Sacco, Rodolfo

There are limited and discordant results on the comparison between microwave ablation (MWA) and radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). This meta-analysis aims to compare the two treatments in terms of efficacy and safety, based on a meta-analysis of randomized-controlled trials (RCTs). A computerized bibliographic search was performed on the main databases throughout August 2020. The primary outcome was the complete response rate, while survival rate (at 1-, 2-, 3-, and 5-year), disease-free survival rate (at 1-, 2-, 3-, and 5-year), local and distant recurrence rate, adverse event rate, and number of treatment sessions were the secondary outcomes. Seven RCTs enrolling 921 patients were included. No difference in terms of complete response between the two treatments was observed (risk ratio (RR) 1.01, 95% CI 0.99–1.02). Survival rates were constantly similar, with RRs ranging from 1.05 (0.96–1.15) at 1 year to 0.91 (0.81–1.03) at 5 years. While local recurrence rate was similar between MWA and RFA (RR 0.70, 0.43–1.14), distant recurrence rate was significantly lower with MWA (RR 0.60, 0.39–0.92). Disease-free survival at 1, 2, and 3 years was similar between the two groups with RR 1.00 (0.96–1.04), 0.94 (0.84–1.06), and 1.06 (0.93–1.21), respectively. On the other hand, RR for disease-free survival at 5 years was significantly in favor of MWA (3.66, 1.32–42.27). Adverse event rate was similar between the two treatments (RR 1.06, 0.48–2.34), with bleeding and hematoma representing the most frequent complications. Our results indicate a similar efficacy and safety profile between the two techniques. MWA seems to decrease the rate of long-term recurrences, but this finding needs to be confirmed in further trials.

Despite the advances in screening protocols and treatment options, hepatocellular carcinoma (HCC) is still considered to be the most lethal malignancy in patients with liver cirrhosis. Moreover, the survival outcomes after failure of first-line therapy for unresectable HCC is still poor with limited therapeutic options. One of these options is immune checkpoint inhibitors. The aim of this study is to comprehensively review the efficacy and safety of immune checkpoint inhibitors for patients with HCC.

Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan–Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10–40 mm) and alpha-fetoprotein was 25 (1.1–2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42–51) in group 1, 51 months (42–88) in group 2, and 63 months (51–84) in group 3 (p = 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24–35) in group 1, 41 (23–72) in group 2 and 51 months (42–88) in group 3 (p = 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.

Hepatitis B virus is mainly considered to cause hepatocellular carcinoma which is the fourth leading cause of cancer-related mortality worldwide. Treatment of Hepatitis B virus with nucleos(t)ide analogues can decrease the progression of the disease and subsequently decreases the incidence of hepatocellular carcinoma. In this review, we have discussed the different classes of nucleos(t)ide analogues used in the treatment of Hepatitis B virus and their relationship with the development of hepatocellular carcinoma. Furthermore, we discussed the effect of treatment of Hepatitis B virus with Nucleoside analogues (NAs) before, during and after surgery, chemoembolization, radiofrequency ablation, and chemotherapy for the treatment of hepatocellular carcinoma.

Statins can decrease hepatocellular carcinoma (HCC) occurrence, but the magnitude and the predictors of these effects remain unclear. This meta-analysis provides a pooled estimate of the impact of statin use on HCC occurrence. Pooled effects were calculated using a random-effects model by means of the DerSimonian and Laird test. Primary endpoint was the time-dependent correlation between statin use and HCC incidence expressed as hazard ratio (HR), both crude and adjusted. The crude and adjusted odds ratios (OR) for HCC occurrence between statin users and non-users were analyzed. Twenty-five studies with 1,925,964 patients were included. Crude OR for HCC incidence was 0.59 (95% CI: 0.47–0.74), confirmed in adjusted analysis (OR: 0.74, 95% CI: 0.70–0.78). Adjusted HR was 0.73 (95% CI: 0.69–0.76). This effect was more pronounced in HBV patients (HR: 0.46, 95% CI: 0.36–0.60) and with a cumulative daily dose beyond 365 (HR: 0.27, 95% CI: 0.11–0.67). Lipophilic statins were associated with reduced HCC incidence (HR: 0.49, 95% CI: 0.39–0.62). Atorvastatin determined the greater magnitude of effect (HR: 0.43, 95% CI: 0.28–0.65). This meta-analysis demonstrates the beneficial chemopreventive effect of statins against HCC occurrence. This effect is dose-dependent and more pronounced with lipophilic statins.

Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46–12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68–3.86). The pooled objective response rate was 10.1% (7.8–12.5%) while the disease control rate was 65.5% (61.3–69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.