Nucleot(s)ide Analogues for Hepatitis B Virus-Related Hepatocellular Carcinoma after Curative Treatment: A Systematic Review and Meta-Analysis

<div><p>Aim</p><p>The benefit of nucleot(s)ide analogues (NA) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment has been widely debated due to the relatively weak evidence. The objective of this systematic review was to evaluate the effect of NA on recurrence and survival after curative treatment of HBV-HCC.</p><p>Methods</p><p>A systematic electronic search was performed. All controlled trials comparing NA versus placebo or no treatment were considered for inclusion. Results were expressed as Hazard Ratio for recurrence and survival with 95% confidence intervals using RevMan 5.2.</p><p>Results</p><p>We included 13 trials with 6350 patients. There were significant improvements for recurrence-free survival (HR 0.66, 95% CI 0.54–0.80; p<0.0001) and overall survival (HR 0.56, 95% CI 0.43–0.73; p<0.0001) in the adjuvant NA group compared with the control group. Sensitivity analyses confirmed the robustness of the results. There were no serious adverse effects being reported. Lamivudine resistance was from 28.6% to 37.5% but could be rescued by other types of NA or combination therapy.</p><p>Conclusion</p><p>Our study suggested benefits of adjuvant NA therapy following curative treatment of HBV-HCC. Since the great proven efficacy of NA in improving clinical and viral parameters besides HCC, further studies should be focused on broadening the indications for NA therapy after curative treatment of HBV-HCC.</p></div

Forest plot of 13 studies on the use of NA after curative treatment of HBV-HCC.

<p>(A) Forest plot showing significant benefit of NA therapy for recurrence free survival. (B) Forest plot showing significant benefit of NA therapy for overall survival.</p

Characteristics of the included studies.

<p>Abbreviations: T, treated; C, control; HCC, hepatocellular carcinoma; NOS, Newcastle-Ottawa Scale; NA, not available; HBeAg+, hepatitis B virus e antigen positive; RFA, radiofrequency ablation; LAM, lamivudine; ADV, adefovir; ETV, entecavir; PCEI, percutaneous ethanol injection.</p

Sensitivity analyses comparing nucleoside analogues versus control.

<p>Abbreviation: No., number; HR, hazard ratio; CI, confidence interval; df, degrees of freedom; RFS, recurrence free survival; OS, overall survival.</p><p>*Yin 2013 is a two-stage longitudinal clinical study and considered as 2 studies and the randomized controlled trial (RCT) is treated as high quality of non- RCT here.</p