在低乙肝病毒定量的患者中，高水平的乙肝表面抗原(HBsAg)能够增加患原发性肝癌的风险
背景：慢性乙型肝炎病毒感染的患者发生原发性肝癌(HCC)的风险较高，低水平乙肝表面抗原的患者比那些高水平的乙肝表面抗原患者更容易出现乙肝表面抗原的消失。然而，很少人知道高水平乙肝表面抗原的患者是否能增加原发性肝癌的风险。方法：我们随访了没有明确肝硬化迹象的2688例乙肝表面抗原阳性的台湾患者平均期限14.7年。另外加入了已知的有明确高风险因素的原发性肝癌的患者，我们调查了乙肝表面抗原水平和原发性肝癌发生的相关性。结果：随诊的病人中，有191例发展为原发性肝癌，年均发病率为0.5%。基线水平的乙肝表面抗原HBsAg和乙型肝炎病毒HBV与肝癌的发展存在着相关性，以及风险的增加与水平有关。相比乙型肝炎表面抗原水平，用ROC曲线(受试者工作特征曲线，又称感受性曲线）分析，HBV DNA水平能更好地预测肝癌的发展超过10年和15年期（均为p<0.001）。然而，当我们在评价HBV DNA < 2000IU/mL的乙肝e抗原(HBeAg) 阴性的患者，决定肝癌发生的危险因素包括性别，年龄，和谷丙转氨酶(ALT)的水平以及乙肝病毒表面抗原（HBsAg） （≧1000 IU/mL ），而不是HBV DNA的水平。多变量分析显示，调整后的发生原发性肝癌的患者的危险比为：乙肝表面抗原水平≧1000比<1000 IU/mL为13.7（95%可信区间，4.8-39.3）。结论：在感染乙肝病毒基因型B或C型的患者中，发生原发性肝癌的危险因素包括他们的性别、年龄、乙肝e抗原（HBeAg）的情况、乙型肝炎病毒(HBV)基因型和转氨酶(ALT)的水平以及HBV DNA水平，而不是乙型肝炎表面抗原的水平。在低病毒载量的HBeAg阴性患者中，发生原发性肝癌的风险是由乙肝表面抗原HBsAg的水平、ALT水平及年龄决定的，而不是HBV DNA水平。
吉林大学第一医院肝胆胰内科 沙秀娟 摘译
High Levels of Hepatitis B Surface Antigen Increase Risk of Hepatocellular Carcinoma in Patients with Low HBV Load.
BACKGROUND & AIMS:
Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with lower levels of hepatitis B surface antigen (HBsAg) have higher chances of losing HBsAg than those with high levels. However, little is known about whether higher levels of HBsAg increase the risk for HCC.
METHODS:
We followed 2688 Taiwanese HBsAg-positive patients without evidence of cirrhosis for a mean time period of 14.7 years. In addition to known risk factors of HCC, we investigated association between levels of HBsAg and the development of HCC.
RESULTS:
Of the patients followed, 191 developed HCC, with an average annual incidence rate of 0.5%. Baseline levels of HBsAg and HBV were associated with the development of HCC, and risk increased with level. Compared to HBsAg level, by receiver operating characteristic curve analysis, HBV DNA level better predicted the development of HCC over 10-year and 15-year periods (both P<.001). However, when we evaluated hepatitis B e antigen (HBeAg)-negative patients with levels of HBV DNA <2000 IU/mL, factors that determined HCC risk included sex, age, and levels of alanine aminotransferase (ALT) and HBsAg (≧1000 IU/mL), but not level of HBV DNA. Multivariate analysis showed that the adjusted hazard ratio for HCC in patients with levels of HBsAg ≧1000 vs <1000 IU/mL was 13.7 (95% confidence interval, 4.8-39.3).
CONCLUSIONS:
Among patients infected with HBV genotypes B or C, determinants of HCC risk include their sex, age, HBeAg status, HBV genotype and levels of ALT and HBV DNA, but not level of HBsAg. Among HBeAg-negative patients with low viral loads, HCC risk is determined by levels of HBsAg and ALT and age, but not HBV DNA.
