Al Ashgar Hamad, Peedikayil Musthafa C, Al Quaiz Mohammed, Al Sohaibani Fahad, Al Fadda Abdulrahman, Khan Mohammed Q, Thoralsson Einar, Al Thawadi Sahar, Al Jedai Ahmed, Al Kahtani Khalid
Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Department of Microbiology Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Saudi J Gastroenterol. 2017 May-Jun;23(3):190-198. doi: 10.4103/sjg.SJG_541_16.
BACKGROUND/AIMS: The ideal end point of treatment for chronic hepatitis B virus (HBV) infection is sustained off-therapy hepatitis B surface antigen (HBsAg) loss with or even without seroconversion to anti-HBs. We investigated the role of adding PEGylated interferon (PEG IFN) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance.
In this randomized controlled trial, chronic HBV patients who have been receiving tenofovir for >6 months with HBV viral load <2000 IU/ml were randomized into two groups. One group (add-on therapy) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir. Patients in the other group received only tenofovir 300 mg orally on a daily basis. Patients in both groups were followed up for a total of two years, and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance.
Twenty-three patients were allocated to the PEG IFN and tenofovir (add-on therapy) group, and another 25 patients were recruited to the tenofovir monotherapy group. Before randomization, patients had received tenofovir for 1135 mean days (range203 to 1542 days). One patient (4.3%) in add-on therapy lost HBsAg and seroconverted. Within two years, mean HBsAg decreased significantly with add-on therapy (from 4753 IU/ml to 2402; P= 0.03); and it decreased from 5957 IU/ml to 4198; P= 0.09 in tenofovir monotherapy group. More patients in the add-on group developed serious side effects, with treatment discontinuation, and dose reductions (P = 0.3).
PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3% of the patients. Add-on therapy patients had a significant decrease in HBsAg levels in two years; and no significant decrease in HBsAg levels with the tenofovir monotherapy. With no significant HBsAg clearance, the utility of this combination regimen is questionable.
背景/目的：慢性乙型肝炎病毒（HBV）感染的理想治疗终点是在停止治疗后持续出现乙肝表面抗原（HBsAg）消失，甚至无论是否发生抗-HBs血清学转换。我们研究了在慢性HBV患者正在进行的替诺福韦治疗中加用聚乙二醇化干扰素（PEG IFN）以实现HBsAg清除的作用。
在这项随机对照试验中，将接受替诺福韦治疗超过6个月且HBV病毒载量<2000 IU/ml的慢性HBV患者随机分为两组。一组（联合治疗组）除替诺福韦外，每周皮下注射PEG IFN 180 mcg，共12个月。另一组患者仅每日口服替诺福韦300 mg。两组患者总共随访两年，两组患者均无限期每日给予替诺福韦300 mg，直至出现HBsAg清除。
23例患者被分配至PEG IFN联合替诺福韦（联合治疗）组，另外25例患者被纳入替诺福韦单药治疗组。随机分组前，患者接受替诺福韦治疗的平均天数为1135天（范围为203至1542天）。联合治疗组中有1例患者（4.3%）HBsAg消失并发生血清学转换。在两年内，联合治疗组的平均HBsAg显著下降（从4753 IU/ml降至2402；P = 0.03）；替诺福韦单药治疗组则从5957 IU/ml降至4198；P = 0.09。联合治疗组有更多患者出现严重副作用、治疗中断和剂量减少（P = 0.3）。
PEG IFN联合替诺福韦治疗使4.3%的患者成功实现HBsAg清除和血清学转换。联合治疗组患者在两年内HBsAg水平显著下降；而替诺福韦单药治疗组HBsAg水平无显著下降。由于未实现显著的HBsAg清除，这种联合治疗方案的实用性值得怀疑。
