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Published in: Journal of Gastroenterology 3/2015

01-03-2015 | Original Article—Liver, Pancreas, and Biliary Tract

Skeletal muscle depletion is an independent prognostic factor for hepatocellular carcinoma

Authors: Soichi Iritani, Kenji Imai, Koji Takai, Tatsunori Hanai, Takayasu Ideta, Tsuneyuki Miyazaki, Atsushi Suetsugu, Makoto Shiraki, Masahito Shimizu, Hisataka Moriwaki

Published in: Journal of Gastroenterology | Issue 3/2015

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Abstract

Background

Skeletal muscle depletion or sarcopenia has been identified as a poor prognostic factor for various diseases. The aim of this study is to determine whether muscle depletion is a prognostic factor for hepatocellular carcinoma (HCC).

Methods

We evaluated 217 consecutive patients with primary HCC. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the total body fat-free mass (FFM) and L3 skeletal muscle index (L3 SMI) were obtained. The factors contributing to overall survival (OS) were analyzed by univariate and multivariate Cox proportional hazards model.

Results

In univariate analysis, FFM (P = 0.0422), Child-Pugh classification (P = 0.0058), serum albumin level (P < 0.0001), serum AFP level (P < 0.0001), serum proteins induced by vitamin K absence or antagonist-II level (P < 0.0001), cancer stage (P < 0.0001), and curability of the initial treatment (P < 0.0001) were significantly associated with the prognosis of HCC. Multivariate analysis indicated that FFM (P = 0.0499), albumin level (P = 0.0398), and curability of the initial treatment (P = 0.0008) were independent prognostic factors. Sarcopenia was defined as an L3 SMI value of ≤29.0 cm2/m2 for women and ≤36.0 cm2/m2 for men, and 24 patients (11.1 %) have sarcopenia. Sarcopenic patients showed a significantly lower OS than those without sarcopenia (P = 0.0043). Sarcopenic patients who were overweight (BMI >22) died earlier (P = 0.0129).

Conclusions

Skeletal muscle depletion is an independent prognostic factor. Intervention to prevent muscle wasting might be an effective strategy for improving the outcome of HCC.
Appendix
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Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90 (Epub 2011/02/08).CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90 (Epub 2011/02/08).CrossRefPubMed
2.
go back to reference El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5 Suppl 2):S72–8 (Epub 2002/10/24).CrossRefPubMed El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5 Suppl 2):S72–8 (Epub 2002/10/24).CrossRefPubMed
3.
go back to reference op den Winkel M, Nagel D, Sappl J, op den Winkel P, Lamerz R, Zech CJ, et al. Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort. PloS One. 2012;7(10):e45066 (Epub 2012/10/17).CrossRefPubMedCentralPubMed op den Winkel M, Nagel D, Sappl J, op den Winkel P, Lamerz R, Zech CJ, et al. Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort. PloS One. 2012;7(10):e45066 (Epub 2012/10/17).CrossRefPubMedCentralPubMed
4.
go back to reference Tajika M, Kato M, Mohri H, Miwa Y, Kato T, Ohnishi H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition. 2002;18(3):229–34 (Epub 2002/03/08).CrossRefPubMed Tajika M, Kato M, Mohri H, Miwa Y, Kato T, Ohnishi H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition. 2002;18(3):229–34 (Epub 2002/03/08).CrossRefPubMed
5.
go back to reference Montano-Loza AJ, Meza-Junco J, Prado CM, Lieffers JR, Baracos VE, Bain VG, et al. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2012;10(2):166–173 e1 (Epub 2011/09/07).CrossRef Montano-Loza AJ, Meza-Junco J, Prado CM, Lieffers JR, Baracos VE, Bain VG, et al. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2012;10(2):166–173 e1 (Epub 2011/09/07).CrossRef
6.
go back to reference Periyalwar P, Dasarathy S. Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses. Clin Liver Dis. 2012;16(1):95–131 (Epub 2012/02/11).CrossRefPubMed Periyalwar P, Dasarathy S. Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses. Clin Liver Dis. 2012;16(1):95–131 (Epub 2012/02/11).CrossRefPubMed
7.
go back to reference Poon RT. Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge. Hepatology. 2011;54(3):757–9 (Epub 2011/07/28).CrossRefPubMed Poon RT. Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge. Hepatology. 2011;54(3):757–9 (Epub 2011/07/28).CrossRefPubMed
8.
go back to reference Shiraki M, Nishiguchi S, Saito M, Fukuzawa Y, Mizuta T, Kaibori M, et al. Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007–2011. Hepatology Res: Off J Jpn Soc Hepatol. 2013;43(2):106–12 (Epub 2013/02/16).CrossRef Shiraki M, Nishiguchi S, Saito M, Fukuzawa Y, Mizuta T, Kaibori M, et al. Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007–2011. Hepatology Res: Off J Jpn Soc Hepatol. 2013;43(2):106–12 (Epub 2013/02/16).CrossRef
9.
go back to reference Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 Suppl):990S–1S (Epub 1997/05/01).PubMed Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 Suppl):990S–1S (Epub 1997/05/01).PubMed
10.
go back to reference Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in older people. Age Ageing. 2010;39(4):412–23 (Epub 2010/04/16).CrossRefPubMedCentralPubMed Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in older people. Age Ageing. 2010;39(4):412–23 (Epub 2010/04/16).CrossRefPubMedCentralPubMed
11.
go back to reference Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35 (Epub 2008/06/10).CrossRefPubMed Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35 (Epub 2008/06/10).CrossRefPubMed
12.
go back to reference Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2009;15(22):6973–9 (Epub 2009/11/06).CrossRef Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2009;15(22):6973–9 (Epub 2009/11/06).CrossRef
13.
go back to reference Sabel MS, Lee J, Cai S, Englesbe MJ, Holcombe S, Wang S. Sarcopenia as a prognostic factor among patients with stage III melanoma. Ann Surg Oncol. 2011;18(13):3579–85 (Epub 2011/08/09).CrossRefPubMed Sabel MS, Lee J, Cai S, Englesbe MJ, Holcombe S, Wang S. Sarcopenia as a prognostic factor among patients with stage III melanoma. Ann Surg Oncol. 2011;18(13):3579–85 (Epub 2011/08/09).CrossRefPubMed
14.
go back to reference van Vledder MG, Levolger S, Ayez N, Verhoef C, Tran TC, Ijzermans JN. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg. 2012;99(4):550–7 (Epub 2012/01/17).CrossRefPubMed van Vledder MG, Levolger S, Ayez N, Verhoef C, Tran TC, Ijzermans JN. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg. 2012;99(4):550–7 (Epub 2012/01/17).CrossRefPubMed
15.
go back to reference Dodson RM, Firoozmand A, Hyder O, Tacher V, Cosgrove DP, Bhagat N, et al. Impact of sarcopenia on outcomes following intra-arterial therapy of hepatic malignancies. J Gastrointest Surg: Off J Soc Surg Aliment Tract. 2013;17(12):2123–32 (Epub 2013/09/26).CrossRef Dodson RM, Firoozmand A, Hyder O, Tacher V, Cosgrove DP, Bhagat N, et al. Impact of sarcopenia on outcomes following intra-arterial therapy of hepatic malignancies. J Gastrointest Surg: Off J Soc Surg Aliment Tract. 2013;17(12):2123–32 (Epub 2013/09/26).CrossRef
16.
go back to reference Mir O, Coriat R, Blanchet B, Durand JP, Boudou-Rouquette P, Michels J, et al. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PloS One. 2012;7(5):e37563 (Epub 2012/06/06).CrossRefPubMedCentralPubMed Mir O, Coriat R, Blanchet B, Durand JP, Boudou-Rouquette P, Michels J, et al. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PloS One. 2012;7(5):e37563 (Epub 2012/06/06).CrossRefPubMedCentralPubMed
17.
go back to reference Meza-Junco J, Montano-Loza AJ, Baracos VE, Prado CM, Bain VG, Beaumont C, et al. Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma. J Clin Gastroenterol. 2013;47(10):861–70 (Epub 2013/06/12).CrossRefPubMed Meza-Junco J, Montano-Loza AJ, Baracos VE, Prado CM, Bain VG, Beaumont C, et al. Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma. J Clin Gastroenterol. 2013;47(10):861–70 (Epub 2013/06/12).CrossRefPubMed
18.
go back to reference Kaido T, Ogawa K, Fujimoto Y, Ogura Y, Hata K, Ito T, et al. Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transplant: Off J Am Soc Transplant Am Soc Transpl Surg. 2013;13(6):1549–56 (Epub 2013/04/23).CrossRef Kaido T, Ogawa K, Fujimoto Y, Ogura Y, Hata K, Ito T, et al. Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transplant: Off J Am Soc Transplant Am Soc Transpl Surg. 2013;13(6):1549–56 (Epub 2013/04/23).CrossRef
19.
go back to reference Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol (1985). 1998;85(1):115–22 (Epub 1998/07/09). Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol (1985). 1998;85(1):115–22 (Epub 1998/07/09).
20.
go back to reference Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab = Physiol Appl Nutr Metab. 2008;33(5):997–1006 (Epub 2008/10/17).CrossRef Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab = Physiol Appl Nutr Metab. 2008;33(5):997–1006 (Epub 2008/10/17).CrossRef
21.
go back to reference Clinical Practice Guidelines for Hepatocellular Carcinoma. The Japan Society of Hepatology 2009 update. Hepatol Res: Off J Jpn Soc Hepatol. 2010;40(Suppl 1):2–144 (Epub 2010/07/01). Clinical Practice Guidelines for Hepatocellular Carcinoma. The Japan Society of Hepatology 2009 update. Hepatol Res: Off J Jpn Soc Hepatol. 2010;40(Suppl 1):2–144 (Epub 2010/07/01).
22.
go back to reference Kudo M, Kubo S, Takayasu K, Sakamoto M, Tanaka M, Ikai I, et al. Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version). Hepatol Res: Off J Jpn Soc Hepatol. 2010;40(7):686–92 (Epub 2010/07/17).CrossRef Kudo M, Kubo S, Takayasu K, Sakamoto M, Tanaka M, Ikai I, et al. Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version). Hepatol Res: Off J Jpn Soc Hepatol. 2010;40(7):686–92 (Epub 2010/07/17).CrossRef
23.
go back to reference The general rules for the clinical and pathological study of primary liver cancer. Liver Cancer Study Group of Japan. Jpn J Surg. 1989;19(1):98–129 (Epub 1989/01/01). The general rules for the clinical and pathological study of primary liver cancer. Liver Cancer Study Group of Japan. Jpn J Surg. 1989;19(1):98–129 (Epub 1989/01/01).
24.
go back to reference Ikai I, Kudo M, Arii S, Omata M, Kojiro M, Sakamoto M, et al. Report of the 18th follow-up survey of primary liver cancer in Japan. Hepatol Res. 2010;40(11):1043–59.CrossRef Ikai I, Kudo M, Arii S, Omata M, Kojiro M, Sakamoto M, et al. Report of the 18th follow-up survey of primary liver cancer in Japan. Hepatol Res. 2010;40(11):1043–59.CrossRef
25.
go back to reference Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi). Hepatology. 1996;23(5):1041–6 (Epub 1996/05/01).CrossRefPubMed Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi). Hepatology. 1996;23(5):1041–6 (Epub 1996/05/01).CrossRefPubMed
26.
go back to reference Imai K, Takai K, Nishigaki Y, Shimizu S, Naiki T, Hayashi H, et al. Insulin resistance raises the risk for recurrence of stage I hepatocellular carcinoma after curative radiofrequency ablation in hepatitis C virus-positive patients: a prospective, case series study. Hepatol Res: Off J Jpn Soc Hepatol. 2010;40(4):376–82 (Epub 2010/03/20).CrossRef Imai K, Takai K, Nishigaki Y, Shimizu S, Naiki T, Hayashi H, et al. Insulin resistance raises the risk for recurrence of stage I hepatocellular carcinoma after curative radiofrequency ablation in hepatitis C virus-positive patients: a prospective, case series study. Hepatol Res: Off J Jpn Soc Hepatol. 2010;40(4):376–82 (Epub 2010/03/20).CrossRef
27.
go back to reference Shimizu M, Tanaka T, Moriwaki H. Obesity and hepatocellular carcinoma: targeting obesity-related inflammation for chemoprevention of liver carcinogenesis. Semin Immunopathol. 2013;35(2):191–202 (Epub 2012/09/05).CrossRefPubMed Shimizu M, Tanaka T, Moriwaki H. Obesity and hepatocellular carcinoma: targeting obesity-related inflammation for chemoprevention of liver carcinogenesis. Semin Immunopathol. 2013;35(2):191–202 (Epub 2012/09/05).CrossRefPubMed
28.
go back to reference Prado CM, Wells JC, Smith SR, Stephan BC, Siervo M. Sarcopenic obesity: a Critical appraisal of the current evidence. Clin Nutr. 2012;31(5):583–601 (Epub 2012/07/20).CrossRefPubMed Prado CM, Wells JC, Smith SR, Stephan BC, Siervo M. Sarcopenic obesity: a Critical appraisal of the current evidence. Clin Nutr. 2012;31(5):583–601 (Epub 2012/07/20).CrossRefPubMed
29.
go back to reference Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care. 2008;11(6):693–700 (Epub 2008/10/02).CrossRefPubMedCentralPubMed Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care. 2008;11(6):693–700 (Epub 2008/10/02).CrossRefPubMedCentralPubMed
30.
go back to reference Harimoto N, Shirabe K, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y, et al. Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma. Br J Surg. 2013;100(11):1523–30 Epub 2013/09/17.CrossRefPubMed Harimoto N, Shirabe K, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y, et al. Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma. Br J Surg. 2013;100(11):1523–30 Epub 2013/09/17.CrossRefPubMed
31.
go back to reference Lutz CT, Quinn LS. Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism. Aging. 2012;4(8):535–46 (Epub 2012/09/01).PubMedCentralPubMed Lutz CT, Quinn LS. Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism. Aging. 2012;4(8):535–46 (Epub 2012/09/01).PubMedCentralPubMed
32.
go back to reference Jones JC, Coombes JS, Macdonald GA. Exercise capacity and muscle strength in patients with cirrhosis. Liver Transplant: Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2012;18(2):146–51 (Epub 2011/12/06).CrossRef Jones JC, Coombes JS, Macdonald GA. Exercise capacity and muscle strength in patients with cirrhosis. Liver Transplant: Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2012;18(2):146–51 (Epub 2011/12/06).CrossRef
33.
go back to reference Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, et al. ESPEN Guidelines on Enteral Nutrition: liver disease. Clin Nutr. 2006;25(2):285–94 (Epub 2006/05/19).CrossRefPubMed Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, et al. ESPEN Guidelines on Enteral Nutrition: liver disease. Clin Nutr. 2006;25(2):285–94 (Epub 2006/05/19).CrossRefPubMed
34.
go back to reference Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124(7):1792–801 (Epub 2003/06/14).CrossRefPubMed Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124(7):1792–801 (Epub 2003/06/14).CrossRefPubMed
35.
go back to reference Moriwaki H, Shiraki M, Fukushima H, Shimizu M, Iwasa J, Naiki T, et al. Long-term outcome of branched-chain amino acid treatment in patients with liver cirrhosis. Hepatol Res: Off J Jpn Soc Hepatol. 2008;38(Suppl 1):S102–6 (Epub 2009/01/08).CrossRef Moriwaki H, Shiraki M, Fukushima H, Shimizu M, Iwasa J, Naiki T, et al. Long-term outcome of branched-chain amino acid treatment in patients with liver cirrhosis. Hepatol Res: Off J Jpn Soc Hepatol. 2008;38(Suppl 1):S102–6 (Epub 2009/01/08).CrossRef
36.
go back to reference Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2005;3(7):705–13 (Epub 2005/10/07).CrossRef Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2005;3(7):705–13 (Epub 2005/10/07).CrossRef
37.
go back to reference Vincent HK, Raiser SN, Vincent KR. The aging musculoskeletal system and obesity-related considerations with exercise. Ageing Res Rev. 2012;11(3):361–73 (Epub 2012/03/24).CrossRefPubMedCentralPubMed Vincent HK, Raiser SN, Vincent KR. The aging musculoskeletal system and obesity-related considerations with exercise. Ageing Res Rev. 2012;11(3):361–73 (Epub 2012/03/24).CrossRefPubMedCentralPubMed
Metadata
Title
Skeletal muscle depletion is an independent prognostic factor for hepatocellular carcinoma
Authors
Soichi Iritani
Kenji Imai
Koji Takai
Tatsunori Hanai
Takayasu Ideta
Tsuneyuki Miyazaki
Atsushi Suetsugu
Makoto Shiraki
Masahito Shimizu
Hisataka Moriwaki
Publication date
01-03-2015
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 3/2015
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-014-0964-9

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