HEPATOCELLULAR carcinoma (HCC) remains a leading cause of cancer-related mortality globally, ranking as the sixth most common malignancy and the third most common cause of cancer death. For early-stage HCC, hepatic resection is regarded as the standard curative treatment. However, long-term survival post-resection remains suboptimal, primarily due to high recurrence rates. The recurrence of HCC is often attributed to both intrahepatic metastases and multicentric carcinogenesis, necessitating strategies to mitigate recurrence risks and improve long-term survival outcomes.
Obesity and diabetes mellitus (DM) are widely acknowledged risk factors for the development of steatotic liver diseases, contributing to liver cirrhosis and HCC. The concept of metabolic dysfunction-associated steatotic liver disease (MASLD) now encompasses these conditions, identifying their role in promoting hepatocarcinogenesis, independent of other liver disease comorbidities. Both obesity and DM have been associated with increased cancer risk, including HCC, often displaying synergistic effects. Recent studies have indicated that the coexistence of obesity and DM enhances the risk of HCC development more significantly than either condition alone.
This study evaluated the impact of obesity and DM on HCC recurrence and survival after hepatic resection, considering their synergistic effects. Multivariate analysis revealed that patients with both obesity and DM exhibited a 1.3-fold increased risk for recurrence-free survival (RFS) and overall survival (OS) compared to those without these comorbidities. Although no significant differences were observed for early recurrence (within 2 years postoperatively), patients with both conditions had a 1.5-fold higher risk for late recurrence beyond 2 years postoperatively. This indicates that the presence of obesity and DM amplifies the risk of multicentric carcinogenesis, reducing long-term survival outcomes.
Furthermore, the study highlighted tumour-related factors such as AFP levels, tumour size, and microvascular invasion, which are associated with early recurrence, while liver-related factors such as elevated ALT levels, low platelet counts, and liver cirrhosis were linked to late recurrence. The synergistic effects of obesity and DM were particularly linked to increased late recurrence risk, suggesting their role in promoting multicentric carcinogenesis postoperatively.
Insulin resistance, driven by obesity and DM, has been implicated in promoting HCC through mechanisms such as increased IGF-1 production, which enhances HCC proliferation and angiogenesis. The study’s findings suggest that the coexistence of obesity and DM contributes to a higher risk of late recurrence due to their synergistic effects, further emphasising the need for sustained postoperative surveillance beyond 5 years.
Management strategies addressing both comorbidities, including lifestyle modifications, diabetes control, and weight management, could contribute to improved survival outcomes in these patients. Further prospective studies are required to explore the mechanisms underlying these associations and evaluate therapeutic interventions targeting metabolic comorbidities.
Katie Wright, EMJ
Reference
Shinkawa H et al. Impact of diabetes mellitus and obesity comorbidities on survival outcomes after hepatocellular carcinoma resection: A multicenter retrospective study. Liver Cancer. 2024;DOI:10.1159/000540858.
