Background: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). Methods: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis. The LHL15 index (uptake ratio of the liver to that of the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium-labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 × [1 − (resected liver weight − tumor volume)/whole liver volume without tumor]. Results: A total of 163 patients were classified as having no PHLF, whereas 17, 37, and 1 patient had PHLF grade A, B, and C, respectively. There were significant differences in indocyanine green R15, serum albumin, prothrombin time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a cut-off value of 0.755. Conclusions: Remnant LHL15 was an independent risk factor for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should be carefully monitored for PHLF.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011; 61: 69–90.
Tomimaru Y, Eguchi H, Marubashi S, Wada H, Kobayashi S, Tanemura M, Umeshita K, Doki Y, Mori M, Nagano H: Equivalent outcomes after anatomical and non-anatomical resection of small hepatocellular carcinoma in patients with preserved liver function. Dig Dis Sci 2012; 57: 1942–1948.
Lai EC, Fan ST, Lo CM, Chu KM, Liu CL, Wong J: Hepatic resection for hepatocellular carcinoma. An audit of 343 patients. Ann Surg 1995; 221: 291–298.
Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y, Kubota K, Zucchi A: No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach. Arch Surg 1999; 134: 984–992.
Fukushima K, Fukumoto T, Kuramitsu K, Kido M, Takebe A, Tanaka M, Itoh T, Ku Y: Assessment of ISGLS definition of posthepatectomy liver failure and its effect on outcome in patients with hepatocellular carcinoma. J Gastrointest Surg 2014; 18: 729–736.
Capussotti L, Muratore A, Amisano M, Polastri R, Bouzari H, Massucco P: Liver resection for hepatocellular carcinoma on cirrhosis: analysis of mortality, morbidity and survival – a European single center experience. Eur J Surg Oncol 2005; 31: 986–993.
Chok KS, Ng KK, Poon RT, Lo CM, Fan ST: Impact of postoperative complications on long-term outcome of curative resection for hepatocellular carcinoma. Br J Surg 2009; 96: 81–87.
Yokoyama Y, Ebata T, Igami T, Sugawara G, Ando M, Nagino M: Predictive power of prothrombin time and serum total bilirubin for postoperative mortality after major hepatectomy with extrahepatic bile duct resection. Surgery 2014; 155: 504–511.
Yoo H, Kim JH, Ko GY, Kim KW, Gwon DI, Lee SG, Hwang S: Sequential transcatheter arterial chemoembolization and portal vein embolization versus portal vein embolization only before major hepatectomy for patients with hepatocellular carcinoma. Ann Surg Oncol 2011; 18: 1251–1257.
Ribero D, Abdalla EK, Madoff DC, Donadon M, Loyer EM, Vauthey JN: Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome. Br J Surg 2007; 94: 1386–1394.
Aoki T, Imamura H, Hasegawa K, Matsukura A, Sano K, Sugawara Y, Kokudo N, Makuuchi M: Sequential preoperative arterial and portal venous embolizations in patients with hepatocellular carcinoma. Arch Surg 2004; 139: 766–774.
Iguchi K, Hatano E, Yamanaka K, Tanaka S, Taura K, Uemoto S: The impact of posthepatectomy liver failure on the recurrence of hepatocellular carcinoma. World J Surg 2014; 38: 150–158.
Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Buchler MW, Weitz J: Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 2011; 149: 713–724.
Yoshida M, Shiraishi S, Sakamoto F, Beppu T, Utsunomiya D, Okabe H, Tomiguchi S, Baba H, Yamashita Y: Assessment of hepatic functional regeneration after hepatectomy using Tc-GSA SPECT/CT fused imaging. Ann Nucl Med 2014; 28: 780–788.
de Graaf W, Bennink RJ, Vetelainen R, van Gulik TM: Nuclear imaging techniques for the assessment of hepatic function in liver surgery and transplantation. J Nucl Med 2010; 51: 742–752.
Yumoto Y, Yagi T, Sato S, Nouso K, Kobayashi Y, Ohmoto M, Yumoto E, Nagaya I, Nakatsukasa H: Preoperative estimation of remnant hepatic function using fusion images obtained by (99m)Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography. Br J Surg 2010; 97: 934–944.
Wakamatsu H, Nagamachi S, Kiyohara S, Fujita S, Kamimura K, Futami S, Nishii R, Nagano M, Kondou K, Kai M, Chijiiwa K, Tamura S: Predictive value of Tc-99m galactosyl human serum albumin liver SPECT on the assessment of functional recovery after partial hepatectomy: a comparison with CT volumetry. Ann Nucl Med 2010; 24: 729–734.
Mao Y, Du S, Ba J, Li F, Yang H, Lu X, Sang X, Li S, Che L, Tong J, Xu Y, Xu H, Zhao H, Chi T, Liu F, Du Y, Zhang X, Wang X, Dong J, Zhong S, Huang J, Yu Y, Wang J: Using Dynamic 99mT c-GSA SPECT/CT fusion images for hepatectomy planning and postoperative liver failure prediction. Ann Surg Oncol 2015; 22: 1301–1307.
Yoshida M, Shiraishi S, Sakaguchi F, Utsunomiya D, Tashiro K, Tomiguchi S, Okabe H, Beppu T, Baba H, Yamashita Y: Fused 99m-Tc-GSA SPECT/CT imaging for the preoperative evaluation of postoperative liver function: can the liver uptake index predict postoperative hepatic functional reserve? Jpn J Radiol 2012; 30: 255–262.
Iimuro Y, Kashiwagi T, Yamanaka J, Hirano T, Saito S, Sugimoto T, Watanabe S, Uyama N, Fujimoto J: Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters. J Hepatobiliary Pancreat Sci 2010; 17: 673–681.
Hayashi H, Beppu T, Okabe H, Kuroki H, Nakagawa S, Imai K, Nitta H, Chikamoto A, Ishiko T, Baba H: Functional assessment versus conventional volumetric assessment in the prediction of operative outcomes after major hepatectomy. Surgery 2015; 157: 20–26.
Kwon AH, Ha-Kawa SK, Uetsuji S, Kamiyama Y, Tanaka Y: Use of technetium 99m diethylenetriamine-pentaacetic acid-galactosyl-human serum albumin liver scintigraphy in the evaluation of preoperative and postoperative hepatic functional reserve for hepatectomy. Surgery 1995; 117: 429–434.
Kawamura H, Kamiyama T, Nakagawa T, Nakanishi K, Yokoo H, Tahara M, Kamachi H, Toi H, Matsushita M, Todo S: Preoperative evaluation of hepatic functional reserve by converted ICGR15 calculated from Tc-GSA scintigraphy. J Gastroenterol Hepatol 2008; 23: 1235–1241.
Lam CM, Fan ST, Lo CM, Wong J: Major hepatectomy for hepatocellular carcinoma in patients with an unsatisfactory indocyanine green clearance test. Br J Surg 1999; 86: 1012–1017.
Couinaud C: Liver lobes and segments: notes on the anatomical architecture and surgery of the liver. Presse Med 1954; 62: 709–712.
Hasegawa K, Kokudo N, Imamura H, Matsuyama Y, Aoki T, Minagawa M, Sano K, Sugawara Y, Takayama T, Makuuchi M: Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg 2005; 242: 252–259.
Kashiwagi T, Yutani K, Fukuchi M, Naruse H, Iwasaki T, Yokozuka K, Inoue S, Kondo S: Correction of nonuniform attenuation and image fusion in SPECT imaging by means of separate X-ray CT. Ann Nucl Med 2002; 16: 255–261.
Ha-Kawa SK, Tanaka Y, Hasebe S, Kuniyasu Y, Koizumi K, Ishii Y, Yamamoto K, Kashiwagi T, Ito A, Kudo M, Ikekubo K, Tsuda T, Murase K: Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: a multicentre study. Eur J Nucl Med 1997; 24: 130–137.
Wu J, Ishikawa N, Takeda T, Tanaka Y, Pan XQ, Sato M, Todoroki T, Hatakeyama R, Itai Y: The functional hepatic volume assessed by 99mTc-GSA hepatic scintigraphy. Ann Nucl Med 1995; 9: 229–235.
Suda K, Ohtsuka M, Ambiru S, Kimura F, Shimizu H, Yoshidome H, Miyazaki M: Risk factors of liver dysfunction after extended hepatic resection in biliary tract malignancies. Am J Surg 2009; 197: 752–758.
Ferrero A, Vigano L, Polastri R, Muratore A, Eminefendic H, Regge D, Capussotti L: Postoperative liver dysfunction and future remnant liver: where is the limit? Results of a prospective study. World J Surg 2007; 31: 1643–1651.
Rahman SH, Evans J, Toogood GJ, Lodge PA, Prasad KR: Prognostic utility of postoperative C-reactive protein for posthepatectomy liver failure. Arch Surg 2008; 143: 247–253; discussion 253.
Hirai I, Kimura W, Fuse A, Suto K, Urayama M: Evaluation of preoperative portal embolization for safe hepatectomy, with special reference to assessment of nonembolized lobe function with 99mTc-GSA SPECT scintigraphy. Surgery 2003; 133: 495–506.
Kudo M, Vera DR, Stadalnik RC, Trudeau WL, Ikekubo K, Todo A: In vivo estimates of hepatic binding protein concentration: correlation with classical indicators of hepatic functional reserve. Am J Gastroenterol 1990; 85: 1142–1148.
Vera DR, Stadalnik RC, Krohn KA: Technetium-99m galactosyl-neoglycoalbumin: preparation and preclinical studies. J Nucl Med 1985; 26: 1157–1167.
Koizumi K, Uchiyama G, Arai T, Ainoda T, Yoda Y: A new liver functional study using Tc-99m DTPA-galactosyl human serum albumin: evaluation of the validity of several functional parameters. Ann Nucl Med 1992; 6: 83–87.
Ohkura Y, Mizuno S, Kishiwada M, Hamada T, Usui M, Sakurai H, Tabata M, Yamada T, Isaji S: Benefit of technetium-99m galactosyl human serum albumin scintigraphy instead of indocyanine green test in patients scheduled for hepatectomy. Hepatol Res 2014; 44:E118–E128.
Kubota Y, Kitagawa S, Inoue K, Ha-Kawa SK, Kojima M, Tanaka Y: Hepatic functional scintigraphic imaging with 99mtechnetium galactosyl serum albumin. Hepatogastroenterology 1993; 40: 32–36.
Sugai Y, Komatani A, Hosoya T, Yamaguchi K: Response to percutaneous transhepatic portal embolization: new proposed parameters by 99mTc-GSA SPECT and their usefulness in prognostic estimation after hepatectomy. J Nucl Med 2000; 41: 421–425.
Nanashima A, Yamaguchi H, Shibasaki S, Morino S, Ide N, Takeshita H, Tsuji T, Sawai T, Nakagoe T, Nagayasu T, Ogawa Y: Relationship between CT volumetry and functional liver volume using technetium-99m galactosyl serum albumin scintigraphy in patients undergoing preoperative portal vein embolization before major hepatectomy: a preliminary study. Dig Dis Sci 2006; 51: 1190–1195.
Yokoyama Y, Ebata T, Igami T, Sugawara G, Mizuno T, Yamaguchi J, Nagino M: The predictive value of indocyanine green clearance in future liver remnant for posthepatectomy liver failure following hepatectomy with extrahepatic bile duct resection. World J Surg 2016; 40: 1440–1447.
Sumiyoshi T, Shima Y, Okabayashi T, Noda Y, Hata Y, Murata Y, Kozuki A, et al: Functional discrepancy between two liver lobes after hemilobe biliary drainage in patients with jaundice and bile duct cancer: an appraisal using (99m)Tc-GSA SPECT/CT fusion imaging. Radiology 2014; 273: 444–451.
Kadono J, Kumemura H, Nishida S, Nakamura N, Gejima K, Nakajo M, Tsuchimochi S, Tokumaru T, Nakamura T, Uka K: 99mTc-DTPA-galactosyl-human-serum-albumin liver scintigraphy for evaluating hepatic functional reserve before hepatectomy in a patient with indocyanine green excretory defect: report of a case. Surg Today 2006; 36: 481–484.
Maeda H, Okabayashi T, Kobayashi M, Sugimoto T, Namikawa T, Okamoto K, Araki K: Hepatectomy for hepatocellular carcinoma with indocyanine green excretory defect: a case report. Hepatogastroenterology 2007; 54: 1810–1812.
Nagino M, Kamiya J, Nishio H, Ebata T, Arai T, Nimura Y: Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up. Ann Surg 2006; 243: 364–372.
Yokoyama Y, Nishio H, Ebata T, Igami T, Sugawara G, Nagino M: Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer. Br J Surg 2010; 97: 1260–1268.
Hwang S, Ha TY, Song GW, Jung DH, Ahn CS, Moon DB, Kim KH, Lee YJ, Lee SG: Quantified risk assessment for major hepatectomy via the indocyanine green clearance rate and liver volumetry combined with standard liver volume. J Gastrointest Surg 2015; 19: 1305–1314.
Okabe H, Beppu T, Hayashi H, Mima K, Nakagawa S, Kuroki H, Imai K, Nitta H, Masuda T, Hashimoto D, Chikamoto A, Watanabe M, Ishiko T, Yoshida M, Yamashita Y, Baba H: Rank classification based on the combination of indocyanine green retention rate at 15 min and (99m)Tc-DTPA-galactosyl human serum albumin scintigraphy predicts the safety of hepatic resection. Nucl Med Commun 2014; 35: 478–483.
Yoshida M, Beppu T, Shiraishi S, Tsuda N, Sakamoto F, Okabe H, Hayashi H, Baba H, Yamashita Y: (99m)Tc-GSA SPECT/CT fused images for assessment of hepatic function and hepatectomy planning. Ann Transl Med 2015; 3: 17.
Cieslak KP, Bennink RJ, van Gulik TM: Prediction of postoperative liver failure in patients diagnosed with hepatocellular carcinoma using (99m)Tc-GSA SPECT/CT. Hepatobiliary Surg Nutr 2015; 4: 203–205.
Saito S, Yamanaka J, Miura K, Nakao N, Nagao T, Sugimoto T, Hirano T, Kuroda N, Iimuro Y, Fujimoto J: A novel 3D hepatectomy simulation based on liver circulation: application to liver resection and transplantation. Hepatology 2005; 41: 1297–1304.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.