| Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and thethird most frequent cause of cancer-related death worldwide. Due to the prevalence of theviral hepatitis, obesity, and so on, the incidence rates of HCC are increasing all over theworld. Half of these cases were estimated to occur in China. Hepatitis B virus (HBV) andhepatitis C virus (HCV) are the main cause of HCC. Nowadays, for patients with earlytumor stage and compensated liver function, surgical resection or ablation is the maincurative treatment choice. But approximately70%of patients suffered from recurrenceafter curative treatment within five years. Besides, there was not any effective strategy toprevent HCC recurrence. Antiviral regimens have been shown to improve the liverpathology and reduce the risk of HCC in patients with chronic viral hepatitis. It ishypothesized that adjuvant antiviral therapy following curative treatment of HCC wouldprevent recurrence and meanwhile improve survival. But available published work reportscontroversial results.Aim:1. To evaluate the effect of adjuvant antiviral therapy on recurrence and survivalafter curative treatment of HBV/HCV-related HCC;2. To evaluate the safety of adjuvantantiviral therapy;3. Stratified analyses: adjuvant interferon (IFN) therapy versus placebo orno treatment, adjuvant nucleos(t)ide analogs (NA) therapy versus placebo or no treatment,subgroup of HBV-related HCC and subgroup of HCV-related HCC will be analyzed if thenecessary data is provided. Methods: We conducted a systematic search using electronic databases (PubMed,EMBASE, Cochrane Library databases and Science Citation Index Expanded) for all thepublished studies without restriction of language or publication type (last date of searchingpublished work:19December,2012). Reference lists of all identified papers (includedstudies and relevant reviews) were checked for additional studies suitable for inclusion. Allrandomized controlled trials comparing adjuvant antiviral therapy versus placebo or notreatment were considered for this review. Two authors independently identified the trialsfor inclusion, extracted data and assessed the risk of bias. Results were expressed as HazardRatio (HR) for time-to-event outcomes with95%confidence intervals (CI). The statisticswere performed by RevMan version5.1and STATA version11.0. All studies wereanalyzed using the ’intention to treat’ principle.Results: We included nine trials (three of low risk of bias and six of unclear risk of bias)with954patients randomized:493to the adjuvant antiviral therapy group and461to thecontrol group. All the included studies used conventional IFN as adjuvant antiviral therapy;none of them used pegylated IFN or NA. There were significant improvements forrecurrence free survival (HR=0.81,95%CI=0.68~0.95; P=0.01) and overall survival(HR=0.59,95%CI=0.46~0.76; P <0.0001) in the adjuvant IFN group compared withthe control group. Subgroup analysis also showed a significant difference favoring IFNtherapy in HCV-related HCC patients, but for HBV-related patients, the difference failed toreach statistical significance between the two groups. A dose reduction was needed in28.3%of patients and discontinuation of IFN therapy happened in8.2%of patients due tomoderate to severe side-effects like leucocytopenia, neutropenia, thrombocytopenia andhepatic toxicity.Conclusion: Our study suggested potential benefits of adjuvant IFN therapy followingcurative treatment of HBV/HCV-HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more potent adjuvant antiviral regimens, eitherused alone or in combination, for virus-related HCC, especially HBV-related HCC, areneeded. Future trials should also focus on other clinically relevant aspects, such as qualityof life and adverse effects. |
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