| Background:Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most frequent cause of cancer-related death worldwide. Due to the prevalence of the viral hepatitis, obesity, and so on, the incidence rates of HCC are increasing all over the world. Half of these cases were estimated to occur in China. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the main cause of HCC. Nowadays, for patients with early tumor stage and compensated liver function, surgical resection or ablation is the main curative treatment choice. But approximately70%of patients suffered from recurrence after curative treatment within five years. Besides, there was not any effective strategy to prevent HCC recurrence. Antiviral regimens have been shown to improve the liver pathology and reduce the risk of HCC in patients with chronic viral hepatitis. It is hypothesized that adjuvant antiviral therapy following curative treatment of HCC would prevent recurrence and meanwhile improve survival. But available published work reports controversial results.Aim:1. To evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HBV/HCV-related HCC;2. To evaluate the safety of adjuvant antiviral therapy;3. Stratified analyses:adjuvant interferon (IFN) therapy versus placebo or no 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 the necessary data is provided. Methods:We conducted a systematic search using electronic databases (PubMed, EMBASE, Cochrane Library databases and Science Citation Index Expanded) for all the published studies without restriction of language or publication type (last date of searching published work:19December,2012). Reference lists of all identified papers (included studies and relevant reviews) were checked for additional studies suitable for inclusion. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Two authors independently identified the trials for inclusion, extracted data and assessed the risk of bias. Results were expressed as Hazard Ratio (HR) for time-to-event outcomes with95%confidence intervals (CI). The statistics were performed by RevMan version5.1and STATA version11.0. All studies were analyzed 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 the control group. All the included studies used conventional IFN as adjuvant antiviral therapy; none of them used pegylated IFN or NA. There were significant improvements for recurrence 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 with the control group. Subgroup analysis also showed a significant difference favoring IFN therapy in HCV-related HCC patients, but for HBV-related patients, the difference failed to reach 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 to moderate to severe side-effects like leucocytopenia, neutropenia, thrombocytopenia and hepatic toxicity.Conclusion:Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HBV/HCV-HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more potent adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed. Future trials should also focus on other clinically relevant aspects, such as quality of life and adverse effects. |
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