述评 - 现在不必要慢性HBV感染的口服抗病毒药物组合

StephenW

SUMMARY AND COMMENT | GASTROENTEROLOGY

August 8, 2013

Combination Oral Antivirals Are Now Unnecessary for Chronic HBV Infection

Atif Zaman, MD, MPH Reviewing Gordon SC et al., Hepatology 2013 Aug 58:505

Tenofovir suppressed the virus in nearly all patients, even those with high pretreatment viral loads.

With the availability of potent antiviral agents (e.g., entecavir, tenofovir), the majority of hepatitis B virus (HBV)-infected patients will achieve successful viral suppression. But is this also true for patients with high viral load (HVL)? Or do they require an additional anti-HBV medication to achieve suppression and prevent the development of resistance?

To answer this question, researchers analyzed virologic response (HBV DNA <400 copies/mL) in patients with and without HVL (baseline viral load ≥9 log10 copies/mL) who had been followed for 240 weeks as part of two previous registration trials comparing tenofovir disoproxil fumarate (TDF) and adefovir for treating HBV infection. The trials included both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients and both treatment-experienced and treatment-naive patients. At week 48, patients on adefovir were switched to TDF. Patients with persistent viremia (never achieving HBV DNA <400 copies/mL) at week 72 were given the option of continuing TDF alone or adding emtricitabine.

Of 641 patients enrolled, 129 (20%) had HVL. By week 240, virologic response was achieved in 98.3% of patients with HVL and 99.2% of patients without HVL. Patients with HVL took longer to achieve response, but by week 96, rates were similar between the two groups. Notably, in patients with HVL, adding emtricitabine to TDF did not affect virologic response rates. No patient with HVL at week 240 had persistent viremia or developed TDF resistance. Of 13 instances of viral breakthrough, 62% were attributed to noncompliance.
Comment

This study highlights several key features of modern therapy with antivirals for hepatitis B virus infection. First, although patients with high viral loads take longer (up to 96 weeks) to achieve undetectability, eventually all will achieve it. Second, while awaiting HBV DNA undetectability, resistance development is not a worry. Third, the main cause of viral breakthrough is noncompliance. Finally, combination therapy does not improve HBV response or outcomes.
Editor Disclosures at Time of Publication

    Disclosures for Atif Zaman, MD, MPH at time of publication Speaker’s bureau Bristol-Myers Squibb; Genentech; Gilead; Kadmon; Merck; Salix; Vertex

Citation(s):

    Gordon SC et al. Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load. Hepatology 2013 Aug; 58:505. (http://dx.doi.org/10.1002/hep.26277)

StephenW

泰诺福韦抑制病毒几乎所有的患者，甚至是那些与预处理高病毒载量的。

强效抗病毒药物（例如，恩替卡韦，替诺福韦）的可用性，大部分的B型肝炎病毒（HBV）感染的患者将达到成功的病毒抑制。但是，这也适用于高病毒载量的患者（HVL）？或者他们需要额外的抗乙肝病毒药物，以达到抑制和防止耐药性的发展？

要回答这个问题，研究人员分析了病毒学应答（HBV DNA <400拷贝/毫升）的患者HVL（基线病毒载量≥9 log10拷贝/毫升）已240周作为前两次登记试验比较的一部分，没有富马酸替诺福韦（TDF）和阿德福韦治疗HBV感染。试验包括B型肝炎e抗原（HBeAg）阳性，阳性和HBeAg阴性患者，治疗经验和治疗初治患者。 48周时，患者对阿德福韦切换到TDF。患者持续病毒血症（从来没有达到HBV DNA <400拷贝/ ml），72周时分别给予持续TDF单独或加入恩曲他滨的选择。

在641例患者中，有129（20％）有HVL。 240周时的病毒学应答，实现HVL患者的98.3％和99.2％的患者没有HVL。 HVL患者需要更长的时间来实现的反应，但96周，分别为两组之间的相似。值得注意的是，在HVL患者，恩曲他滨TDF病毒学应答率没有影响。周240 HVL没有病人有持续性的病毒血症或发展TDF阻力。病毒突破的13个实例，有62％是由于违规。
评论

这项研究强调的几个主要特点的现代治疗B型肝炎病毒感染的抗病毒药物。首先，尽管与高病毒载量的患者需要更长的时间（96周）达到不可检测，最终都将实现这一目标。其次，虽然等待HBV DNA不可检测，耐药性的发展是不是一个担心。第三，病毒突破的主要原因是违规。最后，联合用药不提高HBV的反应或结果。
编辑在出版时的披露

tonychant

真希望这样的结果也存在于亚洲人身上，但是个人隐约感到目前学术界对替诺福韦的宣传很像当年的佩乐能，真希望都能创造新的希望！

StephenW

回复 tonychant 的帖子


                                 高病毒量HVL (n = 129)    非高病毒量Non-HVLa (n = 512)
HBV 基因型genotype (%)               
A                                28 (22.0)                        75 (15.0)   
B                                12 (9.4)                          62 (12.4)     
C                                19 (15.0)                        93 (18.6)     
D                                62 (48.8)                      253 (50.5)     
Other                           6 (4.7)                         18 (3.6)

B, C最有可能是亚洲人.