Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

Table 1 Studies that included the incidence/prevalence and risk factors for hepatocellular carcinoma in non-alcoholic fatty liver disease without cirrhosis

Ref.	Study design	Aim	Number of patients	Results and conclusion
Mohamad et al[5], 2016	Retrospective	To characterize patients with NAFLD and HCC comparing cirrhotic vs non-cirrhotic patients	All patients with NAFLD and HCC between 2003-2012 (n = 83)	36 (43.4%) NAFLD HCC non-cirrhotic vs 47 (56.6%) NAFLD HCC cirrhotic patients. HCC patients without cirrhosis are more likely to present at an older age with larger tumor and higher rates of tumor recurrence
Piscaglia et al[6], 2016	Multicenter observational prospective	To assess the clinical features of patients with NAFLD-related HCC and to compare to those with HCV related HCC	N = 756 (145 NAFLD vs 611 HCV)	Cirrhosis was present in about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Survival was significantly shorter in patients with NAFLD-HCC than in those with HCV-HCC (25.5 mo vs 33.7 mo)
Stine et al[9], 2018	Systematic review with meta-analysis	To compare the prevalence of NAFLD-related HCC to other chronic liver diseases	19 studies (n = 168571)	The prevalence of NAFLD-related HCC in patients with NASH without cirrhosis is approximately 38% compared with 14% for other liver diseases
Tobari et al[24], 2020	Prospective	To evaluate the characteristics of HCC in non-cirrhotic NAFLD	48 non-cirrhotic HCC vs 71 cirrhotic HCC patients	In patients with non-cirrhotic NAFLD, important risk factors for HCC were male gender, alcohol consumption, and the FIB-4 index. HCC recurrence and survival were only influenced by the tumor stage
Kanwal et al[27], 2018	Retrospective	To estimate the risk of incident HCC among patients with NAFLD	296707 NAFLD vs 296707 matched controls	NAFLD individuals with cirrhosis had the highest annual incidence of HCC. 20% of NAFLD patients with HCC had no evidence of cirrhosis. The absolute risk of HCC in patients without cirrhosis is too low to recommend HCC surveillance
Orci et al[28], 2022	Systematic review with meta-analysis	Evaluate the pooled HCC incidence in patients with NAFLD at distinct severity stages	18 studies (470404 individuals)	Evidence documenting the risk in patients with NASH or simple steatosis is limited, but the incidence of HCC in these populations may lie below thresholds used to recommend a screening (0.03 per 100 person-years)
Donati et al[34], 2017	Sectional	To evaluate whether the MBOAT7 rs641738 risk T allele predisposes to HCC in NAFLD patients stratified by the presence of severe fibrosis	765 Italian NAFLD patients	The MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis
Demirtaş et al[71], 2021	Retrospective	To investigate the characteristics and survival course of non-cirrhotic individuals with HCC	N = 384 HCC; 43 (11.2%) without cirrhosis; 10 (23%) with NAFLD	HCC in non-cirrhotic liver is diagnosed at more advanced stage and with larger tumor size. The overall survival is shorter in HCC without cirrhosis, due to late recognition

NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; MBOAT7: Membrane-bound o-acyltransferase domain-containing 7.