Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
PLoS One. 2011;6(6):e20752. doi: 10.1371/journal.pone.0020752. Epub 2011 Jun 13.
Interferon-α/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg) seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV), but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-α/ribavirin combination therapy in HBV/HCV dually-infected patients.
METHODOLOGY/PRINCIPAL FINDINGS: Eighty-one patients who received interferon-α/ribavirin combination therapy for 24 weeks with a follow-up period of >24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-of-treatment, respectively. Fifteen (18.5%) patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5-5.1) years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR), 95% confidence intervals (CI) of 16.6, 1.8-153 and 9.2, 1.4-62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5-745). Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss.
We demonstrated that interferon-α/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCV-infected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were significant factors associated with HBsAg seroclearance.
干扰素-α/利巴韦林联合治疗可能会促进乙型肝炎和丙型肝炎病毒（HBV/HCV）双重感染患者的乙型肝炎表面抗原（HBsAg）血清清除，但长期效果尚不清楚。我们旨在研究 HBV/HCV 双重感染患者接受干扰素-α/利巴韦林联合治疗 24 周后，长期随访期间 HBsAg 血清清除率及其相关因素。
方法/主要发现：共纳入 81 例接受干扰素-α/利巴韦林联合治疗 24 周且随访时间超过 24 周的患者。每 6 个月检测一次 HBV 血清学标志物和 HBV DNA。治疗结束后 6 个月内 HBsAg 丢失定义为早期 HBsAg 血清清除，6 个月后 HBsAg 丢失定义为晚期 HBsAg 血清清除。平均随访 3.4（0.5-5.1）年后，15 例（18.5%）患者 HBsAg 血清清除。5 年累积发生率为 25.6%。基线肝硬化和治疗结束后 1 年 HBV DNA 阴性是 HBsAg 血清清除的独立预测因素，Cox 回归风险分析的优势比（OR）分别为 16.6、1.8-153 和 9.2、1.4-62.1。4 例患者出现早期 HBsAg 血清清除，11 例患者出现晚期 HBsAg 血清清除。Cox 回归风险分析显示，早期 HBsAg 血清清除与任何因素无关，而治疗结束后 1 年 HBV DNA 阴性是晚期 HBsAg 丢失的唯一显著预测因素（OR，43.0；CI，2.5-745）。5 例患者 HBsAg 血清转换，5 年累积发生率为 8.3%。基线 HBV DNA 阴性和治疗结束后 1 年 HBV DNA 阴性有 HBsAg 血清转换的趋势。HCV 反应与 HBsAg 丢失无关。
我们证明干扰素-α/利巴韦林对 HBV/HCV 双重感染患者的 HBsAg 血清清除具有长期疗效。基线肝硬化和治疗结束后 1 年 HBV DNA 血清清除是与 HBsAg 血清清除相关的显著因素。
