Hepatocellular Carcinoma in Metabolic Liver Disease

Hepatocellular carcinoma (HCC) arising in the context of metabolic liver disease has emerged as a major contributor to global cancer mortality. Once predominantly linked to viral hepatitis and alcohol use, HCC now increasingly develops on the background of metabolic dysfunction-associated fatty liver disease, which encompasses a spectrum from simple steatosis to steatohepatitis and cirrhosis. Central to pathogenesis is systemic metabolic dysregulation, including insulin resistance, lipotoxicity and chronic low-grade inflammation. Genetic predispositions and alterations in the gut microbiome further modulate carcinogenic pathways. Notably, a substantial proportion of metabolic-associated HCC occurs in non-cirrhotic livers, challenging traditional surveillance strategies that focus on advanced fibrosis. Clinically, these tumours often present at a more advanced stage, yet preserved hepatic function may allow for curative interventions such as resection or ablation. The therapeutic landscape is evolving with molecularly targeted agents and immune-checkpoint inhibitors, although responses in metabolic HCC may differ from those in viral-related disease. A comprehensive approach integrating risk stratification, novel biomarkers and tailored therapy is essential to address this growing burden.

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Hepatocellular Carcinoma in Metabolic Liver Disease publication trend

The graph below shows the total number of articles in hepatocellular carcinoma in metabolic liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Hepatocellular carcinoma (HCC): A primary malignancy of liver parenchymal cells, often arising in chronically diseased liver.

Steatosis: Accumulation of fat within hepatocytes, which may progress to inflammation and fibrosis.

Metabolic dysfunction-associated fatty liver disease (MAFLD): A diagnosis based on hepatic steatosis in conjunction with overweight/obesity, type 2 diabetes or other metabolic risk factors.

Non-alcoholic fatty liver disease (NAFLD): Hepatic fat deposition in the absence of significant alcohol intake, often overlapping with metabolic syndrome.

Cirrhosis: The end-stage of chronic liver injury characterised by fibrosis, nodule formation and impaired hepatic function.

References

1. MASLD-related HCC: Multicenter study comparing patients with and without cirrhosis. JHEP Reports (2024).
2. MAFLD: an optimal framework for understanding liver cancer phenotypes. Journal of Gastroenterology (2023).
3. Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology (2018).