HBsAg阴性HBV相关肝细胞癌的临床特点

Clinical features of HBsAg-negative HBV-related hepatocellular carcinoma

目的探讨HBsAg阴性HBV相关肝细胞癌(HCC)临床特点。方法收集2005年1月-2012年1月于解放军三〇二医院初诊为HCC患者。根据HBV相关血清学标志物的表现将患者分为HBsAg阴性HBV相关HCC组(HBsAg阴性组)和乙型肝炎相关HCC组(乙型肝炎组)。回顾性分析人选患者初次诊断时的临床数据,包括性别、年龄、HBV血清标志物、TBil、Alb、AFP、HBV DNA、BMI、饮酒史、糖尿病史、治疗方法以及随访结果。符合正态分布的计量资料2组间比较采用t检验;不符合正态分布的计量资料2组间比较采用Wilcoxon秩和检验;计数资料组间比较采用χ~2检验。生存曲线统计采用log-rank检验,生存差异采用KaplanMeier检验。结果HBsAg阴性组患者的平均(59.42±11.13)岁、年龄>60岁比例(46.85%)、体质量过轻比例(12.24%)、超重比例(20.98%)均明显高于乙型肝炎组和总体患者差异有统计学意义(P值均<0.01)。HBsAg阴性组患者男女比例(2.86:1)、每年参加健康体检定期筛查比例(10.41%)、HBV DNA阳性率(1.77%)、吸烟史、饮酒史比例均明显低于总体患者和乙型肝炎组,差异有统计学意义(P值均<0.01)。HBsAg阴性组患者中以抗-HBs、抗-HBe和抗-HBc均为阳性的患者居多(64.08%),抗-HBe和抗-HBc均为阳性次之(21.13%),仅抗-HBc阳性者最少(14.79%)。HBsAg阴性组患者的AFP水平明显低于总体患者和乙型肝炎组,差异有统计学意义(P=0.039)。且HBsAg阴性组患者初诊时的多发病灶所占比例、肿瘤平均最大直径以及肿瘤肝外转移例数均明显高于总体患者和乙型肝炎组,差异有统计学意义(P值均<0.001)。HBsAg阴性组患者初诊时ECOG-PS评分为0者占17.69%,高于乙型肝炎组患者,且BCLC分期中早期(A、B)患者占30.26%,明显低于乙型肝炎组(51.60%),其晚期(C、D)患者例数是乙型肝炎组的1.83倍,差异有统计学意义(P值均<0.001)。HBsAg阴性组患者中位生存期15.22个月,低于总体患者(25.98个月)和乙型肝炎组(26.55个月)差异有统计学意义(P=0.024、0.031)。预后方面,HBsAg阴性组的1、3年生存率(56.0%、24.0%)明显低于总体患者(61.7%、45.2%)、乙型肝炎组患者(66.2%、44.1%)(χ~2=4.93、6.87,P=0.026、0.009)。结论HBsAg阴性HBV相关HCC多发生于抗-HBs、抗-HBe和抗-HBc均为阳性的60岁以上人群,建议将60岁以上的HBV感染后人群确立为HCC高危险人群,推荐每6个月行HCC筛查以提高HBsAg阴性HBV相关HCC的早期诊断率。

Objective To investigate the clinical features of HBsAg - negative HBV - related hepatocellular carcinoma （HCC）. Methods The patients who were newly diagnosed with HCC from January 2005 to January 2012 were enrolled. According to the HBV - related serological markers, the patients were divided into HBsAg - negative HBV - related HCC group and hepatitis B - related HCC group. A retrospective analysis was performed for the clinical and laboratory examination data at initial diagnosis, including sex, age, hepatitis B virus markers, total bilirubin （TBil）, albumin （Alb）, alpha -fetoprotein （AFP）, HBV DNA, body mass index （BMI）, drinking history, history of diabetes, therapies, and follow - up results. The t - test was used for comparison of normally distributed continuous data between groups ; the non - normally distributed data were expressed as median and interquartile range （ Q1 and Q3 ）, and the Wilcoxon rank sum test was used for comparison of non - normally distributed continuous data between groups ; the chi - square test or Fisher＇s exact test were used for comparison of categorical data. The log - rank test was used to compare survival curves between the two groups, and the Kaplan - Meier method was used to calculate survival rates. Results Compared with the hepatitis B group and all patients, the HBsAg - negative group had a significantly higher mean age （59.42 ± 11.13 years） and significantly higher proportions of patients with age 〉 60 years （46.85%）, low body weight （ 12.24% ）, and overweight （20.98%） （ all P 〈0.01 ）. Compared with all patients and the hepatitis B group, the HBsAg - negative group had a significantly lower male -to -female ratio （2.86：1 ）, a significantly lower proportion of patients regularly undergoing physical examination every year （ 10.41% ）, a significantly lower HBV DNA positive rate （ 1.77% ）, and significantly lower proportions of patients with smoking and drinking histories （ all P 〈0.01 ）. Of all patients in the HBsAg - negative group, 64.08% had positive anti - HBs, anti - HBe, and anti -HBc, 21.13% had positive anti -HBe and anti -HBc, and 14.79% only had positive anti -HBc. The HBsAg- negative group had a significantly lower AFP level than all patients and the hepatitis B group （ P = 0. 039 ）. Compared with the hepatitis B group and all patients, the HBsAg - negative group had a significantly higher proportion of multiple lesions, a significantly greater mean maximum tumor diameter, and a significantly higher number of patients with extrahepatic metastasis （all P 〈 0.001 ）. Compared with the hepatitis B group, the HBsAg - negative group had a higher proportion of patients with an Eastern Cooperative Oncology Group Performance Status score of 0 at initial diagnosis （ 17.69% ） and a lower proportion of patients with early - to - medium Barcelona Clinic Liver Cancer stage （ stages A and B） （30.26% vs 51.60%, P 〈0.001 ） ; the number of patients with stages C and D in the HBsAg - negative group was 1.83 times that in the hepatitis B group （ P 〈0.001 ）. The HBsAg - negative group had a significantly lower median survival time （ 15.22 months） than all patients and the hepatitis B group （P =0. 024,0. 031 ）. Compared with all patients and the hepatitis B group, the HBsAg negative group had significantly lower 1 - and 3 - year survival rates （ 1 - year survival rate ： 56.0% vs 61.7% and 66.2%, X^2 = 4. 93, P = 0.026 ; 3 - year survival rate ： 24.0% vs 45.2% and 44.1%, X^2 = 6. 867, P = 0. 009）. Conclusion HBsAg - negative HBV - related HCC is commonly seen in patients aged 〉 60 years with positive anti - HBs, anti - HBe, and anti - HBc. The population aged 〉 60 years with HBV infection should be the high - risk population for HCC, and it is recommended to perform HCC screening every 6 months to increase the early diagnostic rate of HBsAg - negative HBV - related HCC.