Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease

Figures & data

Figure 1 Patient flow diagram.

Abbreviations: CT, computed tomography; HCC, hepatocellular carcinoma; MAFLD, metabolic dysfunction-associated fatty liver disease; MRI, magnetic resonance imaging; PSM, propensity score matching.

Table 1 Baseline Characteristics of Total Cohort and PSM Cohort

	Total Cohort			PSM Cohort
	MAFLD (n=199)	Non-MAFLD (n=425)	p value	MAFLD (n=186)	Non-MAFLD (n=186)	p value
Age (years)^+	57.0 (48.0–63.5)	56.0 (49.0–63.0)	0.431	56.5 (48.0–63.8)	57.0 (50.0–64.0)	0.876
Gender (male)	163 (81.9)	357 (84.0)	0.514	153 (82.3)	147 (79.0)	0.431
BMI (kg/m2)^+	25.7 (24.1–28.0)	24.8 (23.1–26.9)	0.000	25.7 (24.0–28.0)	24.9 (23.2–27.1)	0.000
Type 2 diabetes	36 (18.1)	70 (16.5)	0.616	32 (17.2)	39 (21.0)	0.356
Hypertension	73 (36.7)	107 (25.2)	0.003	68 (36.6)	42 (22.6)	0.003
Liver cirrhosis	165 (82.9)	366 (86.1)	0.295	158 (84.9)	158 (84.9)	1.000
HBV	155 (77.9)	368 (86.6)	0.006	150 (80.6)	149 (80.1)	0.896
Alcohol	53 (26.6)	106 (24.9)	0.651	52 (28.0)	47 (25.3)	0.557
ECOG PS (>0)	45 (22.6)	94 (22.1)	0.890	41 (22.0)	45 (24.2)	0.623
AFP (>1000 ng/mL)	37 (19.1)	81 (19.6)	0.886	37 (20.3)	42 (23.0)	0.543
Histopathology			0.426			0.310
Well	17 (9.9)	28 (7.0)		17 (10.3)	10 (5.7)
Moderate	120 (70.2)	297 (74.4)		115 (69.7)	128 (73.1)
Poor	34 (19.9)	74 (18.6)		33 (20.0)	37 (21.1)
Tumor number (>1)	32 (16.2)	69 (16.2)	0.981	32 (17.2)	29 (15.6)	0.674
Tumor size (cm)^+	3.8 (2.6–6.3)	4.0 (2.7–6.9)	0.184	3.9 (2.6–6.4)	4.5 (2.7–7.0)	0.066
Microvascular invasion	42 (21.2)	94 (22.2)	0.788	42 (22.6)	52 (28.0)	0.233
Metastases	9 (4.5)	36 (8.5)	0.077	9 (4.8)	16 (8.6)	0.213
Satellite nodules	21 (10.6)	50 (11.8)	0.665	21 (11.3)	22 (11.8)	0.871
Child B and C	18 (9.1)	28 (6.6)	0.273	17 (9.1)	18 (9.7)	0.859
MELD^+	7.0 (7.0–8.0)	8.0 (7.0–9.0)	0.040	7.0 (7.0–8.0)	8.0 (7.0–9.0)	0.089
BCLC			0.875			0.772
0	14 (7.2)	23 (5.4)		10 (5.4)	12 (6.5)
A	38 (19.6)	77 (18.2)		37 (19.9)	32 (17.2)
B	89 (45.9)	197 (46.6)		87 (46.8)	80 (43.0)
C	50 (25.8)	119 (28.1)		49 (26.3)	59 (31.7)
D	3 (1.5)	7 (1.7)		3 (1.6)	3 (1.6)
CNLC			0.983			0.762
I	130 (67.0)	278 (65.9)		122 (65.6)	113 (60.8)
II	13 (6.7)	27 (6.4)		13 (7.0)	13 (7.0)
III	48 (24.7)	110 (26.0)		48 (25.8)	57 (30.6)
IV	3 (1.6)	7 (1.6)		3 (1.6)	3 (1.6)
Initial therapy			0.008			0.587
Liver resection	112 (56.3)	281 (66.1)		111 (59.7)	103 (55.4)
Laparoscopic resection	61 (30.7)	120 (28.2)		56 (30.1)	69 (37.1)
Others	26(13.0)	24(5.7)		19 (10.2)	14 (7.5)
HBeAg positive	43 (21.6)	95 (22.6)	0.789	40 (21.5)	35 (18.8)	0.518
HBV DNA (log10 IU/mL)^+	2.8 (1.8–4.9)	3.0 (1.6–4.8)	0.777	2.8 (1.9–4.9)	2.3 (1.4–3.9)	0.078

Notes: ⁺Data are medians, with interquartile ranges in parentheses. p value of < 0.05 was considered statistically significant and shown in bold values. Except where indicated, Data are numbers of patients, with percentages in parentheses.

Abbreviations: AFP, alpha fetoprotein; ALBI, albumin-bilirubin grade; BCLC, Barcelona Clinic Liver Cancer staging system; BMI, Body mass index; Child B and C, Child-Pugh class B and C; CNLC, China liver cancer staging system; ECOG PS, Eastern Cooperative Oncology Group performance status; HBV, hepatitis B virus; HCV, hepatitis C virus; HBeAg, hepatitis B e antigen; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; MAFLD, metabolic dysfunction-associated fatty liver disease; PSM, propensity score matching; SMD, standardized mean difference.

Figure 2 (A) OS before matching. (B) OS after matching. (C) OS in patients with hepatitis B after matching. (D) OS in patients without hepatitis B after matching.

Abbreviations: HCC, hepatocellular carcinoma; MAFLD, metabolic dysfunction-associated fatty liver disease; OS, overall survival.

Figure 3 (A) Patients with MAFLD stratified by HBeAg status. (B) Patients with MAFLD stratified by HBV DNA levels. (C) Patients with non-MAFLD stratified by HBeAg status. (D) Patients with non-MAFLD stratified by HBV DNA levels.

Abbreviations: CHB, chronic hepatitis B; HCC, hepatocellular carcinoma; MAFLD, metabolic dysfunction-associated fatty liver disease; HBeAg, hepatitis B e-antigen; HBV, hepatitis B virus.

Table 2 Prognostic Factor Analysis for Overall Survival in CHB-HCC Patients

Variables	Overall Survival
	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p value	HR (95% CI)	p value
Age (years)	1.00 (0.98–1.02)	0.903
Gender (male)	0.75 (0.48–1.19)	0.219
MAFLD	0.29 (0.19–0.46)	0.000	0.36 (0.22–0.57)	0.000
BMI	0.89 (0.83–0.94)	0.000	0.91 (0.86–0.97)	0.006
Type 2 diabetes	0.80 (0.45–1.44)	0.464
Hypertension	0.69 (0.43–1.10)	0.118
Liver cirrhosis	0.79 (0.48–1.31)	0.358
ECOG PS (>0)	2.01 (1.35–2.99)	0.001	2.13 (1.40–3.24)	0.000
Alcohol	1.32 (0.88–1.97)	0.186
AFP (>1000 ng/mL)	1.77 (1.17–2.68)	0.007	0.81 (0.50–1.32)	0.398
Child B and C	2.60 (1.54–4.38)	0.000	1.58 (0.87–2.88)	0.133
Histological grade		0.041		0.193
Well	(ref)		(ref)
Moderate	2.43 (0.76–7.76)	0.133	1.91 (0.46–7.94)	0.372
Poor	3.77 (1.13–12.61)	0.031	2.76 (0.63–12.00)	0.177
Tumor number (>1)	1.42 (0.90–2.26)	0.136
Tumor size	1.15 (1.09–1.21)	0.000	1.06 (1.00–1.13)	0.048
Microvascular invasion	3.95 (2.67–5.83)	0.000	3.01 (1.96–4.64)	0.000
Metastases	2.33 (1.27–4.25)	0.006	0.96 (0.48–1.93)	0.911
Satellite nodules	2.05 (1.26–3.35)	0.004	1.19 (0.69–2.03)	0.538

Note: p value of < 0.05 was considered statistically significant and shown in bold values.

Abbreviations: AFP, alpha fetoprotein; BMI, Body mass index; Child B and C, Child-Pugh class B and C; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; HBsAg, Hepatitis B surface antigen; MAFLD, metabolic dysfunction-associated fatty liver disease.

Figure 4 Subgroup analyses by two groups of non-MAFLD and MAFLD after matching.

Abbreviations: HR, hazard ratio; MAFLD, metabolic associated fatty liver disease.