Manesis E K, Moschos M, Brouzas D, Kotsiras J, Petrou C, Theodosiadis G, Hadziyannis S
Academic Department of Medicine, Hippokration General Hospital, Athens, Greece.
Hepatology. 1998 May;27(5):1421-7. doi: 10.1002/hep.510270533.
Following our earlier observation of clinically evident optic tract neuropathy in patients receiving low-dose interferon (IFN) therapy, we prospectively evaluated 53 consecutive patients treated for chronic hepatitis B or C with a median dose of 3 MU of IFN-a2b thrice weekly. Measurements included routine ophthalmologic evaluation and recordings of visual evoked responses (VER), electroretinograms (ERG), visual acuity, and visual fields, before, at the end of IFN treatment, and at follow-up visits. Baseline P100 latencies of VERs (base-VER) were abnormally prolonged in 24 patients (32 of 106 eyes, 30.2%); age was the only significant covariate associated with increased risk for an abnormal base-VER by multiple logistic regression (relative risk [RR] 5.3 per each 5-year increase in age). In 45 patients (74 eyes) with normal baseline P100 latencies, the end-of-treatment VERs (end-VER) were significantly prolonged compared with baseline, becoming abnormal in 11 (15 of 74 eyes, 20.3%) (138.8+/-8.7 vs. 117.7+/-5.2 ms, P < .001). This subgroup had older age (59.1+/-11.0 vs. 47.5+/-15.3, P=.007) and reduced visual sensitivity compared with their own pretreatment measurements (24.5+/-1.6 vs. 23.0+/-1.2db, P=.019). Changes of end-VERs by age had a sigmoid distribution with a steep increase of values beyond the 5th decade (R2=.326, P < .001). In a logistic regression model, significant predictors of abnormal end-VERs were, patients' age (RR 5.6 per each 5-year increase), presence of hepatitis B virus (HBV) infection (RR 15.1 compared with hepatitis C virus [HCV] infection) and serum cholesterol levels above 240 mg% (RR 7.1 compared with values < 240 mg%). Subconjunctival hemorrhages were seen in 2 cases and funduscopic examination revealed cotton wool spots in one other. ERG recordings and the P100 amplitude remained unchanged. After stopping IFN, the treatment-associated neurovisual abnormalities reversed to normal in 7 patients (10 of 15 eyes) and persisted in 5 (5 of 15 eyes, 33.3%) for up to 37 (median 7.3) months observation, all patients remaining clinically asymptomatic. In conclusion, subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function.
在我们早期观察到接受低剂量干扰素（IFN）治疗的患者出现临床明显的视束神经病变后，我们前瞻性地评估了53例连续接受治疗的慢性乙型或丙型肝炎患者，他们接受的是中位剂量为3MU的IFN-α2b，每周三次。测量内容包括常规眼科评估以及在IFN治疗前、治疗结束时和随访时记录视觉诱发电位（VER）、视网膜电图（ERG）、视力和视野。24例患者（106只眼中的32只，30.2%）的VER基线P100潜伏期异常延长；通过多因素逻辑回归分析，年龄是与异常基线VER风险增加相关的唯一显著协变量（每增加5岁，相对风险[RR]为5.3）。在45例基线P100潜伏期正常的患者（74只眼）中，治疗结束时的VER与基线相比明显延长，11例（74只眼中的15只，20.3%）变为异常（138.8±8.7 vs. 117.7±5.2毫秒，P<.001）。该亚组患者年龄较大（59.1±11.0 vs. 47.5±15.3，P = .007），与治疗前测量值相比视觉敏感度降低（24.5±1.6 vs. 23.0±1.2分贝，P = .019）。按年龄划分的治疗结束时VER变化呈S形分布，在50岁以后数值急剧增加（R2 = .326，P<.001）。在逻辑回归模型中，治疗结束时VER异常的显著预测因素为患者年龄（每增加5岁RR为5.6）、乙型肝炎病毒（HBV）感染（与丙型肝炎病毒[HCV]感染相比RR为15.1）以及血清胆固醇水平高于240mg%（与<240mg%的值相比RR为7.1）。2例患者出现结膜下出血，另1例眼底检查发现棉絮斑。ERG记录和P100波幅保持不变。停止IFN治疗后，7例患者（15只眼中的10只）与治疗相关的神经视觉异常恢复正常，5例（15只眼中的5只，33.3%）持续异常长达37个月（中位7.3个月），所有患者临床均无症状。总之，亚临床神经视觉损害是低剂量IFN治疗常见但大多未被认识到的并发症，慢性乙型肝炎患者和年龄较大者似乎最易发生。这种明显无害的并发症持续时间长，在某些患者中可能不可逆转，对视觉功能的影响尚不确定。
