Tsubota A, Kumada H, Chayama K, Arase Y, Saitoh S, Koida I, Suzuki Y, Kobayashi M, Murashima N, Ikeda K
Department of Gastroenterology, Toranomon Hospital, Minato-ku, Tokyo, Japan.
J Hepatol. 1997 Jul;27(1):49-55. doi: 10.1016/s0168-8278(97)80279-6.
BACKGROUND/AIMS: Although biochemical and virological responses to interferon-alpha therapy for chronic hepatitis C virus infection have been extensively studied, long-term changes in liver histology have not been well documented.
We retrospectively analyzed 105 paired liver biopsy specimens taken before and after treatment from 93 patients who persistently showed biochemical remission and an absence of viremia for up to 68 months.
The grading scores for necroinflammatory and fibrotic activity in the liver biopsy specimens decreased significantly after interferon-alpha therapy. Histological scores graded according to Knodell's components improved significantly in every category after interferon-alpha therapy. However, inflammatory cell infiltrates remained within the portal tracts for long periods; necroinflammation in the periportal and lobular regions were absent in most of the post-therapy specimens. The cumulative disappearance rate, calculated using the Kaplan-Meier method, was significantly lower for portal inflammation than for periportal or lobular necroinflammation but was equivalent to that for histological disease activity. On univariate analysis, age and fibrosis at the onset of treatment were significant factors influencing the response of histological disease activity to interferon-alpha therapy (p=0.025 and 0.049, respectively). Using Cox's proportional hazard analysis, age was the only significant independent predictor of histological response to treatment (p=0.035).
Clinical remission of chronic hepatitis C virus infection is associated with histological resolution of necroinflammation in the periportal and lobular regions. Host-related factors are likely to influence whether early remission of inflammation after interferon-alpha therapy occurs.
背景/目的：尽管针对慢性丙型肝炎病毒感染的干扰素-α治疗的生化和病毒学反应已得到广泛研究，但肝脏组织学的长期变化尚未得到充分记录。
我们回顾性分析了93例患者治疗前后的105对肝脏活检标本，这些患者持续出现生化缓解且无病毒血症长达68个月。
干扰素-α治疗后，肝脏活检标本中的坏死性炎症和纤维化活动分级评分显著降低。根据Knodell成分分级的组织学评分在干扰素-α治疗后各类别均有显著改善。然而，炎症细胞浸润长期存在于门管区；大多数治疗后的标本中门周和小叶区域无坏死性炎症。使用Kaplan-Meier方法计算的累积消失率，门管区炎症显著低于门周或小叶坏死性炎症，但与组织学疾病活动的累积消失率相当。单因素分析显示，治疗开始时的年龄和纤维化是影响组织学疾病活动对干扰素-α治疗反应的重要因素（分别为p = 0.025和0.049）。使用Cox比例风险分析，年龄是治疗组织学反应的唯一显著独立预测因素（p = 0.035）。
慢性丙型肝炎病毒感染的临床缓解与门周和小叶区域坏死性炎症的组织学消退相关。宿主相关因素可能影响干扰素-α治疗后炎症早期缓解是否发生。
