Yegin Ender G, Ozdogan Osman Cavit
Department of Gastroenterology, Marmara University Faculty of Medicine, Istanbul, Turkey.
Hepatobiliary Pancreat Dis Int. 2014 Dec;13(6):602-11. doi: 10.1016/s1499-3872(14)60303-9.
The definition of partial virological response (PVR) was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues (NA) is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir monotherapy in NA-naive patients with chronic hepatitis B in routine clinical practice.
We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July 2013.
Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 (6-147) months. PVR rates at 24 weeks were similar among three NAs (lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P=0.981). For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough (VBR) for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR (HR: 3.09; 95% CI: 1.09-8.74; P=0.034); also lamivudine treated patients older than 50 years seemed to have a tendency for VBR (HR: 2.80; 95% CI: 0.99-8.18; P=0.052). A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations.
Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.
部分病毒学应答（PVR）的定义因其临床相关性而被提出。PVR与随后导致治疗方案调整的治疗失败相关。这种理论依据是否适用于所有核苷酸类似物（NA）尚不清楚。本研究旨在分析在常规临床实践中，PVR对初治慢性乙型肝炎患者接受拉米夫定、恩替卡韦或替诺福韦单药治疗期间治疗结局的影响。
我们回顾性分析了150例初治慢性乙型肝炎患者。这些受试者在2001年2月至2013年7月期间接受拉米夫定、恩替卡韦或替诺福韦单药治疗。
69例患者接受拉米夫定治疗，35例接受恩替卡韦治疗，46例接受替诺福韦治疗。中位治疗时长为19.5（6 - 147）个月。三种NA在24周时的PVR率相似（拉米夫定33.3%，恩替卡韦35.0%，替诺福韦32.4%，P = 0.981）。对于所有三种NA，基线病毒载量较高或HBeAg阳性的患者在第24周和48周时通过聚合酶链反应检测的血清病毒阳性率更高。接受拉米夫定治疗的患者5年时病毒学突破（VBR）的累积概率为67%，24周时的PVR是VBR的独立危险因素（HR：3.09；95%CI：1.09 - 8.74；P = 0.034）；此外，年龄大于50岁的拉米夫定治疗患者似乎有VBR倾向（HR：2.80；95%CI：0.99 - 8.18；P = 0.052）。除1例因耐药突变发生VBR的恩替卡韦治疗患者外，大多数恩替卡韦和替诺福韦部分应答者通过延长单药治疗实现并维持了病毒学应答。
由于拉米夫定治疗与高得不可接受的VBR概率相关，其治疗管理策略应将根据PVR调整治疗方案作为治疗反应参数。类似结论不应直接套用于恩替卡韦或替诺福韦治疗。
