Skip to main content
Top
Published in: World Journal of Surgery 1/2020

01-01-2020 | Liver Transplantation | Original Scientific Report

Prognostic Impact of Osteopenia in Patients Who Underwent Living Donor Liver Transplantation for Hepatocellular Carcinoma

Authors: Takeo Toshima, Tomoharu Yoshizumi, Yukiko Kosai-Fujimoto, Shoichi Inokuchi, Shohei Yoshiya, Kazuki Takeishi, Shinji Itoh, Noboru Harada, Toru Ikegami, Yuji Soejima, Masaki Mori

Published in: World Journal of Surgery | Issue 1/2020

Login to get access

Abstract

Background

Osteopenia, loss of bone mineral density (BMD), was recently identified to be independently associated with early marker of deconditioning that precedes sarcopenia in patients with hepatocellular carcinoma (HCC). The aim of this study was to clarify the impact of osteopenia as the risk factor for mortality after living donor liver transplantation (LDLT) compared with already-reported biological markers.

Methods

Data were collected retrospectively for all consecutive patients who underwent LDLT for HCC at our institution between January 1998 and December 2015. BMD was evaluated with computed tomographic measurement of pixel density in the midvertebral core of the 11th thoracic vertebra. Data related to clinicopathological parameters and prognosis were analyzed.

Results

The median value of BMD was 163.6 Hounsfield units and osteopenia was identified in 103 (53.4%) of the 193 recipients, according to the age-specific formula. In addition to the other tumor burdens, such as tumor numbers ≥5 (HR 2.521, P = 0.027), DCP levels >200 mAU/mL (HR 2.678, P = 0.006), and neutrophil-to-lymphocyte ratio ≥3.01 (HR 2.068, P = 0.025), osteopenia (HR 2.106, P = 0.024) was independent risk factor for mortality by multivariate analysis. Overall survival of the patients who met the two risk factors and more was significantly lower than the others (HR 5.382, P < 0.001). Besides, the calibration plot for the 5-year overall survival using nomogram was predicted very well (C-index 0.746).

Conclusions

Preoperative osteopenia was independently associated with post-LDLT mortality among patients with HCC. Moreover, risk score and nomogram with calibration curve were developed to confirm the clinical usefulness of osteopenia for post-LDLT patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Benjamin AJ, Baker TB, Talamonti MS et al (2018) Liver transplant offers a survival benefit over margin negative resection in patients with small unifocal hepatocellular carcinoma and preserved liver function. Surgery 163:582–586CrossRef Benjamin AJ, Baker TB, Talamonti MS et al (2018) Liver transplant offers a survival benefit over margin negative resection in patients with small unifocal hepatocellular carcinoma and preserved liver function. Surgery 163:582–586CrossRef
2.
go back to reference Liu JB, Baker TB, Suss NR et al (2017) Orthotopic liver transplantation provides a survival advantage compared with resection in patients with hepatocellular carcinoma and preserved liver function. Surgery 162:1032–1039CrossRef Liu JB, Baker TB, Suss NR et al (2017) Orthotopic liver transplantation provides a survival advantage compared with resection in patients with hepatocellular carcinoma and preserved liver function. Surgery 162:1032–1039CrossRef
3.
go back to reference Taketomi A, Sanefuji K, Soejima Y et al (2009) Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation. Transplantation 87:531–537CrossRef Taketomi A, Sanefuji K, Soejima Y et al (2009) Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation. Transplantation 87:531–537CrossRef
4.
go back to reference Yoshizumi T, Ikegami T, Yoshiya S et al (2013) Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma. Hepatol Res 43:709–716CrossRef Yoshizumi T, Ikegami T, Yoshiya S et al (2013) Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma. Hepatol Res 43:709–716CrossRef
5.
go back to reference Motomura T, Shirabe K, Mano Y et al (2013) Neutrophil–lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol 58:58–64CrossRef Motomura T, Shirabe K, Mano Y et al (2013) Neutrophil–lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol 58:58–64CrossRef
6.
go back to reference Mehta N, Dodge JL, Roberts JP et al (2018) Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database. Am J Transplant 18:1206–1213CrossRef Mehta N, Dodge JL, Roberts JP et al (2018) Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database. Am J Transplant 18:1206–1213CrossRef
7.
go back to reference Sharma P, Parikh ND, Yu J et al (2016) Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients. Liver Transplant 22:1092–1098CrossRef Sharma P, Parikh ND, Yu J et al (2016) Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients. Liver Transplant 22:1092–1098CrossRef
8.
go back to reference Masuda T, Shirabe K, Ikegami T et al (2014) Sarcopenia is a prognostic factor in living donor liver transplantation. Liver Transplant 20:401–407CrossRef Masuda T, Shirabe K, Ikegami T et al (2014) Sarcopenia is a prognostic factor in living donor liver transplantation. Liver Transplant 20:401–407CrossRef
9.
go back to reference Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43CrossRef Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43CrossRef
10.
go back to reference Urata K, Kawasaki S, Matsunami H et al (1995) Calculation of child and adult standard liver volume for liver transplantation. Hepatology 21:1317–1321CrossRef Urata K, Kawasaki S, Matsunami H et al (1995) Calculation of child and adult standard liver volume for liver transplantation. Hepatology 21:1317–1321CrossRef
11.
go back to reference Yonemura Y, Taketomi A, Soejima Y et al (2005) Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography. Liver Transplant 11:1556–1562CrossRef Yonemura Y, Taketomi A, Soejima Y et al (2005) Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography. Liver Transplant 11:1556–1562CrossRef
12.
go back to reference Toshima T, Yoshizumi T, Ikegami T et al (2018) Impact of osteopenia in liver cirrhosis: special reference to standard bone mineral density with age. Anticancer Res 38:6465–6471CrossRef Toshima T, Yoshizumi T, Ikegami T et al (2018) Impact of osteopenia in liver cirrhosis: special reference to standard bone mineral density with age. Anticancer Res 38:6465–6471CrossRef
13.
go back to reference Yoshizumi T, Shirabe K, Nakagawara H et al (2014) Skeletal muscle area correlates with body surface area in healthy adults. Hepatol Res 44:313–318CrossRef Yoshizumi T, Shirabe K, Nakagawara H et al (2014) Skeletal muscle area correlates with body surface area in healthy adults. Hepatol Res 44:313–318CrossRef
14.
go back to reference Harimoto N, Yoshizumi T, Shimokawa M et al (2016) Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma. Hepatol Res 46:1247–1255CrossRef Harimoto N, Yoshizumi T, Shimokawa M et al (2016) Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma. Hepatol Res 46:1247–1255CrossRef
15.
go back to reference Toshima T, Taketomi A, Ikegami T et al (2012) V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation. Transplantation 93:929–935CrossRef Toshima T, Taketomi A, Ikegami T et al (2012) V5-drainage-preserved right lobe grafts improve graft congestion for living donor liver transplantation. Transplantation 93:929–935CrossRef
16.
go back to reference Toshima T, Ikegami T, Kimura K et al (2014) Application of postoperative model for end-stage liver disease scoring system for evaluating liver graft function after living donor liver transplantation. Transplant Proc 46:81–86CrossRef Toshima T, Ikegami T, Kimura K et al (2014) Application of postoperative model for end-stage liver disease scoring system for evaluating liver graft function after living donor liver transplantation. Transplant Proc 46:81–86CrossRef
17.
go back to reference Tang XR, Li YQ, Liang SB et al (2018) Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study. Lancet Oncol 19:382–393CrossRef Tang XR, Li YQ, Liang SB et al (2018) Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study. Lancet Oncol 19:382–393CrossRef
18.
go back to reference Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259CrossRef Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259CrossRef
19.
go back to reference Karunakaran P, Maharajan C, Chockalingam R et al (2019) The effect of total thyroidectomy on the recovery of bone mineral density in subjects with hyperthyroidism. Surgery 165:80–84CrossRef Karunakaran P, Maharajan C, Chockalingam R et al (2019) The effect of total thyroidectomy on the recovery of bone mineral density in subjects with hyperthyroidism. Surgery 165:80–84CrossRef
20.
go back to reference Pickhardt PJ, Pooler BD, Lauder T et al (2013) Opportunistic screening for osteoporosis using abdominal computed tomography scans obtained for other indications. Ann Intern Med 158:588–595CrossRef Pickhardt PJ, Pooler BD, Lauder T et al (2013) Opportunistic screening for osteoporosis using abdominal computed tomography scans obtained for other indications. Ann Intern Med 158:588–595CrossRef
21.
go back to reference Shin YH, Gong HS, Lee KJ, et al (2019) Older age and higher body mass index are associated with a more degraded trabecular bone score compared to bone mineral density. J Clin Densitom 22:266–271CrossRef Shin YH, Gong HS, Lee KJ, et al (2019) Older age and higher body mass index are associated with a more degraded trabecular bone score compared to bone mineral density. J Clin Densitom 22:266–271CrossRef
22.
go back to reference Schreiber JJ, Anderson PA, Rosas HG et al (2011) Hounsfield units for assessing bone mineral density and strength: a tool for osteoporosis management. J Bone Jt Surg Am 93:1057–1063CrossRef Schreiber JJ, Anderson PA, Rosas HG et al (2011) Hounsfield units for assessing bone mineral density and strength: a tool for osteoporosis management. J Bone Jt Surg Am 93:1057–1063CrossRef
23.
go back to reference Wu K, Feskanich D, Fuchs CS et al (2007) A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst 99:1120–1129CrossRef Wu K, Feskanich D, Fuchs CS et al (2007) A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst 99:1120–1129CrossRef
24.
go back to reference Lee JE, Li H, Giovannucci E et al (2009) Prospective study of plasma vitamin B6 and risk of colorectal cancer in men. Cancer Epidemiol Biomark Prev 18:1197–1202CrossRef Lee JE, Li H, Giovannucci E et al (2009) Prospective study of plasma vitamin B6 and risk of colorectal cancer in men. Cancer Epidemiol Biomark Prev 18:1197–1202CrossRef
25.
go back to reference Styrkarsdottir U, Stefansson OA, Gunnarsdottir K et al (2019) GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. Nat Commun 10:2054CrossRef Styrkarsdottir U, Stefansson OA, Gunnarsdottir K et al (2019) GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. Nat Commun 10:2054CrossRef
26.
go back to reference Li CJ, Cheng P, Liang MK et al (2015) MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Investig 125:1509–1522CrossRef Li CJ, Cheng P, Liang MK et al (2015) MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Investig 125:1509–1522CrossRef
27.
go back to reference Itoh S, Yoshizumi T, Kimura K et al (2016) Effect of sarcopenic obesity on outcomes of living-donor liver transplantation for hepatocellular carcinoma. Anticancer Res 36:3029–3034PubMed Itoh S, Yoshizumi T, Kimura K et al (2016) Effect of sarcopenic obesity on outcomes of living-donor liver transplantation for hepatocellular carcinoma. Anticancer Res 36:3029–3034PubMed
28.
go back to reference Pereira FB, Leite AF, de Paula AP (2015) Relationship between pre-sarcopenia, sarcopenia and bone mineral density in elderly men. Arch Endocrinol Metab 59:59–65CrossRef Pereira FB, Leite AF, de Paula AP (2015) Relationship between pre-sarcopenia, sarcopenia and bone mineral density in elderly men. Arch Endocrinol Metab 59:59–65CrossRef
29.
go back to reference Hanada M, Soyama A, Hidaka M et al (2019) Effects of quadriceps muscle neuromuscular electrical stimulation in living donor liver transplant recipients: phase-II single-blinded randomized controlled trial. Clin Rehabil 33:875–884CrossRef Hanada M, Soyama A, Hidaka M et al (2019) Effects of quadriceps muscle neuromuscular electrical stimulation in living donor liver transplant recipients: phase-II single-blinded randomized controlled trial. Clin Rehabil 33:875–884CrossRef
Metadata
Title
Prognostic Impact of Osteopenia in Patients Who Underwent Living Donor Liver Transplantation for Hepatocellular Carcinoma
Authors
Takeo Toshima
Tomoharu Yoshizumi
Yukiko Kosai-Fujimoto
Shoichi Inokuchi
Shohei Yoshiya
Kazuki Takeishi
Shinji Itoh
Noboru Harada
Toru Ikegami
Yuji Soejima
Masaki Mori
Publication date
01-01-2020
Publisher
Springer International Publishing
Published in
World Journal of Surgery / Issue 1/2020
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-019-05206-5

Other articles of this Issue 1/2020

World Journal of Surgery 1/2020 Go to the issue