丙型肝炎相关肝细胞癌的临床特征和预后

摘要/Abstract

摘要： 目的分析丙型肝炎(HCV)相关肝细胞癌(HCC)的临床特征及抗病毒治疗对HCC预后的影响。方法回顾性分析2011年1月至2020年12月在上海交通大学医学院附属瑞金医院住院的115例HCV相关HCC患者的临床资料,按抗病毒治疗情况分未治疗组(UCHC)、治疗失败(TF)组及持续病毒学应答(SVR)组,比较三组的临床特点及直接抗病毒药物(direct antiviral agent,DAA)对预后的影响。结果本组115例患者中,男72例(62.6%),女43例(37.4%);年龄36～84(62.6±7.1)岁。传播途径主要为输血或相关血制品占57.4%,其次吸毒占11.3%。基因型1型59.1%,基因2型14.8%,基因3型14.8%,基因6型5.2%,未测出6.1%。三组在发生HCC时的年龄、性别、输血史、基因1型、WBC计数、Hb、TBil水平差异均无统计学意义(P>0.05)。SVR组患者的肝硬化失代偿比例、HBsAg阴性、抗HBc-IgG阳性患者比例、ALT、AST、AFP水平低于TF组和UCHC组,差异均有统计学意义(P<0.05)。而SVR组的PLT、Alb、eGFR水平高于TF组和UCHC组,差异均有统计学意义(P<0.05)。SVR组门静脉癌栓的发生率为18.9%,明显低于TF组(36.4%)和UCHC组(30.4%),差异有统计学意义(P<0.01)。随访2年,SVR组患者疾病进展为10.3%,明显低于TF组(54.5%)和UCHC(43.5%),差异有统计学意义(P<0.001)。进一步分析TF组和UCHC组肿瘤治疗9个月内完成DAA治疗的患者疾病进展分别为42.9%和20.0%,明显低于未使用DAA患者的75.0%和61.5%,差异均有统计学意义(P<0.01)。SVR组患者2年内死亡率为6.9%,低于TF组(36.4%)和UCHC组(17.4%),差异有统计学意义(P<0.05)。结论本研究为HCV相关HCC采取广泛、有效的DAA抗病毒治疗,以提高对HCC治疗效果、降低HCC的转移及恶化提供了依据。

关键词: 慢性丙型肝炎, 肝细胞癌, 直接抗病毒药物, 持续病毒学应答, 预后

Abstract: Objective To investigate the clinical characteristics of hepatitis C (HCV) associated hepatocellular carcinoma (HCC) and the effect of antiviral therapy on the prognosis of HCC.Methods The clinical data of 115 patients with HCV-related HCC hospitalized in our hospital from January 2011 to December 2020 were retrospectively analyzed. The patients were divided into untreated group (UCHC), treatment failure group (TF) and sustained virologic response group (SVR) according to antiviral treatment. The clinical characteristics and the effect of direct antiviral agent (DAA) on prognosis of the 3 groups were compared.Results Among 115 patients, 72 (62.6%) were male and 43 (37.4%) were female. The age ranged from 36 to 84 years old (62.6±7.1). The main route of transmission was blood transfusion or related blood products (57.4%), followed by drug use (11.3%). Genotype 1 59.1%, genotype 2 14.8%, genotype 3 14.8%, genotype 6 5.2%, 6.1% undetected. There was no significant difference in age, gender, blood transfusion history, genotype 1, white blood cell (WBC) count, hemoglobin (Hb) and total bilirubin (TBil) levels among the 3 groups at the time of HCC (P > 0.05). The proportion of cirrhosis decompensation, proportion of HBsAg negative and anti-HBc-IgG positive patients, alanine transaminase (ALT), aspartate transaminase (AST) and alpha fetoprotein (AFP) levels in SVR group were lower than those in TF group and UCHC group, with statistical significance (P<0.05). The levels of platelet (PLT), albumin (Alb) and epidermal growth factor receptor (eGFR) in SVR group were higher than those in TF group and UCHC group, with statistical significance (P<0.05). The incidence of portal vein cancer thrombus was 18.9% in SVR group, which was significantly lower than 36.4% in TF group and 30.4% in UCHC group (P<0.01). During the 2-year follow-up, the disease progression in SVR group was 10.3%, which was significantly lower than that in TF group (54.5%) and UCHC group (43.5%), with statistical significance (P<0.001). Further analysis showed that the disease progression rates within 9 months of patients who completed DAA treatment in TF group and UCHC group were 42.9% and 20.0%, significantly lower than those of patients who did not use DAA (75.0% and 61.5%), with statistical significance (P<0.01). The 2-year mortality in SVR group was 6.9%, which was lower than that in TF group and UCHC group (36.4% and 17.4%, P<0.05).Conclusion This study suggests that it is necessary for patients with HCV-associated HCC to get DAA antiviral therapy, which is helpful to improve the therapeutic effect, as well as reduce the metastasis and deterioration of HCC.

Key words: Chronic hepatitis C, Hepatocellular carcinoma, Direct antiviral agent, Sustained virological response, Prognosis

史冬梅, 项晓刚, 赵刚德, 王晓琳. 丙型肝炎相关肝细胞癌的临床特征和预后[J]. 肝脏, 2022, 27(6): 628-633.

SHI Dong-mei, XIANG Xiao-gang, ZHAO Gang-de, WANG Xiao-lin. Clinical features and prognosis of hepatitis C-associated hepatocellular carcinoma[J]. Chinese Hepatolgy, 2022, 27(6): 628-633.

参考文献

[1] Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus disease burden and cost in the United States. Hepatology,2013,57:2164-2170.
[2] Wang FS, Fan JG, Zhang Z, et al. The global burden of liver disease: the major impact of China. Hepatology, 2014,60:2099-2108.
[3] Ogawa E, Furusyo N, Kajiwara E et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma of patients with chronic hepatitis C: a prospective multicenter study. J Hepatol,2013,58:495-501.
[4] Nagaoki Y. Aikata H,Miyaki D,et al. Clinical features and prognosis in patients with hepatocellular carcinoma that developed after hepatitis C virus eradication with interferon therapy. J Gastroenterol, 2011,46 :799-808.
[5] 中华医学会肝病学分会,中华医学会感染病学会分会. 丙型肝炎防治指南(2019年版).实用肝脏病杂志,2020,23(01);33-52.
[6] 中华人民共和国国家卫生和计划生育委员会. 原发型肝癌诊疗规范(2019年版). 临床肝胆病杂志,2020,36(02):277-292.
[7] Bruix J, Sherman M, American Association for the Study of Liver Disease. Management of hepatocellular carcinoma: an update. Hepatology,2011,53(3): 1020-1022.
[8] Lencioni R, LIovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis, 2010, 30(1):52-60.
[9] Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol,2014,61(Suppl 1): S45-S57.
[10] Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet,2003,362:1907-1917.
[11] Tong MJ, Theodoro CF, Salvo RT. Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance. J Dig Dis, 2018,19(7):411-420.
[12] 曾庆磊,付艳玲,吕君,等. 慢性丙型肝炎持续病毒学应答后发生肝癌患者的临床特征分析.肝脏,2015,20:772-775.
[13] Kanwal F, Kramer J, Asch SM et al. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology, 2017, 153(4):996-1005.
[14] Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol,2017.
[15] Leroy V, Angus P, Bronowicki JP, et al. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: a randomized Phase III study (ALLY-3+). Hepatology,2016,63 (5):1430-1441.
[16] Ikeda K, Kawamura Y, Kobayashi M, et al. Direct-acting antivirals decreased tumor recurrence after initial treatment of hepatitis C virus-related hepatocellular carcinoma. Dig Dis Sci,2017,62(10):2932-2942.
[17] Kostadinova L, Shive CL, Zebrowski E, et al. Soluble markers of immune activation differentially normalize and selectively associate with improvement in AST, ALT, Albumin, and transient elastography during IFN-free HCV therapy. Pathog Immun,2018,3(1):149-163.
[18] Persico M,Rosato V, Aglitti A,et al. Sustained virological response by direct antiviral agents in HCV leads to an early and significant improvement of liver fibrosis. Antivir Ther,2018,23(2):129-138.
[19] Cabibbo G, Celsa C, Calvaruso V, et al. Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients. J Hepatol,2019,71(2):265-273.
[20] Huang AC, Mehta N, Dodge JL, et al. Direct-acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local-regional therapy or liver transplant waitlist dropout. Hepatology,2018,68(2):449-461.