van Zonneveld Monika, Zondervan Pieter E, Cakaloglu Yilmaz, Simon Christopher, Akarca Ulus S, So Thomas M K, Flink Hajo J, de Man Robert A, Schalm Solko W, Janssen Harry L A
Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
Liver Int. 2006 May;26(4):399-405. doi: 10.1111/j.1478-3231.2006.01257.x.
The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon alpha-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system.
Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 points, respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% of responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P=0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no significant association between virological and biochemical endpoints and histological improvement.
Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome.
聚乙二醇化干扰素或其与拉米夫定联合使用对慢性乙型肝炎（CHB）患者肝脏组织学的影响尚不清楚。在一项双盲、随机、多中心研究中，我们评估了110例乙肝e抗原（HBeAg）阳性的CHB患者，这些患者接受聚乙二醇化干扰素α-2b（PEG-IFN）联合拉米夫定或安慰剂治疗52周后的组织学变化。在治疗前和治疗结束时进行肝脏活检。所有活检标本均进行盲法处理，并根据Ishak系统进行评分。
PEG-IFN/拉米夫定联合治疗组25例患者（48%）和PEG-IFN单药治疗组31例患者（53%）的坏死性炎症评分有所改善（定义为至少降低2分）。联合治疗组17例患者（33%）的纤维化评分有所改善（至少降低1分），而PEG-IFN单药治疗组为13例患者（22%）（P = 0.23）。治疗结束时血清HBeAg阴性的应答者（n = 42）的坏死性炎症评分下降幅度大于无应答者（平均下降分别为2.3分和1.2分，P = 0.02）。在接受PEG-IFN单药治疗的患者中，应答者的坏死性炎症改善更为频繁（应答者为78%，无应答者为43%，P = 0.01），谷丙转氨酶（ALT）恢复正常的患者也是如此（ALT正常的患者为76%，ALT异常的患者为40%，P = 0.01）。PEG-IFN单药治疗组中，应答者的纤维化评分改善情况（39%）比无应答者（15%）更为常见（P = 0.04）。在PEG-IFN/拉米夫定联合治疗组中，我们未发现病毒学和生化终点与组织学改善之间存在显著关联。
PEG-IFN治疗可改善HBeAg阳性CHB患者的肝脏坏死性炎症，尤其是治疗应答者。PEG-IFN还可改善应答者的纤维化。在PEG-IFN中添加拉米夫定并未进一步改善组织学结果。
