Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
BMJ Open. 2013 Aug 14;3(8):e003265. doi: 10.1136/bmjopen-2013-003265.
The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV.
Random-effects pairwise meta-analysis of randomised trials and observational studies.
Electronic and manual searches were combined. Randomised controlled trials (RCTs) were included in the primary analyses. Observational studies were included in sensitivity analyses.
The primary outcome measures were HCC incidence and mortality. The secondary outcome measure was HCC mortality.
We included 8 RCTs, 8 prospective cohort studies and 19 case-control studies with a total of 3433 patients allocated to antiviral therapy and 4625 controls. The maximum duration of follow-up was 23 years. Randomised trials found no effect of antiviral therapy on HCC or mortality. Cohort studies found that antiviral therapy increased the risk of HCC (risk ratio 1.43; 95% CI 1.06 to 1.95), whereas case-control studies found a decreased risk of HCC in the intervention group (risk ratio 0.69; 95% CI 0.54 to 0.88). There was a clear difference between the results of RCTs and observational studies (test for subgroup differences, p<0.001). Antiviral therapy did not affect mortality in cohort studies, but reduced mortality in case-control studies (relative risk 0.71; 95% CI 0.54 to 0.93; test for subgroup differences, p=0.406).
The effect of antiviral therapy on clinical outcomes in HBV remains to be established. Although there was a positive effect in the sensitivity analyses, the strength of the evidence does not allow for extrapolation to clinical practice as research design plays an essential role in the overall assessment.
Prospero number CRD42013003881.
抗病毒治疗对慢性乙型肝炎病毒（HBV）患者临床结局的影响尚未确定。本研究旨在评估干扰素和/或核苷（酸）类似物与安慰剂或不干预相比，对预防 HBV 患者肝细胞癌（HCC）和死亡的影响。
随机对照试验和观察性研究的效应量合并的成对随机效应荟萃分析。
电子和手动检索相结合。将随机对照试验（RCT）纳入主要分析，将观察性研究纳入敏感性分析。
主要结局指标为 HCC 发生率和死亡率。次要结局指标为 HCC 死亡率。
共纳入 8 项 RCT、8 项前瞻性队列研究和 19 项病例对照研究，共纳入 3433 例接受抗病毒治疗的患者和 4625 例对照组。最长随访时间为 23 年。随机试验未发现抗病毒治疗对 HCC 或死亡率有影响。队列研究发现抗病毒治疗增加了 HCC 的风险（风险比 1.43；95%CI 1.06 至 1.95），而病例对照研究发现干预组 HCC 的风险降低（风险比 0.69；95%CI 0.54 至 0.88）。RCT 和观察性研究的结果存在明显差异（亚组检验，p<0.001）。抗病毒治疗对队列研究的死亡率没有影响，但对病例对照研究的死亡率有降低作用（相对危险度 0.71；95%CI 0.54 至 0.93；亚组检验，p=0.406）。
抗病毒治疗对 HBV 患者临床结局的影响仍有待确定。虽然敏感性分析显示出阳性效果，但由于研究设计在整体评估中起着至关重要的作用，因此证据强度不足以推广到临床实践中。
PROSPERO 注册号 CRD42013003881。
