Hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease differs clinically from HCC due to other causes

1. Patients with NAFLD-related HCC have longer disease-free survival than those with HCC from other causes.

2. Tumors from patients with HCC related to NAFLD were often larger in diameter than patients with HCC from other causes.

Level of evidence assessment: 1 (Excellent)

Summary of the study: This systematic review and meta-analysis aimed to compare the clinical presentation and outcome of hepatocellular carcinoma (HCC) due to non-alcoholic fatty liver disease (NAFLD) with HCC from other causes. Outcome measures of interest included: proportion of HCC secondary to NAFLD as well as a comparison of patient and tumor characteristics, overall survival (OS) and disease-free survival outcomes, and other measures between NAFLD-related HCC and HCC due to other causes. The proportion of HCC secondary to NAFLD was 15.1% and an increasing trend over time was noted. Patients who had HCC due to NAFLD were older with higher BMI and had a higher likelihood of comorbidities, including diabetes, hypertension, hyperlipidemia, or cardiovascular disease, compared to patients with HCC due to other causes. Patients with NAFLD-related HCC also had a higher likelihood of being non-cirrhotic. The tumors of patients with HCC due to NAFLD were larger in diameter and these patients had a higher likelihood of uninodular lesions. OS results did not differ between patients with HCC due to NAFLD and those with HCC from other causes, but disease-free survival was longer in patients with HCC due to NAFLD. Limitations of this study include those intrinsic to the meta-analyses, the exclusion of pediatric populations, and a smaller number of studies from the Southeast Asian and South American regions. Overall, the proportion of HCCs linked to NAFLD is increasing over time and an increase in surveillance strategies would be valuable for high-risk patients with NAFLD.

Click to read the study in The Lancet Oncology

Relevant reading: Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

In depth [systematic review and meta-analysis]: This systematic review and meta-analysis included 94,636 patients in 61 studies from many countries completed between January 1980 and May 2021. The proportion of HCC secondary to NAFLD was 15.1% (95% confidence interval (CI) , 11.9%-18.9%). Patients with HCC due to NAFLD had higher BMI (mean difference 2.99 kg/m^2, 95% CI 2.20 – 3.78 kg/m^2) and were older ( mean difference 5.62 years, 95% CI 4.63 – 6.61 years). Patients with NAFLD-related HCC had a higher likelihood of comorbidities, including diabetes (odds ratio (OR) 4.31, 95% CI 3.19, 5.80), hypertension (OR 2.84, 95% CI, 2.09 – 3.86), hyperlipidemia (OR 3.43, 95% CI, 2.39 – 4.95) or cardiovascular disease (OR 2.23, 95% CI, 1.43, 3.48) compared to patients with HCC due to other causes. Patients with NAFLD-related HCC also had a higher probability of being non-cirrhotic: 38.5% (95% CI, 27.9% – 50.2%) versus 14.6% (CI at 95%, 8.7% – 23.4%). NAFLD HCC patients often had larger diameter tumors (mean difference 0.67 cm, 95% CI 0.35 to 0.98 cm) and more often uninodular lesions (OR 1.36; CI at 95%, 1.19 to 1.56). Comparison of OS results revealed that there was no difference between the groups (risk ratio (HR) 1.05; 95% CI, 0.92, 1.20). However, patients with NAFLD-related HCC had increased disease-free survival (HR 0.79; 95%, 0.63-0.99).

Picture: PD

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