Journal of Gastrointestinal Surgery

, Volume 18, Issue 4, pp 729–736 | Cite as

Assessment of ISGLS Definition of Posthepatectomy Liver Failure and Its Effect on Outcome in Patients with Hepatocellular Carcinoma

  • Kenji Fukushima
  • Takumi Fukumoto
  • Kaori Kuramitsu
  • Masahiro Kido
  • Atsushi Takebe
  • Motofumi Tanaka
  • Tomoo Itoh
  • Yonson Ku
Original Article



Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients.


We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months.


Thirty-nine (18.6 %) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8 %, respectively (P = 0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3 %, respectively (P = 0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P = 0.047) and RFS (P = 0.019). Extent of resection (P < 0.001), intraoperative blood loss (P = 0.002), and fibrosis stage (P = 0.040) were identified as independent risk factors for developing PHLF.


The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF.


International Study Group of Liver Surgery Posthepatecomy liver failure Hepatocellular carcinoma Hepatectomy Survival 



All authors listed on this manuscript have no financial disclosure.


  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    de Lope CR, Tremosini S, Forner A, Reig M, Bruix J. Management of HCC. J Hepatol 2012; 56: S75-87.PubMedCrossRefGoogle Scholar
  3. 3.
    Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008; 134: 1908–1916.PubMedCrossRefGoogle Scholar
  4. 4.
    Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 2001; 234: 63–70.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Taketomi A, Kitagawa D, Itoh S, Harimoto N, Yamashita Y, Gion T, et al. Trends in morbidity and mortality after hepatic resection for hepatocellular carcinoma: an institute’s experience with 625 patients. J Am Coll Surg 2007; 204: 580–587.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Kawano Y, Sasaki A, Kai S, Endo Y, Iwaki K, Uchida H, et al. Short- and long-term outcomes after hepatic resection for hepatocellular carcinoma with concomitant esophageal varices in patients with cirrhosis. Ann Surg Oncol 2008; 15: 1670–1676.PubMedCrossRefGoogle Scholar
  9. 9.
    Kusano T, Sasaki A, Kai S, Endo Y, Iwaki K, Shibata K, et al. Predictors and prognostic significance of operative complications in patients with hepatocellular carcinoma who underwent hepatic resection. Eur J Surg Oncol 2009; 35: 1179–1185.PubMedCrossRefGoogle Scholar
  10. 10.
    Mizuguchi T, Nagayama M, Meguro M, Shibata T, Kaji S, Nobuoka T, et al. Prognostic impact of surgical complications and preoperative serum hepatocyte growth factor in hepatocellular carcinoma patients after initial hepatectomy. J Gastrointest Surg 2009; 13: 325–333.PubMedCrossRefGoogle Scholar
  11. 11.
    Okamura Y, Takeda S, Fujii T, Sugimoto H, Nomoto S, Nakao A. Prognostic significance of postoperative complications after hepatectomy for hepatocellular carcinoma. J Surg Oncol 2011; 104: 814–821.PubMedCrossRefGoogle Scholar
  12. 12.
    Yang T, Zhang J, Lu JH, Yang GS, Wu MC, Yu WF. Risk factors influencing postoperative outcomes of major hepatic resection of hepatocellular carcinoma for patients with underlying liver diseases. World J Surg 2011; 35: 2073–2082.PubMedCrossRefGoogle Scholar
  13. 13.
    Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 2011; 149: 713–724.PubMedCrossRefGoogle Scholar
  14. 14.
    Reissfelder C, Rahbari NN, Koch M, Kofler B, Sutedja N, Elbers H, et al. Postoperative course and clinical significance of biochemical blood tests following hepatic resection. Br J Surg 2011; 98: 836–844.PubMedCrossRefGoogle Scholar
  15. 15.
    Ku Y, Iwasaki T, Tominaga M, Fukumoto T, Takahashi T, Kido M, et al. Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma. Ann Surg 2004; 239: 53–60.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Ku Y. Isolated hepatic perfusion for extensive liver cancers. In: Blumgart LH, ed. Surgery of the liver, biliary tract, and pancreas, 4th ed. Philadelphia: Saunders, 2007; pp 1312–20.CrossRefGoogle Scholar
  17. 17.
    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649–655.PubMedCrossRefGoogle Scholar
  18. 18.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208–1236.PubMedCrossRefGoogle Scholar
  19. 19.
    Bezerra AS, D'Ippolito G, Faintuch S, Szejnfeld J, Ahmed M. Determination of splenomegaly by CT: is there a place for a single measurement? AJR Am J Roentgenol 2005; 184: 1510–1513.PubMedCrossRefGoogle Scholar
  20. 20.
    Sobin LH, Gospodarowicz MK, Wittekind C, eds. Internatinal Union Against Cancer (UICC): TNM classification of malignant tumours, 7th ed. New York: Wiley-Blackwell, 2010.Google Scholar
  21. 21.
    Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24: 289–293.PubMedCrossRefGoogle Scholar
  22. 22.
    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–213.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Tilg H, Kaser A, Moschen AR. How to modulate inflammatory cytokines in liver diseases. Liver Int 2006; 26: 1029–1039.PubMedCrossRefGoogle Scholar
  24. 24.
    Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997; 276: 60–66.PubMedCrossRefGoogle Scholar
  25. 25.
    Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010; 29: 4989–5005.PubMedCrossRefGoogle Scholar
  26. 26.
    Chau GY, Lui WY, Chi CW, Chau YP, Li AF, Kao HL, et al. Significance of serum hepatocyte growth factor levels in patients with hepatocellular carcinoma undergoing hepatic resection. Eur J Surg Oncol 2008; 34: 333–338.PubMedCrossRefGoogle Scholar
  27. 27.
    Schreckenbach T, Liese J, Bechstein WO, Moench C. Posthepatectomy liver failure. Dig Surg 2012; 29: 79–85.PubMedCrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2013

Authors and Affiliations

  • Kenji Fukushima
    • 1
  • Takumi Fukumoto
    • 1
  • Kaori Kuramitsu
    • 1
  • Masahiro Kido
    • 1
  • Atsushi Takebe
    • 1
  • Motofumi Tanaka
    • 1
  • Tomoo Itoh
    • 2
  • Yonson Ku
    • 1
  1. 1.Division of Hepato-Biliary-Pancreatic Surgery, Department of SurgeryKobe University Graduate School of MedicineKobeJapan
  2. 2.Division of Diagnostic Pathology, Department of PathologyKobe University Graduate School of MedicineKobeJapan

Personalised recommendations