Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link

Table 1 Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma based on studies published in the last decade (2011-2020)

Ref.	Year/Country	Study design	HCC patients, n	HCC caused by NAFLD, n (%)	Non-cirrhotics among HCC-related NAFLD, n (%)	Fibrosis stage of NAFLD-HCC patients, n (%)	Tumor size
Yang et al[26]	2011/United States	Retrospective	460	61 (13.27)	NA	NA	NA
Schütte et al[27]	2014/Germany	Retrospective	664	43 (6.5)	6 (13.95)	NA	NA
Chun et al[28]	2014/United States	Retrospective	27	13 (48.1)	NA	NA	NA
Edenvik et al[29]	2015/Sweden	Retrospective	616	69 (11.2)	15 (21.7)	NA	NA
Younossi et al[30]	2015/United States	Retrospective	4979	701 (14.1)	NA	NA	NA
Weinmann et al[31]	2015/Germany	Retrospective	1119	45 (4)	10 (22.2)	NA	Trend towards ↑ tumor size in NASH-HCC (6 cm) vs non-NASH-HCC (4.8 cm) (P = 0.18)
Mittal et al[23]	2016/United States	Retrospective	1500	107 (8)	37 (34.6)	NA	ΝΑ
Wong et al[32]	2017/United States	Retrospective	17.664	5898 (33.4)	3326 (56.4%)	NA	↑ proportion of tumors > 5 cm in NAFLD-HCC vs non-NAFLD-HCC (P < 0.001)
Huang et al[33]	2017/Australia	Prospective	270	38 (14)	9 (23.7)	NA	ΝΑ
Koh et al[34]	2019/Singapore	Prospective	996	152 (15.3)	100 (65.8)	F0 = 78 (51.7); F1 = 10 (6.6); F2 = 45 (29.8); F3 = 9 (6); F4 = 9 (6)	↓ tumor size in NAFLD-HCC (0.7 cm) vs non-NAFLD-HCC (4 cm) (P < 0.001)
Hassan and Gane[35]	2019/New Zealand	Retrospective	1985	159 (5.1) (Undefined cirrhosis stage in 57)	25 (24.5) (based on well-defined stage patients)	F0 = 2 (8); F1 = 3 (14); F2 = 1 (3); F3/4 = 19 (75.5)	NA
Gawrieh et al[36]	2019/United States	Retrospective	5144	767 (14.9)	159 (26.3)	NA	NA
Hester et al[16]	2020/United States	Retrospective	12471	3019	1565	NA	NA
Hong et al[37]	2018/Australia	Prospective	272	39 (14.3)	NA	NA	NA
Jamwal et al[38]	2020/India	Prospective	56	20 (35.7)	20 (100)	NA	NA
Pais et al[15]	2017/France	Retrospective	323	39 (12.1)	30 (76.9)	F0 = 16 (40); F1 = 9 (23); F2 = 0 (0); F3 = 5 (14); F4 = 9 (23)	↑ tumor size in NAFLD-HCC (8.7 cm) vs non-NAFLD-HCC (6.2 cm) (P = 0.002)
Dyson et al[13]	2013/United Kingdom	Prospective	632	136 (21.5)	31 (22.8)	NA	NA
Phipps et al[39]	2020/United States	Retrospective	5327	790 (14.8)	NA	NA	NA
Bengtsson et al[40]	2019/Sweden	Retrospective	1562	225 (14.4)	83 (36.9)	F0 = 1; F1 = 13; F2 = 16; F3 = 5 (Undefined fibrosis stage in 48 patients)	NSD in tumor size between NAFLD-HCC vs non-NAFLD-HCC; ↑ tumor size in non-cirrhotic vs cirrhotic NAFLD-HCC (P = 0.001)
Tokushige et al[41]	2013/Japan	Retrospective	14.530	292 (2)	111 (38)	NA	ΝΑ
Reddy et al[42]	2012/United States	Retrospective	303	52 (NASH) (17.2)	14 (26.9)	NA	NSD in tumor size between NAFLD-HCC (3.2 cm) vs non-NAFLD-HCC (3 cm)
Phan et al[43]	2019/United States	Retrospective	545	28 (5.1)	3 (10.7)	NA	NA
Van Meer et al[44]	2016/Netherlands	Retrospective	1221	181 (14.8)	67 (28)	NA	↑ tumor size in NAFLD-HCC (6 cm) vs HCV-HCC (3 cm) (P < 0.001)
Yang et al[45]	2017/United States	Retrospective	93	10 (11)	3 (27.3)	NA	NA

NAFLD: Non-alcoholic fatty liver disease; HCC: Hepatocellular carcinoma; NASH: Non-alcoholic steatohepatitis; HCV: Hepatitis C virus; NSD: No significant difference; NA: Not applicable.