Updates in Characteristics and Survival Rates of Hepatocellular Carcinoma in a Nationwide Cohort of Real-World US Patients, 2003–2021

Figures & data

Table 1 Baseline Characteristics of the Total HCC Cohort by Liver Disease Etiology, 2003–2021

Characteristic	Total N=34,707	HCV N=8,765 25.3%	HBV N=905 2.6%	ALD N=3,265 9.4%	NAFLD N=13,48,338.9%	Cryptogenic N=6,261 18.0%	Other* N=2,028 5.8%	P-value
Mean age (years±SD)	68.3±11.6	64.2±9.2	65.2±12.6	68.5±10.3	71.1±11.2	68.8±14.0	67.8±12.2	<0.0001
Sex (%)								<0.001
Male	61.4	74.7	72.8	80.8	54.0	48.0	57.6
Female	38.6	25.3	27.2	19.2	46.0	52.1	42.4
Race/ethnicity (%)								<0.001
Caucasian	62.1	54.6	31.9	65.6	63.0	71.0	68.9
African American	11.7	16.3	9.7	8.5	11.5	9.1	7.3
Hispanic	13.7	15.6	9.1	17.3	15.1	7.5	12.1
Asian	4.7	5.8	41.1	1.9	3.0	3.1	3.7
Unknown	7.9	7.7	8.2	6.8	7.5	9.3	8.0
Cirrhosis (%)	73.7	93.3	75.7	83.0	65.8	51.6	93.3	<0.001
Advance care directive (%)	8.0	6.7	8.1	9.1	9.7	6.0	6.7	<0.001
Hospice/palliative care (%)	35.2	30.2	25.5	39.2	38.4	34.1	36.7	<0.001
DCCI (±SD)	9.0±4.2	7.4±4.3	7.2±4.4	8.8±4.3	10.5±3.9	8.7±3.2	8.5±4.0	<0.0001
Antiviral therapy (%)	–			–	–	–	–	–
HCV DAA**		29.8
HBV			40.8
Liver transplant (%)	4.4	11.0	6.5	4.0	1.2	0.4	8.2	<0.001
Follow-up (person-years)	46,670	15,782	1794	3807	15,620	6660	3006	–

Notes: *Other liver diseases: autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson’s disease. **Includes only patients from 2014 and after.

Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus; ALD, alcohol-associated liver disease; NAFLD, non-alcoholic fatty liver disease; DCCI: Deyo Charlson Comorbidity Index.

Table 2 Baseline Characteristics in HCC Subgroup by Study Time Period (A) and Race and Ethnicity (B)

Characteristic	(A) By Time Period			(B) By Race/Ethnicity
	2003–2013 N=11,581	2014–2021 N=23,125	P-value	Caucasian N=21,550	African American N=4051	Hispanic/Latino N=4764	Asian N=1619	P-value
Mean age (years±SD)	65.1±12.6	69.9±10.8	<0.0001	68.5±11.7	68.1±11.0	68.9±11.5	67.2±12.9	<0.0001
Sex (%)			<0.001					<0.001
Male	62.7	60.8		61.6	57.6	62.9	65.4
Female	37.3	39.3		38.4	42.4	37.1	34.6
Race/ethnicity			<0.001	–	–	–	–	–
Caucasian	62.4	61.9
African American	10.3	12.4
Hispanic	11.7	14.7
Asian	5.4	4.3
Unknown	10.2	6.7
Cirrhosis (%)	71.9	74.6	<0.001	72.6	73.1	79.6	73.6	<0.001
Advance care directive (%)	0.9	11.6	<0.001	7.5	9.8	8.9	8.2	<0.001
Hospice/palliative care (%)	19.5	43.0	<0.001	35.7	38.8	35.1	25.0	<0.001
DCCI (±SD)	8.3±4.0	9.4±4.2	<0.0001	9.1±4.1	9.6±4.3	8.9±4.2	7.7±4.3	<0.0001
ALBI			0.21					<0.001
1	56.3	57.4		58.1	58.3	51.4	63.8
2	43.7	42.6		41.9	41.7	48.6	36.2
3	0	0		0	0	0	0
Antiviral treatment (%)
HCV DAA*	–	29.8	–	31.6	31.5	25.6	21.5	<0.001
HBV	39.1	41.8	0.41	24.6	44.3	24.4	56.2	<0.001
Liver transplant (%)	4.8	4.1	0.006	4.2	3.7	5.8	5.6	<0.001
Follow-up (person-years)	22,103	24,567	–	28,779	5053	6779	3518	–

Notes: *Includes only patients from 2014 and after.

Abbreviations: HCC, hepatocellular carcinoma; DCCI, Deyo Charlson Comorbidity Index; HCV, hepatitis C virus; DAA, direct acting antiviral; HBV, hepatitis B virus; ALBI, albumin-bilirubin grade for HCC.

Table 3 Comparison Between NAFLD-Related HCC Patients with and without Cirrhosis

Characteristic	No cirrhosis N=4614	Cirrhosis N=8869	P-value
Mean age (years±SD)	71.1±12.1	71.1±10.7	0.96
Sex			<0.001
Male	50.6	55.8
Female	49.4	44.2
Race/ethnicity (%)			<0.001
Caucasian	62.8	63.1
African American	13.5	10.4
Hispanic	13.1	16.1
Asian	3.0	3.0
Unknown	7.6	7.4
Time period			<0.001
2003–2013	30.5	24.6
2014–2021	69.5	75.4
Diabetes mellitus (%)	75.6	79.2	<0.001
Advance care directive (%)	7.2	11.0	<0.001
Hospice/palliative care	27.9	43.8	<0.001
DCCI (±SD)	10.5±3.8	10.5±3.9	0.97
ALBI grade			<0.001
1	76.0	55.1
2	24.0	44.9
3	0	0
Liver transplant (%)	0.3	1.7	<0.001
Follow-up (person-years)	6135	9486	–

Abbreviations: NAFLD, non-alcoholic fatty liver disease; HCC, hepatocellular carcinoma; DCCI, Deyo Charlson Comorbidity Index; HCC, hepatocellular carcinoma; ALBI, albumin-bilirubin grade for HCC.

Figure 1 Survival of HCC patients by race and ethnicity (A), etiology (B), time period (C) and cirrhosis status in the NAFLD subgroup (D).

Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus; ALD, alcohol-associated liver disease; NAFLD, non-alcoholic fatty liver disease.

Table 4 Cox Proportional Hazards Model for Factors Associated with Mortality for Patients with Hepatocellular Carcinoma

Predictor	Univariable HR (95% CI)	P-value	Multivariable HR (95% CI)	P-value
Age	1.03 (1.02–1.04)	<0.001	1.02 (1.01–1.03)	<0.001
Male	1.06 (1.03–1.09)	<0.001	1.13 (1.08–1.17)	<0.001
Race/ethnicity
Asian	Referent		Referent
Caucasian	1.69 (1.57–1.81)	<0.001	1.46 (1.33–1.60)	<0.001
African American	1.73 (1.60–1.87)	<0.001	1.53 (1.38–1.70)	<0.001
Hispanic	1.54 (1.43–1.66)	<0.001	1.28 (1.16–1.42)	<0.001
Time period
2003–2013	Referent		Referent
2014–2021	1.05 (1.02–1.08)	<0.001	1.12 (1.07–1.17)	<0.001
Etiology
HCV, untreated	Referent		Referent
HCV, treated	0.45 (0.42–0.49)	<0.001	0.53 (0.48–0.59)	<0.001
HBV, untreated	0.94 (0.84–1.05)	0.27	0.97 (0.82–1.14)	0.71
HBV, treated	0.45 (0.38–0.53)	<0.001	0.69 (0.54–0.87)	0.002
ALD	1.28 (1.21–1.34)	<0.001	1.05 (0.97–1.13)	0.23
NAFLD	1.35 (1.31–1.40)	<0.001	1.14 (1.08–1.21)	<0.001
Cryptogenic	1.44 (1.39–1.50)	<0.001	1.45 (1.36–1.55)	<0.001
Other*	1.12 (1.06–1.19)	<0.001	0.98 (0.89–1.07)	0.61
Baseline DCCI	1.05 (1.04–1.06)	<0.001	1.04 (1.03–1.05)	<0.001
Cirrhosis
No cirrhosis	Referent		Referent
Cirrhosis	1.10 (1.07–1.13)	<0.001	1.28 (1.22–1.34)	<0.001
ALBI grade
1	Referent		Referent
2	1.55 (1.50–1.61)	<0.001	1.57 (1.51–1.64)	<0.001
HCC treatment
No transplant	Referent		Referent
Transplant	0.17 (0.15–0.19)	<0.001	0.22 (0.19–0.25)	<0.001

Notes: *Other liver diseases: autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson’s disease.

Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HBV, hepatitis B virus; ALD, alcohol-associated liver disease; NAFLD, non-alcoholic fatty liver disease; ALBI, albumin-bilirubin grade for HCC.