Nonalcoholic fatty liver disease is associated with worse intestinal complications in patients hospitalized for Clostridioides difficile infection

Table 1 Comparison of demographic data for patients hospitalized with Clostridioides difficile infection with coexisting nonalcoholic fatty liver disease, viral liver disease and alcoholic liver disease

Variables	CDI with NAFLD	CDI with VLD	CDI with ALD	P value
n (weighted)	7239	11857	5938	CDI with NAFLD vs CDI with VLD	CDI with NAFLD vs CDI with ALD
Age (yr)	56.32 ± 0.42	57 ± 0.26	56.13 ± 0.37	0.15	0.73
18-39	1133 (15.6%)	791 (6.7%)	557 (9.4%)	< 0.0001	< 0.0001
40-49	1290 (17.8%)	1811 (15.3%)	1051 (17.7%)
50-59	1618 (22.4%)	4873 (41.1%)	2021 (34%)
60-69	1620 (22.4%)	2791 (23.5%)	1439 (24.2%)
≥ 70	1578 (21.8%)	1591 (13.4%)	870 (14.7%)
Sex				< 0.0001	< 0.0001
Female	5023 (69.4%)	5795 (48.9%)	2300 (38.7%)
Race				< 0.0001	0.17
Caucasian	5427 (75%)	6920 (58.4%)	4358 (73.4%)
African American	482 (6.5%)	2773 (23.4%)	525 (8.8%)
Hispanic	648 (9%)	1144 (9.6%)	515 (8.7%)
Hospital bed size				0.033	0.9
Large	4241 (58.6%)	7414 (62.6%)	3461 (58.3%)
Hospital region				< 0.0001	< 0.0001
Northeast	1091 (15.1%)	2618 (22.1%)	1243 (20.9%)
Midwest	1618 (22.3%)	2514 (21.1%)	1584 (26.7%)
South	3008 (41.6%)	4208 (35.5%)	1671 (28.1%)
West	1522 (21%)	2517 (21.2%)	1440 (24.3%)
Hospital type				< 0.0001	0.22
Urban teaching	3401 (47%)	7207 (60.8%)	3065 (51.6%)
Insurance				< 0.0001	< 0.0001
Medicare	3086 (42.6%)	5493 (46.3%)	2239 (37.7%)
Medicaid	914 (12.6%)	3329 (28.1%)	1261 (21.2%)
Private	2526 (34.9%)	1835 (15.5%)	1391 (23.4%)
Median household income for ZIP Code, %				< 0.0001	0.61
Q1	1790 (24.7%)	4205 (35.5%)	1592 (26.8%)
Q2	1824 (25.2%)	3128 (26.4%)	1407 (23.7%)
Q3	1926 (26.6%)	2353 (19.8%)	1503 (25.3%)
Q4	1511 (20.9%)	1657 (14%)	1252 (21.1%)

Values reported as weighted mean ± SE and weighted number [n (%)]. CDI: Clostridioides difficile infection; NAFLD: Nonalcoholic fatty liver disease; VLD: Viral liver disease; ALD: Alcoholic liver disease; Q1: Quartile 1, 0-25th percentile; Q2: Quartile 2, 26th-50th percentile; Q3: Quartile 3, 51th-75th percentile; Q4: Quartile 4, 76th-100th percentile.

Table 2 Comparison of comorbid conditions and complications for patients hospitalized with Clostridioides difficile infection with coexisting nonalcoholic fatty liver disease, viral liver disease and alcoholic liver disease

Variables	CDI with NAFLD	CDI with VLD	CDI with ALD	P value
n (weighted)	7239	11857	5938	CDI with NAFLD vs CDI with VLD	CDI with NAFLD vs CDI with ALD
Number of Elixhauser comorbidities				< 0.0001	< 0.0001
0	0 (0%)	114 (1%)	-
1	244 (3.4%)	574 (4.8%)	116 (2%)
2	656 (9.1%)	1409 (11.9%)	354 (6%)
≥ 3	6338 (87.6%)	9760 (82.3%)	5463 (92%)
Obesity	2012 (27.8%)	850 (7.2%)	372 (6.3%)	< 0.0001	< 0.0001
Diabetes	2750 (38%)	3451 (29.1%)	1170 (19.7%)	< 0.0001	< 0.0001
Hypertension	4300 (59.4%)	6347 (53.5%)	2980 (50.2%)	0.00058	< 0.0001
Dyslipidemia	2619 (36.2%)	1868 (15.8%)	905 (15.2%)	< 0.0001	< 0.0001
Hepatocellular carcinoma	-	253 (2.1%)	45 (0.8%)	< 0.0001	0.0217
Cirrhosis related comorbidities1
Cirrhosis	401 (5.5%)	2508 (21.2%)	3407 (57.4%)	< 0.0001	< 0.0001
Number of cirrhosis complications				0.0013	< 0.0001
0	137 (34.2%)	1773 (70.7%)	2105 (61.8%)
1	244 (60.8%)	688 (27.4%)	1104 (32.4%)
v ≥ 2	20 (5.0%)	47 (1.9%)	198 (5.8%)
Ascites	0 (0%)	0 (0%)	0 (0%)	NA	NA
Esophageal varices bleeding	0 (0%)	-	20 (0.6%)	NA	NA
Hepatic encephalopathy	110 (27.4%)	60 (2.4%)	569 (16.7%)	0.003338	< 0.0001
Hepatorenal syndrome	0 (0%)	15 (0.6%)	33 (1.0%)	NA	NA
Portal hypertension	175 (43.6%)	661 (26.4%)	843 (24.7%)	< 0.0001	< 0.0001
Spontaneous bacterial peritonitis	0 (0%)	38 (1.5%)	40 (1.2%)	NA	NA

¹Value reported as percentage of all cirrhotic patients.

Values reported as weighted number [n (%)].-: Numbers were not displayed due to extremely small numbers were associated with increased risk for identification of persons; CDI: Clostridioides difficile infection; NAFLD: Nonalcoholic fatty liver disease; VLD: Viral liver disease; ALD: Alcoholic liver disease; NA: Not available.

Table 3 Multivariate regression analysis of outcomes for patients hospitalized for Clostridioides difficile infection with coexisting nonalcoholic fatty liver disease vs viral liver disease

Outcomes	CDI with NAFLD	CDI with VLD	Unadjusted ratio (95%CI)	P value	Adjusted ratio1 (95%CI)	P value
n (weighted)	7239	11857
Hospital mortality	59 (0.8%)	186 (1.6%)	1.94 (1.44, 2.6)	< 0.0001	1.87 (0.95, 3.7)	0.071
Acute kidney injury	938 (13%)	2035 (17.2%)	1.39 (1.28, 1.51)	< 0.0001	1.35 (1.1, 1.67)	0.0041
Respiratory failure	192 (2.7%)	504 (4.2%)	1.63 (1.37, 1.92)	< 0.0001	1.83 (1.22, 2.76)	0.0036
Septic shock	39 (0.5%)	115 (1%)	1.8 (1.25, 2.59)	0.0015	1.64 (0.67, 4.02)	0.27
Intestinal perforation	-	-	0.3 (0.1, 0.89)	0.03	0.12 (0.03, 0.57)	0.0075
Intestinal obstruction	331 (4.6%)	527 (4.4%)	0.97 (0.84, 1.12)	0.67	0.94 (0.66, 1.33)	0.725
Peritonitis	61 (0.8%)	106 (0.9%)	1.06 (0.77, 1.45)	0.71	0.72 (0.35, 1.52)	0.39
Colectomy	45 (0.6%)	105 (0.9%)	1.43 (1.01, 2.03)	0.044	1.38 (0.6, 3.15)	0.44
Ileostomy	-	41 (0.3%)	2.47 (1.24, 4.92)	0.01	2.62 (0.66, 10.41)	0.17
LOS (days)	5.75 ± 0.16	6.77 ± 0.15	1.11 (1.06, 1.16)	< 0.0001	1.12 (1.06, 1.18)	< 0.0001
Total hospitalizationcharges (dollars)	38150.34 ± 1757.01	46326.72 ± 1809.82	1.14 (1.07, 1.2)	< 0.0001	1.13 (1.06, 1.2)	< 0.0001

¹Adjusted for age, sex, race, primary insurance payer, hospital type, hospital bed size, hospital region, income quartile, Elixhauser Comorbidity Index score, obesity, diabetes, tobacco use disorder, hypertension, dyslipidemia, cirrhosis and its complications, numbers of cirrhosis complications, and hepatocellular carcinoma.

-: Numbers were not displayed due to extremely small numbers were associated with increased risk for identification of persons. Values reported as weighted mean ± SE and weighted numbers [n (%)]; CDI: Clostridioides difficile infection; NAFLD: Nonalcoholic fatty liver disease; VLD: Viral liver disease; CI: Confidence interval; LOS: Length of stay.

Table 4 Multivariate regression analysis of outcomes for patients hospitalized for Clostridioides difficile infection with coexisting nonalcoholic fatty liver disease vs alcoholic liver disease

Outcomes	CDI with NAFLD	CDI with ALD	Unadjusted ratio (95%CI)	P value	Adjusted ratio1 (95%CI)	P value
n (weighted)	7239	5938
Hospital mortality	59 (0.8%)	159 (2.7%)	3.34 (2.48, 4.52)	< 0.0001	2.63 (1.25, 5.51)	0.0107
Acute kidney injury	938 (13%)	935 (15.8%)	1.26 (1.14, 1.39)	< 0.0001	1.2 (0.93, 1.54)	0.15
Respiratory failure	192 (2.7%)	249 (4.2%)	1.61 (1.33, 1.94)	< 0.0001	1.72 (1.09, 2.72)	0.0201
Septic shock	39 (0.5%)	79 (1.3%)	2.48 (1.69, 3.64)	< 0.0001	2.14 (0.84, 5.46)	0.109
Intestinal perforation	-	0 (0%)	NA	NA	NA	NA
Intestinal obstruction	331 (4.6%)	133 (2.2%)	0.48 (0.39, 0.59)	< 0.0001	0.45 (0.28, 0.72)	0.0010
Peritonitis	61 (0.8%)	69 (1.2%)	1.38 (0.97, 1.95)	0.071	0.54 (0.25, 1.18)	0.12
Colectomy	45 (0.6%)	15 (0.3%)	0.42 (0.23, 0.74)	0.003	0.44 (0.14, 1.39)	0.16
Ileostomy	-	-	0.65 (0.23, 1.85)	0.42	0.99 (0.15, 6.61)	0.98
LOS (days)	5.75 ± 0.16	6.84 ± 0.23	1.14 (1.08, 1.21)	< 0.0001	1.18 (1.1, 1.25)	< 0.0001
Totalhospitalizationcharges (dollars)	38150.34 ± 1757.01	44641.74 ± 1660.66	1.14 (1.07, 1.22)	< 0.0001	1.17 (1.09, 1.26)	< 0.0001

¹Adjusted for age, sex, race, primary insurance payer, hospital type, hospital bed size, hospital region, income quartile, Elixhauser Comorbidity Index score, obesity, diabetes, tobacco use disorder, hypertension, dyslipidemia, cirrhosis and its complications, numbers of cirrhosis complications, and hepatocellular carcinoma.

Values reported as weighted mean ± SE and weighted numbers [n (%)]. -: Numbers were not displayed due to extremely small numbers were associated with increased risk for identification of persons. CDI: Clostridioides difficile infection; NAFLD: Nonalcoholic fatty liver disease; ALD: Alcoholic liver disease; LOS: Length of stay.