长期拉米治疗没有HBeAg消失,停药后的聚乙二醇干扰素

StephenW

http://www.virologyj.com/content/10/1/21/abstract
Efficacy of pegylated interferon alpha2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy                                                   

Xu-Qing Zhang, Hui-Yan Zhang, Jian-Ping You and Qing Mao        

长期拉米夫定治疗没有HBeAg消失,停药后的聚乙二醇干扰素alpha2a治疗效

Virology Journal 2013, 10:21 doi:10.1186/1743-422X-10-21
Published: 15 January 2013                        
Abstract (provisional)
Background

Improving the HBe seroconversion rate of patients without HBeAg loss after long-term   lamivudine therapy has become an urgent clinical problem that we have to face. Unfortunately,   there is no consensus on the mananement of these patients. The aim of this study was   to evaluate the efficacy of pegylated interferon (PEG-IFN) alpha2a in patients without   HBeAg loss after the withdrawal of long-term lamivudine therapy.

Methods

Fifty patients with chronic hepatitis B without the loss of HBeAg after >=96 weeks   of lamivudine treatment were enrolled to withdraw from treatment to induce a biochemical   breakthrough. Patients who achieved a biochemical breakthrough within 24 weeks received   48-weeks of PEG-IFN alpha2a therapy, and were then assessed during a subsequent 24-week   follow-up period.

Results

Forty-three (86.0%) patients achieved a biochemical breakthrough within 24 weeks of   lamivudine withdrawal. The rates of combined response (both undetectable HBV DNA and   HBeAg loss) and HBsAg loss were alone 51.2% and 20.9%, respectively after 48 weeks   of PEG-IFN alpha2a therapy, and 44.2% and 18.6%, respectively, at 24 weeks after treatment   cessation. The end-of-treatment combined response rate was 65.4% among patients with   a baseline HBsAg <20,000 IU/mL, which was significantly higher than 29.4% of patients   with HBsAg >=20,000 IU/mL (P=0.031). For patients with HBsAg levels<1,500 IU/mL at   12 and 24 weeks therapy, the end-of-treatment combined response rate was 68.2% and   69.0%, which were both significantly higher than patients with HBsAg>=1,500 IU/mL   (33.3% and 14.3%; P=0.048 and 0.001). The end-of-treatment combined response rate   was significantly higher among patients with HBV DNA<105 copies/mL (76.2%) compared   to patients with HBV DNA>=105 copies/mL (27.3%) after 24 weeks of therapy (P=0.004).

Conclusion

Retreatment with PEG-IFN alpha2a was effective and safe for patients without HBeAg   loss after the withdrawal of long-term lamivudine therapy. HBsAg levels at the baseline,   12 and 24 weeks of therapy, and HBV DNA levels at 24 weeks of therapy, can predict   the effect of PEG-IFN alpha2a after 48 weeks of therapy.

                  The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.         

StephenW

长期拉米夫定治疗没有HBeAg消失,停药后的聚乙二醇干扰素alpha2a疗效

徐青，张慧艳，张坚平，清毛


2013年病毒学杂志，10:21 DOI：10.1186/1743-422X-10-21
出版日期：2013年1月15日
摘要（临时）
背景

长期拉米夫定治疗HBeAg消失后，已成为一个紧迫的问题是我们必须面对的临床患者无改善HBe血清转换率。不幸的是，还没有达成共识这些患者的mananement上。本研究的目的是评价疗效的聚乙二醇化干扰素（PEG-IFN）alpha2a患者无停药后的长期拉米夫定治疗HBeAg消失。
方法

> = 96周的拉米夫定治疗后HBeAg无损失50例慢性乙型肝炎患者退出治疗诱导的生化突破。患者谁取得了24个星期内生化突破48的周的PEG-IFN alpha2a的治疗，并在随后的24周的随访期间，然后评估。
结果

拉米夫定停药后24周，48个（86.0％）患者达到生化突破。的综合反应（检测不到HBV DNA和HBeAg消失），HBsAg转阴率分别为单独51.2％和20.9％，分别经过48周PEG-IFN alpha2a的治疗，44.2％和18.6％，分别在24周的治疗后，戒烟。结束治疗的综合反应率为65.4％，其中患者的基线HBsAg的20,000 IU / mL，是显着高于29.4％的患者中乙型肝炎表面抗原（HbsAg）> = 20,000 IU /毫升（P = 0.031）。对于患者的HBsAg水平<1500 IU / mL的12周和24周治疗，治疗结束的组合应答率分别为68.2％和69.0％，均显着高于患者的乙型肝炎表面抗原（HBsAg）> = 1500 IU /毫升（33.3 ％和14.3％，P = 0.048和0.001）。治疗结束的组合应答率显着高于其他患者的HBV DNA <105拷贝/ ml（76.2％）相比，患者HBV DNA> 105拷贝/毫升（27.3％），经过24周的治疗后（P = 0.004）。
结论

再处理与PEG-IFN alpha2a的的是有效的，安全性好，无停药后的长期拉米夫定治疗HBeAg消失。乙肝表面抗原在基线水平，12和24周的治疗后，HBV DNA水平在治疗24周48周的治疗后，可以预测的效果PEG-IFN alpha2a的。
完整的文章可以作为一个临时的PDF。在生产中完全格式化的PDF和HTML版本。

StephenW

Methods
Selections of patients and study design
Inclusion criteria included: i) age 18–60 years; ii) continuous lamivudine treatment >96
weeks; iii) serum HBV DNA levels <103 copies/mL;iv) positive for HBsAg and HBeAg, but
negative for anti-HBs and anti-HBe;v) normal liver function tests;vi) no history of liver
failure or cirrhosis,and the lack of cirrhosis confirmed by a computed tomography scan; vii)
neutrophil count ≥ 1.5×109/L and platelet count≥100×109/L. The exclusion criteria included:
i) superinfection with hepatitis A, C, D or E, cytomegalovirus, HIV, or Epstein–Barr virus as
confirmed by enzyme-linked immunosorbent assay; ii) other liver diseases such as alcoholic
liver disease, drug-induced hepatitis, Wilson disease and autoimmune hepatitis; iii) severe
medical or psychiatric illness; iv) a history of diabetes, cardiac disease, hypertension, or
renal, pulmonary disease or thyroid disease; v) pregnant or breastfeeding women; vi) an
unwillingness or inability to provide informed consent or fulfill the the requirements of the
study.
Fifty outpatients with chronic hepatitis B (35 male, 15 female; median age, 33 years; range,
20–52 years) were recruited at the Southwest Hospital, Third Military Medical University,
China, between January 2006 and June 2010. They were asked to withdraw from lamivudine
and any other medications. Liver function tests were performed every 4 weeks. When a
biochemical breakthrough was observed, patients underwent a serum HBV DNA test and
retreatment with either PEG-IFN α2a (180 μg, once per week) or lamivudine, in accordance
with the study design shown in Figure 1. This study was conducted in accordance with the
guidelines of the Declaration of Helsinki. The ethics committee of Southwest Hospital
approved the study protocol, and all patients gave witnessed, written informed consent.
Figure 1 Study design. Liver function was tested 4-weekly within 24 weeks of lamivudine
withdrawal and 12-weekly after 24 weeks of lamivudine withdrawal. ALT: alanine
aminotransferase; ULN: upper limit of normal; IFN: interferon; T-Bil: total bilirubin; LAM:
lamivudine.

StephenW

StephenW

Background
Chronic infection with hepatitis B virus (HBV) is a major global health problem, which
affects more than 400 million people worldwide [1,2]. Approximately 15–40% of infected
patients develop cirrhosis, liver failure or hepatocellular carcinoma (HCC). Appropriate
antiviral treatment has been confirmed to be effective in preventing advanced liver disease
and reducing the number of HBV-related deaths.
The current treatment options for chronic HBV infection consist of interferon-α (IFN-α) and
nucleos(t)ide analogues (NUCs), such as lamivudine, adefovir, entecavir and telbivudine.
Since lamivudine was initially approved for the treatment of chronic HBV infection in China,
several million affected patients have received long-term antiviral treatment with NUCs to
prevent disease progression. Most patients hope that the period of antiviral treatment is
temporary. In HBeAg- positive patients, durable HBe seroconversion is a satisfactory endpoint as it is associated with an improved prognosis [1]. However, it is very difficult for most HBeAg positive patients to meet the criteria for the cessation of lamivudine treatment. In these patients, the rate of HBe seroconversion with lamivudine treatment has been reported to be 16-17% at 48 weeks, 17-29% at 96 weeks, 23-40% at 144 weeks, and 28-47% at 192 weeks [1-4]. Unfortunately, extended treatment with lamivudine is associated with the development of drug resistance. The cumulative incidence of HBV resistance to lamivudine is 24% at 1 year, 38% at 2 years, 49% at 3 years, 67% at 4 years, and 70% at 5 years.
Therefore, it is very important to institute new treatment strategies to improve the rate of
HBeAg loss or HBe seroconversion for patients without HBeAg loss after long-term
lamivudine treatment. However, there are no definitive guidelines regarding whether
lamivudine therapy should be continued or a new treatment should be commenced and the
optimal stopping point for receiving lamivudine treatment has yet to be determined.
IFN-α exerts an antiviral effect by degrading viral mRNA and proteins, and upregulates the
immunological response to HBV by enhancing human leukocyte antigen class I expression
on hepatocytes, its use has been confirmed as effective in the treatment of chronic HBV
infection [1,5-8]. The use of pegylated interferon (PEG-IFN) α has certain advantages overNUCs, which include the absence of resistance, higher rates of HBeAg loss and
seroconversion, and higher rates of both sustained off-treatment virological responses and
HBsAg loss [1]. For HBeAg-positive patients with PEG-IFNα, higher rates of HBeAg loss or
seroconversion are associated with higher pre-treatment serum alanine aminotransferase
(ALT) levels. Additionally, post-treatment ALT flares with viral proliferation often occur
following the withdrawal of lamivudine. Thus, a new retreatment strategy that involves
switching from lamivudine during a withdrawal-induced ALT flare to PEG-IFN α2a therapy
is a reasonable protocol for patients without HBeAg loss after long-term lamivudine
treatment. However, neither the efficacy nor safety of this new treatment strategy has been
fully demonstrated. The aim of our study was to evaluate the use of PEG-IFN α2a therapy for the retreatment of patients with chronic HBV infection after a lamivudine withdrawal induced biochemical breakthrough. These patients were without HBeAg loss after more than
96 weeks lamivudine treatment.