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Page 4 of 11                                                Garg et al. Hepatoma Res 2019;5:39  I  http://dx.doi.org/10.20517/2394-5079.2019.009

               and gastroesophageal varices. In patients with multiple HCCs, only the largest HCC with histological
               confirmation was assessed. The final imaging features of HCCs were determined by majority. A fifth reader
               blinded to clinical and pathological findings reviewed cases lacking majority. LIRADs criteria is only
               applicable in patients with cirrhosis or chronic viral hepatitis and therefore would not be applicable for
               patients with NAFLD without cirrhosis.


               Statistical analysis
               Continuous variables were expressed as mean ± standard deviation and categorical data as percentage.
                                                                                             [27]
               Inter-rater agreement was determined by prevalence-adjusted bias-adjusted Cohen’s kappa . Agreement
                                                                                                   [27]
               between cirrhotic on CT and pathology was also determined by prevalence-adjusted Cohen’s kappa . Inter
               observer agreement was classified as none (0-0.2), minimal (0.21-0.39), weak (0.40-0.59), moderate (0.60-0.79)
               and strong (0.80-0.90) and almost perfect (> 0.90). Differences between non-cirrhotic and cirrhotic sub-
               groups were compared using an unpaired t-test with equal variance assumption for continuous data and
               Fischer’s exact test for categorical data. Statistical significance was assumed for P values of less than 0.05.
               Data were analyzed using JMP 11.0 (SAS, Cary, NC) and Prism 5.0 (GraphPad Software, Inc, La Jolla, CA).


               RESULTS
               Clinical and pathological characteristics
               Mean age of subjects was 63 years (range 45-79). Patients were predominantly male (n = 26, 68.4%), diabetic
               (n = 28, 73.7%), and obese (BMI ≥ 30; n = 25, 65.8%). Mean ± SD total serum cholesterol and triglyceride
               values were 151.9 ± 39.7 (range: 36-229 mg/dL) and 130.6 ± 53.5 (range: 54-237 mg/dL), respectively. Most
               of the patients underwent liver transplant (n = 21, 55.3%) or hepatic resection or segmentectomy (n = 12,
               31.6%). Of the 21 patients that underwent liver transplant, 16 patients received chemoembolization (14) or
               ablation (2) before transplantation, 4 patients received only ablation or chemoembolization, and 1 patient
               was lost to follow-up. Of 38 patients, 2 (5.3%) patients developed recurrent HCC. CT studies performed
               before any treatment was used for imaging analysis.

               At pathology, HCCs were well differentiated in 14 patients (36.8%), well to moderately differentiated in
               5 patients (13.2%), moderately differentiated in 16 patients (42.1%), moderate to poorly differentiated in 2
               patients (5.3%) and poorly differentiated in 1 patient (2.6%). Hepatic steatosis was minimal (26.3%) in 10
               patients (26.3%), mild in 26 patients (68.4%), and moderate in 2 patients (5.3%). Steatohepatitis was present
               in 25 patients (65.8%) and cirrhosis in 24 patients (63.2%). The clinical and pathological characteristics are
               summarized in Table 1.

               HCC and liver parenchyma imaging characteristics - majority features
               Mean HCC size was 3.6 ± 2.8 cm (range: 1.1-16.0 cm). APHE was seen in 92.1%, PVWO in 55.3% DPWO
               in 81.6% and enhancing capsule in 44.7% [Figures 2 and 3]. Fat within the HCC was present in only one
               patient. Cirrhotic morphology was present in 25 patients (65.8%) and portal hypertension in 24 patients
               (63.2%). The imaging features are summarized in Table 2.

               Non-cirrhotic NAFLD vs . cirrhotic NAFLD
               Non-Cirrhotic NAFLD (NAFL in 7 and NASH in 7) and cirrhotic NAFLD were present in 14 (36.8%)
               and 24 (63.2%) patients respectively. Patients with non-cirrhotic NAFLD were older (P = 0.03), had larger
               mean HCC size (P = 0.008) and higher degree of hepatic steatosis (P = 0.003). PVWO feature was observed
               significantly more in the non-cirrhotic group as compared to the cirrhotic group (78.6% vs. 41.7%, P = 0.04).
               Portal hypertension features were more commonly seen in patients with cirrhotic NAFLD (91.7% vs. 14.3%,
               P < 0.0001). There was no significant difference between the two groups with respect to gender distribution
               (P = 0.47), BMI (P = 0.14), presence of diabetes (P = 0.45), cholesterol level (P = 0.24), triglyceride level
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