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Review
. 2025 May-Jun;15(3):102505.
doi: 10.1016/j.jceh.2025.102505. Epub 2025 Jan 22.

Managing Complex Hepatocellular Carcinoma Subtypes: Diffuse Infiltrative, Large Tumours, and Tumour Rupture-The Challenges and Strategies

Affiliations
Review

Managing Complex Hepatocellular Carcinoma Subtypes: Diffuse Infiltrative, Large Tumours, and Tumour Rupture-The Challenges and Strategies

Ashok Choudhury et al. J Clin Exp Hepatol. 2025 May-Jun.

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer globally, third most common cause of cancer-related death, and most common primary liver malignancy. Whilst nodular well-defined HCC remains the classical phenotype, presentations with infiltrative phenotype, very large HCC, and complications as tumour rupture provide immense diagnostic and therapeutic challenges. Infiltrative HCC is difficult to distinguish against the background cirrhotic liver. They are ill defined on imaging, have poor vascularity, and aggressive biological behaviour. Vascular invasion, metastasis, and poor response to loco-regional, as well as systemic therapy, leads to dismal prognosis. Very large HCCs have a relatively better prognosis than infiltrative HCC and mandate multimodal therapies to downstage for a curative response including liver transplant. Improvement in interventional radiology techniques, emerging evidence with systemic therapies including immunotherapy, and better understanding of tumour biology have opened newer avenues in the management of such complex cases. HCC rupture is a catastrophic moment in the natural history of HCC which has an exponential increase in mortality. Clinical presentation of pain abdomen, hypotension/syncope, new onset, or sudden increase in ascites mandates a strong suspicion of rupture. Presence of hemoperitoneum on diagnostic tap and contrast extravasation in a computed tomography/magnetic resonance imaging are the diagnostic hallmarks. Emergency surgical intervention, locoregional therapies in the form of bland embolisation, or chemoembolisation forms the management cornerstone. The long-term survival and liver transplant as a curative therapy still needs more data as fear of tumour spread is a possibility. This review summarises the clinical challenges with this advance HCC and provides an algorithmic approach for management.

Keywords: downstaging; infiltrative; large HCC; rupture.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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