Clinical Scorecard: Evaluating Imaging Techniques for Molecular and Pathological Classification of Hepatocellular Carcinoma: A Review and Future Perspectives
At a Glance
Category
Detail
Condition
Hepatocellular carcinoma (HCC), a biologically heterogeneous liver malignancy
Key Mechanisms
Molecular heterogeneity (proliferative vs non-proliferative classes) and pathological heterogeneity influencing prognosis and treatment response
Target Population
Patients with HCC, including those with chronic HBV, HCV, ALD, MASH, and other liver disease etiologies
Care Setting
Clinical oncology and hepatology settings involving imaging and therapeutic decision-making
Key Highlights
HCC is classified molecularly into proliferative (approx. 50%) and non-proliferative classes with distinct molecular drivers and clinical outcomes.
Pathological subtypes include conventional HCC and eight distinct variants, with some correlating to molecular classes (e.g., MTM and progenitor with proliferative).
Noninvasive imaging (multiphase CT and multiparametric MRI) shows promise in inferring molecular and pathological HCC subtypes to guide prognosis and treatment.
Guideline-Based Recommendations
Diagnosis
Use multiphase CT and multiparametric MRI to assess imaging features correlating with molecular and pathological HCC subtypes.
Recognize that invasive tissue sampling remains the gold standard but is limited by availability and sampling error.
Consider molecular classification (proliferative vs non-proliferative) to understand tumor biology and prognosis.
Management
Tailor therapeutic decisions based on molecular and pathological subtype information when available.
Account for proliferative class association with aggressive behavior and poorer outcomes, especially in chronic HBV patients.
Recognize non-proliferative class tumors often have better prognosis and are associated with ALD, MASH, and HCV etiologies.
Monitoring & Follow-up
Monitor serum biomarkers such as AFP and DCP, which tend to be higher in proliferative HCC.
Use imaging follow-up to detect features suggestive of subtype changes or progression.
Risks
Sampling errors and invasiveness limit tissue-based classification accuracy.
Molecular heterogeneity within tumors may complicate classification and treatment response prediction.
CTNNB1 mutations linked to immune exclusion may confer resistance to immunotherapy.
Patient & Prescribing Data
Patients diagnosed with HCC across various etiologies including HBV, HCV, ALD, and MASH
Molecular subtype influences prognosis and therapeutic responsiveness; proliferative tumors may require more aggressive treatment and have poorer outcomes, while non-proliferative tumors may respond differently, highlighting the need for individualized management.
Clinical Best Practices
Integrate multiphase CT and multiparametric MRI imaging features with clinical and serum biomarker data to noninvasively infer HCC molecular and pathological subtypes.
Consider molecular and pathological classification to inform prognosis and guide personalized treatment strategies.
Recognize limitations of current classifications and the need for further research on tumor heterogeneity and imaging correlations.
A large audit of biomedical publications suggests fabricated references are increasingly appearing in peer-reviewed papers — often in ways that are difficult for reviewers and readers to detect.
