Kim Soo Ki, Fujii Takako, Kim Soo Ryang, Nakai Atsushi, Lim Young-Suk, Hagiwara Satoru, Kudo Masatoshi
Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan.
Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Liver Cancer. 2022 Aug 23;11(6):497-510. doi: 10.1159/000525518. eCollection 2022 Dec.
Long-term therapy with nucleos(t)ide analogs (NAs) such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF) favorably affects the incidence of hepatocellular carcinoma (HCC) on the basis of data from randomized or matched control studies. Recent data suggest a lower HCC incidence after 5 years of ETV or TDF therapy in chronic hepatitis B (CHB) patients, especially those with baseline cirrhosis.
Three controversial issues remain to be resolved regarding hepatitis B virus (HBV) treatment and HCC. (1) The efficacy of antiviral treatment for the prevention of HCC is not established. The guidelines of the American Association for the Study of Liver Diseases (AASLD), the Asian Pacific Association for the Study of the Liver (APASL), and the European Association for the Study of the Liver (EASL) for the management of HBV infection state that antiviral treatment of HBV with interferon and NAs prevents the development of HCC. Among experts in CHB treatment, however, there is disagreement on the HCC prevention effects of antiviral treatment. (2) The rationale for antiviral management in patients with high HBV DNA and normal levels of alanine aminotransferase is unclear. The AASLD, EASL, and APASL guidelines do not recommend antiviral treatment for immune-tolerant CHB patients, and the terms and methods of treating such patients remain to be clarified. (3) The efficacy of first-line treatment with NAs, including ETV, TDF, and tenofovir alafenamide fumarate (TAF), to prevent HCC in CHB patients remains unknown. Several studies have produced controversial results regarding the effects of NAs on the risk and prevention of HCC. In the present review, we discuss these 3 issues, citing recent studies and clinical management guidelines from major international associations.
Suggested approaches for reaching a consensus including applying the propensity score matching method, performing randomized controlled studies, and performing clinical studies with larger numbers of subjects and longer follow-up.
基于随机或配对对照研究的数据，使用恩替卡韦（ETV）和替诺福韦酯（TDF）等核苷（酸）类似物（NAs）进行长期治疗对肝细胞癌（HCC）的发病率有积极影响。近期数据表明，慢性乙型肝炎（CHB）患者接受ETV或TDF治疗5年后HCC发病率较低，尤其是那些基线有肝硬化的患者。
关于乙型肝炎病毒（HBV）治疗和HCC仍有三个有争议的问题有待解决。（1）抗病毒治疗预防HCC的疗效尚未确定。美国肝病研究协会（AASLD）、亚太肝病研究协会（APASL）和欧洲肝病研究协会（EASL）关于HBV感染管理的指南指出，使用干扰素和NAs对HBV进行抗病毒治疗可预防HCC的发生。然而，在CHB治疗专家中，对于抗病毒治疗对HCC的预防效果存在分歧。（2）HBV DNA水平高但丙氨酸转氨酶水平正常的患者进行抗病毒管理的基本原理尚不清楚。AASLD、EASL和APASL指南不建议对免疫耐受的CHB患者进行抗病毒治疗，此类患者的治疗条件和方法仍有待阐明。（3）包括ETV、TDF和富马酸替诺福韦艾拉酚胺（TAF）在内的NAs一线治疗预防CHB患者发生HCC的疗效仍不清楚。几项研究在NAs对HCC风险和预防的影响方面产生了有争议的结果。在本综述中，我们引用主要国际协会的近期研究和临床管理指南来讨论这三个问题。
达成共识的建议方法包括应用倾向得分匹配法、开展随机对照研究以及开展受试者数量更多、随访时间更长的临床研究。
