
go back to reference Miller AL, Englesbe MJ, Diehl KM, et al. Preoperative psoas muscle size predicts postoperative delirium in older adults undergoing surgery: a pilot cohort study. J Am Geriatr Soc. 2016;65:e23–e24.CrossRef Miller AL, Englesbe MJ, Diehl KM, et al. Preoperative psoas muscle size predicts postoperative delirium in older adults undergoing surgery: a pilot cohort study. J Am Geriatr Soc. 2016;65:e23–e24.CrossRef
23.
go back to reference Otemuyiwa B, Derstine BA, Zhang P, et al. Dorsal muscle attenuation may predict failure to respond to interleukin-2 therapy in metastatic renal cell carcinoma. Acad Radiol. 2017;24:1094–1100.CrossRef Otemuyiwa B, Derstine BA, Zhang P, et al. Dorsal muscle attenuation may predict failure to respond to interleukin-2 therapy in metastatic renal cell carcinoma. Acad Radiol. 2017;24:1094–1100.CrossRef
24.
go back to reference Parikh ND, Zhang P, Singal AG, et al. Body composition predicts survival in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Cancer Res Treat. 2018;50:530–537.CrossRef Parikh ND, Zhang P, Singal AG, et al. Body composition predicts survival in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Cancer Res Treat. 2018;50:530–537.CrossRef
25.
go back to reference Pienta MJ, Zhang P, Derstine BA, et al. Analytic morphomics predict outcomes after lung transplantation. Ann Thorac Surg. 2018;105:399–405.CrossRef Pienta MJ, Zhang P, Derstine BA, et al. Analytic morphomics predict outcomes after lung transplantation. Ann Thorac Surg. 2018;105:399–405.CrossRef
26.
go back to reference Sharma P, Parikh ND, Yu J, et al. Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients. Liver Transplant. 2016;22:1092–1098.CrossRef Sharma P, Parikh ND, Yu J, et al. Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients. Liver Transplant. 2016;22:1092–1098.CrossRef
27.
go back to reference Stidham RW, Waljee AK, Day NM, et al. Body fat composition assessment using analytic morphomics predicts infectious complications after bowel resection in Crohnʼs disease. Inflamm Bowel Dis. 2015;1:1306–1313. Stidham RW, Waljee AK, Day NM, et al. Body fat composition assessment using analytic morphomics predicts infectious complications after bowel resection in Crohnʼs disease. Inflamm Bowel Dis. 2015;1:1306–1313.
28.
go back to reference Terjimanian MN, Underwood PW, Cron DC, et al. Morphometric age and survival following kidney transplantation. Clin Transplant. 2017;31:e13066.CrossRef Terjimanian MN, Underwood PW, Cron DC, et al. Morphometric age and survival following kidney transplantation. Clin Transplant. 2017;31:e13066.CrossRef
30.
go back to reference Huang Y-H, Liang K-H, Chien R-N, et al. A circulating MicroRNA signature capable of assessing the risk of hepatocellular carcinoma in cirrhotic patients. Sci Rep. 2017;7:523.CrossRef Huang Y-H, Liang K-H, Chien R-N, et al. A circulating MicroRNA signature capable of assessing the risk of hepatocellular carcinoma in cirrhotic patients. Sci Rep. 2017;7:523.CrossRef
31.
go back to reference Liang K-H, Ahn SH, Lee HW, et al. A novel risk score for hepatocellular carcinoma in Asian cirrhotic patients: a multicentre prospective cohort study. Sci Rep. 2018;8:8608.CrossRef Liang K-H, Ahn SH, Lee HW, et al. A novel risk score for hepatocellular carcinoma in Asian cirrhotic patients: a multicentre prospective cohort study. Sci Rep. 2018;8:8608.CrossRef
32.
go back to reference Konerman MA, Verma A, Zhao B, Singal AG, Lok AS, Parikh ND. Frequency and outcomes of abnormal imaging in patients with cirrhosis enrolled in a hepatocellular carcinoma surveillance program. Liver Transplant. 2019;25:369–379.CrossRef Konerman MA, Verma A, Zhao B, Singal AG, Lok AS, Parikh ND. Frequency and outcomes of abnormal imaging in patients with cirrhosis enrolled in a hepatocellular carcinoma surveillance program. Liver Transplant. 2019;25:369–379.CrossRef
33.
go back to reference Santos LA, Romeiro FG. Diagnosis and management of cirrhosis-related osteoporosis. Biomed Res Int. 2016;2016:1423462.CrossRef Santos LA, Romeiro FG. Diagnosis and management of cirrhosis-related osteoporosis. Biomed Res Int. 2016;2016:1423462.CrossRef
34.
go back to reference Wu DB, Wang ML, Chen EQ, Tang H. New insights into the role of vitamin D in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2018;12:287–294.CrossRef Wu DB, Wang ML, Chen EQ, Tang H. New insights into the role of vitamin D in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2018;12:287–294.CrossRef
35.
go back to reference Miles LM. Food, nutrition, physical activity and the prevention of cancer: a global perspective—the WCRF/AICR second report. Nutr Bull. 2005;30:168–172.CrossRef Miles LM. Food, nutrition, physical activity and the prevention of cancer: a global perspective—the WCRF/AICR second report. Nutr Bull. 2005;30:168–172.CrossRef
36.
go back to reference Hann HW, Fu X, Myers RE, et al. Predictive value of alpha-fetoprotein in the long-term risk of developing hepatocellular carcinoma in patients with hepatitis B virus infection–results from a clinic-based longitudinal cohort. Eur J Cancer. 2012;48:2319–2327.CrossRef Hann HW, Fu X, Myers RE, et al. Predictive value of alpha-fetoprotein in the long-term risk of developing hepatocellular carcinoma in patients with hepatitis B virus infection–results from a clinic-based longitudinal cohort. Eur J Cancer. 2012;48:2319–2327.CrossRef
Metadata
Title
Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients
Authors
Kung-Hao Liang
Peng Zhang
Chih-Lang Lin
Stewart C. Wang
Tsung-Hui Hu
Chau-Ting Yeh
Grace L. Su
Publication date
01-07-2020
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2020
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05915-w

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