Jang Heejoon, Yoon Jun Sik, Park Soo Young, Lee Han Ah, Jang Myoung-Jin, Kim Seung Up, Sinn Dong Hyun, Seo Yeon Seok, Kim Hwi Young, Kim Sung Eun, Jun Dae Won, Yoon Eileen L, Sohn Joo Hyun, Ahn Sang Bong, Shim Jae-Jun, Jeong Soung Won, Cho Yong Kyun, Kim Hyoung Su, Nam Joon Yeul, Lee Yun Bin, Kim Yoon Jun, Yoon Jung-Hwan, Zoulim Fabien, Lampertico Pietro, Dalekos George N, Idilman Ramazan, Sypsa Vana, Berg Thomas, Buti Maria, Calleja Jose Luis, Goulis John, Manolakopoulos Spilios, Janssen Harry LA, Papatheodoridis George V, Lee Jeong-Hoon
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
Clin Gastroenterol Hepatol. 2022 Jun;20(6):1343-1353.e16. doi: 10.1016/j.cgh.2021.09.001. Epub 2021 Sep 6.
BACKGROUND & AIMS: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC.
The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort.
A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67).
This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.
从乙肝e抗原（HBeAg）阳性状态开始进行抗病毒治疗，可能会减弱乙肝病毒DNA整合到宿主基因组中，从而引发肝细胞癌（HCC）。我们研究了抗病毒治疗开始时HBeAg状态对HCC风险的影响。
在韩国慢性乙型肝炎患者中评估HCC的发病率，这些患者在HBeAg阳性或HBeAg阴性阶段开始使用恩替卡韦或替诺福韦。韩国队列的结果在白种人的PAGE - B队列中得到验证。
共纳入9143例韩国患者（平均年龄49.2岁）：49.1%为HBeAg阳性，49.2%有肝硬化。在随访期间（中位数为5.1年），916例患者（10.0%）发生了HCC。在整个队列或肝硬化亚组中，基线HBeAg阳性与HCC风险无关。然而，在非肝硬化亚组中，多变量分析（调整后风险比[aHR]，0.41；95%置信区间[CI]，0.26 - 0.66）、倾向评分匹配分析（aHR，0.46；95%CI，0.28 - 0.76）和逆概率加权分析（aHR，0.44；95%CI，0.28 - 0.70）显示，HBeAg阳性与较低的HCC风险独立相关。在白种人队列（n = 719；平均年龄51.8岁；HBeAg阳性，20.3%；肝硬化，34.8%）中，在整个队列或肝硬化亚组中，HBeAg阳性与HCC风险也无关。在非肝硬化亚组中，HBeAg阳性组无一例发生HCC，尽管差异未达到统计学意义（aHR，0.21；95%CI，0.00 - 1.67）。
这项多国队列研究表明，抗病毒治疗开始时HBeAg阳性似乎是慢性乙型肝炎无肝硬化患者HCC风险较低的一个独立相关因素，但在有肝硬化的患者中并非如此。
