Gluud L L, Krogsgaard K, Gluud C
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Rigshospitalet, Dept. 3344, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
Cochrane Database Syst Rev. 2007 Jul 18;2002(2):CD002234. doi: 10.1002/14651858.CD002234.pub2.
Hepatitis C is a major cause of liver-related morbidity and mortality. Ribavirin plus interferon combination therapy is presently considered the optimal treatment of interferon naive patients with chronic hepatitis C, but its role in relapsers and non-responders to previous interferon therapy is not established.
To assess the efficacy and safety of ribavirin alone or in combination with alpha interferon in interferon naive patients, relapsers, and non-responders with chronic hepatitis C.
Eligible trials were identified through searches on electronic databases: The Cochrane Hepato-Biliary Group Controlled Trials Register (August 2001), The Cochrane Controlled Trials Register on The Cochrane Library Issue 3, 2001, MEDLINE (1966 - August 2001), and EMBASE (1985 - August 2001). Manual searches of bibliographies and journals were done as well as authors of trials and pharmaceutical companies producing ribavirin or interferon were contacted.
We included all randomised trials comparing ribavirin with or without alpha interferon versus no intervention, placebo, or alpha interferon for chronic hepatitis C.
The primary outcome measures were the 'sustained' (six months after treatment) virological response, and morbidity plus mortality. The secondary outcome measures were the 'end of treatment' and 'sustained' biochemical response, the 'end of treatment' virologic response, histology, quality of life, and adverse events.
We included eight trials in which 271 patients were randomised to ribavirin versus placebo or no intervention and 48 trials in which 6585 patients were randomised to interferon with or without ribavirin. Compared with placebo or no intervention, ribavirin monotherapy had no significant effect on the virological response or histology and only a transient effect on the biochemical response. Compared with interferon, combination therapy reduced the risk of not having a sustained virological response by 26% in naive patients (relative risk (RR) 0.74; 95% confidence interval (CI) 0.70-0.78), 33% in relapsers (RR 0.67; 95% CI 0.57-0.78), and 11% in non-responders (RR 0.89; 95% CI 0.83-0.96). There was no significant effect on morbidity plus mortality (Peto odds ratio 0.45; 95% CI 0.19-1.06). Irrespective of previous therapy, combination therapy significantly reduced the risk of not having a sustained biochemical response (RR 0.76; 95% CI 0.59-0.84) or improved histology (RR 0.67; 95% CI 0.56-0.81). Combination therapy also significantly increased the risk of treatment discontinuation (RR 1.28; 95% CI 1.07-1.52) and several types of adverse events.
AUTHORS' CONCLUSIONS: Combination therapy increased the number of naive patients, relapsers, and non-responders with a sustained virological, biochemical, or histological response, but also the occurrence of adverse events.
丙型肝炎是导致肝脏相关发病和死亡的主要原因。目前，利巴韦林加干扰素联合疗法被认为是初治慢性丙型肝炎患者的最佳治疗方法，但对于复发患者和既往干扰素治疗无应答者，其作用尚不明确。
评估单用利巴韦林或与α干扰素联合应用于初治、复发及既往干扰素治疗无应答的慢性丙型肝炎患者的疗效和安全性。
通过检索电子数据库来确定符合条件的试验：Cochrane肝胆疾病组对照试验注册库（2001年8月）、Cochrane图书馆2001年第3期的Cochrane对照试验注册库、MEDLINE（1966年 - 2001年8月）以及EMBASE（1985年 - 2001年8月）。同时对手稿目录和期刊进行手工检索，并联系试验作者以及生产利巴韦林或干扰素的制药公司。
我们纳入了所有比较利巴韦林加或不加α干扰素与不干预、安慰剂或α干扰素用于慢性丙型肝炎治疗的随机试验。
主要结局指标为“持续”（治疗后6个月）病毒学应答以及发病率和死亡率。次要结局指标为“治疗结束时”和“持续”生化应答、“治疗结束时”病毒学应答、组织学、生活质量以及不良事件。
我们纳入了8项试验，其中271例患者被随机分配接受利巴韦林与安慰剂或不干预治疗，48项试验中6585例患者被随机分配接受干扰素加或不加利巴韦林治疗。与安慰剂或不干预相比，利巴韦林单药治疗对病毒学应答或组织学无显著影响，对生化应答仅有短暂影响。与干扰素相比，联合治疗使初治患者无持续病毒学应答的风险降低了(26%)（相对危险度（RR）(0.74)；(95%)置信区间（CI）(0.70 - 0.78)），复发患者降低了(33%)（RR (0.67)；(95%)CI (0.57 - 0.78)），无应答者降低了(11%)（RR (0.89)；(95%)CI (0.83 - 0.96)）。对发病率和死亡率无显著影响（Peto比值比(0.45)；(95%)CI (0.19 - 1.06)）。无论既往治疗情况如何，联合治疗均显著降低了无持续生化应答的风险（RR (0.76)；(95%)CI (0.59 - 0.84)）或改善了组织学（RR (0.67)；(95%)CI (0.56 - 0.81)）。联合治疗还显著增加了治疗中断的风险（RR (1.28)；(95%)CI (→1.07 - 1.52)）以及多种不良事件的发生。
联合治疗增加了初治患者、复发患者和无应答者出现持续病毒学、生化或组织学应答的人数，但也增加了不良事件的发生。
