Adherence to Oral Nutritional Supplements After Being Discharged from the Hospital is Low but Improves Outcome in Patients with Advanced Chronic Liver Disease

Figures & data

Figure 1 The exact instructions which were given to ACLD patients being discharged from the hospital (A) recommendation on the use of oral nutritional supplements with the record of ingested volume during four 6-hour time-periods, (B) instructions on the frequency, duration, and character of recommended exercises.

Figure 2 Flow-chart of 450 included ACLD patients after being discharged from the hospital illustrating the adherence to oral nutritional supplements and outcome during the first 180 days of follow-up.

Table 1 Summary Statistics and Study Group Characteristics of 450 Hospitalized ACLD Patients

Factor	Group	N (%), Median [25–75%]
n		450
Age, y		56.33 [46.63, 62.28]
Sex (%)	Males	252 (60)
	Females	198 (44.0)
Disease etiology (alcohol/viral/NAFLD/autoimmune/other)	n	287/32/66/50/15
	%	63.8/7.1/14.7/11.1/3.3
Diabetes type 2 (%)		65 (14.4)
Body mass index (kg/m2)		26.26 [23.05, 29.81]
Mid-arm circumference, cm		26.00 [23.62, 30.00]
Tricipital skinfold, mm		12.10 [7.80, 19.00]
Handgrip strength (HGS), kg		23.50 [16.78, 32.35]
Low HGS (men<30, women<20, kg)		246 (54.6)
White blood cells, count*10*9/l		5.70 [3.90, 8.67]
C-reactive protein, mg/l		12.03 [5.11, 26.93]
Refractory ascites (%)		106 (23.5)
MELD-Na score		16.00 [11.00, 21.00]
MELD-Na score>16		209 (46.4)
Child-Pugh-Turcotte score		9.00 [8.00, 11.00]
Child-Pugh-Turcotte stage C (>9)		220 (48.9)
Serum bilirubin, umol/l		54.80 [24.00, 124.67]
Serum albumin, g/l		26.00 [23.00, 31.00]
Number connection test, s		103.00 [74.25, 136.00]
Mortality 30 days (%)		61 (13.6)
Mortality 90 days (%)		106 (23.6)
Mortality 180 days (%)		140 (31.1)
Follow-up event (%)	None	156 (34.7)
	LT	62 (13.8)
	Death	232 (51.6)
Days of follow-up by event	All	452.00 [91.50, 1268.25]
	None	1347 [1225, 1576]
	LT	270 [151, 470]
	Death	111.5 [27.75, 414.25]

Abbreviations: ACLD, advanced chronic liver disease; HGS, hand-grip strength; NAFLD, nonalcoholic fatty liver disease; MELD, model for end-stage liver disease; LT, liver transplantation.

Table 2 Reported Causes of Non-Adherence During the First 30 Days of Treatment with ONS

Nutritional Supplements	n	%
Unknown	136	64.7
Abdominal fullness	15	7.1
Non-compliance	13	6.2
Diarrhea	10	4.8
Intolerance, other	8	3.8
Diabetes/glycaemia control	7	3.3
Nausea	6	2.9
Abdominal pain	5	2.4
Weigh gain	4	1.9
Anorexia	3	1.4
Constipation	1	0.5
Heartburn	1	0.5
Skin eruptions	1	0.5
Total	210	100

Abbreviation: ONS, oral nutritional supplements.

Table 3 Factors Associated with Adherence >30 Days in Univariate and Multivariate Analysis

	Univariate				Multivariate*
	OR		95% CI	P value	OR	95% CI	P value
Age, y	0.976	*	0.959–0.994	0.01
Sex (%), male	0.99	*	0.6626–1.48	0.241
Alcoholic etiology (%)	1.07	*	0.71–1.61	0.22
Diabetes type 2 (%)	0.665	*	0.371–1.19	0.352
Baseline parameters
Body mass index (kg/m2)	0.983	*	0.955–1.011	0.438
Mid-arm circumference, cm	0.985	*	0.945–1.027	0.474	0.929	0.876–0.984	0.013
Tricipital skinfold, mm	0.987	*	0.962–1.013	0.327
Hand-grip strength, kg	1.016	*	0.997–1.035	0.095	1.03	1.01–1.06	0.015
Leucocytes, x10*9/l	1.029	*	0.982–1.079	0.223
C-reactive protein, mg/l	0.999	*	0.989–1.008	0.803
Refractory ascites (%)	0.535	*	0.318–0.900	0.018	0.429	0.244–0.756	0.003
MELD-Na score	1.005	*	0.976–1.034	0.76
Serum bilirubin, umol/l	1.002	*	1.000–1.004	0.02
Serum albumin, g/l	1.025	*	0.993–1.059	0.13
Number connection test, s	0.996	*	0.9916–1.000	0.099
Outcome
Mortality at 90 days	0.549		0,285–1,06	0.073
Mortality at 180 days	0.619		0,372–1,03	0.064

Notes: *Variables in the multivariate logistic regression model; Overall model fit, chi-squared 15.5; P=0.0014; Nagelkerke R² =0.064; AUROC=0.62±0,03; 95% CI 0,564–0,674.

Figure 3 The cumulative incidence of liver transplantation (left pane) and death (right pane) in discharged ACLD patients according to adherence to oral nutritional supplements (>30 days, yes or no).

Figure 4 The cumulative incidence of death in discharged ACLD patients according to adherence to oral nutritional supplements (>30 days, dotted line) or not (solid line), a comparison of subgroups: (A) low or normal hand grip strength, (B) refractory ascites, yes or no, (C) MELD score>16 or ≤16.

Table 4 Changes in the Prognostic, Nutritional and Laboratory Parameters in ACLD Patients After Discharge from the Hospital According to Adherence to ONS

	Baseline		Day 30	Day 90		Day 180		Comparison vs Baseline
								D30 vs Baseline		D90 vs Baseline		D180 vs Baseline
	n*	Median/%	Median/%	n*	Median/%	n*	Median/%	Median Difference	P	Median Difference	P	Median Difference	P
Patients adherent to ONS
MELD score	173	15.00	14.00	97	13	59	12	−1.00	0.0027	−1	<0.0001	−2	<0.0001
Hand-grip strength (cm)	168	24.85	26.00	86	29.1	58	26.1	0.90	0.0295	1.5	0.0023	2.2	0.0245
Reractory ascites (%)	123	16.30	21.20	74	14.9	48	16.6	4.88	0.1094	1.35	1	8.33	0.125
Mid-arm ciscumference (cm)	172	26.00	27.00	85	27	58	28	0.00	0.0787	1	0.0005	1	0.0021
Tricipital skinfold (mm)	171	11.80	13.50	85	14	58	13.8	0.00	0.4756	0.4	0.1401	0.8	0.157
Mid-arm muscle area (cm2)	170	39.80	40.40	85	42.7	58	42.6	0.40	0.4545	1.2	0.0668	2.9	0.0065
Serum albumin (g/l)	178	27.00	31.00	107	33	65	37	3.00	<0.0001	4	<0.0001	6	<0.0001
C-reactive protein (mg/l)	177	10.10	8.30	105	6.1	66	4.7	−0.40	0.0109	−0.5	0.0082	−1.3	0.0056
Number connection test (s)	172	96.50	81.00	87	76	59	79	−6.00	<0.0001	−8	0.0005	−11	0.0001
Patients not adherent to ONS
MELD score	28	16.5	13.5	21	12	17	14	−2	0.0056	0	0.1591	0	0.4143
Hand-grip strength (cm)	4	32	29.3	18	22.7	11	28	1.7	0.875	1.4	0.3465	3.2	0.4648
Reractory ascites (%)	22	27.3	22.7	17	35.3	16	6.3	4.55	1	5.88	1	25	0.125
Mid-arm ciscumference (cm)	4	24.5	25	18	28.5	11	29	0.5	0.1817	−0.5	0.2676	−2	0.375
Tricipital skinfold (mm)	4	8.2	8.3	18	15.2	11	18	−1.6	0.875	−2.2	0.4423	−1.4	0.3203
Mid-arm muscle area (cm2)	4	38.6	40	18	42.5	11	39.3	1.8	0.125	−0.83	0.766	−4.8	0.5195
Serum albumin (g/l)	32	26	30	23	31	17	30	3	0.0013	3	0.0056	2	0.2435
C-reactive protein (mg/l)	31	10.7	7.4	25	5.8	17	9.8	−1.5	0.1169	−1.1	0.2879	−1.1	0.7119
Number connection test (s)	4	103.5	93	18	99.5	11	99	7.5	0.875	6.5	0.9661	7	0.2061

Notes: *Available data for paired comparison (Wilcoxon test for numerilcal variables, McNemar test for proportions).

Abbreviation: ONS, oral nutritional supplements.