Hepatocellular carcinoma in patients with metabolic dysfunction-associated fatty liver disease: Can we stratify at-risk populations?

Table 1 Studies that evaluated hepatocellular carcinoma risk in a cohort with cirrhosis or advanced fibrosis due to nonalcoholic steatohepatitis or cryptogenic cirrhosis (presumptively nonalcoholic steatohepatitis-related) and in a comparison cohort with hepatitis C virus-related cirrhosis or advanced fibrosis

Ref.	n	Age (yr)	Male gender (%)	HCC incidence	P value
Ratziu et al[22]	27 CC-O	62.1 ± 10.6	(M/F) 1.7	8/27 (29.6%)	NS
	85 HCV	62.1 ± 10.6	(M/F) 1.7	18/85 (21%)
Sanyal et al[23]	152 NASH	54.7 ± 11.6	39.7	10/149 (6.7%)	NS
	150 HCV	48.3 ± 11.3	64.8	25/147 (17%)
Kojima et al[24]	24 CC	58.2 ± 10.6	NA	9/24 (37.5%)	P < 0.01
	48 HCV	58.7 ± 8.1	NA	36/48 (75%)
Yatsuji et al[25]	68 NASH	62.7 ± 13.2	43	5-yr 11.3%	NS
	69 HCV	61.3 ± 5.8	43	5-yr 30.5%
Ascha et al[26]	195 NASH	56.6	44.1	Annual cumulative 2.6%	P = 0.09
	315 HCV	48.2	76.5	Annual cumulative 4.0%
Bhala et al[27]	247 NAFLD	54.7	39.5	6/247 (2.4%)	P = 0.03
	264 HCV	48.3	67.5	18/264 (6.8%)

NAFLD: Nonalcoholic fatty liver disease; HCC: Hepatocellular carcinoma; NASH: Nonalcoholic steatohepatitis; HCV: Hepatitis C virus; CC-O: Overweight patients with cryptogenic cirrhosis; (M/F): Male/female ratio; NS: Non-significant; CC: Cryptogenic cirrhosis.

Table 2 Studies that analyzed the prevalence of cirrhosis among patients with nonalcoholic fatty liver disease-related hepatocellular carcinoma and in controls with other etiologies-related hepatocellular carcinoma

Ref.	n	Prevalence of cirrhosis (in percentage)
Ertle et al[18]	36 NAFLD	52.8
	35 HCV	94.3 in HCV
	29 HBV	93.1 in HBV
	19 ALD	94.7 in ALD
Reddy et al[31]	52 NAFLD	73.1
	162 HCV/ALD	93.8
Dyson et al[20]	136 NAFLD	77.2
	178 ALD	100 in ALD
	65 HCV	96.9 in HCV
	29 HBV	82.7 in HBV
Mittal et al[33]	107 NAFLD	65.4
	1133 ALD	88.9 in ALD
	952 HCV	91.1 in HCV
	65 HBV	92.3 in HBV
Piscaglia et al[19]	145 NAFLD	53.8
	611 HCV	97.2 in HCV
Yasui et al[17]	87	51
	No control group	NA

NAFLD: Nonalcoholic fatty liver disease; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; HBV: Hepatitis B virus; ALD: Alcoholic liver disease; NA: Not available.

Table 3 Incidence rate of hepatocellular carcinoma and independent risk factors among patients with non-alcoholic fatty liver disease/metabolic-dysfunction associated fatty liver disease without cirrhosis

Ref.	Population studied	n	Mean follow-up (yr)	Incidence rate of HCC	Independent risk factors
Kanwal et al[28]	VHA database (United States)	295.623	9.0 ± 2.2	0.08/1000 person-years	Male gender; Age > 65 yr; hispanics
Lee et al[35]	General population-based study (Taiwan of China)	18.081	Median 6.32	10-yr cumulative incidence 2.73% (95%CI: 1.69–3.76)	Age > 55 yr; elevated ALT
Alexander et al[36]	General population-based study (Europe)	136.703	Median 3.3	0.3/1000 person-years	Diabetes
Kawamura et al[38]	Clinic-based study (Japan)	6.508	Median 5.6	Annual incidence 0.043%	AST ≥ 40 IU/L; platelet count < 150 × 103/μL; age > 60 yr; diabetes
Arase et al[40]	Clinic-based study (Japan)	1.600	8.2	0.78/1000 person-years	Age > 70 yr; smoking; elevated glucose level
Kanwal et al[39]	VHA database (United States)	271.906	9.3 ± 2.7	253 cases1	Diabetes

¹Incidence rate of hepatocellular carcinoma was not calculated.

HCC: Hepatocellular carcinoma; VHA: Veterans Health Administration; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 4 Different risk categories for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease/metabolic-dysfunction associated fatty liver disease¹

Risk for HCC	Patients
Very high	Cirrhosis plus	Male gender
		Older age
		Diabetes
		Low serum albumin
High	Cirrhosis
	F3 fibrosis plus	Elevated AST2
		Low platelets2
		Older age
		Diabetes
Low	F3 fibrosis
Very low	Mild or no liver fibrosis

¹Study of polygenic risk score will be important for better stratification of hepatocellular carcinoma risk when clinically available.

²Probably understaged liver fibrosis.

HCC: Hepatocellular carcinoma.