不同抗病毒药物降低HBV相关肝细胞癌风险的作用

吴丽贤; 郑伟强; 韩焕钦

doi:10.3969/j.issn.1001-5256.2022.05.040

不同抗病毒药物降低HBV相关肝细胞癌风险的作用

DOI: 10.3969/j.issn.1001-5256.2022.05.040

广东医科大学附属医院感染内科，广东湛江 524001

基金项目:

广东省自然科学基金面上项目 (2021A1515011589);

广东医科大学附属医院临床研究资助项目 (LCYJ2020B001)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：吴丽贤负责收集、分析资料，撰写综述; 郑伟强负责综述内容设计; 韩焕钦负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
郑伟强，zwqgd@sina.com

韩焕钦，huanqinhan@126.com

计量
- 文章访问数: 517
- HTML全文浏览量: 117
- PDF下载量: 76
- 被引次数: 0
出版历程
- 收稿日期: 2021-11-03
- 出版日期: 2022-05-20

Effect of different antiviral drugs in reducing the risk of hepatitis B virus-related hepatocellular carcinoma

Department of Infectious Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China

Research funding:

Guangdong Basic and Applied Basic Research Foundation (2021A1515011589);

Clinical Research Project of Affiliated Hospital of Guangdong Medical University (LCYJ2020B001)

More Information

Corresponding author: ZHENG Weiqiang, zwqgd@sina.com(ORCID: 0000-0002-6979-2283); HAN Huanqin, huanqinhan@126.com(ORCID: 0000-0002-2333-1561)

摘要

摘要: 抗病毒治疗可降低慢性乙型肝炎患者肝细胞癌(HCC)发生的风险。在一线抗病毒药物中，更多的研究显示富马酸替诺福韦酯降低HCC风险的作用可能优于恩替卡韦，尤其在亚裔患者当中; 极有限的研究表明富马酸丙酚替诺福韦酯降HCC风险的作用可能优于富马酸替诺福韦酯; IFN降HCC风险的效果优于单用核苷(酸)类似物。现有可及的药物中，IFN联合核苷(酸)类似物或是HCC高风险患者降低HCC风险的最佳选择。但上述不同药物降HCC风险作用的比较，循证证据级别偏弱，均有赖于随机对照研究进一步阐明。临床实践中，需根据患者实际情形、基础情况，权衡患者HCC发生风险、对药物的耐受性和经济的可承受性，制订个体化的抗病毒策略。
- 乙型肝炎病毒 /
- 癌，肝细胞 /
- 抗病毒药
Abstract: Antiviral therapy can reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. As for the first-line antiviral drugs, more studies have shown that tenofovir disoproxil fumarate may be better than entecavir in reducing the risk of HCC, especially among Asian patients; a limited number of studies have shown that tenofovir alafenamide fumarate may be better than tenofovir disoproxil fumarate in reducing the risk of HCC; interferon has a better effect than nucleos(t)ide analogues alone in reducing the risk of HCC. Among the currently available drugs, interferon combined with nucleos(t)ide analogues may be the best choice to reduce the risk of HCC in patients at a high risk of HCC. The level of evidence-based medicine is weak for comparing the effect of different drugs in reducing the risk of HCC, and randomized controlled trials are needed for further clarification. In practice, it is necessary to weigh the risk of HCC, drug tolerance and economic affordability based on the patient's basic conditions and actual situations, so as to develop individualized anti-viral strategies.
- Hepatitis B virus /
- Carcinoma, Hepatocellular /
- Antiviral Agents

HTML全文

参考文献(39)

[1]	European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021.
[2]	Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001－5256.2019.12.007. 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]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001－5256.2019.12.007.
[3]	TERRAULT NA, LOK A, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4): 1560-1599. DOI: 10.1002/hep.29800.
[4]	SETO WK, LO YR, PAWLOTSKY JM, et al. Chronic hepatitis B virus infection[J]. Lancet, 2018, 392(10161): 2313-2324. DOI: 10.1016/S0140-6736(18)31865-8.
[5]	WANG X, LIU X, DANG Z, et al. Nucleos(t)ide analogues for reducing hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta-analysis[J]. Gut Liver, 2020, 14(2): 232-247. DOI: 10.5009/gnl18546.
[6]	CHOI WM, YIP TC, LIM YS, et al. Methodological challenges of performing meta-analyses to compare the risk of hepatocellular carcinoma between chronic hepatitis B treatments[J]. J Hepatol, 2022, 76(1): 186-194. DOI: 10.1016/j.jhep.2021.09.017.
[7]	LIAW YF, SUNG JJ, CHOW WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease[J]. N Engl J Med, 2004, 351(15): 1521-1531. DOI: 10.1056/NEJMoa033364.
[8]	HOSAKA T, SUZUKI F, KOBAYASHI M, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection[J]. Hepatology, 2013, 58(1): 98-107. DOI: 10.1002/hep.26180.
[9]	BONILLA GUERRERO R, ROBERTS LR. The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma[J]. J Hepatol, 2005, 42(5): 760-777. DOI: 10.1016/j.jhep.2005.02.005.
[10]	PAPATHEODORIDIS GV, IDILMAN R, DALEKOS GN, et al. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B[J]. Hepatology, 2017, 66(5): 1444-1453. DOI: 10.1002/hep.29320.
[11]	KIM WR, LOOMBA R, BERG T, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B[J]. Cancer, 2015, 121(20): 3631-3638. DOI: 10.1002/cncr.29537.
[12]	CHOI J, KIM HJ, LEE J, et al. Risk of hepatocellular carcinoma in patients treated with Entecavir vs Tenofovir for chronic hepatitis B: A Korean Nationwide Cohort Study[J]. JAMA Oncol, 2019, 5(1): 30-36. DOI: 10.1001/jamaoncol.2018.4070.
[13]	ZHANG H, ZENG W. Lower risk of hepatocellular carcinoma with Tenofovir vs Entecavir in patients with chronic hepatitis B[J]. JAMA Oncol, 2019, 5(6): 914-915. DOI: 10.1001/jamaoncol.2019.0641.
[14]	CHOI J, KO MJ, LIM YS. Lower risk of hepatocellular carcinoma with Tenofovir vs Entecavir in patients with chronic hepatitis B-in reply[J]. JAMA Oncol, 2019, 5(6): 916-917. DOI: 10.1001/jamaoncol.2019.0650.
[15]	KIM SU, SEO YS, LEE HA, et al. A multicenter study of entecavir vs. tenofovir on prognosis of treatment-naïve chronic hepatitis B in South Korea[J]. J Hepatol, 2019, 71(3): 456-464. DOI: 10.1016/j.jhep.2019.03.028.
[16]	LEE SW, KWON JH, LEE HL, et al. Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-naïve patients with chronic hepatitis B in Korea: A large-scale, propensity score analysis[J]. Gut, 2020, 69(7): 1301-1308. DOI: 10.1136/gutjnl-2019-318947.
[17]	PAPATHEODORIDIS GV, DALEKOS GN, IDILMAN R, et al. Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B[J]. J Hepatol, 2020, 73(5): 1037-1045. DOI: 10.1016/j.jhep.2020.06.011.
[18]	TSENG CH, HSU YC, CHEN TH, et al. Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2020, 5(12): 1039-1052. DOI: 10.1016/S2468-1253(20)30249-1.
[19]	CHOI WM, CHOI J, LIM YS. Effects of Tenofovir vs Entecavir on risk of hepatocellular carcinoma in patients with chronic HBV infection: A systematic review and meta-analysis[J]. Clin Gastroenterol Hepatol, 2021, 19(2): 246-258. e9. DOI: 10.1016/j.cgh.2020.05.008.
[20]	DAVE S, PARK S, MURAD MH, et al. Comparative effectiveness of Entecavir versus Tenofovir for preventing hepatocellular carcinoma in patients with chronic hepatitis B: A systematic review and meta-analysis[J]. Hepatology, 2021, 73(1): 68-78. DOI: 10.1002/hep.31267.
[21]	GU L, YAO Q, SHEN Z, et al. Comparison of tenofovir versus entecavir on reducing incidence of hepatocellular carcinoma in chronic hepatitis B patients: A systematic review and meta-analysis[J]. J Gastroenterol Hepatol, 2020, 35(9): 1467-1476. DOI: 10.1111/jgh.15036.
[22]	LI M, LV T, WU S, et al. Tenofovir versus entecavir in lowering the risk of hepatocellular carcinoma development in patients with chronic hepatitis B: A critical systematic review and meta-analysis[J]. Hepatol Int, 2020, 14(1): 105-114. DOI: 10.1007/s12072-019-10005-0.
[23]	YIP TC, WONG VW, CHAN HL, et al. Tenofovir is associated with lower risk of hepatocellular carcinoma than Entecavir in patients with chronic HBV infection in China[J]. Gastroenterology, 2020, 158(1): 215-225. e6. DOI: 10.1053/j.gastro.2019.09.025.
[24]	LIU H, SHI Y, HAYDEN JC, et al. Tenofovir treatment has lower risk of hepatocellular carcinoma than Entecavir treatment in patients with chronic hepatitis B: A systematic review and meta-analysis[J]. Liver Cancer, 2020, 9(4): 468-476. DOI: 10.1159/000507253.
[25]	ZHANG Z, ZHOU Y, YANG J, et al. The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: A meta analysis[J]. BMC Cancer, 2019, 19(1): 511. DOI: 10.1186/s12885-019-5735-9.
[26]	VIGANÒ M, LOGLIO A, GROSSI G, et al. Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?[J]. Expert Rev Anti Infect Ther, 2018, 16(2): 153-161. DOI: 10.1080/14787210.2018.1428561.
[27]	CHAN HLY, LIM YS, SETO WK. Impact of treatment with tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) on hepatocellular carcinoma (HCC) incidence in patients with chronic hepatitis B (CHB)[J]. Gut, 2020, 69(Suppl 2): A1-A95. DOI: org/ 10.1136/gutjnl-2020-IDDF.144.
[28]	LEE HW, CHO YY, LEE H, et al. Effect of tenofovir alafenamide vs. tenofovir disoproxil fumarate on hepatocellular carcinoma risk in chronic hepatitis B[J]. J Viral Hepat, 2021, 28(11): 1570-1578. DOI: 10.1111/jvh.13601.
[29]	YIP TC, WONG GL, CHAN HL, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues[J]. J Hepatol, 2019, 70(3): 361-370. DOI: 10.1016/j.jhep.2018.10.014.
[30]	CHAN HL, FUNG S, SETO WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial[J]. Lancet Gastroenterol Hepatol, 2016, 1(3): 185-195. DOI: 10.1016/S2468-1253(16)30024-3.
[31]	REN H, HUANG Y. Effects of pegylated interferon-α based therapies on functional cure and the risk of hepatocellular carcinoma development in patients with chronic hepatitis B[J]. J Viral Hepat, 2019, 26(Suppl 1): 5-31. DOI: 10.1111/jvh.13150.
[32]	Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association. Expert consensus on antiviral therapy for HBV/HCV-related hepatocellular carcinoma: A 2021 update[J]. J Clin Hepatol, 2021, 37(10): 2292-2302. DOI: 10.3969/j.issn.1001-5256.2021.10.008. 中华医学会肝病学分会肝癌学组. HBV/HCV相关肝细胞癌抗病毒治疗专家共识(2021年更新版)[J]. 临床肝胆病杂志, 2021, 37(10): 2292-2302. DOI: 10.3969/j.issn.1001-5256.2021.10.008.
[33]	BRUNETTO MR, BONINO F. Interferon therapy of chronic hepatitis B[J]. Intervirology, 2014, 57(3-4): 163-170. DOI: 10.1159/000360941.
[34]	LEE SK, KWON JH, LEE SW, et al. Sustained off therapy response after peglyated interferon favours functional cure and no disease progression in chronic hepatitis B[J]. Liver Int, 2021, 41(2): 288-294. DOI: 10.1111/liv.14701.
[35]	REN P, CAO Z, MO R, et al. Interferon-based treatment is superior to nucleos(t)ide analog in reducing HBV-related hepatocellular carcinoma for chronic hepatitis B patients at high risk[J]. Expert Opin Biol Ther, 2018, 18(10): 1085-1094. DOI: 10.1080/14712598.2018.1518423.
[36]	YANG S, LIN Q, LIN W, et al. Effect of adjuvant interferon therapy on hepatitis B virus-related hepatocellular carcinoma: A systematic review[J]. World J Surg Oncol, 2016, 14(1): 159. DOI: 10.1186/s12957-016-0912-7.
[37]	LIANG KH, HSU CW, CHANG ML, et al. Peginterferon is superior to nucleos(t)ide analogues for prevention of hepatocellular carcinoma in chronic hepatitis B[J]. J Infect Dis, 2016, 213(6): 966-974. DOI: 10.1093/infdis/jiv547.
[38]	MAO QG, LIANG HQ, YIN YL, et al. Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B[J]. Clin Res Hepatol Gastroenterol, 2021, 46(1): 101758. DOI: 10.1016/j.clinre.2021.101758.
[39]	LI SY, LI H, XIONG YL, et al. Peginterferon is preferable to entecavir for prevention of unfavourable events in patients with HBeAg-positive chronic hepatitis B: A five-year observational cohort study[J]. J Viral Hepat, 2017, 24(Suppl 1): 12-20. DOI: 10.1111/jvh.12755.