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Page 4 of 13 Farrell et al. Hepatoma Res 2020;6:18 I http://dx.doi.org/10.20517/2394-5079.2019.019

Limitations/Bias Retrospective study design Small cohort, with low numbers of HCC and comparator group was those with treatment naïve HCV or treatment non-responders in pre DAA Surgical resection bias could account for high proportion of patients without significant fibrosis Small cohort, with low numbers of HCC and comparator group was those with treatment naïve HCV or treatment non-responders in pre DAA Small cohort, with low number

Proportion of NAFLD with cirrhosis (%) N/A 100% therapy era N/A 100% therapy era 100% therapy era 46% 52.2% therapy era 58.3% controls

Cryptogenic cirrhosis 2nd leading of NAFLD 0.01) HCC had F0-2 fibrosis and 30.5% for HCV NASH Cirrhotics had a yearly w 4% in HCV cirrhosis of HCC followed by diabetes (36%) Of 729,018 patients with NAFLD/ at one time (incident or prevalent case) HCC occurred more commonly in patients with HCV cirrhosis than in = 0.03] NAFLD and NASH most common but cryptogenic made up 15.3%

Results cause of HCC (n = 30, 29%) and 6 of those cases had histological features of NASH, while 8 had clinical features NASH had a lower risk of developing hepatocellular carcinoma compared to those with HCV cirrhosis (10/149 patients vs. 25/147 patients at risk; P < 65.5% of cases with Met Sy associated 5-year HCC rate was 11.3% for NASH cumulative incidence of HCC 2.6% c/ NASH patients were older at diagnosis of cirrhosis (56.6 years

Definition of NAFLD Histologic features of steatohepatitis and cirrhosis Histologic features of steatohepatitis and cirrhosis Histologic features of NASH or cryptogenic cirrhosis in the presence of metabolic syndrome and without a history of significant Documentation of diagnosis based Histologic features of advanced fibrotic NAFLD as well as elevated aminotransferases for at least 6 NAFLD/NASH was defined according to the histologica

Histology N/A alcohol intake on ICD-9 coding months

Number of participants 105 152 128 68 195 4406 247 162

Design/Method Single centre retrospective cohort of consecutive HCC cases Single centre prospective cohort of patients with NASH cirrhosis Retrospective review of HCC liver resection specimens between 1995 and 2007 Prospective cohort study of patients with NASH and HCV cirrhosis Prospective analysis of patients with NASH and HCV cirrhosis between 2003 and 2007 Retrospective review of HCC cases identified from a

Table 1. Overview of trials Country Author USA Marrero et al. [69] USA Sanyal et al. [47] France Paradis et al. [70] Japan Yatsuji et al. [46] USA Ascha et al. [44] USA Sanyal et al. [36] Australia, Bhala et al. [45] USA, UK, Italy Germany Ertle et al. [50]