HCC Related to Nonalcoholic Fatty Liver Disease Vs Other Causes Linked With Lower Rates of Cirrhosis, Surveillance

Individuals with nonalcoholic fatty liver disease–related hepatocellular carcinoma were found to have lower rates of surveillance vs other potential causes of disease.

Lower surveillance rates and cirrhosis prevalence were identified in patients with nonalcoholic fatty liver disease (NAFLD)–related hepatocellular carcinoma (HCC) compared with other potential disease causes, according to findings from a systematic review and meta-analysis published in Lancet Oncology.

Investigators noted that fewer patients with NAFLD-related HCC received surveillance at 32.8% (95% CI, 12.0%-63.7%) compared with 55.7% (95% CI, 24.0%-83.3%) in patients with HCC secondary to other causes (P <.0001). Between the 2 groups, there were no significant differences in treatment allocation, including curative therapy, palliative therapy, and best supportive care. Although there were no differences in overall survival between the 2 groups (HR, 1.05; 95% CI, 0.92-1.20; P = .43), patients with NAFLD-related HCC had a longer disease-free survival compared with patients whose disease was tied to other causes (HR, 0.79; 95% CI, 0.63-0.99; P = .044).

“This study provides high-level evidence that a substantially higher proportion of patients with NAFLD-related hepatocellular carcinoma do not have cirrhosis and have lower surveillance rates than patients with hepatocellular carcinoma due to other causes. The proportion of hepatocellular carcinoma secondary to NAFLD is rising globally, and urgent measures are required to tackle the metabolic risk factors associated with NAFLD-related hepatocellular carcinoma. Further studies are required to improve hepatocellular carcinoma surveillance strategies for patients with NAFLD who are at high-risk of hepatocellular carcinoma without cirrhosis,” the investigators wrote.

Investigators initially identified 3631 potential articles for review, of which 61 were included in the final analysis following screening. These studies included 94,636 patients, of whom 15,377 had NAFLD-related disease and 79,259 had disease related to other causes.

The study’s primary outcomes were proportion of HCC secondary to NAFLD globally; comparison of patient and tumor characteristics between groups; and comparison of surveillance, treatment allocation, and survival outcomes between groups.

Patients had a median age of 67.8 years. Most patients with NAFLD-related HCC were located in South-East Asia, the Western Pacific, Europe, and the Americas. Investigators noted an increase in disease secondary to NAFLD from before the year 2000 (9.77%; 95% CI, 7.33%-12.92%) to 2010 and beyond (16.97%; 95% CI, 12.17%-23.16%; P = .045).

Patients in the NAFLD cohort were found to be older (mean difference, 5.62 years; 95% CI, 4.63-6.61; P <.0001) and had a higher body mass index (mean difference, 2.99 kg/m2; 95% CI, 2.20-3.78; P <.0001) than the comparator arm. Compared with individuals whose HCC was due to other causes, the NAFLD arm was more likely to present with metabolic complications such as diabetes (OR, 4.31; 95% CI, 3.19-5.80; P <.0001), hypertension (OR, 2.84; 95% CI, 2.09-3.86; P <.0001), and hyperlipidemia (OR, 3.43; 95% CI, 2.39-4.95; P <.0001).

Notably, 38.5% (95% CI, 27.9%-50,2%) with NAFLD-related HCC did not have cirrhosis compared with 14.6% (95% CI, 8.7%-23.4%; P <.0001) for all other causes. Broken down further, HCC without cirrhosis occurred in 21.7% of those with disease related to hepatitis B, 6.4% to hepatitis C, and 9.1% with alcohol. Compared with those whose disease was related to other causes, those with NAFLD-related disease had a greater tumor diameter (mean difference, 0.67 cm; 95% CI, 0.35-0.98; P = .0087) and were more likely to have unimodular lesions (OR, 1.36; 95% CI, 1.19-1.56; P = .0003).

Additional findings from the analysis indicated that 65.0% of patients in the NAFLD arm were assigned to receive curative therapy and 42.1% received palliative therapy. Moreover, 3.9% of patients in this group underwent liver transplant, 33.6% underwent resection, and 12.0% received ablation.


Tan DJH, Ng CH, Lin SY, et al. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis. Lancet Oncol. 2022;23(4):P521-530. doi:10.1016/S1470-2045(22)00078-X