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Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69–5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83–14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93–2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02–3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44–1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45–1.08). Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC. [ABSTRACT FROM AUTHOR]

The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs. The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS). Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40–0.56; PFS:HR = 0.39, 95%CI:0.33–0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82–2.89; PFS:HR = 2.34, 95%CI = 1.69–3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41–0.62; PFS:HR = 0.39, 95%CI:0.30–0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16–0.71; PFS:HR = 0.22, 95%CI:0.10–0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment. AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy. The review was not registered. [ABSTRACT FROM AUTHOR]

Backgrounds: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer., Methods: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest., Results: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05)., Conclusion: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings., (© The Author(s) 2024. Published by Oxford University Press.)