1. Patients with NAFLD-related HCC have longer disease-free survival compared to those with HCC from other causes.
2. Tumours of patients with NAFLD-related HCC were often larger in diameter than patients with HCC from other causes.
Evidence Rating Level: 1 (Excellent)
Study Rundown: This systematic review and meta-analysis aimed to compare the clinical presentation and outcomes of hepatocellular carcinoma (HCC) due to non-alcoholic fatty liver disease (NAFLD) with HCC from other causes. Outcome measures of interest included: the proportion of HCC secondary to NAFLD as well as a comparison of patient and tumour 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 upward 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 as compared to patients with HCC due to other causes. Patients with NAFLD-related HCC also had a higher likelihood of being non-cirrhotic. The tumours of patients with HCC due to NAFLD were larger in diameter and these patients had a higher likelihood of uninodular lesions. OS outcomes did not differ between patients with HCC due to NAFLD vs. those with HCC from other causes, but disease-free survival was longer in patients with HCC due to NAFLD. Limitations to this study include those intrinsic to meta-analyses, the exclusion of pediatric populations, and a smaller number of studies from the regions of South-East Asia and South America. Overall, the proportion of NAFLD-related HCC is increasing over time and an increase in surveillance strategies would be valuable for high-risk patients with NAFLD.
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 who had HCC due to NAFLD had a higher BMI (mean difference 2.99 kg/m^2, 95% CI, 2.20 – 3.78 kg/m^2) and were older (mean difference of 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) as compared to patients with HCC due to other causes. Patients with NAFLD-related HCC also had a higher likelihood of being non-cirrhotic: 38.5% (95% CI, 27.9% – 50.2%) vs. 14.6% (95% CI, 8.7% – 23.4%). Patients with HCC from NAFLD often had larger diameter tumours (mean difference 0.67 cm, 95% CI, 0.35 – 0.98cm) and more often had uninodular lesions (OR 1.36; 95% CI, 1.19 – 1.56). The comparison of OS outcomes revealed that there was no difference between the groups (hazard 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).
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