Characteristics of Nonalcoholic Fatty Liver Disease–Related HCC vs HCC From Other Causes

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In a meta-analysis reported in The Lancet Oncology, Tan et al found that patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) were more likely to have metabolic/cardiovascular comorbidity, less likely to have cirrhosis, and less likely to undergo surveillance prior to diagnosis vs patients with HCC from other causes. Treatments received and overall survival did not differ.

Study Details

The analysis included 61 English-language studies performed between January 1980 and May 2021, including a total of 94,636 patients with HCC. Of these, 15,377 (15.1%) had NAFLD-related HCC.

Key Findings

Compared with patients with HCC from other causes, those with NAFLD-related HCC:

  • Were older (mean difference = 5.62 years, P < .0001)
  • Had higher body mass index (mean difference = 2.99 kg/m², P < .0001)
  • Were more likely to have metabolic comorbidities, including diabetes (odds ratio [OR] = 4.31, P < .0001), hypertension (OR = 2.84, P < .0001), and hyperlipidemia (OR = 3.43, P < .0001), and cardiovascular disease (OR = 2.23, P = .0055)
  • Were more likely to be noncirrhotic (38.5% vs 4.6%, OR = 3.71, P < .0001). 

Patients with NAFLD-related HCC had larger tumor diameters (mean difference = 0.67 cm, P .0087) and were more likely to have uninodular lesions (OR = 1.36, P = .0003). No differences between groups were observed in Barcelona Clinic Liver Cancer stages, TNM stages, alpha fetoprotein concentration, or Eastern Cooperative Oncology Group performance status.

Patients with NAFLD-related HCC were less likely to undergo surveillance prior to diagnosis (32.8% vs 55.7%, OR = 0.36, P < .0001). There were no significant differences in treatment allocation (curative therapy, palliative therapy, or best supportive care). Overall survival did not differ between the two groups (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.92–1.20, P = .43). Patients with NAFLD-related HCC had improved disease-free survival (HR = 0.79, 95% CI = 0.63–0.99, P = .044).

The investigators concluded, “NAFLD-related HCC is associated with a higher proportion of patients without cirrhosis and lower surveillance rates than HCC due to other causes. Surveillance strategies should be developed for patients with NAFLD without cirrhosis who are at high risk of developing HCC.”

Daniel Q. Huang, MBBS, MRCP, of the Yong Loo Lin School of Medicine, National University of Singapore, is the corresponding author for The Lancet Oncology article.

Disclosure: The investigators reported no external funding for the study. For full disclosures of the study authors, visit

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