Brillanti S, Miglioli M, Barbara L
Istituto di Clinica Medica e Gastroenterologia, University of Bologna, Italy.
J Hepatol. 1995;23 Suppl 2:13-5; discussion 15-6.
BACKGROUND/AIMS: A sustained biochemical and virologic response to standard interferon therapy for chronic hepatitis C is seen in no more than 25% of patients, and the efficacy of re-treatment or of higher doses in non-responders and relapsers has not been established. A more effective therapy for interferon alfa-resistant hepatitis C is needed.
A study of ribavirin plus interferon alfa combination therapy was conducted in 30 patients with chronic hepatitis C resistant to a previous standard course of interferon alfa (14 interferon non-responders, 16 interferon relapsers). Patients were randomly assigned to receive either ribavirin, 800 mg daily, and interferon alfa, 3 MU thrice weekly (n = 15), or interferon alfa alone, 3 MU thrice weekly (n = 15), for 6 months.
At the end of treatment, normal alanine aminotransferase levels were observed in eight patients in the combination therapy group: one (14%) interferon non-responder and seven (87%) interferon relapsers (p = 0.01). Six months post-therapy, sustained normalization of alanine aminotransferase was achieved in seven (87%) interferon alfa relapsers, but not in any of the interferon alfa non-responders (p = 0.001). In the group of patients treated with interferon alfa alone, sustained normalization of alanine aminotransferase was observed in one interferon relapser only. Serum HCV RNA became negative in eight patients receiving combination therapy--two (28%) interferon non-responders and six (75%) interferon relapsers. Six months later, circulating HCV RNA remained negative in seven patients: one (14%) interferon non-responder and six (75%) interferon relapsers (p = 0.04). Sustained clearance of HCV RNA was not observed in patients re-treated with interferon alone. The sustained response to combination therapy was accompanied by reduced hepatic necroinflammatory activity on liver biopsy. Hepatitis C virus genotype was not significantly associated with response to combination therapy. Side effects were mild and well tolerated.
Our experience indicates that combination therapy of ribavirin plus interferon alfa induces sustained biochemical, virologic, and histologic responses in most patients who are interferon relapsers.
背景/目的：接受标准干扰素治疗的慢性丙型肝炎患者中，生化和病毒学持续应答率不超过25%，且再治疗或增加剂量对无应答者和复发者的疗效尚未明确。因此，需要一种对干扰素α耐药的丙型肝炎更有效的治疗方法。
对30例对先前标准疗程干扰素α耐药的慢性丙型肝炎患者（14例干扰素无应答者，16例干扰素复发者）进行了利巴韦林联合干扰素α的治疗研究。患者被随机分为两组，一组接受每日800mg利巴韦林和每周三次3MU干扰素α治疗（n = 15），另一组仅接受每周三次3MU干扰素α治疗（n = 15），疗程均为6个月。
治疗结束时，联合治疗组有8例患者丙氨酸转氨酶水平恢复正常：1例（14%）干扰素无应答者和7例（87%）干扰素复发者（P = 0.01）。治疗后6个月，7例（87%）干扰素α复发者丙氨酸转氨酶持续正常，但干扰素α无应答者均未出现（P = 0.001）。仅接受干扰素α治疗的患者组中，只有1例干扰素复发者丙氨酸转氨酶持续正常。接受联合治疗的8例患者血清HCV RNA转阴——2例（28%）干扰素无应答者和6例（75%）干扰素复发者。6个月后，7例患者循环HCV RNA仍为阴性：1例（14%）干扰素无应答者和6例（75%）干扰素复发者（P = 0.04）。仅接受干扰素再治疗的患者未观察到HCV RNA的持续清除。联合治疗的持续应答伴随着肝活检时肝脏坏死性炎症活动的减轻。丙型肝炎病毒基因型与联合治疗的应答无显著相关性。副作用轻微，耐受性良好。
我们的经验表明，利巴韦林联合干扰素α治疗能使大多数干扰素复发的患者产生持续的生化、病毒学和组织学应答。
