Comparison of liver resection and radiofrequency ablation in long-term survival among patients with early-stage hepatocellular carcinoma: a meta-analysis of randomized trials and high-quality propensity score-matched studies.

BACKGROUND: Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS: Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively). CONCLUSIONS: Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.

Can adjuvant immune checkpoint inhibitors improve the long-term outcomes of hepatocellular carcinoma with high-risk recurrent factors after liver resection? A meta-analysis and systematic review.

Background: Administering adjuvant therapy following liver resection is crucial for patients with hepatocellular carcinoma (HCC) exhibiting high-risk recurrence factors. Immune checkpoint inhibitors (ICIs) are effective against unresectable HCC; however, their effectiveness and safety for this specific patient group remain uncertain. Methods: We conducted an extensive literature search across four scholarly databases to identify relevant studies. Our primary endpoints were overall survival (OS), recurrence-free survival (RFS), and adverse events (AEs). OS and RFS were quantified using hazard ratios (HRs), whereas the 1-, 2-, and 3-year OS and RFS rates were expressed as risk ratios (RRs). Additionally, the incidence of AEs was calculated. Results: Our meta-analysis included 11 studies (N = 3,219 patients), comprising two randomized controlled trials (RCTs) and nine retrospective studies. Among these, eight studies reported HRs for OS, showing a statistically significant improvement in OS among patients receiving adjuvant ICIs (HR, 0.60; 95% confidence interval [CI], 0.45-0.80; p < 0.0001). All included studies reported HRs for RFS, indicating a favorable impact of adjuvant ICIs (HR, 0.62; 95% CI, 0.52-0.73; p < 0.0001). Moreover, aggregated data demonstrated improved 1- and 2-year OS and RFS rates with adjuvant ICIs. The incidence rate of AEs of any grade was 0.70 (95% CI, 0.49-0.91), with grade 3 or above AEs occurring at a rate of 0.12 (95% CI, 0.05-0.20). Conclusion: Adjuvant ICI therapy can enhance both OS and RFS rates in patients with HCC exhibiting high-risk recurrence factors, with manageable AEs. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023488250.

A systematic review and meta-analysis comparing the impact of tenofovir and entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma patients undergoing liver resection.

Background: Tenofovir (TDF) and entecavir (ETV) are highly effective and well-tolerated nucleos(t)ide analogs commonly prescribed for hepatitis B virus (HBV) treatment. Yet, it is unclear whether survival outcomes differ for HBV-related hepatocellular carcinoma (HCC) patients treated with ETV and TDF. Thus, this meta-analysis aimed to compare the prognostic effectiveness of ETV and TDF in HBV-related HCC patients. Methods: We comprehensively searched four databases, PubMed, Web of Science, Embase, and the Cochrane Library, to identify pertinent studies utilizing keywords "entecavir," "tenofovir," "hepatocellular carcinoma," and "liver resection." Our primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HRs). Results: Our search yielded 10 studies encompassing 11 datasets involving 7,400 patients. Our meta-analysis revealed that patients treated with TDF achieved better OS (HR = 0.53; 95% confidence interval [CI] = 0.40-0.70, p < 0.0001), RFS (HR = 0.68; 95% CI = 0.57-0.80; p < 0.0001), early recurrence (HR = 0.80; 95% CI = 0.67-0.94; p < 0.0077), and late recurrence (HR = 0.64; 95% CI = 0.43-0.97; p = 0.0368). We detected publication bias potentially affecting OS but not RFS. Conclusion: Our findings demonstrated that TDF outperformed ETV regarding RFS for HBV-related HCC patients. However, to bolster the evidence and establish more conclusive conclusions, further validation via extensive and high-quality randomized controlled trials is essential. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD 42024542579.

Prognostic value of tertiary lymphoid structures in hepatocellular carcinoma: a meta-analysis and systematic review.

Background: Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC. Methods: We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords "tertiary lymphoid structures" and "hepatocellular carcinoma." The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR). Results: Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients. Conclusion: The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.