Obesity and hepatocellular carcinoma

Area of Science:

• Hepatology
• Oncology
• Metabolic Syndrome

Background:

• Obesity and type 2 diabetes are established risk factors for hepatocellular carcinoma (HCC).
• Nonalcoholic fatty liver disease (NAFLD) is frequently associated with obesity and diabetes, and can progress to cirrhosis and HCC.
• The precise mechanistic link between obesity, diabetes, NAFLD, and HCC requires further elucidation.

Purpose of the Study:

• To explore the likely pathway linking obesity and diabetes to hepatocellular carcinoma through nonalcoholic fatty liver disease.
• To discuss the potential mechanisms involved in the progression of NAFLD to HCC.
• To review the current understanding of HCC risk in NAFLD and identify areas for future research.

Main Methods:

• Review of epidemiological studies and case reports.
• Discussion of proposed pathogenetic mechanisms involving cellular senescence, hyperplasia, inflammation, and genetic mutations.
• Synthesis of evidence regarding HCC risk in NAFLD-related cirrhosis.

Main Results:

• Obesity and diabetes likely contribute to HCC through the progression of underlying NAFLD to cirrhosis.
• Mechanisms may involve hepatocyte senescence, progenitor cell hyperplasia, chronic inflammation, and DNA damage from lipid peroxidation.
• HCC risk in nonalcoholic steatohepatitis (NASH)-related cirrhosis appears comparable to that in hepatitis C virus (HCV)-related cirrhosis, particularly in older males.

Conclusions:

• NAFLD, driven by obesity and diabetes, is a probable pathway to HCC, often via cirrhosis.
• Further research is needed to confirm therapeutic strategies for NAFLD in HCC risk reduction and to investigate prophylactic measures and cancer surveillance in at-risk populations.
• The HCC risk in NASH-related cirrhosis warrants attention, especially in specific demographic groups.