Zang W W, Su M H, Ling X Z, Wang R M, Cao B C, Wu Y L, Deng D L, Wei H L, Liang X S, Jiang J N
Department of Infectious Diseases, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Zhonghua Gan Zang Bing Za Zhi. 2020 Aug 20;28(8):679-685. doi: 10.3760/cma.j.cn501113-20200228-00074.
To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, = 0.007). The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.
回顾性分析长期接受核苷（酸）类似物（NAs）治疗并得到全程管理的乙型肝炎相关肝硬化（LC）患者发生肝癌的危险因素。研究对象来源于2004年2月至2019年9月在广西医科大学第一附属医院感染科接受抗病毒治疗的慢性乙型肝炎和肝硬化随访队列。纳入符合入选标准的LC患者。采用寿命表法计算肝癌发病率。使用多变量Cox回归模型分析可能影响LC患者发生肝癌的危险因素。对发生肝癌的肝硬化患者进行亚组分析，以评估抗病毒治疗依从性的有效性。采用（2）检验进行率的比较。198例接受NAs治疗的LC患者的中位随访时间为6.0年（1.0 - 15.3年）。至随访结束时：（1）16.2%（32/198）的LC患者发生了肝癌，1、3、5、7和9年的肝癌累积发病率分别为0、8.9%、14.3%、18.6%和23.4%，年均发病率为3.1%。在32例肝癌患者中，68.7%发生了小肝癌（22/32）。（2）单变量Cox模型分析显示，肝癌的发生与四个因素有关，即是否存在LC结节、基线是否为一线用药、肝癌家族史以及患者依从性。多变量Cox模型分析结果显示，患者依从性差和基线非一线用药是肝癌的危险因素。（3）对数秩检验亚组分析结果显示，有硬化结节患者的肝癌5年累积发病率显著高于无硬化结节患者（21.7%对11.5%，=0.029）。非一线用药患者的肝癌5年累积发病率显著高于一线用药患者（22.0%对8.2%，=0.003）。依从性差的患者的肝癌5年累积发病率显著高于依从性好的患者（21.3%对12.7%，=0.014）。有肝癌家族史患者的肝癌5年累积发病率显著高于无肝癌家族史患者（22.3%对8.1%，=0.006）。（4）与依从性差的患者相比，依从性好的患者有更高的HBV DNA阴性血清学转换率（98.7%对87.8%，=0.005），且病毒学突破率更低（12.1%对29.3%，=0.007）。长期NAs抗病毒治疗可降低肝癌风险，但不能完全预防肝癌的发生，尤其是在有肝癌家族史和基线有硬化结节（肝癌高危）的患者中。此外，全程管理可提高患者依从性，确保抗病毒治疗疗效，降低肝癌发生风险，从而实现肝癌的二级预防，即早期发现、诊断和治疗。
