Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Sasaki Y, Kakumu S, Kiyosawa K, Okita K
Department of General Medicine, Osaka University Hospital, Osaka, Japan; First Department of Medicine, Osaka University School of Medicine, Osaka, Japan; First Department of Medicine, Aichi Medical School, Aichi, Japan; Second Department of Med.
J Viral Hepat. 2000 Sep;7(5):343-51. doi: 10.1046/j.1365-2893.2000.00250.x.
During long-term follow-up of patients chronically infected with the hepatitis C virus (HCV) and treated with interferon (IFN), we identified some who had persistent normalization of serum alanine aminotransferase (ALT) but remained positive for HCV RNA. The aims of this study were to clarify the characteristics of these patients and to examine their clinical outcome after treatment. Nine hundred and ninety-eight patients treated with IFN were followed-up biochemically and virologically, and by liver ultrasound, for 13-95 months. A short-term biochemical sustained response, where ALT remained within the normal range for 6 months after the completion of IFN therapy, was found in 296 patients; in 240 of these patients serum HCV RNA remained undetectable during long-term follow-up. The rate of HCV RNA persistence was 7.09 times greater in short-term biochemical sustained responders with a high viral load than in those with a low viral load (P=0.0001, odds ratio [OR]=7.09), and 3. 70-fold lower in those treated with a large dose of IFN than in those treated with a small dose (P=0.02, OR=0.27). Thirty-three (59%) of 56 patients without HCV eradication showed continuous ALT normalization for 26-80 months after cessation of IFN therapy. Short-term biochemical sustained responders who were older (P=0.009, OR=10.43) and who were male (P=0.03, OR=6.98) had a significantly greater probability of maintaining a normal ALT level, even when serum HCV RNA was positive. When the incidence of HCC was investigated during long-term follow-up in patients without HCV eradication, it was found to be significantly lower in patients with persistently normal ALT levels than in those with abnormal ALT levels (P=0.03). Hence, when HCV is not eradicated as a result of IFN therapy, it may induce a long-term carrier state of HCV infection with normal ALT levels in older or male patients, in whom the cumulative incidence of HCC is markedly decreased.
在对慢性丙型肝炎病毒（HCV）感染且接受干扰素（IFN）治疗的患者进行长期随访期间，我们发现一些患者血清丙氨酸氨基转移酶（ALT）持续正常，但HCV RNA仍为阳性。本研究的目的是阐明这些患者的特征，并检查其治疗后的临床结局。对998例接受IFN治疗的患者进行了长达13 - 95个月的生化、病毒学及肝脏超声随访。296例患者出现短期生化持续应答，即IFN治疗结束后ALT在正常范围内持续6个月；其中240例患者在长期随访期间血清HCV RNA仍未检测到。高病毒载量的短期生化持续应答者中HCV RNA持续存在的发生率比低病毒载量者高7.09倍（P = 0.0001，比值比[OR] = 7.09），大剂量IFN治疗者比小剂量治疗者低3.70倍（P = 0.02，OR = 0.27）。56例未实现HCV清除的患者中有33例（59%）在IFN治疗停止后ALT持续正常26 - 80个月。年龄较大（P = 0.009，OR = 10.43）及男性（P = 0.03，OR = 6.98）的短期生化持续应答者即使血清HCV RNA为阳性，维持ALT正常水平的可能性也显著更高。在未实现HCV清除的患者长期随访期间调查HCC发生率时，发现ALT持续正常的患者HCC发生率显著低于ALT异常的患者（P = 0.03）。因此，若IFN治疗未能清除HCV，可能会在年龄较大或男性患者中诱导出ALT水平正常的HCV感染长期携带状态，此类患者中HCC的累积发生率明显降低。
