Division of Gastroenterology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA.
Am J Gastroenterol. 2010 Jul;105(7):1551-60. doi: 10.1038/ajg.2010.3. Epub 2010 Jan 26.
Neuropsychiatric toxicity is a common dose-limiting side effect of interferon therapy. The primary aim of this study was to determine whether patients receiving long-term low-dose peginterferon therapy had a higher incidence of cognitive side effects compared with untreated patients enrolled in the Hepatitis C Antiviral Long-Term treatment against Cirrhosis (HALT-C) Trial.
A total of 129 patients with chronic hepatitis C and advanced fibrosis completed a battery of 10 neuropsychological tests and the Beck Depression Inventory at pretreatment baseline and at months 12, 24, 36, and 48 while receiving long-term peginterferonalpha2a (90 microg/week) or no therapy during the randomized phase of the HALT-C Trial. Cognitive impairment was defined as a global deficit score (GDS) > or = 1.0.
The mean age was 51.2 years, 67% were male, and 42% had cirrhosis. After accounting for baseline GDS scores, the mean GDS scores did not significantly change over time (P=0.46) nor with treatment group (P=0.49). Cognitive function was also not influenced by medication adherence in the 66 patients receiving maintenance peginterferon (P=0.14) after controlling for baseline GDS scores and time. Beck Depression scores did not significantly increase over time (P=0.60), nor did they vary by treatment group (P=0.74). Although 32% of patients experienced objective worsening of their liver disease during follow-up, the frequency and severity of cognitive impairment did not differ in those with and without disease progression (P=0.71).
Measures of cognitive function were neither influenced by low-dose peginterferon treatment nor with objective evidence of liver disease progression in patients with advanced chronic hepatitis C prospectively followed up for 3.5 years.
神经精神毒性是干扰素治疗的常见剂量限制副作用。本研究的主要目的是确定接受长期低剂量聚乙二醇干扰素治疗的患者与未接受治疗的慢性丙型肝炎患者相比,在接受长期聚乙二醇干扰素α2a(90μg/周)治疗或未接受治疗的情况下,是否会出现更高的认知副作用发生率抗肝硬化的丙型肝炎抗病毒长期治疗(HALT-C)试验的随机阶段。
129 例慢性丙型肝炎和晚期纤维化患者在接受长期聚乙二醇干扰素α2a(90μg/周)治疗或 HALT-C 试验随机阶段未接受治疗时,在治疗前基线和第 12、24、36 和 48 个月时完成了 10 项神经心理学测试和贝克抑郁量表。认知障碍定义为总体缺陷评分(GDS)≥1.0。
平均年龄为 51.2 岁,67%为男性,42%有肝硬化。在考虑基线 GDS 评分后,平均 GDS 评分随时间变化无显著差异(P=0.46),也不受治疗组影响(P=0.49)。在控制基线 GDS 评分和时间后,在接受维持性聚乙二醇干扰素治疗的 66 例患者中,药物依从性也不会影响认知功能(P=0.14)。贝克抑郁评分随时间无显著增加(P=0.60),也不受治疗组影响(P=0.74)。尽管在随访过程中有 32%的患者出现了肝脏疾病的客观恶化,但在疾病进展和无疾病进展的患者中,认知障碍的频率和严重程度没有差异(P=0.71)。
在前瞻性随访 3.5 年的慢性丙型肝炎患者中,低剂量聚乙二醇干扰素治疗或客观肝脏疾病进展均不会影响认知功能的测量。