Risk factors for early recurrence after hepatocellular carcinoma hepatectomy and its treatment_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Yuhang ¹ , LU Xuemei ¹ , CONG Yun ¹ , LI Zonglin ¹ ,  SHAO Yingmei ^1,2

1. Department of Hepatobiliary Hydatid Disease Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P. R. China;
2. State Key Laboratory of Central Asian High-Prevalence Disease Etiology and Prevention, Xinjiang Medical University, Urumqi 830054, P. R. China;

Corresponding?author：

SHAO Yingmei, Email: syingmei1@163.com

Keywords：

hepatocellular carcinoma; hepatectomy; early recurrence; risk factor; treatment

DOI：

10.7507/1007-9424.202506142

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective This study aims to summarize the risk factors and therapeutic strategies for early recurrence after hepatocellular carcinoma (HCC) resection, so as to provide a reference for the prediction of postoperative early recurrence and the treatment of recurrent HCC. Methods The article gives a summary of the risk factors for early recurrence and treatment after hepatectomy for HCC by searching for relevant studies at home and abroad in recent years. Results HCC is a common and highly fatal malignant tumor worldwide. Surgical resection remains the preferred treatment method, but the early recurrence rate (recurrence within 2 years after surgery) is as high as 40%-50%, which seriously affects the prognosis of patients. The risk factors for early recurrence of HCC include patient factors (gender, marital status, liver status, inflammatory indicators, nutritional status, etc.), tumor factors (tumor markers, diameter, number, degree of differentiation, margin and capsule, microvascular invasion, satellite nodules, etc.) and surgical factors (whether anatomical resection or not, resection margin, perioperative blood transfusion, etc.); treatment methods include reoperation (laparoscopic, open), salvage liver transplantation, radiofrequency ablation, interventional therapy (transarterial chemoembolization, transhepatic arterial infusion chemotherapy, transarterial radioembolization) and systemic therapy (targeted immunotherapy, antiviral therapy and traditional Chinese medicine therapy). Conclusion Early recurrence after HCC hepatectomy severely compromises the long-term survival of patients. Going forward, efforts should be devoted to developing accurate prediction models for postoperative early recurrence, further clarifying the optimal therapeutic regimens for recurrent HCC under different clinical scenarios, and providing evidence for individualized treatment to improve the overall prognosis of patients.

Citation： YANG Yuhang, LU Xuemei, CONG Yun, LI Zonglin, SHAO Yingmei. Risk factors for early recurrence after hepatocellular carcinoma hepatectomy and its treatment. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(1): 119-126. doi: 10.7507/1007-9424.202506142 Copy

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12.	Luo H, Li C, Chen L. Preoperative albumin-bilirubin grade combined with aspartate aminotransferase-to-platelet count ratio index predict outcomes of patients with hepatocellular carcinoma within Milan criteria after liver resection. Biosci Trends, 2019, 13(2): 176-181.
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15.	Minici R, Siciliano MA, Ammendola M, et al. Prognostic role of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-C reactive protein ratio (LCR) in patients with hepatocellular carcinoma (HCC) undergoing chemoembolizations (TACE) of the liver: the unexplored corner linking tumor microenvironment, biomarkers and interventional radiology. Cancers (Basel), 2022, 15(1): 257. doi: 10.3390/cancers15010257.
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17.	Qu Z, Lu YJ, Feng JW, et al. Preoperative prognostic nutritional index and neutrophil-to-lymphocyte ratio predict survival outcomes of patients with hepatocellular carcinoma after curative resection. Front Oncol, 2022, 11: 823054. doi: 10.3389/fonc.2021.823054.
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32.	Kwon JH, Lee JW, Lee JW, et al. Effects of anatomical or non-anatomical resection of hepatocellular carcinoma on survival outcome. J Clin Med, 2022, 11(5): 1369. doi: 10.3390/jcm11051369.
33.	Wong KC, Lee KF, Lo EYJ, et al. Minimally invasive versus open liver resection for hepatocellular carcinoma: a propensity score matching analysis of 224 patients. Langenbecks Arch Surg, 2023, 408(1): 118. doi: 10.1007/s00423-023-02857-w.
34.	Tsilimigras DI, Sahara K, Moris D, et al. Effect of surgical margin width on patterns of recurrence among patients undergoing R0 hepatectomy for T1 hepatocellular carcinoma: an international multi-institutional analysis. J Gastrointest Surg, 2020, 24(7): 1552-1560.
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1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. Sagnelli E, Macera M, Russo A, et al. Epidemiological and etiological variations in hepatocellular carcinoma. Infection, 2020, 48(1): 7-17.
3. Nevola R, Ruocco R, Criscuolo L, et al. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol, 2023, 29(8): 1243-1260.
4. Yan WT, Li C, Yao LQ, et al. Predictors and long-term prognosis of early and late recurrence for patients undergoing hepatic resection of hepatocellular carcinoma: a large-scale multicenter study. Hepatobiliary Surg Nutr, 2023, 12(2): 155-168.
5. Wang R, Liu Y, Sun H, et al. Estradiol is significantly associated with prognosis in non-surgical liver cancer patients: from bench to bedside. Aging (Albany NY), 2021, 13(3): 3483-3500.
6. Chen F, Wu Y, Xu H, et al. Impact of marital status on overall survival in patients with early-stage hepatocellular carcinoma. Sci Rep, 2022, 12(1): 19923. doi: 10.1038/s41598-022-14120-1.
7. Chen X, Zhang M, Li N, et al. Nucleotide variants in hepatitis B virus preS region predict the recurrence of hepatocellular carcinoma. Aging (Albany NY), 2021, 13(18): 22256-22275.
8. Wang X, Zhao Y, Bai T, et al. Serum immune biomarker levels combined with hepatitis B virus infection status predict early recurrence of early-stage hepatocellular carcinoma with microvascular invasion after liver resection. Acta Chir Belg, 2023, 123(6): 659-665.
9. Linye H, Zijing X, Xiaoyun Z, et al. Tenofovir versus entecavir on the prognosis of hepatitis B-related hepatocellular carcinoma after surgical resection: a randomised controlled trial. Int J Surg, 2023, 109(10): 3032-3041.
10. Yin G, Zhang N, BuHe A, et al. Risk factors of secondary infection/recurrence after ablation for liver cancers: a systemic review and meta-analysis. J Cancer Res Ther, 2022, 18(5): 1352-1359.
11. Hu K, Yuan J, Tang B, et al. Albumin-bilirubin index and platelet-albumin-bilirubin index contribute to identifying survival benefit candidates in patients with hepatocellular carcinoma and Child-Pugh grade A undergoing transcatheter arterial chemoembolization with sorafenib treatment. Ann Transl Med, 2021, 9(3): 237. doi: 10.21037/atm-20-3118.
12. Luo H, Li C, Chen L. Preoperative albumin-bilirubin grade combined with aspartate aminotransferase-to-platelet count ratio index predict outcomes of patients with hepatocellular carcinoma within Milan criteria after liver resection. Biosci Trends, 2019, 13(2): 176-181.
13. Yun SO, Kim JM, Rhu J, et al. Fibrosis-4 index, a predictor for prognosis of hepatocellular carcinoma patients after curative hepatectomy even in hepatitis B virus dominant populations. Ann Surg Treat Res, 2023, 104(4): 195-204.
14. Bae BK, Park HC, Yoo GS, et al. The significance of systemic inflammation markers in intrahepatic recurrence of early-stage hepatocellular carcinoma after curative treatment. Cancers (Basel), 2022, 14(9): 2081. doi: 10.3390/cancers14092081.
15. Minici R, Siciliano MA, Ammendola M, et al. Prognostic role of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-C reactive protein ratio (LCR) in patients with hepatocellular carcinoma (HCC) undergoing chemoembolizations (TACE) of the liver: the unexplored corner linking tumor microenvironment, biomarkers and interventional radiology. Cancers (Basel), 2022, 15(1): 257. doi: 10.3390/cancers15010257.
16. Xu C, Wu F, Du L, et al. Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis. Front Immunol, 2023, 14: 1211399. doi: 10.3389/fimmu.2023.1211399.
17. Qu Z, Lu YJ, Feng JW, et al. Preoperative prognostic nutritional index and neutrophil-to-lymphocyte ratio predict survival outcomes of patients with hepatocellular carcinoma after curative resection. Front Oncol, 2022, 11: 823054. doi: 10.3389/fonc.2021.823054.
18. Hayashi H, Shimizu A, Kubota K, et al. Combination of sarcopenia and prognostic nutritional index to predict long-term outcomes in patients undergoing initial hepatectomy for hepatocellular carcinoma. Asian J Surg, 2023, 46(2): 816-823.
19. Zhang H, Li H, Lan X, et al. Diabetes mellitus affects long-term survival in hepatitis B virus-related hepatocellular carcinoma patients: a propensity score-matched analysis. Medicine (Baltimore), 2021, 100(4): e24354. doi: 10.1097/MD.0000000000024354.
20. Kobayashi A, Kaido T, Hamaguchi Y, et al. Impact of sarcopenic obesity on outcomes in patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg, 2019, 269(5): 924-931.
21. Li WF, Yen YH, Liu YW, et al. Preoperative predictors of early recurrence after resection for hepatocellular carcinoma. Am J Surg, 2022, 223(5): 945-950.
22. Wang MD, Sun LY, Qian GJ, et al. Prothrombin induced by vitamin K Absence-Ⅱ versus alpha-fetoprotein in detection of both resectable hepatocellular carcinoma and early recurrence after curative liver resection: a retrospective cohort study. Int J Surg, 2022, 105: 106843. doi: 10.1016/j.ijsu.2022.106843.
23. Norman JS, Li PJ, Kotwani P, et al. Enhancing the prognostic accuracy of the RETREAT score with AFP-L3 and DCP tumor markers. Liver Transpl, 2025, 31(6): 727-736.
24. Zhu Y, Gu L, Chen T, et al. Factors influencing early recurrence of hepatocellular carcinoma after curative resection. J Int Med Res, 2020, 48(8): 300060520945552. doi: 10.1177/0300060520945552.
25. Zeng J, Zeng J, Lin K, et al. Development of a machine learning model to predict early recurrence for hepatocellular carcinoma after curative resection. Hepatobiliary Surg Nutr, 2022, 11(2): 176-187.
26. Xia W, Peng T, Guan R, et al. Development of a novel prognostic nomogram for the early recurrence of liver cancer after curative hepatectomy. Ann Transl Med, 2021, 9(20): 1541. doi: 10.21037/atm-21-4837.
27. Wu Y, Ye Z, Yang T, et al. Preoperative prediction of early recurrence in hepatocellular carcinoma using simultaneous multislice diffusion kurtosis imaging. Eur Radiol, 2025, 35(11): 7398-7409.
28. Fuster-Anglada C, Mauro E, Ferrer-Fàbrega J, et al. Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection. J Hepatol, 2024, 81(6): 995-1004.
29. 王愷悌, 巴登才仁·安蕊, 叢赟, 等. 肝細胞癌微血管侵犯術后早期復發的研究進展. 中國普外基礎與臨床雜志, 2024, 31(11): 1399-1405.
30. Xu XF, Diao YK, Zeng YY, et al. Association of severity in the grading of microvascular invasion with long-term oncological prognosis after liver resection for early-stage hepatocellular carcinoma: a multicenter retrospective cohort study from a hepatitis B virus-endemic area. Int J Surg, 2023, 109(4): 841-849.
31. Zhang J, Wang Z, Wu Q, et al. Nomogram for predicting early recurrence of hepatocellular carcinoma with narrow resection margin. Sci Rep, 2024, 14(1): 28103. doi: 10.1038/s41598-024-79760-x.
32. Kwon JH, Lee JW, Lee JW, et al. Effects of anatomical or non-anatomical resection of hepatocellular carcinoma on survival outcome. J Clin Med, 2022, 11(5): 1369. doi: 10.3390/jcm11051369.
33. Wong KC, Lee KF, Lo EYJ, et al. Minimally invasive versus open liver resection for hepatocellular carcinoma: a propensity score matching analysis of 224 patients. Langenbecks Arch Surg, 2023, 408(1): 118. doi: 10.1007/s00423-023-02857-w.
34. Tsilimigras DI, Sahara K, Moris D, et al. Effect of surgical margin width on patterns of recurrence among patients undergoing R0 hepatectomy for T1 hepatocellular carcinoma: an international multi-institutional analysis. J Gastrointest Surg, 2020, 24(7): 1552-1560.
35. Park MS, Cho JY, Kim E, et al. Surgical treatment of hepatocellular carcinoma: an expert consensus-based practical recommendation from the Korean Liver Cancer Association. Ann Surg Treat Res, 2025, 109(3): 123-143.
36. Tai YH, Wu HL, Mandell MS, et al. The association of allogeneic blood transfusion and the recurrence of hepatic cancer after surgical resection. Anaesthesia, 2020, 75(4): 464-471.
37. Lin N, Li J, Ke Q, et al. Does the intermittent Pringle maneuver affect the recurrence following surgical resection for hepatocellular carcinoma? A systematic review. PLoS One, 2020, 15(3): e0229870.
38. Hu L, Wang A, Qiao Y, et al. Effect of intermittent pringle maneuver on perioperative outcomes and long-term survival following liver resection in patients with hepatocellular carcinoma: a meta-analysis and systemic review. World J Surg Oncol, 2023, 21(1): 359. doi: 10.1186/s12957-023-03244-x.
39. 王青青, 謝琴芬, 鄭樹森. 肝細胞癌根治性切除術后復發的預測因素. 中華腫瘤防治雜志, 2025, 32(14): 876-884.
40. 國家科技部傳染病防治重大專項課題《病毒性肝炎相關肝癌外科綜合治療的個體化和新策略研究》專家組. 肝細胞癌肝切除術后復發預防和治療中國專家共識 (2020版). 中國實用外科雜志, 2021, 41(1): 20-30.
41. Nomi T, Kaibori M, Tanaka S, et al. Short- and long-term outcomes of laparoscopic versus open repeat liver resection for hepatocellular carcinoma: a multicenter study. J Hepatobiliary Pancreat Sci, 2023, 30(3): 283-292.
42. Majno PE, Sarasin FP, Mentha G, et al. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis. Hepatology, 2000, 31(4): 899-906.
43. Guerrini GP, Esposito G, Olivieri T, et al. Salvage versus primary liver transplantation for hepatocellular carcinoma: a twenty-year experience meta-analysis. Cancers (Basel), 2022, 14(14): 3465. doi: 10.3390/cancers14143465.
44. Zhu X, Li X. A commentary on “comparison on the efficacy and prognosis of different strategies for intrahepatic recurrent hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis” (Int J Surg 2020; 83: 196-204). Int J Surg, 2021, 90: 105963. doi: 10.1016/j.ijsu.2021.105963.
45. Chen Z, Wang J, Lin Y. Comparison of the efficacy and safety of repeated hepatectomy and radiofrequency ablation in the treatment of primary recurrent liver cancer: a meta-analysis. World J Surg Oncol, 2022, 20(1): 182. doi: 10.1186/s12957-022-02649-4.
46. Feng Y, Wu H, Huang DQ, et al. Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤5 cm) after initial curative resection. Eur Radiol, 2020, 30(11): 6357-6368.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Risk factors for early recurrence after hepatocellular carcinoma hepatectomy and its treatment

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