Jindal Ankur, Vyas Ashish Kumar, Kumar Devesh, Kumar Guresh, Sharma Manoj Kumar, Sarin Shiv Kumar
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Hepatol Res. 2018 May;48(6):451-458. doi: 10.1111/hepr.13049. Epub 2018 Mar 12.
Monotherapy with pegylated interferon-α (Peg-IFNα) or the nucleos(t)ide analogs (NA) currently approved for treating chronic hepatitis B (CHB) has limited efficacy. Studies on the combination of Peg-IFNα/NA have shown conflicting results. We investigated whether sequentially adding on Peg-IFNα to tenofovir enhances serological response rates.
Treatment-naïve, hepatitis B envelope antigen (HBeAg)-positive CHB patients with moderately elevated alanine aminotransferase (ALT; 48-200 IU/mL) were started on tenofovir (300 mg/day) and enrolled at week 12 in a 1:1 ratio to either receive Peg-IFNα2b add-on (1.5 μg/kg/week) from week 12 to 36 (n = 53) or continue tenofovir monotherapy (n = 53). Both treatment arms received tenofovir consolidation therapy until week 72. The primary end-point was HBeAg loss at week 72.
At week 72, the rate of HBeAg loss was higher in the Peg-IFNα2b add-on group (35.8%) compared to the tenofovir monotherapy group (17%) (P = 0.028; odds ratio, 2.73, 95% confidence interval, 1.09-6.79), and considerably higher in patients with a baseline hepatitis B virus (HBV)-DNA level >6 log IU/mL (32.6% vs 11.4%; P = 0.021). Rates of HBV-DNA loss (77.4% vs 71.7%; P = 0.51), ALT normalization (62.3% vs 52.8%; P = 0.32), and sustained virologic response (20.8% vs 11.3%; P = 0.18) at week 72 were comparable between the two groups. Significantly more patients in the add-on group had >3 log HBV-DNA reduction at week 36 (92.5% vs 66%; P = 0.001). Four patients treated with Peg-IFNα2b add-on achieved hepatitis B surface antigen (HBsAg) loss compared with one patient receiving tenofovir monotherapy. Decline of HBV-DNA of >2 log at week 4 led to higher HBeAg loss at week 72, independent of treatment arm. No patient had treatment-related adverse effects requiring treatment discontinuation.
Twenty-four weeks of Peg-IFNα2b as an add-on sequential regimen to tenofovir is safe and resulted in greater loss of HBeAg and HBsAg compared to tenofovir monotherapy in selected HBeAg-positive patients. Viral load reduction followed by immune modulation is a potentially useful approach.
聚乙二醇化干扰素-α（Peg-IFNα）单药治疗或目前批准用于治疗慢性乙型肝炎（CHB）的核苷（酸）类似物（NA）疗效有限。关于Peg-IFNα/NA联合治疗的研究结果相互矛盾。我们研究了在替诺福韦基础上序贯加用Peg-IFNα是否能提高血清学应答率。
初治的、乙型肝炎e抗原（HBeAg）阳性的CHB患者，丙氨酸氨基转移酶（ALT）中度升高（48 - 200 IU/mL），开始接受替诺福韦（300 mg/天）治疗，并在第12周按1:1比例入组，从第12周起至36周，一组接受Peg-IFNα2b加用治疗（1.5 μg/kg/周）（n = 53），另一组继续接受替诺福韦单药治疗（n = 53）。两个治疗组均接受替诺福韦巩固治疗至第72周。主要终点是第72周时HBeAg消失。
在第72周时，Peg-IFNα2b加用组的HBeAg消失率（35.8%）高于替诺福韦单药治疗组（17%）（P = 0.028；优势比，2.73，95%置信区间，1.09 - 6.79），在基线乙型肝炎病毒（HBV）-DNA水平>6 log IU/mL的患者中差异更为显著（32.6%对11.4%；P = 0.021）。两组在第72周时的HBV-DNA消失率（77.4%对71.7%；P = 0.51）、ALT复常率（62.3%对52.8%；P = 0.32）和持续病毒学应答率（20.8%对11.3%；P = 0.18）相当。加用组在第36周时HBV-DNA下降>3 log的患者明显更多（92.5%对66%；P = 0.001）。接受Peg-IFNα2b加用治疗的4例患者实现了乙型肝炎表面抗原（HBsAg）消失，而接受替诺福韦单药治疗的患者为1例。第4周时HBV-DNA下降>2 log导致第72周时HBeAg消失率更高，与治疗组无关。没有患者出现需要停药的治疗相关不良反应。
在选定的HBeAg阳性患者中，24周的Peg-IFNα2b作为替诺福韦序贯加用方案是安全的，与替诺福韦单药治疗相比，导致更多的HBeAg和HBsAg消失。病毒载量降低后进行免疫调节是一种潜在有用的方法。
