Maria Erquiaga

Background: Hepatocellular carcinoma (HCC) is the most common cancer of the liver,¹ with incidence continuing to rise alongside non-alcoholic fatty liver disease.² Particularly alarming is its high five year recurrence of ~70-80%,¹ correlated to the initial tumor stage,² size of hepatectomy,² and whether the patient received a full or partial transplant.⁶ While chronic liver damage impairs regeneration, the cells and environment of normal regenerative liver hyperplasia are largely favorable to HCC development or recurrence: both HCC and regenerating liver cells reallocate nutrients⁷ and experience dysplasia;⁸ normal regenerating hepatocytes undergo epithelial-to-mesenchymal transition (EMT)⁹ generally observed in metastasizing malignancies. While subtle differences in growth mechanisms have been noted, the high HCC recurrence rate in the regenerating liver has fueled interest in innate or innovated mechanisms of metaplasticity detection and prevention.

Methods: PubMed article searches used at least one of the following keywords: “hepatocellular carcinoma recurrence,” “regenerative liver hyperplasia,” “liver metaplasticity.” Additional key words (e.g., “hepassocin,” “polyploidy”) were permutated with established search terms to supplement and expand on previously found sources and to identify innovations alluded to in review articles (e.g., “microfluidics.”)

Results: Liver protections against HCC may be broadly grouped as immune or hepatocellular. Immune cell modulation¹⁰ and reliance on the complement system² check liver regeneration to prevent excess or uncontrolled growth. Moreover, hepatocytes defend against HCC via polyploid mitotic slowing,² typical angiogenesis factors nonessentialism,³ and variable protein expression.² However, these mechanisms may dually enhance and inhibit regeneration,² have limited efficacy against HCC,² or increase risk of de novo neoplasm.² Thus, much innovative effort explores alternative means to diagnose HCC in the regenerating liver via cells⁴ or microenvironment⁶ before high-HCC-risk procedures become the best mode of care.

Conclusions: While this review identified several physiological and innovative means to prevent HCC in the regenerating liver, many are poorly understood or carry significant risk of delayed recurrence. Moreover, fundamental similarities between these conditions hinder accurate diagnosis and effective HCC prevention strategies. Clinicians may therefore consider more routine screening for high-risk patients and less injurious modes of treating HCC. Future research and innovations should also seek more precise means of detection and treatment to minimize risk of recurrence.

Works Cited

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