van Zonneveld Monika, Honkoop Pieter, Hansen Bettina E, Niesters Hubertus G M, Darwish Murad Sarwa, de Man Robert A, Schalm Solko W, Janssen Harry L A
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Dr. Molewaterplein 40, Room Ca 326, 3015 GD Rotterdam, The Netherlands.
Hepatology. 2004 Mar;39(3):804-10. doi: 10.1002/hep.20128.
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.
关于干扰素α（IFN）治疗对慢性乙型肝炎（CHB）患者疾病进展和死亡率的长期影响的数据有限。为了评估影响临床结局和生存的因素，我们对1978年至2002年间接受IFN治疗的165例乙肝e抗原（HBeAg）阳性CHB患者进行了一项随访研究。IFN的中位剂量为30兆单位（MU）/周（范围为2 - 70 MU/周），中位治疗持续时间为16周（范围为1 - 92周）。治疗反应定义为IFN治疗结束后12个月内HBeAg消失。中位随访时间为8.8年（范围为0.3 - 24年）。54例患者（33%）对IFN治疗有反应。54例有反应者中有7例（13%）复发（HBeAg重新激活）。52%的有反应者乙肝表面抗原（HBsAg）消失，而无反应者中这一比例为9%（P <.001）。肝组织学显示有反应者的坏死性炎症活动减少，纤维化进展减缓。26例患者在随访期间死亡。8例患者发现肝细胞癌（HCC），其中6例为无反应者。在发生HCC的2例有反应者中，1例在治疗中断后复发。多因素分析显示，有反应者的生存率显著提高（死亡相对风险（RR）为0.28，95%可信区间为0.10 - 0.78），发生HCC的风险降低（RR为0.084，95%可信区间为0.09 - 0.75）。总之，对IFN治疗的反应导致临床缓解期延长，HBsAg血清学转换率增加，肝组织学改善。我们的结果表明，校正基线因素后，对IFN治疗的反应可提高生存率并降低发生HCC的风险。
