Lancet. 1998 May 23;351(9115):1535-9.
There is debate about whether interferon-alpha treatment lowers the risk of progression to hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis and whether any effect is limited to certain subgroups. We investigated these issues by retrospective analysis of data for 913 patients from Italy and Argentina.
21 centres reported patients from their records who had chronic viral hepatitis and Child's A cirrhosis, were positive for HBsAg or hepatitis-C-virus antibodies (anti-HCV), and had been screened yearly for at least 3 years by ultrasonography and alpha-1-fetoprotein testing. Prognostic risk factors for hepatocellular carcinoma defined by multivariate Cox regression analysis and individual observation time were used for group matching and conditional logistic regression analysis of the independent interferon-alpha treatment effect.
After group matching, the number of patients was reduced to 637. Age, male sex, and portal hypertension were significant risk factors for hepatocellular carcinoma (each p < 0.001); hepatic inflammation (p = 0.21) and iron storage (p = 0.18) were also included in the model 66 (19%) of 356 untreated patients and 29 (10%) of 281 treated patients developed hepatocellular carcinoma (relative risk 1.99 [95% CI 1.09-3.64]); the corresponding proportions for anti-HCV-positive patients were 48 (18.5%) of 259 versus 21 (9.1%) of 232 (3.14 [1.46-6.80]), and those for hepatitis-B-virus-infected (HBV) patients were 18 (10%) of 97 and eight (16%) of 49 (0.98 [0.33-2.92]). Among anti-HCV patients without HBV markers, 29 (20%) of 129 untreated and six (5%) of 116 treated patients developed hepatocellular carcinoma (6.28 [1.65-23.8]).
Interferon treatment lowered the rate of progression to hepatocellular carcinoma two fold. The risk reduction was apparently greater for patients with chronic hepatitis C and no evidence of HBV infection. Future studies should stratify HCV-infected patients by HBV status.
对于α干扰素治疗是否能降低慢性病毒性肝炎和肝硬化患者进展为肝细胞癌的风险，以及这种效果是否仅限于某些亚组，存在争议。我们通过对来自意大利和阿根廷的913例患者的数据进行回顾性分析来研究这些问题。
21个中心报告了其记录中的患者，这些患者患有慢性病毒性肝炎且为Child's A级肝硬化，HBsAg或丙型肝炎病毒抗体（抗-HCV）呈阳性，并且每年至少接受3年的超声检查和甲胎蛋白检测。通过多变量Cox回归分析和个体观察时间确定的肝细胞癌预后危险因素用于组匹配和独立α干扰素治疗效果的条件逻辑回归分析。
组匹配后，患者数量减少至637例。年龄、男性和门静脉高压是肝细胞癌的显著危险因素（各p<0.001）；肝炎症（p = 0.21）和铁储存（p = 0.18）也纳入模型。356例未治疗患者中有66例（19%）发生肝细胞癌，281例治疗患者中有29例（10%）发生肝细胞癌（相对风险1.99 [95% CI 1.09 - 3.64]）；抗-HCV阳性患者的相应比例为259例中的48例（18.5%）对232例中的21例（9.1%）（3.14 [1.46 - 6.80]），乙肝病毒感染（HBV）患者的相应比例为97例中的18例（10%）对49例中的8例（16%）（0.98 [0.33 - 2.92]）。在无HBV标志物的抗-HCV患者中，129例未治疗患者中有29例（20%）发生肝细胞癌，116例治疗患者中有6例（5%）发生肝细胞癌（6.28 [1.65 - 23.8]）。
干扰素治疗使进展为肝细胞癌的发生率降低了两倍。对于慢性丙型肝炎且无HBV感染证据的患者，风险降低似乎更大。未来的研究应根据HBV状态对HCV感染患者进行分层。
