Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

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Original Article

Volume 000, Number 000, August 2025, pages 000-000

Predictors of Development of Hepatocellular Carcinoma in Non-Cirrhotic Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease/Metabolic Dysfunction-Associated Steatohepatitis - A Retrospective Analysis of the National Inpatient Sample Database

Figure 1. Consort diagram for non-cirrhotic HCC. HCC: hepatocellular carcinoma; MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis.

**Table 1.** Clinical Characteristics and Outcomes of Non-Cirrhotic Patients With MASLD/MASH (Univariate Analysis)
Variables	N = 1,326,230 (n (%) or mean (SD))
MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis; SD: standard deviation; FNH: focal nodular hyperplasia; HTN: hypertension; DM: diabetes mellitus; HLD: hyperlipidemia; AFIB/AFL: atrial fibrillation/atrial flutter; H. pylori: Helicobacter pylori; C. diff: Clostridium difficile; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.
Age	53.75 (15.601)
Gender (female)	689,670 (52.0%)
Race
White/Caucasian	860,645 (66.5%)
African American/Black	143,005 (11.1%)
Hispanic	205,650 (15.9%)
Asian	31,505 (2.4%)
Lab abnormalities
Anemia	116,905 (8.8%)
Leukopenia	9,145 (0.7%)
Thrombocytopenia	86,445 (6.5%)
Hyponatremia	161,470 (12.2%)
Hypoalbuminemia	18,155 (1.4%)
Benign liver lesions
Hepatic adenoma	545 (0.0%)
FNH	13,685 (1.0%)
Liver hemangioma	4,365 (0.3%)
Comorbidities
HTN	613,645 (46.3%)
DM	200,605 (15.1%)
HLD	477,685 (36.0%)
AFIB/AFL	126,170 (9.5%)
Liver abscess	1,785 (0.1%)
Cholelithiasis	59,385 (4.5%)
Cholecystitis	9,785 (0.7%)
Cholangitis	1,850 (0.1%)
Pancreatitis	54,330 (4.1%)
Gastritis	44,275 (3.3%)
H. pylori infection	4,120 (0.3%)
C. diff infection	19,275 (1.5%)
Stroke	5,520 (0.4%)
Dementia	17,830 (1.3%)
COPD	109,775 (8.3%)
CKD	36,395 (2.7%)
Diverticulosis	27,190 (2.1%)
Autoimmune disorders
RA	25,215 (1.9%)
SLE	9,305 (0.7%)
Sjogren’s syndrome	3,490 (0.3%)
Scleroderma	840 (0.1%)
Hashimoto thyroiditis	3,615 (0.3%)

Table 1. Clinical Characteristics and Outcomes of Non-Cirrhotic Patients With MASLD/MASH (Univariate Analysis)

Variables

N = 1,326,230 (n (%) or mean (SD))

MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis; SD: standard deviation; FNH: focal nodular hyperplasia; HTN: hypertension; DM: diabetes mellitus; HLD: hyperlipidemia; AFIB/AFL: atrial fibrillation/atrial flutter; H. pylori: Helicobacter pylori; C. diff: Clostridium difficile; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.

Age

53.75 (15.601)

Gender (female)

689,670 (52.0%)

Race

White/Caucasian

860,645 (66.5%)

African American/Black

143,005 (11.1%)

Hispanic

205,650 (15.9%)

Asian

31,505 (2.4%)

Lab abnormalities

Anemia

116,905 (8.8%)

Leukopenia

9,145 (0.7%)

Thrombocytopenia

86,445 (6.5%)

Hyponatremia

161,470 (12.2%)

Hypoalbuminemia

18,155 (1.4%)

Benign liver lesions

Hepatic adenoma

545 (0.0%)

FNH

13,685 (1.0%)

Liver hemangioma

4,365 (0.3%)

Comorbidities

HTN

613,645 (46.3%)

200,605 (15.1%)

HLD

477,685 (36.0%)

AFIB/AFL

126,170 (9.5%)

Liver abscess

1,785 (0.1%)

Cholelithiasis

59,385 (4.5%)

Cholecystitis

9,785 (0.7%)

Cholangitis

1,850 (0.1%)

Pancreatitis

54,330 (4.1%)

Gastritis

44,275 (3.3%)

H. pylori infection

4,120 (0.3%)

C. diff infection

19,275 (1.5%)

Stroke

5,520 (0.4%)

Dementia

17,830 (1.3%)

COPD

109,775 (8.3%)

CKD

36,395 (2.7%)

Diverticulosis

27,190 (2.1%)

Autoimmune disorders

25,215 (1.9%)

SLE

9,305 (0.7%)

Sjogren’s syndrome

3,490 (0.3%)

Scleroderma

840 (0.1%)

Hashimoto thyroiditis

3,615 (0.3%)

**Table 2.** Predictors of Development of HCC in Non-Cirrhotic Patients With MASLD/MASH (Bivariate Analysis)
Variables	Development of hepatocellular carcinoma	Odds ratio/P value
HCC: hepatocellular carcinoma; MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis; FNH: focal nodular hyperplasia; HTN: hypertension; DM: diabetes mellitus; HLD: hyperlipidemia; AFIB/AFL: atrial fibrillation/atrial flutter; H. pylori: Helicobacter pylori; C. diff: Clostridium difficile; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; GI: gastrointestinal; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.
Age	62.08 (12.413)	53.64 (15.609)	(< 0.0001)
Gender (female)	10,220 (58.4%)	679,450 (51.9%)	1.301 (< 0.001)
Race
White/Caucasian	11,620 (66.4%)	849,025 (64.9%)	1.052 (0.002)
African American/Black	1,525 (8.7%)	141,480 (10.8%)	0.781 (< 0.001)
Hispanic	2,380 (13.6%)	203,270 (15.5%)	0.849 (< 0.001)
Asian	760 (4.3%)	30,745 (2.3%)	1.875 (< 0.001)
Lab abnormalities
Anemia	2,150 (12.3%)	114,755 (8.8%)	1.458 (< 0.001)
Leukopenia	150 (0.9%)	8,995 (0.7%)	1.250 (0.007)
Thrombocytopenia	1,270 (7.3%)	85,175 (6.5%)	1.124 (< 0.001)
Hyponatremia	2,850 (16.3%)	158,620 (12.1%)	1.411 (< 0.001)
Hypoalbuminemia	530 (3.0%)	17,625 (1.3%)	2.289 (< 0.001)
Benign liver lesions
Hepatic adenoma	10 (0.1%)	535 (0.0%)	(0.291)
FNH	275 (1.6%)	13,410 (1.0%)	1.543 (< 0.001)
Liver hemangioma	80 (0.5%)	4,285 (0.3%)	1.398 (0.003)
Comorbidities
HTN	8,265 (47.2%)	605,480 (46.3%)	1.040 (0.010)
DM	3,090 (17.7%)	197,515 (15.1%)	1.207 (< 0.001)
HLD	6,260 (35.8%)	471,425 (36.0%)	(0.512)
AFIB/AFL	1,675 (9.6%)	124,495 (9.5%)	(0.783)
Liver abscess	60 (0.3%)	1,725 (0.1%)	2.607 (< 0.001)
Cholelithiasis	895 (5.1%)	58,490 (4.5%)	1.152 (< 0.001)
Cholangitis	95 (0.5%)	1,755 (0.1%)	4.066 (< 0.001)
H. pylori infection	65 (0.4%)	4,055 (0.3%)	(0.145)
C. diff infection	225 (1.3%)	19,050 (1.5%)	(0.063)
Stroke	65 (0.4%)	5,455 (0.4%)	(0.355)
Dementia	240 (1.4%)	17,590 (1.3%)	(0.751)
COPD	1,540 (8.8%)	108,235 (8.3%)	1.071 (0.011)
CKD	690 (3.9%)	35,705 (2.7%)	1.464 (< 0.001)
GI bleed	180 (1.0%)	12,425 (0.9%)	(0.282)
Diverticulosis	460 (2.6%)	26,730 (2.0%)	1.295 (0.001)
Autoimmune disorders
RA	280 (1.6%)	24,935 (1.9%)	0.837 (0.003)
SLE	50 (0.3%)	9,255 (0.7%)	0.402 (< 0.001)
Sjogren’s syndrome	45 (0.3%)	3,445 (0.3%)	(0.877)
Scleroderma	10 (0.1%)	830 (0.1%)	(0.744)
Hashimoto thyroiditis	60 (0.3%)	3,555 (0.3%)	(0.072)

Table 2. Predictors of Development of HCC in Non-Cirrhotic Patients With MASLD/MASH (Bivariate Analysis)

Variables

Development of hepatocellular carcinoma

Odds ratio/P value

Yes (n = 17,495, 1.3%)

No (1,308,735)

HCC: hepatocellular carcinoma; MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis; FNH: focal nodular hyperplasia; HTN: hypertension; DM: diabetes mellitus; HLD: hyperlipidemia; AFIB/AFL: atrial fibrillation/atrial flutter; H. pylori: Helicobacter pylori; C. diff: Clostridium difficile; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; GI: gastrointestinal; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.

Age

62.08 (12.413)

53.64 (15.609)

(< 0.0001)

Gender (female)

10,220 (58.4%)

679,450 (51.9%)

1.301 (< 0.001)

Race

White/Caucasian

11,620 (66.4%)

849,025 (64.9%)

1.052 (0.002)

African American/Black

1,525 (8.7%)

141,480 (10.8%)

0.781 (< 0.001)

Hispanic

2,380 (13.6%)

203,270 (15.5%)

0.849 (< 0.001)

Asian

760 (4.3%)

30,745 (2.3%)

1.875 (< 0.001)

Lab abnormalities

Anemia

2,150 (12.3%)

114,755 (8.8%)

1.458 (< 0.001)

Leukopenia

150 (0.9%)

8,995 (0.7%)

1.250 (0.007)

Thrombocytopenia

1,270 (7.3%)

85,175 (6.5%)

1.124 (< 0.001)

Hyponatremia

2,850 (16.3%)

158,620 (12.1%)

1.411 (< 0.001)

Hypoalbuminemia

530 (3.0%)

17,625 (1.3%)

2.289 (< 0.001)

Benign liver lesions

Hepatic adenoma

10 (0.1%)

535 (0.0%)

(0.291)

FNH

275 (1.6%)

13,410 (1.0%)

1.543 (< 0.001)

Liver hemangioma

80 (0.5%)

4,285 (0.3%)

1.398 (0.003)

Comorbidities

HTN

8,265 (47.2%)

605,480 (46.3%)

1.040 (0.010)

3,090 (17.7%)

197,515 (15.1%)

1.207 (< 0.001)

HLD

6,260 (35.8%)

471,425 (36.0%)

(0.512)

AFIB/AFL

1,675 (9.6%)

124,495 (9.5%)

(0.783)

Liver abscess

60 (0.3%)

1,725 (0.1%)

2.607 (< 0.001)

Cholelithiasis

895 (5.1%)

58,490 (4.5%)

1.152 (< 0.001)

Cholangitis

95 (0.5%)

1,755 (0.1%)

4.066 (< 0.001)

H. pylori infection

65 (0.4%)

4,055 (0.3%)

(0.145)

C. diff infection

225 (1.3%)

19,050 (1.5%)

(0.063)

Stroke

65 (0.4%)

5,455 (0.4%)

(0.355)

Dementia

240 (1.4%)

17,590 (1.3%)

(0.751)

COPD

1,540 (8.8%)

108,235 (8.3%)

1.071 (0.011)

CKD

690 (3.9%)

35,705 (2.7%)

1.464 (< 0.001)

GI bleed

180 (1.0%)

12,425 (0.9%)

(0.282)

Diverticulosis

460 (2.6%)

26,730 (2.0%)

1.295 (0.001)

Autoimmune disorders

280 (1.6%)

24,935 (1.9%)

0.837 (0.003)

SLE

50 (0.3%)

9,255 (0.7%)

0.402 (< 0.001)

Sjogren’s syndrome

45 (0.3%)

3,445 (0.3%)

(0.877)

Scleroderma

10 (0.1%)

830 (0.1%)

(0.744)

Hashimoto thyroiditis

60 (0.3%)

3,555 (0.3%)

(0.072)

**Table 3.** Odds of Development of HCC in Non-Cirrhotic MASLD/MASH Patients in Bivariate and Multivariate Analysis (Multivariate Logistic Regression Analysis)
Variables	Bivariate analysis	Multivariate analysis
HCC: hepatocellular carcinoma; MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis; FNH: focal nodular hyperplasia; HTN: hypertension; DM: diabetes mellitus; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.
Age		(< 0.0001)		< 0.0001
Gender (female)	1.301	(< 0.001)	1.303	< 0.001
Race
White/Caucasian	1.052	(0.002)	0.670	< 0.001
African American/Black	0.781	(< 0.001)	0.609	< 0.001
Hispanic	0.849	(< 0.001)	0.716	< 0.001
Asian	1.875	(< 0.001)	1.135	0.012
Lab abnormalities
Anemia	1.458	(< 0.001)	1.247	< 0.001
Leukopenia	1.250	(0.001)	1.360	< 0.001
Thrombocytopenia	1.124	(< 0.001)	1.031	0.310
Hyponatremia	1.411	(< 0.001)	1.389	< 0.001
Hypoalbuminemia	2.289	(< 0.001)	2.041	< 0.001
Benign liver lesions
FNH	1.543	(< 0.001)	1.269	< 0.001
Liver hemangioma	1.398	(0.003)	1.475	0.001
Comorbidities
HTN	1.040	(0.010)	0.934	< 0.001
DM	1.207	(< 0.001)	1.114	< 0.001
Liver abscess	2.607	(< 0.001)	2.073	< 0.001
Cholelithiasis	1.152	(< 0.001)	0.976	0.499
Cholangitis	4.066	(< 0.001)	3.093	< 0.001
COPD	1.071	(0.011)	0.827	< 0.001
CKD	1.464	(< 0.001)	1.072	0.088
Diverticulosis	1.295	(0.001)	1.008	0.864
Autoimmune disorders
RA	0.837	(0.003)	0.679	< 0.001
SLE	0.402	(< 0.001)	0.456	< 0.001

Table 3. Odds of Development of HCC in Non-Cirrhotic MASLD/MASH Patients in Bivariate and Multivariate Analysis (Multivariate Logistic Regression Analysis)

Variables

Bivariate analysis

Multivariate analysis

Crude OR

P value

Adjusted OR

P value

HCC: hepatocellular carcinoma; MASLD: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction-associated steatohepatitis; FNH: focal nodular hyperplasia; HTN: hypertension; DM: diabetes mellitus; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.

Age

(< 0.0001)

< 0.0001

Gender (female)

1.301

(< 0.001)

1.303

< 0.001

Race

White/Caucasian

1.052

(0.002)

0.670

< 0.001

African American/Black

0.781

(< 0.001)

0.609

< 0.001

Hispanic

0.849

(< 0.001)

0.716

< 0.001

Asian

1.875

(< 0.001)

1.135

0.012

Lab abnormalities

Anemia

1.458

(< 0.001)

1.247

< 0.001

Leukopenia

1.250

(0.001)

1.360

< 0.001

Thrombocytopenia

1.124

(< 0.001)

1.031

0.310

Hyponatremia

1.411

(< 0.001)

1.389

< 0.001

Hypoalbuminemia

2.289

(< 0.001)

2.041

< 0.001

Benign liver lesions

FNH

1.543

(< 0.001)

1.269

< 0.001

Liver hemangioma

1.398

(0.003)

1.475

0.001

Comorbidities

HTN

1.040

(0.010)

0.934

< 0.001

1.207

(< 0.001)

1.114

< 0.001

Liver abscess

2.607

(< 0.001)

2.073

< 0.001

Cholelithiasis

1.152

(< 0.001)

0.976

0.499

Cholangitis

4.066

(< 0.001)

3.093

< 0.001

COPD

1.071

(0.011)

0.827

< 0.001

CKD

1.464

(< 0.001)

1.072

0.088

Diverticulosis

1.295

(0.001)

1.008

0.864

Autoimmune disorders

0.837

(0.003)

0.679

< 0.001

SLE

0.402

(< 0.001)

0.456

< 0.001