Meta‐analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C – an updated Cochrane review

Aliment Pharmacol Ther 2010; 32: 840–850

Summary

Background Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C. Aim To meta‐analyse the effect of adding ribavirin to interferon for chronic hepatitis C. Methods The results of randomized trials were combined in cumulative meta‐analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver‐related morbidity plus all‐cause mortality. Results We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64–0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P‐value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes. Conclusions The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes.     

Meta‐analysis: reduction in hepatic events following interferon‐alfa therapy of chronic hepatitis B

Aliment Pharmacol Ther 2010; 32: 1059–1068

Summary

Background The long‐term benefit of interferon‐alfa (IFN‐α) treatment in preventing various hepatic complications is not certain. Aim To study the effects of IFN‐α on reducing the risk of developing overall hepatic events (hepatocellular carcinoma, cirrhotic complications and liver‐related mortality) in chronic hepatitis B patients. Methods Randomized controlled trials, case–control studies and cohort studies were retrieved from electronic databases and conference abstracts. Relative risks (RRs) of different hepatic complications among patients treated by IFN‐α vs. no treatment or placebo were studied. Results Eleven studies were identified totalling 975 patients treated by IFN‐α vs. 1147 untreated controls for analysis. Patients were treated by IFN‐α for 1–24 months with a post‐treatment follow‐up of 1–13 years. Treatment by IFN‐α reduced the risk of overall hepatic events (RR 0.55, 95% confident interval or CI 0.43–0.70, P < 0.001) and cirrhotic complications (RR 0.46, 95% CI 0.32–0.67, P < 0.001) by 45% and 54% respectively. Patients who responded to IFN‐α had more profound reduction in overall hepatic events (RR 0.20, 95% CI 0.05–0.87, P = 0.03) and cirrhotic complications (RR 0.19, 95% CI 0.09–0.38, P < 0.001) vs. the untreated controls. Conclusion Interferon‐alfa treatment reduces the risk of hepatic events particularly among responders to treatment.     

Meta‐analysis: levamisole improves the immune response to hepatitis B vaccine in dialysis patients

Background Patients undergoing maintenance dialysis often fail to mount protective antibodies to hepatitis B virus surface antigen (HBsAg) following vaccination against hepatitis B virus (HBV). Some authors have suggested that levamisole improves immune response to HBV vaccine in dialysis population. However, consistent information on this issue does not exist. Aim To evaluate efficacy and safety of levamisole as adjuvant to hepatitis B virus (HBV) vaccine in dialysis patients by performing a systematic review of the literature with a meta‐analysis of clinical trials. Methods We used the random‐effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. Only trials comparing the seroresponse rate in study subjects (levamisole plus HBV vaccine) vs. controls (HBV vaccine alone) were included. The end point of interest was the rate of patients showing seroprotective anti‐hepatitis B titres at completion of HBV vaccine schedule in study vs. control groups. Results We identified four studies involving 328 unique patients on regular dialysis. Only prospective, randomized clinical trials (RCTs) were included. Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs. control (HBV vaccine alone) patients; the pooled Odds Ratio was 2.432 (95% Confidence Intervals, 1.34; 4.403), P = 0.002. No study heterogeneity was found. These results did not change in various subgroups of interest. Conclusions Our meta‐analysis showed that levamisole significantly improves immune response to hepatitis B vaccine in dialysis population. The limited number of patients precluded more conclusions.     

Meta‐analysis: isosorbide‐mononitrate alone or with either beta‐blockers or endoscopic therapy for the management of oesophageal varices

Aliment Pharmacol Ther 2010; 32: 859–871

Summary

Background The evidence concerning the use of isosorbide‐mononitrate (IsMn) for oesophageal varices is equivocal. Aim To assess the effects of IsMn for patients with oesophageal varices and no previous bleeding (primary prevention) or previous variceal bleeding (secondary prevention). Methods Systematic review with meta‐analyses of randomized trials on IsMn alone or with beta‐blockers or endoscopic therapy for oesophageal varices. Electronic and manual searches were combined. Randomized trials on primary and secondary prevention were included. The primary outcome measure was mortality. Intention‐to‐treat random effects meta‐analyses were performed. The robustness of the results was assessed in trial sequential analyses. Results Ten randomized trials on primary and 17 on secondary prevention were included. Evidence of bias was identified. No apparent effect of IsMn on mortality compared with placebo or beta‐blockers or IsMn plus beta‐blockers vs. beta‐blockers was identified. Compared with endoscopic therapy, IsMn plus beta‐blockers had no apparent effect on bleeding, but did seem to reduce mortality in secondary prevention (RR 0.73, 95% CI 0.59–0.89), but not in primary prevention. The effect of IsMn plus beta‐blockers on mortality in secondary prevention was not confirmed in trial sequential analysis. Conclusions Isosorbide‐mononitrate used alone or in combination with beta blockers does not seem to offer any reduction in bleeding in the primary or secondary prevention of oesophageal varices. Compared with endoscopic therapy, there may be a survival advantage in using IsMn and beta‐blockers, but additional large multicentre trials are needed to verify this finding.     

肝切除、射频消融和肝移植三种方案治疗小肝癌的临床疗效比较

目的对小肝癌(小肝细胞癌)的3种常用外科治疗方法进行疗效比较,为小肝癌的临床治疗方案选择提供参考。方法选取2006年1月—2015年12月解放军401医院外科治疗的660例小肝癌病例进行研究。根据肿瘤直径分为0~2.0 cm、2.1~3.0 cm、3.1~5.0 cm和多发组,根据治疗方案分为肝切除组、射频消融组和肝移植组。比较各组之间整体生存时间和整体生存率、无瘤生存时间和无瘤生存率的差异。结果在0~2.0 cm组和2.1~3.0 cm组中,肝切除和射频消融的疗效相当,而肝移植的疗效优于肝切除和射频消融(P<0.05);在3.1~5.0 cm组中,肝移植的疗效最优,肝切除次之,射频消融效果最差(P<0.05);在多发组中,肝切除和射频消融的疗效相当,而肝移植的疗效优于肝切除和射频消融(P<0.05)。结论小肝癌瘤体的直径和数目对治疗方案的选择具有重要的临床意义,其中肝移植治疗小肝癌疗效最佳。     

乙型肝炎病毒相关性肝细胞癌射频消融后肿瘤复发多因素分析

目的探讨乙型肝炎病毒(HBV)相关性肝细胞癌(HCC)射频消融(RFA)治疗后肿瘤复发的危险因素,为进一步明确预后,指导治疗提供依据。方法回顾性分析山西省肿瘤医院就诊的72例HBV相关性HCC患者超声引导下行RFA规范化治疗的资料,所有病例均经超声造影、增强CT或磁共振成像(MRI)规律随访,统计分析影响复发的相关因素。结果40例发生肿瘤复发,中位复发时间为18.5个月。单因素分析显示肿瘤数目、病理分级、术前HBV DNA载量及是否抗病毒治疗与肿瘤复发相关;COX多因素分析显示肿瘤数目(P=0.006)是否抗病毒治疗(P=0.025)是独立影响因素。结论肿瘤数目、是否抗病毒治疗是HBV相关性HCC RFA治疗后复发的独立影响因素,有效的抗病毒治疗能抑制病毒复制,降低复发率,提高疗效,改善生存。