Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and the Risk of Cirrhosis in Patients with Chronic Hepatitis B—A Retrospective Cohort Study

Figures & data

Table 1 Baseline Characteristics of Patients Before and After IPTW

Variables	Before IPTW		P values	After IPTW		P values
	CHB-MAFLD Group	CHB Group		CHB-MAFLD Group	CHB Group
	(n=355)	(n=868)		(n=1078)	(n=1076)
Clinical characteristics (No.[%])
Follow-up duration (median [IQR]), (years)	5.33 (2.88–7.33)	5.21 (2.92–7.17)	0.620	5.41 (3.08–7.41)	5.33 (3.08–7.33)	0.501
Age (median [IQR]), (years)	41.00 (36.00–50.00)	39.00 (31.00–48.00)	<0.001	41.00 (35.00–49.00)	40.00 (33.00–52.00)	0.515
Sex			<0.001			0.206
Male	300 (84.5)	554 (63.8)		794 (73.7)	818 (76.0)
Female	55 (15.5)	314 (36.2)		284 (26.3)	258 (24.0)
Alcohol intake habit	30 (8.4)	29 (3.3)	<0.001	80 (7.4)	46 (4.3)	0.003
BMI (median [IQR]), (kg/m^2)	25.06 (23.63–26.84)	21.12 (19.47–23.03)	<0.001	24.95 (23.46–26.57)	21.49 (19.58–23.44)	<0.001
Antiviral treatment status			0.856			0.074
No	161 (45.4)	387 (44.6)		488 (45.3)	445 (41.4)
Yes	194 (54.6)	481 (55.4)		590 (54.7)	631 (58.6)
Diabetes mellitus	43 (12.1)	27 (3.1)	<0.001	122 (11.3)	54 (5.0)	<0.001
Hypertension	50 (14.1)	45 (5.2)	<0.001	147 (13.6)	72 (6.7)	<0.001
Laboratory data (median [IQR])
Albumin (g/L)	45.80 (42.90–48.35)	45.40 (42.50–47.90)	0.039	45.30 (42.80–48.00)	45.50 (42.45–48.10)	0.412
Total bilirubin (umol/L)	12.20 (9.40–15.95)	12.50 (9.50–16.40)	0.590	12.40 (9.50–17.15)	13.12 (10.00–17.00)	0.457
ALP (U/L)	72.00 (59.00–84.00)	69.00 (57.00–84.00)	0.096	71.00 (58.00–84.00)	71.00 (59.00–85.00)	0.699
ALT (U/L)	37.00 (24.00–58.00)	33.00 (21.00–59.00)	0.040	36.00 (24.00–58.00)	33.00 (22.00–58.00)	0.308
GGT (U/L)	32.00 (22.50–48.50)	23.00 (15.00–39.00)	<0.001	27.00 (19.00–45.00)	26.00 (17.00–42.00)	0.344
AST (U/L)	27.00 (21.00–36.00)	28.00 (21.00–44.00)	0.051	27.00 (21.00–37.65)	27.00 (21.00–42.00)	0.087
Glucose (mmol/L)	5.31 (4.87–5.74)	4.92 (4.64–5.30)	<0.001	5.26 (4.84–5.76)	5.04 (4.70–5.42)	<0.001
UA (umol/L)	386.50 (326.00–450.00)	341.00 (281.00–396.00)	<0.001	381.00 (321.00–441.00)	346.00 (291.00–401.79)	<0.001
TG (mmol/L)	5.31 (4.88–5.76)	4.97 (4.65–5.31)	<0.001	1.19 (0.88–1.72)	0.96 (0.74–1.27)	<0.001
TC (mmol/L)	1.28 (0.92–1.79)	0.91 (0.71–1.24)	<0.001	4.84 (4.21–5.50)	4.57 (3.96–5.24)	<0.001
HDL-C (mmol/L)	4.90 (4.18–5.54)	4.56 (3.96–5.22)	<0.001	1.10 (0.96–1.31)	1.24 (1.03–1.49)	<0.001
LDL-C (mmol/L)	1.07 (0.94–1.28)	1.31 (1.10–1.56)	<0.001	3.24 (2.70–3.77)	2.94 (2.35–3.51)	<0.001
HBV DNA (log^10 IU/mL)	4.45 (2.40–6.47)	5.42 (3.04–7.31)	<0.001	4.74 (2.75–6.68)	4.71 (2.40–6.77)	0.107
HBeAg (positive),(No.[%])	130 (36.6)	189 (21.8)	0.015	348 (32.3)	316 (29.3)	0.140

Abbreviations: IPTW, inverse probability treatment weighting; IQR, Interquartile range; CHB, chronic hepatitis B; MAFLD, metabolic dysfunction-associated fatty liver disease; BMI, body mass index; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; UA, uric acid; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HBV, hepatitis B virus; HBeAg, hepatitis B e antigen.

Figure 1 Flowchart of the study cohorts.

Figure 2 Metabolic characteristics of patients in the CHB-MAFLD group. In the CHB-MAFLD group, the proportions of patients with BMI ≥ 23 kg/m², with BMI < 23 kg/m² and metabolic dysfunctions, with BMI < 23 kg/m² and DM were 85.64%, 11.83%, and 2.53%, respectively (A), while 82.53% of these CHB-MAFLD patients had at least one metabolic risk factor (B).

Figure 3 Cumulative incidence of cirrhosis per year after IPTW. The different weighted cumulative incidence of cirrhosis per year between the CHB-MAFLD group and the CHB group after IPTW.

Figure 4 Cumulative incidence of cirrhosis after IPTW. The cumulative incidence of cirrhosis in the CHB-MAFLD group was significantly higher than that in the CHB group (12.6% and 7.1%, respectively, P=0.015).

Figure 5 Cumulative incidence of cirrhosis after IPTW, by antiviral treatment status.

Notes: (A) Patients without antiviral treatment. (B) Patients with antiviral treatment. The weighted cumulative incidence of cirrhosis was significantly higher in the CHB-MAFLD group compared to the CHB group, whether in patients without antiviral treatment (A) or in patients with antiviral treatment (B).

Table 2 Weighted Univariate and Multivariate Cox Analysis of Risk Factors Related to Cirrhosis After IPTW

	Univariate Analysis		Multivariate Analysis
	Weighted HR (95% CI)	P values	Adjusted Weighted HR (95% CI)	P values
Age (years)
≤40	1 [Reference]		1 [Reference]
>40	1.864 (1.094–3.176)	0.022	1.950 (1.141–3.332)	0.015
Male	1.028 (0.333–3.174)	0.434
Alcohol intake habit
No	1 [Reference]	0.112	1 [Reference]
Yes	2.029 (0.849–4.852)		1.854 (0.779–4.414)	0.163
BMI (kg/m2)	1.108 (1.003–1.224)	0.957
Antiviral treatment status
>5 years	1 [Reference]		1 [Reference]
≤5 years	1.522 (0.785–2.951)	0.213	1.581 (0.792–3.156)	0.194
Untreated	2.032 (1.176–3.509)	0.011	2.037 (1.164–3.567)	0.013
Diabetes mellitus
No	1 [Reference]		1 [Reference]
Yes	1.434 (1.262–4.696)	0.008	1.883 (1.026–3.456)	0.041
Hypertension
No	1 [Reference]
Yes	2.298 (0.943–5.656)	0.130
MAFLD
No	1 [Reference]		1 [Reference]
Yes	1.774 (1.113–2.827)	0.016	1.790 (1.095–2.926)	0.020
Albumin (g/dL)	0.964 (0.905–1.028)	0.256
Total bilirubin (umol/L)	1.003 (0.998–1.009)	0.193
ALP (U/L)	1.005 (0.995–1.009)	0.108
ALT (U/L)	0.998 (0.994–1.003)	0.494
AST (U/L)	0.999 (0.993–1.005)	0.640
GGT (U/L)	1.007 (1.004–1.011)	<0.001	1.004 (1.001–1.007)	0.005
UA (umol/L)	0.998 (0.995–1.001)	0.117
Glucose (mg/dL)	0.998 (0.992–1.004)	0.480
TG (mg/dL)	0.775 (0.408–1.472)	0.437
TC (mmol/L)	0.716 (0.530–1.067)	0.329
HDL-C (mg/dL)	0.725 (0.325–1.618)	0.432
LDL-C (mg/dL)	0.711 (0.525–1.062)	0.271
HBV DNA (log^10 IU/mL)
≤2.4	1 [Reference]		1 [Reference]
>2.4	1.767 (1.021–3.059)	0.042	1.756 (1.013–3.042)	0.045
HBeAg (positive)	1.181 (0.496–2.841)	0.692

Note: Bold font indicates P<0.05.

Abbreviations: IPTW, inverse probability treatment weighting; HR, hazard ratio; CI, confidence interval; CHB, chronic hepatitis B; MAFLD, metabolic dysfunction-associated fatty liver disease; BMI, body mass index; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; UA, uric acid; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HBV, hepatitis B virus; HBeAg, hepatitis B e antigen.

Figure 6 Subgroup analysis of cirrhosis risk after IPTW, by antiviral treatment status.

Notes: (A) All patients. (B) Patients with alcohol consumption are excluded. MAFLD was associated with an increased risk of cirrhosis in CHB patients receiving or not receiving antiviral therapy, whether in all patients (A) or in patients without alcohol use (B).