两篇关于IFN治疗CHB的长期疗效的Paper

^.^

两篇比较老的paper了。来自03年和04年Hepatology。早几天在网上找关于IFN治疗提高表抗转阴率的文章，看到了这两篇。当然这里说的是普通干扰素，毕竟PEG-IFN用于乙肝的治疗还没几年，临床统计数据恐怕一时还没那么快出来。两篇文章关于表抗转阴率的统计结果应该说差不多，即治疗后8年累计大概有20%左右的表抗转阴率。

——————————————————————————————————————

Long-Term Suppression of HBeAg-Negative CHB by24-Month Interferon Therapy

(HEPATOLOGY, Vol. 37, No. 4, 2003: 756-763.)

Pietro Lampertico（Univ. Milan，意大利米兰）et al.

【Abstract】

To assess whether extended treatment with interferon improves the outcome of hepatitis B e
antigen (HBeAg)-negative chronic hepatitis B, 101 consecutive patients were treated with 6
MU of interferon alfa 2b 3 times weekly for 24 months. During the 68-month study, 30
patients (30%) had a sustained response (i.e., normal serum transaminase levels and undetectable
hepatitis B virus DNA by non–polymerase chain reaction [PCR] assays), and 15
cleared serum surface antigen. Twenty-five nonresponders, 16 relapsers, and 30 who discontinued
treatment were considered treatment failures. Multivariate analysis predicted a sustained
response for young age (odds ratio, 0.94; 95% confidence interval, 0.89-0.99; P =
.041) and high pretreatment serum levels of immunoglobulinM(IgM) anti– hepatitis B core
antigen (HBc) (odds ratio, 4.52; 95% confidence interval, 1.63-12.5; P=.004). Liver disease
progressed in none of the sustained responders but in 16 with treatment failure (0% vs. 22%,
P = .002); hepatocellular carcinoma (HCC) developed with similar frequency in both
groups (7%). Overall, estimated 8-year complication-free survival was longer for the 30
sustained responders than the 71 patients with treatment failure (90% vs. 60%, P < .001),
but 8-year patient survival was similar in the 2 groups (100% and 90%). Short complicationfree
survival was predicted by failure to respond to interferon (hazard ratio, 7.8; 95%
confidence interval, 1.8-34.0; P=.006) and high scores for liver fibrosis (hazard ratio, 1.71;
95% confidence interval, 1.17-2.50; P =.005). In conclusion, 24 months of treatment with
interferon alfa 2b led to sustained disease suppression in a significant proportion of patients
with HBeAg-negative chronic hepatitis B. (HEPATOLOGY 2003;37:756-763.)

【主要内容】

为了评估针对HBeAg阴性CHB的干扰素治疗，延长疗程能否获得更好的治疗效果，101位患者接受了为期24个月的IFNα-2b（Intron A，先灵葆雅，意大利米兰）治疗，每周三次，每次6MU(即600万国际单位)。在68个月的随访期间，30例患者获得持续应答（转氨酶正常，HBV-DNA[PCR定量]低于检测值下限），其中15例患者HBsAg转阴（11例产生抗体）；共71例治疗失败，其中25例无应答，16例复发，30例提前中止治疗。

多元分析显示，低龄及治疗前较高的HBcAgIgM水平提示较好的持续应答。

持续应答组中无炎症进展情况发生，而治疗失败组中有16例炎症加剧。但HCC的发生率两组无明显差异。两组的八年期存活率无显著差别（100%vs90%），但并发症发生率长期应答组显著低于治疗失败组。

总的来说，24个月的长期IFN-alfa-2b治疗对持续疾病抑制有显著意义。

文中提到，预计8年持续应答率45%，表抗转阴率18%。

^.^

———————————————————————————————————————

Long-Term Follow-up of Alpha-Interferon Treatment ofPatients With CHB

(HEPATOLOGY, Vol. 39, No. 3, 2004: 804-810.)

Monika van Zonneveld（Erasmus Medical Center，荷兰鹿特丹）etal.

【Abstract】

Data on the long-term effects of interferon alfa (IFN) treatment on disease progression and
mortality in patients with chronic hepatitis B (CHB) are limited. To evaluate factors that
influence clinical outcome and survival, we performed a follow-up study on 165 hepatitis B
e antigen (HBeAg) positive CHB patients treated with IFN between 1978 and 2002. The
median IFN dose was 30 megaunits (MU)/week (range, 2–70 MU/week), and the median
duration of therapy was 16 weeks (range, 1–92 weeks). Response to treatment was defined as
HBeAg loss within 12 months after the end of IFN therapy. Median follow-up was 8.8 years
(range, 0.3–24 years). Fifty-four patients (33%) responded to IFN treatment. Relapse
(HBeAg reactivation) occurred in 7 of the 54 (13%) responders. Fifty-two percent of the
responders lost hepatitis B surface antigen (HBsAg) as compared with 9% of the nonresponders
(P<.001). Liver histology showed a decreased necroinflammatory activity and less
progression of fibrosis in responders. Twenty-six patients died during follow-up. Hepatocellular
carcinoma (HCC) was found in 8 patients, 6 of whom were nonresponders. Of the
two responders who developed HCC, one patient had relapsed after discontinuation of
therapy. Multivariate analysis showed significantly improved survival (relative risk (RR) of
death 0.28, 95% CI 0.10–0.78) and reduced risk of developing HCC (RR 0.084, 95% CI
0.09–0.75) in responders. In conclusion, response to IFN therapy results in a prolonged
clinical remission with an increased rate of HBsAg seroconversion and improved liver histology.
Our results indicate that after correction for baseline factors, response to IFN therapy
increases survival and reduces the risk of developing HCC. (HEPATOLOGY 2004;39:804–810.)

【主要内容】

IFN-α治疗对CHB疾病进展及死亡率的长期影响的数据很有限。为了评估干扰素治疗的临床效果以及存活率，随访了165位于1978-2002年间接受了干扰素治疗的HBeAg阳性CHB患者。IFN用量中线值30MU/周（区间值2-70MU/周）。持续治疗时间中线值16周（区间值1-92周）。治疗应答定义为治疗结束后12个月内HBeAg持续阴性。随访时间中线值为8.8年（区间值0.3-24年）。

54位患者（33%）获得治疗应答。应答者中52%[28例]表抗消失，而非应答者中只有9%[10例]。即所有接受治疗的165例患者中，表抗转阴率23%[38例]。

肝脏组织学显示，应答者炎症活动减少，纤维化进展减缓。随访期间，26例死亡。8例HCC，其中6例是非应答者。两例应答者HCC中，其中一例属于治疗结束后复发。多元分析显示，应答显著提高存活率，减少HCC发生率。

总之，IFN治疗应答有助于获得更高的HBsAg血清转换即肝组织学改善，并且提高存活率，减少HCC发生率。

^.^

看PDF能不能传上来~



[ 本帖最后由 ^.^ 于 2008-9-2 00:33 编辑 ]

^.^

呃，不错。继续~

^.^

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FORRESTFU

文章太老了，按那个朝代的那套评价方法，干扰的“应答”还是不高的。

当然后续跟踪部分的研究有些意义。

小小刘

这些文章非常有价值，非常感谢楼主。根本就不是FORRESTFU说说的 太老了。

楼主是 小三阳吗？

^.^

嗯。确实是老文章。不过我关注的不是应答情况（这方面的文献很多），我就是想了解下IFN对表抗转阴率到底有多大的提高。关于PEG-IFN提高表抗转阴率的文献我还没有找到。

要看新文章，可以搜一下他们的这两年的被参考文献。我把它们贴在这里，也是作为记事本，想到时候找来读读。这段时间比较忙，再过半个月大概就有空了。

^.^

关于应答，因为是长时间随访，所以随访对象甚至有1978年开始治疗的，治疗持续时间也长短不一。那个时候不如现在有经验，治疗策略大概很难是最优的。

而且两篇paper给出的“应答”的definition也不一样：“转氨酶正常，HBV-DNA[PCR定量]低于检测值下限”，以及“治疗结束后12个月内HBeAg持续阴性”。