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

Journal website https://www.gastrores.org

Original Article

Volume 15, Number 2, April 2022, pages 82-90

Burden and Predictors of Non-Alcoholic Fatty Liver Disease in a Retrospective Cohort of Patients With Crohn’s Disease

Figure 1. Case selection flowchart. NAFLD: non-alcoholic fatty liver disease; HCUP: Healthcare Cost and Utilization Project; NRD: Nationwide Readmissions Database.

**Table 1.** Baseline Characteristics of CD Patients With and Without NAFLD
	NAFLD absent, n = 209,781	NAFLD present, n = 5,268	P value
^aMann-Whitney test. ^bPearson Chi-square test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; IQR: interquartile range.
Median age, years (IQR)	53 (36 - 68)	53 (42 - 63)	0.59^a
Age group, %
Age 18 - 44	37.1	29.8	< 0.001^b
Age 45 - 64	32.5	47.8
Age 65 or older	30.4	22.3
Gender, %
Male	42.3	40.6	0.014^b
Female	57.7	59.4
Median household income for patient’s ZIP code, %
0 - 25th percentile	23.4	23.4	0.06^b
26th - 50th percentile	26.5	27.8
51st - 75th percentile	26.5	26.5
76th - 100th percentile	23.6	22.3
Bed size of the hospital, %
Small	15.8	17	0.021^b
Medium	27.9	28.3
Large	56.3	54.7
Expected primary payer, %
Medicare	40.4	37.7	0.002^b
Medicaid	14.5	14.6
Private insurance	38.2	40.3
Self-pay	3.6	4.1
Others	0.5	0.5
Patient location, %
Central counties of metro areas	24.4	23.7	0.037^b
Fringe counties of metro areas	29.5	29.2
Counties in metro areas of 250,000 - 999,999 population	22.6	24.4
Counties in metro areas of 50,000 - 249,999 population	10	10
Micropolitan counties	8	7.2
Not metropolitan or micropolitan counties	5.6	5.6

Table 1. Baseline Characteristics of CD Patients With and Without NAFLD

NAFLD absent, n = 209,781

NAFLD present, n = 5,268

P value

^aMann-Whitney test. ^bPearson Chi-square test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; IQR: interquartile range.

Median age, years (IQR)

53 (36 - 68)

53 (42 - 63)

0.59^a

Age group, %

Age 18 - 44

37.1

29.8

< 0.001^b

Age 45 - 64

32.5

47.8

Age 65 or older

30.4

22.3

Gender, %

Male

42.3

40.6

0.014^b

Female

57.7

59.4

Median household income for patient’s ZIP code, %

0 - 25th percentile

23.4

0.06^b

26th - 50th percentile

26.5

27.8

51st - 75th percentile

26.5

76th - 100th percentile

23.6

22.3

Bed size of the hospital, %

Small

15.8

0.021^b

Medium

27.9

28.3

Large

56.3

54.7

Expected primary payer, %

Medicare

40.4

37.7

0.002^b

Medicaid

14.5

14.6

Private insurance

38.2

40.3

Self-pay

3.6

4.1

Others

0.5

Patient location, %

Central counties of metro areas

24.4

23.7

0.037^b

Fringe counties of metro areas

29.5

29.2

Counties in metro areas of 250,000 - 999,999 population

22.6

24.4

Counties in metro areas of 50,000 - 249,999 population

Micropolitan counties

7.2

Not metropolitan or micropolitan counties

5.6

**Table 2.** Comorbid Diseases Among CD Patients With and Without NAFLD
	NAFLD absent, n = 209,781	NAFLD present, n = 5,268	P value
^aPearson Chi-square test. ^bFisher’s exact test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; LFT: liver function test.
Hypertension, %	29.8	41.5	< 0.001^a
Diabetes mellitus, %	15.2	28.5	< 0.001^a
Obesity, %	11.3	29.3	< 0.001^a
Dyslipidemia, %	21.1	28.2	< 0.001^a
Metabolic syndrome, %	0.1	0.7	< 0.001^a
Vitamin A deficiency, %	0.01	0.2	< 0.001^a
Vitamin D deficiency, %	3.1	4.9	< 0.001^a
Vitamin E deficiency, %	0.01	0.1	0.009^b
Vitamin K deficiency, %	0.04	0.1	0.49^b
Pyridoxine deficiency, %	0.01	0.01	0.616^a
Thrombocytopenia, %	3.6	9.4	< 0.001^a
Vitamin B12 deficiency, %	0.4	0.6	0.026^a
Abnormal LFT, %	0.2	0.6	< 0.001^a
Gallstone disease, %	1.1	4.2	< 0.001^a
Chronic pancreatitis, %	0.8	2.7	< 0.001^a
Clostridium difficile enterocolitis, %	2.6	3.6	< 0.001^a
Portal hypertension, %	0.6	5	< 0.001^a

Table 2. Comorbid Diseases Among CD Patients With and Without NAFLD

NAFLD absent, n = 209,781

NAFLD present, n = 5,268

P value

^aPearson Chi-square test. ^bFisher’s exact test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; LFT: liver function test.

Hypertension, %

29.8

41.5

< 0.001^a

Diabetes mellitus, %

15.2

28.5

< 0.001^a

Obesity, %

11.3

29.3

< 0.001^a

Dyslipidemia, %

21.1

28.2

< 0.001^a

Metabolic syndrome, %

0.1

0.7

< 0.001^a

Vitamin A deficiency, %

0.01

0.2

< 0.001^a

Vitamin D deficiency, %

3.1

4.9

< 0.001^a

Vitamin E deficiency, %

0.01

0.1

0.009^b

Vitamin K deficiency, %

0.04

0.1

0.49^b

Pyridoxine deficiency, %

0.01

0.616^a

Thrombocytopenia, %

3.6

9.4

< 0.001^a

Vitamin B12 deficiency, %

0.4

0.6

0.026^a

Abnormal LFT, %

0.2

0.6

< 0.001^a

Gallstone disease, %

1.1

4.2

< 0.001^a

Chronic pancreatitis, %

0.8

2.7

< 0.001^a

Clostridium difficile enterocolitis, %

2.6

3.6

< 0.001^a

Portal hypertension, %

0.6

< 0.001^a

**Table 3.** Gastrointestinal Complications Among CD Patients With and Without NAFLD
	NAFLD absent, n = 209,781	NAFLD present, n = 5,268	P value^a
^aP value for Pearson Chi-square test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease.
CD with fistula, %	3.5	2.2	< 0.001
CD with rectal bleeding, %	3.9	5.1	< 0.001
CD with abscess, %	3.3	2.1	< 0.001
CD with intestinal obstruction, %	10.4	9.3	0.017

Table 3. Gastrointestinal Complications Among CD Patients With and Without NAFLD

NAFLD absent, n = 209,781

NAFLD present, n = 5,268

P value^a

^aP value for Pearson Chi-square test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease.

CD with fistula, %

3.5

2.2

< 0.001

CD with rectal bleeding, %

3.9

5.1

< 0.001

CD with abscess, %

3.3

2.1

< 0.001

CD with intestinal obstruction, %

10.4

9.3

0.017

**Table 4.** Hospitalization Outcomes for CD Patients With and Without NAFLD
	NAFLD absent, n = 209,781	NAFLD present, n = 5,268	P value
^aMann-Whitney test. ^bPearson Chi-square test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; LOS: length of stay; IQR: interquartile range.
Median LOS, days (IQR)	3 (2 - 6)	4 (2 - 6)	< 0.001^a
Mortality, %	1.2	1	0.204^b
All-cause 30-day non-elective readmission, %	11.1	11.7	0.172^b
Median total charges (IQR)	$30,782 ($16,847 - $58,667)	$32,305.5 ($18,600 - $61,599)	< 0.001^a

Table 4. Hospitalization Outcomes for CD Patients With and Without NAFLD

NAFLD absent, n = 209,781

NAFLD present, n = 5,268

P value

^aMann-Whitney test. ^bPearson Chi-square test. CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; LOS: length of stay; IQR: interquartile range.

Median LOS, days (IQR)

3 (2 - 6)

4 (2 - 6)

< 0.001^a

Mortality, %

1.2

0.204^b

All-cause 30-day non-elective readmission, %

11.1

11.7

0.172^b

Median total charges (IQR)

$30,782 ($16,847 - $58,667)

$32,305.5 ($18,600 - $61,599)

< 0.001^a

**Table 5.** Hospitalization Outcomes for CD Patients With and Without NASH
	NASH absent, n = 214,149	NASH present, n = 900	P value
^aMann-Whitney test. ^bPearson Chi-square test. CD: Crohn’s disease; NASH: non-alcoholic steatohepatitis; LOS: length of stay; IQR: interquartile range.
Median LOS, days (IQR)	3 (2 - 6)	4 (2 - 6)	< 0.001^a
Mortality, %	1.2	2.2	0.004^b
All-cause 30-day non-elective readmission, %	11.1	15.6	< 0.001^b
Median total charges (IQR)	$30,821 ($16,891 - $58,718)	$30,422 ($17,683 - $66,474)	0.083^a

Table 5. Hospitalization Outcomes for CD Patients With and Without NASH

NASH absent, n = 214,149

NASH present, n = 900

P value

^aMann-Whitney test. ^bPearson Chi-square test. CD: Crohn’s disease; NASH: non-alcoholic steatohepatitis; LOS: length of stay; IQR: interquartile range.

Median LOS, days (IQR)

3 (2 - 6)

4 (2 - 6)

< 0.001^a

Mortality, %

1.2

2.2

0.004^b

All-cause 30-day non-elective readmission, %

11.1

15.6

< 0.001^b

Median total charges (IQR)

$30,821 ($16,891 - $58,718)

$30,422 ($17,683 - $66,474)

0.083^a

**Table 6.** Most Common Causes of 30-Day Readmission Among CD Patients With NASH
30-day readmission primary diagnosis	Rate^a
^aRate as per 100 readmission records. CD: Crohn’s disease; NASH: non-alcoholic steatohepatitis.
Sepsis, unspecified organism	1.7
Hepatic failure, unspecified with coma	1.7
Acute kidney failure, unspecified	1.6
CD without complications	1.4
Unspecified cirrhosis of liver	1.3
CD of small intestine with intestinal obstruction	0.9
Enterocolitis due to Clostridium difficile	0.7
Hypertensive heart and chronic kidney disease	0.6
Pneumonia, unspecified organism	0.6
Acute and subacute hepatic failure without coma	0.6
Nonalcoholic steatohepatitis (NASH)	0.6

Table 6. Most Common Causes of 30-Day Readmission Among CD Patients With NASH

30-day readmission primary diagnosis

Rate^a

^aRate as per 100 readmission records. CD: Crohn’s disease; NASH: non-alcoholic steatohepatitis.

Sepsis, unspecified organism

1.7

Hepatic failure, unspecified with coma

1.7

Acute kidney failure, unspecified

1.6

CD without complications

1.4

Unspecified cirrhosis of liver

1.3

CD of small intestine with intestinal obstruction

0.9

Enterocolitis due to Clostridium difficile

0.7

Hypertensive heart and chronic kidney disease

0.6

Pneumonia, unspecified organism

0.6

Acute and subacute hepatic failure without coma

0.6

Nonalcoholic steatohepatitis (NASH)

0.6

**Table 7.** Logistic Regression Model for Factors Associated With NAFLD in Patients With CD
Predictor	Odds ratio	95% CI (lower - upper)	P value
CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; CI: confidence interval; LFT: liver function test.
Vitamin A deficiency	9.89	4.49 - 21.76	< 0.001
Portal hypertension	5.35	4.60 - 6.21	< 0.001
Abnormal LFT	3.29	2.29 - 4.72	< 0.001
Metabolic syndrome	2.69	1.84 - 3.94	< 0.001
Obesity	2.84	2.65 - 3.04	< 0.001
Diabetes mellitus	1.81	1.68 -1.96	< 0.001
Vitamin D deficiency	1.43	1.25 - 1.63	< 0.001
Hypertension	1.45	1.41 - 1.6	< 0.001
Vitamin B12 deficiency	1.56	1.1 - 2.21	0.013
CD with rectal bleeding	1.31	1.16 - 1.49	< 0.001
Dyslipidemia	1.29	1.2 - 1.39	< 0.001
CD with fistula	0.76	0.63 - 0.91	0.004
Female sex	1.07	1.01 - 1.13	0.023
Gallstone disease	3.44	2.97 - 3.99	< 0.001
Chronic pancreatitis	2.73	2.28 - 3.27	< 0.001
Thrombocytopenia	2.14	1.93 - 2.38	< 0.001
Clostridium difficile enterocolitis	1.41	1.22 - 1.64	< 0.001
Age (years)
18 - 44	Reference
45 - 64	1.23	1.14 - 1.32	< 0.001
≥ 65	0.59	0.54 - 0.64	< 0.001

Table 7. Logistic Regression Model for Factors Associated With NAFLD in Patients With CD

Predictor

Odds ratio

95% CI (lower - upper)

P value

CD: Crohn’s disease; NAFLD: non-alcoholic fatty liver disease; CI: confidence interval; LFT: liver function test.

Vitamin A deficiency

9.89

4.49 - 21.76

< 0.001

Portal hypertension

5.35

4.60 - 6.21

< 0.001

Abnormal LFT

3.29

2.29 - 4.72

< 0.001

Metabolic syndrome

2.69

1.84 - 3.94

< 0.001

Obesity

2.84

2.65 - 3.04

< 0.001

Diabetes mellitus

1.81

1.68 -1.96

< 0.001

Vitamin D deficiency

1.43

1.25 - 1.63

< 0.001

Hypertension

1.45

1.41 - 1.6

< 0.001

Vitamin B12 deficiency

1.56

1.1 - 2.21

0.013

CD with rectal bleeding

1.31

1.16 - 1.49

< 0.001

Dyslipidemia

1.29

1.2 - 1.39

< 0.001

CD with fistula

0.76

0.63 - 0.91

0.004

Female sex

1.07

1.01 - 1.13

0.023

Gallstone disease

3.44

2.97 - 3.99

< 0.001

Chronic pancreatitis

2.73

2.28 - 3.27

< 0.001

Thrombocytopenia

2.14

1.93 - 2.38

< 0.001

Clostridium difficile enterocolitis

1.41

1.22 - 1.64

< 0.001

Age (years)

18 - 44

Reference

45 - 64

1.23

1.14 - 1.32

< 0.001

≥ 65

0.59

0.54 - 0.64

< 0.001