乙型肝炎病毒DNA载量与肝癌切除术后肝功能变化关系的研究

doi:10.3969/j.issn.1009-976X.2024.04.001

摘要/Abstract

摘要： 目的探讨术前血清乙型肝炎病毒DNA（HBV-DNA）载量对乙肝相关性肝细胞癌（HBV-HCC）术后肝功能的影响。方法根据术前血清HBV-DNA载量将91例HBV-HCC分为高复制组（A组30例,HBV-DNA载量≥10⁴ IU/mL）、中复制组（B组23例,HBV-DNA载量≥500 IU/mL,且<10⁴IU/mL）和低复制组（C组38例,HBV-DNA载量<500 IU/mL）。比较组间手术时长、出血量、术后肝功能指标、术后住院时间的差异。结果 A组手术时间长于B组和C组（P<0.05）。三组丙氨酸氨基转移酶（ALT）及天冬氨酸氨基转移酶（AST）均在术后第1天达到峰值。术后第1天,ALT、AST值A组>B组>C组（P<0.05）;术后第3天,ALT值A组>B组>C组（P<0.05）;术后第1天,C组凝血酶原时间（PT）时间短于A组和B组（P<0.05）。而三组在术中出血量、术后住院时间、术后白蛋白（ALB）、总胆红素（TBIL）和术后第3天AST的差异比较无统计学意义（P>0.05）。另HBV-DNA载量≥10⁴ IU/mL且抗乙肝病毒时间<10 d者,手术时长、术后第1 d 的ALT和AST高于其他患者（P<0.05）;且出现2例术后肝衰竭,1人因肝衰竭而死亡。结论术前血清HBV-DNA高载量HCC术后肝损伤更严重,术前适当延长抗乙肝病毒时间可能有助于减少术后肝衰竭及死亡的发生。

Abstract: Objective The purpose of this study was to explore the effect of preoperative serum hepatitis B virus DNA（HBV-DNA） load on postoperative liver function in patients with hepatocellular carcinoma （HCC）. Methods Ninety-one patients were divided into high replication group （30 cases in Group A, preoperative serum HBV-DNA load ≥10⁴ IU/ml）, medium replication group（23 cases in Group B, preoperative serum HBV-DNA load ≥500 IU/ml and <10⁴ IU/ml）, and low replication group （38 cases in Group C, preoperative serum HBV-DNA load <500 IU/ml）based on preoperative serum HBV-DNA load. The operating time, intraoperative blood loss, liver function indexes, postoperative hospital stay of patients were analyzed and compared between the three groups. Results The group A demonstrated a longer operating time compared with the group B and Group C（P<0.05）. The vakues of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） of three groups achieved peak on the 1st day after operation. The values of ALT and AST of patients on the 1st day after operation, group A>group B>group C（P<0.05）. The ALT values of patients on the 3rd day after operation, group A>group B>group C（P<0.05）. The prothrombin time （PT） of Group C was significantly shorter than the Group A and group B on the 1st day after operation（P<0.05）. However, there was no significant difference in intraoperative blood loss, postoperative hospital stay, albumin （ALB） and total bilirubin （TBIL） after operation, and the AST on the 3rd day after operation among the groups（P>0.05）. The group A, the group B and the group C were divided into smaller groups according to preoperative antiviral therapy for 10 days. The operating time, the ALT and AST of patients on the 1st day after operation in the group that the preoperative serum HBV-DNA load ≥10⁴ IU/ml and the preoperative antiviral therapy less than 10 days were significantly higher than those in other groups（P<0.05）. There were two patients in the group that the preoperative serum HBV-DNA load ≥10⁴ IU/ml and the preoperative antiviral therapy was less than 10 days experienced postoperative liver failure, of which one died. Conclusion The HCC patients with highly preoperative serum HBV-DNA load who experienced more severely liver injury after operation, and properly prolonging the time of antiviral therapy before operation may help reduce the occurrence of postoperative liver failure and death.

Key words: hepatitis B virus related hepatocellular carcinoma（HBV-HCC）, hepatitis B virus DNA（HBV-DNA）, liver function, resection, complications

中图分类号:

谭勇, 刘晖, 吴黎明, 刘文瑛, 欧阳再兴, 胡竻生, 宋灏, 黄从云, 吴青松. 乙型肝炎病毒DNA载量与肝癌切除术后肝功能变化关系的研究[J]. 岭南现代临床外科, 2024, 24(04): 209-214.

TAN Yong, LIU Hui, WU Li-ming, LIU Wen-ying, OU-YANG Zai-xing, HU Le-sheng, SONG Hao, HUANG Cong-yun, WU Qing-song. The relationship between preoperative serum hepatitis B virus DNA load and postoperative liver function in patients with hepatocellular carcinoma resection[J]. Lingnan Modern Clinics In Surgery, 2024, 24(04): 209-214.

参考文献

[1] Sung H, Ferlay J, Siegel RL, et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Pan R, Zhu M, Yu C, et al.Cancer incidence and mortality: A cohort study in China, 2008-2013[J]. Int J Cancer, 2017, 141(7): 1315-1323.
[3] 国家卫生健康委办公厅. 原发性肝癌诊疗指南(2022年版)[J]. 中华外科杂志, 2022, 60(4): 273-309.
[4] Vogel A, Meyer T, Sapisochin G, et al.Hepatocellular carcinoma[J]. Lancet, 2022, 400(10360): 1345-1362.
[5] 曾勇超, 丁宏达, 邹若媱, 等. 肝切除术后肝功能衰竭危险因素与防治的研究进展[J]. 中华肝胆外科杂志, 2019, 25(9): 711-715.
[6] Reissfelder C, Rahbari NN, Koch M, et al.Postoperative
course and clinical significance of biochemical blood tests following hepatic resection[J]. Br J Surg, 2011, 98(6): 836-844.
[7] Makuuchi M, Thai BL, Takayasu K, et al.Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report[J]. Surgery, 1990, 107(5): 521-527.
[8] Schnitzbauer AA, Lang SA, Goessmann H, et al.Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings[J]. Ann Surg, 2012, 255(3): 405-414.
[9] Peng SY, Wang XA, Huang CY, et al.Evolution of associating liver partition and portal vein ligation for staged hepatectomy: Simpler, safer and equally effective methods[J]. World J Gastroenterol, 2017, 23(23): 4140-4145.
[10] 王铭. 术前抗病毒治疗对大肝癌切除术后肝功能恢复、并发症及近期预后的影响[D]. 广西医科大学, 2021.
[11] Golriz M, Majlesara A, El Sakka S, et al.Small for Size and Flow (SFSF) syndrome: An alternative description for posthepatectomy liver failure[J]. Clin Res Hepatol Gastroenterol, 2016, 40(3): 267-275.
[12] Huang G, Lau WY, Shen F, et al.Preoperative hepatitis B virus DNA level is a risk factor for postoperative liver failure in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma[J]. World J Surg, 2014, 38(9): 2370-2376.
[13] 广东省抗癌协会肝癌专业委员会. 肝癌MDT团队建立和多学科联合治疗的专家共识[J]. 肝癌电子杂志, 2014, 1(3): 4-20.
[14] 杨连粤. 孤立性大肝癌的外科治疗进展[J]. 中华外科杂志, 2020, 58(1): 13-16.
[15] 陈孝平, 张志伟. 大肝癌和巨大肝癌外科治疗策略[J]. 中华普外科手术学杂志(电子版), 2009, 3(4): 702-706.
[16] 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 中华肝脏病杂志, 2019, 27(12): 938-961.
[17] 金烁. 恩替卡韦与乙肝表面抗原阳性合并肝癌切除术对病毒抑制的协同作用[D]. 吉林大学, 2015.
[18] 王鹏, 李又春, 殷飞. 乙肝相关性肝癌患者术前HBV-DNA载量水平与术后肝功能恢复的关系分析[J]. 肝胆外科杂志, 2017, 25(5): 370-373.
[19] 李巨仕, 刘国华, 郑核. 抗病毒治疗对行根治切除术肝癌合并乙肝病毒感染患者的应用价值[J]. 中国普通外科杂志, 2013, 22(7): 880-884.
[20] Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load[J]. Gastroenterology, 2012, 142(5): 1140-1149.e1143; quiz e1113-1144.
[21] Liang YJ, Chiou YW, Chiu AP, et al.Antiviral therapy reduces hepatocellular carcinoma through suppressing hepatitis B virus replication may improve ER stress, mitochondrial and metabolic dysfunctions and decrease p62 in hybridized mice with single HBV transgene and miR-122[J]. J Med Virol, 2023, 95(12): e29325.
[22] 姚豫桐, 安志明, 罗兰云, 等. 乙肝相关性肝癌术前乙型肝炎病毒DNA载量与围手术期并发症的关系[J]. 中国普通外科杂志, 2016, 25(1): 19-24.
[23] Wang M, Qiu N, Lu S, et al.Serum hepatitis B surface antigen is correlated with intrahepatic total HBV DNA and cccDNA in treatment-naive patients with chronic hepatitis B but not in patients with HBV related hepatocellular carcinoma[J]. J Med Virol, 2013, 85(2): 219-227.
[24] Huang L, Li J, Yan J, et al.Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial[J]. J Viral Hepat, 2013, 20(5): 336-342.
[25] Thi Vo T, Poovorawan K, Charoen P, et al.Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis[J]. Asian Pac J Cancer Prev, 2019, 20(8): 2239-2246.