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Armstrong et al. Hepatoma Res 2021;7:18 I http://dx.doi.org/10.20517/2394-5079.2020.118 Page 9 of 12
[48]
28% response occurred if the PD-L1 expression rate was > 1% . The role of PD-L1 expression in HCC
patients treated with checkpoint inhibitors remains unknown and warrants further research.

CONCLUSION
In conclusion, HCC is a heterogeneous disease with many faces. It evades early detection, which
provides the greatest chance of cure by resection/transplant, and systemic treatments end up being of
modest benefit at best, despite recent therapeutic strides. Current developments in immunotherapy and
its combinations have changed the HCC therapeutic landscape, and clinical trials continue to pave the
way into the future. Immunotherapy leads to prolongation of survival rates and durably controls cancer
in subsets of patients with HCC, while also maintaining a well-managed side effect profile. Further
investigation of immunotherapy in combination with current treatments for early and intermediate stages
of HCC may provide benefit for a broader range of patients. Biomarkers to identify those who will benefit
from immunotherapy are still needed, and continued exploration into PD-1/PD-L1, TMB, ctDNA, DNA
mismatch repair, microsatellite stability, cytokines, neutrophil/lymphocyte ratio and cellular peripheral
immune response will hopefully identify the most reliable marker for selecting and sequencing systemic
treatments to achieve the best outcome in HCC patients. Although there are such exciting therapeutic
changes in HCC, numerous challenges remain. The research community needs to elucidate how to best
sequence these therapies for the best possible response, manage toxicities, and identify markers to monitor
for response and relapse.

DECLARATIONS
Acknowledgments
Many thanks to Marion L Hartley for her invaluable edits to this manuscript.

Authors’ contributions
Made substantial contributions to the conception and design of the study, and performed data analysis and
interpretation: Armstrong S, Prins P, He AR

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.

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