Objective:

To characterize gut microbiome differences in ICI-treated patients with intermediate-to-advanced HCC and evaluate their associations with clinical outcomes.

Approach:

• Search Strategy: Four databases—PubMed, Embase, Web of Science, and the Cochrane Library—were searched for relevant articles published before May 31, 2026, using specific search terms related to gut microbiome and hepatocellular carcinoma.
• Statistical Analysis: A random-effects model was used to calculate standard mean differences and pooled hazard ratios, with additional subgroup, sensitivity, and publication bias analyses performed.

Key Findings:

• Beta diversity differed significantly in over 68% of studies, while alpha diversity indices did not differ significantly between responders and non-responders.
• Actinobacteriota was enriched among responders, while Bacteroides was depleted in non-responders.
• Protective taxa correlated with lower mortality risk included Collinsella and Ruminococcus, while risky taxa associated with worse outcomes included Bacteroides.AF20_13LB and Veillonella atypica.
• Reduced progression risk was linked to protective genera like Collinsella, while detrimental taxa were associated with worse progression-free survival outcomes.
• Responder enrichment of pathways for bile acid metabolism and fatty acid biosynthesis was observed, while non-responders showed increases in secondary bile acid metabolism.

Interpretation:

Distinct gut microbiome alterations are observed in HCC patients based on treatment response.

Limitations:

• The analysis is limited to studies published before May 31, 2026, which may not encompass the most current research.
• Variability in study designs and methodologies may affect the comparability of results.

Conclusion:

Gut microbiome profiles may indicate disease status in HCC patients undergoing ICI therapy.

Sources:

• Systematic Review Registration