Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks.
Wang Xiaomei,Wang Zhongfeng,Chi Xiumei,Wu Ruihong,Jin Qinglong,Xu Hongqin,Gao Xiuzhu,Yu Lei,Chen Yuping,Shang Jia,Liu Longgen,Zhang Shuqin,Jiang Yongfang,Zhang Mingxiang,Tong Qiaoxia,Zhang Lunli,Tan Youwen,Ma Anlin,Dang Shuangsuo,Xu Bin,Jin Zhenjing,Li Jia,Li Xiaobo,Lu Fengmin,Niu Junqi
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
BACKGROUND:In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported. METHODS:A total of 111 HBeAg-positive patients were enrolled in our study. The dynamic changes of serum HBV RNA and the correlation of HBV RNA with other HBV markers were investigated in the early treatment period of 144-week ETV treatment. Intrahepatic cccDNA was detected at baseline and week 48. Receiver operating characteristic analyses were used to identify HBV RNA levels associated with HBeAg seroconversion. RESULTS:The serum HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. The levels of HBV RNA decreased slower compared with the serum HBV DNA, irrespective of whether the patients achieved HBeAg seroconversion or not. Although the serum HBV RNA was positively correlated with cccDNA at baseline among all patients, no significant correlation was observed in the patients with HBeAg seroconversion at week 48 (r=0.094, P=0.588). The area under the receiver operating characteristic (AUROC) of HBV RNA and HBeAg at week 24 was 0.754 and 0.800, respectively. The AUROC of the HBV RNA and HBeAg combination had a higher value (AUROC=0.821). CONCLUSIONS:The level of HBV RNA at week 24 was a powerful predictor of HBeAg seroconversion in HBeAg-positive patients after 144-week ETV treatment, while the combination of HBV RNA and HBeAg was superior to HBV RNA alone in predicting HBeAg seroconversion.
Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study.
Zhang Min,Li Guangdi,Shang Jia,Pan Chen,Zhang Minxiang,Yin Zhibiao,Xie Qing,Peng Yanzhong,Mao Qing,Xiao Xinqiang,Jiang Yongfang,Luo Kaizhong,Xu Yun,Ding Hai,Fan Wenzhou,Diego Vidaurre,Pourkarim Mahmoud Reza,De Clercq Erik,Wang Guiqiang,Gong Guozhong
BACKGROUND:As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses. METHODS:We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72. RESULTS:HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%). CONCLUSION:HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.