Predicting Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Liver Resection for Solitary Hepatocellular Carcinoma


Background and Purpose

Several hepatectomy patients with HCC who are initially transplantable (within MC) developed untransplantable HCC recurrence (beyond MC) after primary curative liver resection. The purpose of our study is to identify the risk factors of untransplantable hepatocellular carcinoma (HCC) recurrence after primary curative resection of solitary HCC and solitary HCC within Milan criteria (MC).


We retrospectively reviewed 592 patients with recurrent HCC who underwent liver resection due to solitary HCC between 2005 and 2011.


All patients were Child-Pugh class A. At primary curative hepatectomy, 411 patients (69.4%) were diagnosed with HCC within MC and 181 patients (30.6%) had HCC beyond MC. The mean time from primary hepatectomy to recurrence was 14 months (range, 1–116 months). At HCC recurrence, 93 patients (15.7%) were diagnosed beyond MC. Multivariate analysis showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with a high risk of HCC recurrence beyond MC in patients who had hepatectomy for solitary HCC. Of the 411 patients within MC at primary curative hepatectomy, 54 patients (13.9%) developed HCC recurrence beyond MC. Multivariate analysis also showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with HCC recurrence beyond MC in these patients.


The present study suggests that the presence of certain unfavorable histological factors in patients who underwent initial liver resection of transplantable HCC within MC with good liver function predicted the development of recurrent HCC beyond MC.

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Fig. 1
Fig. 2



Milan criteria


Hepatitis B virus


Hepatitis C virus


Non-B non-C


Aspartate transaminase


Alanine transaminase




Protein induced by vitamin K absence or antagonist-II


International normalized ratio


Indocyanine green retention test at 15 min


Hepatocellular carcinoma


Transarterial chemoembolization


Radiofrequency ablation


Percutaneous ethanol injection


Liver transplantation


Liver resection


Portal vein tumor thrombosis


Positron emission tomography


Magnetic resonance imaging


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Author information




Jong Man Kim: study design, literature search, data acquisition, analysis, interpretation and writing.

Jae-Won Joh and Nam Joon Yi: study design and data interpretation.

Kyunga Kim: Data analysis and interpretation.

Gyu-Seong Choi, Kwang-Woong Lee, and Kyung-Suk Suh: acquisition of data and analysis of data.

Corresponding author

Correspondence to Jae-Won Joh.

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Kim, J.M., Joh, JW., Yi, NJ. et al. Predicting Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Liver Resection for Solitary Hepatocellular Carcinoma. J Gastrointest Surg 24, 2219–2227 (2020).

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  • Hepatocellular carcinoma
  • Milan criteria
  • Hepatectomy
  • Tumor recurrence
  • Liver transplantation