Davis G L, Lindsay K, Albrecht J, Bodenheimer H C, Balart L A, Perrillo R P, Dienstag J L, Tamburro C, Schiff E R, Carey W
Section of Hepatobiliary Diseases, JHMHC, University of Florida, Gainesville 32610-0214, USA.
J Viral Hepat. 1994;1(1):55-63. doi: 10.1111/j.1365-2893.1994.tb00062.x.
Chronic non-A, non-B hepatitis (NANBH) is a common and often progressive liver disease. Based on current serological tests, hepatitis C virus (HCV) infection is responsible for most cases. Interferon-alpha (IFN) treatment at a dose of 3 x 10(6) units given three times per week for 24 weeks has been shown to be effective in normalizing serum alanine aminotransferase (ALT) levels and reducing hepatic inflammation in approximately 40% of these patients. The purpose of this study was to identify pretreatment characteristics in patients with chronic hepatitis C(CH-C) which would best predict a favourable response to IFN treatment (normalization of serum ALT). One hundred and sixty-three adult patients who had participated in a large multicentre treatment trial were included in the study group; 84 had been treated with 3 x 10(6) units of recombinant IFN-alpha-2b (rIFN) subcutaneously three times per week for 24 weeks and 79 patients had been treated with 1 x 10(6) units rIFN in the same dosage schedule. Forty-one pretreatment historical, clinical, laboratory and histological variables were evaluated. In addition, early biochemical improvement during treatment was evaluated as a predictor of ultimate response. Univariate analysis identified six variables (dose, dose m-2, weight, body surface area, ongoing ethanol use, white blood cell count and the presence of symptoms) as potential predictors of response (two-tailed, P < 0.15). By multivariate analysis, however, only the 3 x 10(6) dose of rIFN was independently predictive of response (P < 0.01). When the analysis of response was confined to those patients who received treatment with 3 x 10(6) units of rIFN, seven variables [body weight, surface area, dose m-2, current ethanol use, serum albumin and the presence of chronic persistent hepatitis (CPH) on entry liver biopsy] were more frequent in patients who responded to therapy. In a multivariate model, only CPH and body weight predicted an increased likelihood of response (P < 0.01). However, the model was not a sensitive predictor of response as only 18% of the study group had CPH on liver biopsy. A decrease in serum ALT levels within the first 12-16 weeks of rIFN treatment was found to be the strongest indicator of an ultimate response to treatment. Thus, assessment of early response to IFN treatment is the only practical means of predicting complete response and avoiding prolonged and unnecessary therapy in those with little chance of response.
慢性非甲非乙型肝炎（NANBH）是一种常见且通常呈进行性发展的肝脏疾病。根据目前的血清学检测，丙型肝炎病毒（HCV）感染是大多数病例的病因。已证明，以3×10⁶单位的剂量每周皮下注射三次、持续24周的α干扰素（IFN）治疗，可使约40%的此类患者血清丙氨酸转氨酶（ALT）水平恢复正常并减轻肝脏炎症。本研究的目的是确定慢性丙型肝炎（CH-C）患者的治疗前特征，这些特征最能预测对IFN治疗（血清ALT恢复正常）的良好反应。研究组纳入了163名参与大型多中心治疗试验的成年患者；其中84名患者接受了3×10⁶单位重组α-2b干扰素（rIFN）皮下注射，每周三次，共24周；79名患者接受了相同给药方案的1×10⁶单位rIFN治疗。评估了41项治疗前的病史、临床、实验室和组织学变量。此外，还将治疗期间早期的生化改善作为最终反应的预测指标进行了评估。单因素分析确定了六个变量（剂量、每平方米剂量、体重、体表面积、持续饮酒、白细胞计数和症状的存在）为反应的潜在预测指标（双侧，P<0.15）。然而，通过多因素分析，只有3×10⁶剂量的rIFN可独立预测反应（P<0.01）。当将反应分析局限于接受3×10⁶单位rIFN治疗的患者时，七个变量[体重、体表面积、每平方米剂量、当前饮酒情况、血清白蛋白以及肝活检初诊时慢性持续性肝炎（CPH）的存在]在治疗有反应的患者中更为常见。在多变量模型中，只有CPH和体重可预测反应可能性增加（P<0.01）。然而，该模型并非反应的敏感预测指标，因为研究组中只有18%的患者肝活检显示有CPH。发现rIFN治疗前12 - 16周内血清ALT水平下降是治疗最终反应的最强指标。因此，评估对IFN治疗的早期反应是预测完全反应以及避免对反应可能性小的患者进行长期和不必要治疗的唯一实用方法。
