What gaps exist between lab findings and real-world treatment for hepatocellular carcinoma?

Hepatocellular carcinoma (HCC) research has uncovered many molecular mechanisms and potential biomarkers, but applying these lab findings to everyday patient care remains challenging. Gaps exist because tumors are highly variable between patients, clinical trials often don't reflect diverse populations, and promising lab discoveries lack practical tools for doctors to use at the bedside. This answer highlights key gaps identified in recent studies.

What the research says

A narrative review on HCC highlights that the disease is driven by a complex 'aerobic glycolysis-lactate-acidic tumor microenvironment' axis, involving multiple enzymes and transporters ¹. While this pathway offers many potential drug targets, the review notes that HCC is highly heterogeneous, meaning that what works in one patient's tumor may not work in another's ¹. This heterogeneity makes it difficult to translate lab findings into a one-size-fits-all treatment.

Another gap is the lack of validated, non-invasive biomarkers for routine use. For example, a meta-analysis found that a high monocyte-to-lymphocyte ratio (MLR) is linked to poor survival in HCC patients ². However, MLR is not yet a standard test in clinical practice, and more work is needed to confirm its utility across different patient groups ². Similarly, a preoperative model using alpha-fetoprotein, tumor size, and tumor margin can predict microvascular invasion, but this model requires further validation before widespread adoption ⁸.

Racial and ethnic disparities also represent a gap between research and real-world outcomes. A systematic review and meta-analysis found that Black patients have worse survival after liver transplant for HCC compared to White patients, while Asian patients tend to have better outcomes ³. These disparities are not explained by lab findings alone and point to differences in access to care, socioeconomic factors, and potential biological differences that are often understudied ³.

Finally, even when effective treatments exist, their real-world use may be suboptimal. A meta-analysis on immune checkpoint inhibitors (ICIs) found that early time-of-day administration (before 12:00 PM) is associated with better overall survival in advanced solid tumors, including HCC ⁴. Yet, this timing factor is rarely considered in routine practice, representing a simple but overlooked gap ⁴.

What to ask your doctor

• Are there any blood tests or imaging markers that can help predict my tumor's behavior or response to treatment?
• How does my race or ethnicity affect my treatment options and prognosis for HCC?
• If I am receiving immunotherapy, does the time of day I get the infusion matter for my outcome?
• What is my risk of microvascular invasion, and how might that affect my surgery or transplant plan?
• Are there any clinical trials available that target the specific molecular features of my tumor?