Analysis of risk factors affecting prognoses and microvascular invasion of hepatocellular carcinoma patients with China Liver Cancer Staging<b>-</b>stage Ⅰ a_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Yanfang ^1,2 , XU Liangliang ¹ ,  XU Mingqing ¹

1. Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

XU Mingqing, Email: xumingqing0018@163.com

Keywords：

hepatocelluar carcinoma; China Liver Cancer Staging; radical liver resection; prognosis; microvascular invasion; risk factor

DOI：

10.7507/1007-9424.202306048

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Objective To find out the risk factors affecting the prognoses and microvascular invasion (MVI) of patients with China Liver Cancer Staging-stageⅠ a (CNLC Ⅰ a) hepatocellular carcinoma (HCC). Methods Based on the established inclusion and exclusion criteria, the clinicopathologic information and follow-up data of patients with CNLC Ⅰ a HCC were retrospectively collected, who underwent radical resection in the West China Hospital of Sichuan University from Jan. 2012 to Dec. 2016. The Cox proportional hazards regression was utilized to analyze the risk factors affecting the prognosis of patients with CNLC Ⅰ a HCC, and the non-conditional logistic regression was utilized to analyze the preoperative clinical indicators associating with MVI. Results A total of 300 patients with CNLC Ⅰ a HCC were included in this study, among which 51 (17.0%) cases accompanied with MVI. The follow-up period ranged from 2 to 104 months (median 39 months), with a recurrence time ranging from 2 to 104 months (median 52 months), and an overall survival time ranging from 3 to 104 months (median 98 months). During the follow-up period, postoperative recurrence occurred in 145 (48.3%) cases. The Cox proportional hazards regression analysis revealed that: tumor diameter >3 cm, presences of MVI and satellite nodules increased the risk of shortened recurrence time for the patients with CNLC Ⅰ a HCC (P<0.05); Factors including gamma-glutamyltranspeptidase level >60 U/L, tumor low differentiation, presences of MVI and satellite nodules were associated with shortened overall survival time for the patients with CNLC Ⅰ a HCC (P<0.05). The preoperative alpha-fetoprotein level ≥400 μg/L and tumor diameter >3 cm increased the risk of presence of MVI for the patients with CNLC Ⅰ a HCC [χ²=3.059, OR(95%CI)=2.357(1.047, 5.306), P=0.038; χ²=3.002, OR(95%CI)=2.301(1.026, 5.162), P=0.043]. Conclusion The results of this study suggest that adopting corresponding strategies to address the risk factors affecting prognosis of patients with CNLC Ⅰ a HCC and the risk factors associated with MVI can have a significant clinical impact on improving surgical treatment outcomes for these patients.

Citation： ZHANG Yanfang, XU Liangliang, XU Mingqing. Analysis of risk factors affecting prognoses and microvascular invasion of hepatocellular carcinoma patients with China Liver Cancer Staging-stage Ⅰ a. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(12): 1439-1443. doi: 10.7507/1007-9424.202306048 Copy

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2.	El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology, 2012, 142(6): 1264-1273.
3.	Liu J, Fan D. Hepatitis B in China. Lancet, 2007, 369(9573): 1582-1583.
4.	国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版). 中华普通外科学文献(电子版), 2022, 16(2): 81-96.
5.	Feng K, Yan J, Li X, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol, 2012, 57(4): 794-802.
6.	陈哲宇. 肝细胞癌射频消融的利和弊. 中国普外基础与临床杂志, 2022, 29(9): 1139-1142.
7.	Kulik L, Heimbach JK, Zaiem F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: a systematic review and meta-analysis. Hepatology, 2018, 67(1): 381-400.
8.	Jiang HT, Cao JY. Impact of laparoscopic versus open hepatectomy on perioperative clinical outcomes of patients with primary hepatic carcinoma. Chin Med Sci J, 2015, 30(2): 80-83.
9.	Yao LQ, Chen ZL, Feng ZH, et al. Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: a multi-institutional analysis. Ann Surg Oncol, 2022 Feb 22. doi: 10.1245/s10434-022-11454-y.
10.	Wang CC, Iyer SG, Low JK, et al. Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol, 2009, 16(7): 1832-1842.
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12.	Rodríguez-Perálvarez M, Luong TV, Andreana L, et al. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol, 2013, 20(1): 325-339.
13.	Lei Z, Li J, Wu D, et al. Nomogram for preoperative estimation of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma within the Milan criteria. JAMA Surg, 2016, 151(4): 356-363.
14.	Feng LH, Dong H, Lau WY, et al. Novel microvascular invasion-based prognostic nomograms to predict survival outcomes in patients after R0 resection for hepatocellular carcinoma. J Cancer Res Clin Oncol, 2017, 143(2): 293-303.
15.	Fu YP, Yi Y, Huang JL, et al. Prognostic nomograms stratify survival of patients with hepatocellular carcinoma without portal vein tumor thrombosis after curative resection. Oncologist, 2017, 22(5): 561-569.
16.	Nathan H, Schulick RD, Choti MA, et al. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg, 2009, 249(5): 799-805.
17.	Poon RT, Ng IO, Fan ST, et al. Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol, 2001, 19(12): 3037-3044.
18.	Jung KS, Kim SU, Choi GH, et al. Prediction of recurrence after curative resection of hepatocellular carcinoma using liver stiffness measurement (FibroScan®). Ann Surg Oncol, 2012, 19(13): 4278-4286.
19.	Sun JJ, Wang K, Zhang CZ, et al. Postoperative adjuvant transcatheter arterial chemoembolization after R0 hepatectomy improves outcomes of patients who have hepatocellular carcinoma with microvascular invasion. Ann Surg Oncol, 2016, 23(4): 1344-1351.
20.	Shen XH, Li HK, Wang F, et al. Clinical significance of lymph node metastasis in patients undergoing partial hepatectomy for hepatocellular carcinoma. World J Surg, 2010, 34(5): 1028-1033.
21.	Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci, 2001, 38(4): 263-355.
22.	Ju MJ, Qiu SJ, Fan J, et al. Preoperative serum gamma-glutamyl transferase to alanine aminotransferase ratio is a convenient prognostic marker for Child-Pugh A hepatocellular carcinoma after operation. J Gastroenterol, 2009, 44(6): 635-642.
23.	Sasaki K, Matsuda M, Ohkura Y, et al. In hepatocellular carcinomas, any proportion of poorly differentiated components is associated with poor prognosis after hepatectomy. World J Surg, 2014, 38(5): 1147-1153.
24.	Shen J, Liu J, Li C, et al. The impact of tumor differentiation on the prognosis of HBV-associated solitary hepatocellular carcinoma following hepatectomy: a propensity score matching analysis. Dig Dis Sci, 2018, 63(7): 1962-1969.
25.	He LY, Xia ZJ, Zhang XY, 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.
26.	Li L, Li B, Zhang M. HBV DNA levels impact the prognosis of hepatocellular carcinoma patients with microvascular invasion. Medicine (Baltimore), 2019, 98(27): e16308.

1. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6.
2. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology, 2012, 142(6): 1264-1273.
3. Liu J, Fan D. Hepatitis B in China. Lancet, 2007, 369(9573): 1582-1583.
4. 国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版). 中华普通外科学文献(电子版), 2022, 16(2): 81-96.
5. Feng K, Yan J, Li X, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol, 2012, 57(4): 794-802.
6. 陈哲宇. 肝细胞癌射频消融的利和弊. 中国普外基础与临床杂志, 2022, 29(9): 1139-1142.
7. Kulik L, Heimbach JK, Zaiem F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: a systematic review and meta-analysis. Hepatology, 2018, 67(1): 381-400.
8. Jiang HT, Cao JY. Impact of laparoscopic versus open hepatectomy on perioperative clinical outcomes of patients with primary hepatic carcinoma. Chin Med Sci J, 2015, 30(2): 80-83.
9. Yao LQ, Chen ZL, Feng ZH, et al. Clinical features of recurrence after hepatic resection for early-stage hepatocellular carcinoma and long-term survival outcomes of patients with recurrence: a multi-institutional analysis. Ann Surg Oncol, 2022 Feb 22. doi: 10.1245/s10434-022-11454-y.
10. Wang CC, Iyer SG, Low JK, et al. Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol, 2009, 16(7): 1832-1842.
11. Fan ST, Poon RT, Yeung C, et al. Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria. Br J Surg, 2011, 98(9): 1292-1300.
12. Rodríguez-Perálvarez M, Luong TV, Andreana L, et al. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol, 2013, 20(1): 325-339.
13. Lei Z, Li J, Wu D, et al. Nomogram for preoperative estimation of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma within the Milan criteria. JAMA Surg, 2016, 151(4): 356-363.
14. Feng LH, Dong H, Lau WY, et al. Novel microvascular invasion-based prognostic nomograms to predict survival outcomes in patients after R0 resection for hepatocellular carcinoma. J Cancer Res Clin Oncol, 2017, 143(2): 293-303.
15. Fu YP, Yi Y, Huang JL, et al. Prognostic nomograms stratify survival of patients with hepatocellular carcinoma without portal vein tumor thrombosis after curative resection. Oncologist, 2017, 22(5): 561-569.
16. Nathan H, Schulick RD, Choti MA, et al. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg, 2009, 249(5): 799-805.
17. Poon RT, Ng IO, Fan ST, et al. Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol, 2001, 19(12): 3037-3044.
18. Jung KS, Kim SU, Choi GH, et al. Prediction of recurrence after curative resection of hepatocellular carcinoma using liver stiffness measurement (FibroScan®). Ann Surg Oncol, 2012, 19(13): 4278-4286.
19. Sun JJ, Wang K, Zhang CZ, et al. Postoperative adjuvant transcatheter arterial chemoembolization after R0 hepatectomy improves outcomes of patients who have hepatocellular carcinoma with microvascular invasion. Ann Surg Oncol, 2016, 23(4): 1344-1351.
20. Shen XH, Li HK, Wang F, et al. Clinical significance of lymph node metastasis in patients undergoing partial hepatectomy for hepatocellular carcinoma. World J Surg, 2010, 34(5): 1028-1033.
21. Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci, 2001, 38(4): 263-355.
22. Ju MJ, Qiu SJ, Fan J, et al. Preoperative serum gamma-glutamyl transferase to alanine aminotransferase ratio is a convenient prognostic marker for Child-Pugh A hepatocellular carcinoma after operation. J Gastroenterol, 2009, 44(6): 635-642.
23. Sasaki K, Matsuda M, Ohkura Y, et al. In hepatocellular carcinomas, any proportion of poorly differentiated components is associated with poor prognosis after hepatectomy. World J Surg, 2014, 38(5): 1147-1153.
24. Shen J, Liu J, Li C, et al. The impact of tumor differentiation on the prognosis of HBV-associated solitary hepatocellular carcinoma following hepatectomy: a propensity score matching analysis. Dig Dis Sci, 2018, 63(7): 1962-1969.
25. He LY, Xia ZJ, Zhang XY, 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.
26. Li L, Li B, Zhang M. HBV DNA levels impact the prognosis of hepatocellular carcinoma patients with microvascular invasion. Medicine (Baltimore), 2019, 98(27): e16308.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of risk factors affecting prognoses and microvascular invasion of hepatocellular carcinoma patients with China Liver Cancer Staging-stage Ⅰ a

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