Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan; Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.
Hepatology. 2013 Oct;58(4):1253-62. doi: 10.1002/hep.26442. Epub 2013 Aug 19.
The effects of interferon (IFN) treatment and the post-IFN treatment α-fetoprotein (AFP) levels on risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) are unknown. To determine the relationship between AFP and alanine transaminase (ALT) levels and HCC risk, a cohort consisting of 1,818 patients histologically proven to have CHC treated with IFN were studied. Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 years using the Kaplan-Meier method and Cox proportional hazard analysis. HCC developed in 179 study subjects. According to multivariate analysis, older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, non sustained virological response (non-SVR), and higher post-IFN treatment ALT or AFP levels were identified as independent factors significantly associated with HCC development. Cutoff values for ALT and AFP for prediction of future HCC were determined as 40 IU/L and 6.0 ng/mL, respectively, and negative predictive values of these cutoffs were high at 0.960 in each value. The cumulative incidence of HCC was significantly lower in patients whose post-IFN treatment ALT and AFP levels were suppressed to less than the cutoff values even in non-SVR patients. This suppressive effect was also found in patients whose post-IFN treatment ALT and AFP levels were reduced to less than the cutoff values despite abnormal pretreatment levels.
Post-IFN treatment ALT and AFP levels are significantly associated with hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication.
干扰素（IFN）治疗及其治疗后甲胎蛋白（AFP）水平对慢性丙型肝炎（CHC）患者肝细胞癌（HCC）风险的影响尚不清楚。为了确定 AFP 和丙氨酸转氨酶（ALT）水平与 HCC 风险之间的关系，对 1818 例经组织学证实患有 IFN 治疗的 CHC 的患者进行了队列研究。使用 Kaplan-Meier 方法和 Cox 比例风险分析，在平均 6.1 年的随访期间分析累积发病率和 HCC 风险。在 179 名研究对象中发生了 HCC。根据多变量分析，年龄较大、男性、晚期纤维化、严重脂肪变性、较低的血清白蛋白水平、非持续病毒学应答（non-SVR）以及 IFN 治疗后较高的 ALT 或 AFP 水平被确定为与 HCC 发展显著相关的独立因素。确定 ALT 和 AFP 的预测未来 HCC 的截断值分别为 40IU/L 和 6.0ng/mL，每个值的阴性预测值均较高，为 0.960。即使在 non-SVR 患者中，IFN 治疗后 ALT 和 AFP 水平低于截断值的患者 HCC 的累积发生率显著降低。即使在预处理水平异常的情况下，IFN 治疗后 ALT 和 AFP 水平降低至低于截断值的患者也发现了这种抑制作用。
IFN 治疗后的 ALT 和 AFP 水平与肝癌发生显著相关。这些值的测量有助于预测 IFN 治疗后的未来 HCC 风险。即使在没有 HCV 清除的患者中，IFN 治疗后这些值的抑制也降低了 HCC 的风险。
