Clinical burden of physical frailty in patients evaluated for liver transplantation: A retrospective cohort study

Table 1 Demographic and clinical characteristics of the total cohort, n (%)

Characteristic	Study population (n = 266)
Age (years)	58 (50-63)
Sex, male	200 (75)
MELD score	16 (11-19)
Dry weight (kg)	83 (72-99)
BMI kg/m2 [BMI categories (based on estimated dry weight1)]	27 (24-32)
Underweight (≤ 18.49 kg/m2)	7 (3)
Healthy (18.5-24.9 kg/m2)	82 (30)
Overweight (25-29.9 kg/m2)	88 (33)
Obese (≥ 30 kg/m2)	89 (33)
Aetiology of liver disease
Alcohol-related liver disease	103 (39)
Chronic viral hepatitis (HCV/HBV)	61 (23)
MASLD	46 (17)
PBC/PSC	36 (13)
AIH	6 (2)
Cryptogenic	4 (2)
Other2	10 (4)
Those with hepatocellular carcinoma	73 (27)
Type two diabetes	64 (24)
Ascites present	91 (34)
SGA score
A (well nourished)	179 (67)
B (moderately malnourished)	78 (30)
C (severely malnourished)	9 (3)
Frailty
LFI	3.7 (3.3-4.1)
Robust (< 3.2)	50 (19)
Pre-frail (3.2-4.5)	179 (67)
Frail (> 4.5)	37 (14)
Liver transplant recipients3	144 (54)

¹Dry weight was estimated from post-paracentesis weight if available, otherwise by or by subtracting 5%, 10%, or 15% of total body weight for mild, moderate or severe ascites, respectively as previously described.

²Other causes of liver disease: Hepatic sarcoidosis, alpha1-antitrypsin deficiency, Budd-Chiari cirrhosis.

³Two patients still awaiting a liver transplantation at end of study.

An additional 5% was subtracted for bilateral pedal oedema. MELD: Model for end-stage liver disease; BMI: Body mass index; HCV: Hepatitis C virus; HBV: Hepatitis B virus; MASLD: Metabolic-dysfunction associated fatty liver disease; PSC: Primary sclerosing cholangitis; PBC: Primary biliary cirrhosis; AIH: Auto-immune hepatitis; SGA: Subjective global assessment; LFI: Liver frailty index.

Table 2 Liver frailty index and frailty categories (robust, pre-frail, frail) across demographic and clinical characteristics, n (%)

Characteristic grouping	Median LFI (IQR)	P value	Robust	Pre-frail	Frail	P value
Categorical variables
With HCC (n = 73)	3.5 (3.2-3.8)	< 0.001	23 (46)	45 (25)	5 (14)	0.002
Without HCC (n = 193)	3.8 (3.4-4.2)		27 (54)	134 (75)	32 (86)
Well nourished (n = 179)	3.5 (3.2-3.9)	< 0.001	45 (90)	122 (68)	12 (32)	< 0.001
Moderately-severely malnourished (n = 87)	4.2 (3.7-4.6)		5 (10)	57 (32)	25 (68)
Type two diabetes (n = 64)	3.9 (3.5-4.3)	0.020	4 (8)	47 (26)	13 (35)	0.007
No type two diabetes (n = 202)	3.6 (3.2-4.0)		46 (92)	132 (74)	24 (65)
Male (n = 199)	3.7 (3.3-4.1)	0.750	39 (78)	131 (73)	29 (78)	0.680
Female (n = 67)	3.8 (3.3-4.2)		11 (22)	48 (27)	8 (22)
Obese (BMI > 30 kg/m2) (n = 89)	3.8 (3.4-4.2)	0.210	14 (28)	59 (33)	16 (43)	0.320
Non-obese (BMI < 30 kg/m2) (n = 177)	3.6 (3.3-4.1)		36 (72)	120 (67)	21 (57)
Continuous variables
MELD score, median (IQR)	-	-	12 (9-16)	16 (11-19)	19 (15-23)	< 0.001
Age (years), median (IQR)	-	-	57 (49-63)	58 (50-62)	60 (51-64)	0.270
Dry weight (kg), median (IQR)	-	-	82 (73-95)	83 (71-100)	85 (75-101)	0.770

P values are reported to three decimal places, with P < 0.001 shown for values below this threshold. IQR: Interquartile range; LFI: Liver frailty index; HCC: Hepatocellular carcinoma; BMI: Body mass index; MELD: Model for end stage liver disease.

Table 3 Univariable and multivariable regression analysis for the continuous liver frailty index and clinical outcomes

Total cohort (n = 266)	Continuous LFI median (IQR)	Univariable analysis			Multivariable analysis
		Beta value/co-efficient (SE)	OR (95%CI)	P value	Beta value/co-efficient (SE)	OR (95%CI)	P value
Pre transplant
LT recipient		-0.47 (0.19)	0.63 (0.44-0.90)	0.010	-0.62 (0.21)	0.54 (0.36-0.81)	0.003
Yes (n = 144)	3.6 (3.3-4.0)
No (n = 122)	3.8 (3.4-4.2)
Unplanned hospital admission		0.85 (0.20)	2.34 (1.56-3.49)	< 0.001	0.52 (0.22)	1.69 (1.09-2.62)	0.020
No (n = 161)	3.6 (3.2-3.9)
Yes (n = 105)	3.9 (3.5-4.3)
Early post-transplant complications
Grade ≥ 3 post op complication1,2		0.37 (0.26)	1.45 (0.87-2.41)	0.200	0.71 (0.30)	1.19 (0.66-2.12)	0.600
No (n = 72)	3.5 (3.1-4.0)
Yes (n = 72)	3.7 (3.4-4.1)
ICU LOS > 4 days3		0.87 (0.48)	2.38 (0.94-6.05)	0.070	1.17 (0.56)	3.24 (1.06-9.85)	0.040
No (n = 129)	3.6 (3.3-4.0)
Yes (n = 13)	3.9 (3.5-4.8)
Hospital LOS > 18 days3		0.77 (0.35)	2.16 (1.09-4.28)	0.030	0.68 (0.39)	1.98 (0.92-4.26)	0.080
No (n = 114)	3.5 (3.2-4.0)
Yes (n = 28)	3.8 (3.6-4.2)

¹Clavien-Dindo classification (category 3; requirement for re-operation, category 4; requirement for extended intensive care unit stay or ventilation in intensive care unit, category 5; death).

²n = 144 including 2 who died during transplant but have been included in transplant complications.

³n = 142.

The analysis represents a 10 points change in the liver frailty index score. P values are reported to three decimal places, with P < 0.001 shown for values below this threshold. Multivariable analysis was adjusted for cofounders of age, sex, presence of hepatocellular carcinoma and model for end-stage liver disease score. LFI: Liver frailty index; IQR: Interquartile range; LT: Liver transplantation; LOS: Length of stay; ICU: Intensive care unit; OR: Odds ratio; CI: Confidence interval.

Table 4 Univariable and multivariable regression analysis for frailty categories (robust, pre-frail, frail) and clinical outcomes

Clinical outcome across frailty groups total cohort (n = 266)	Univariable analysis		Multivariable analysis
	Beta value/co-efficient (SE)	OR (95%CI)	P value	Beta value/co-efficient (SE)	OR (95%CI)	P value
Pre transplant
LT recipient (yes/total n = 144/266)
Frail (n = 14/37)	-1.16 (0.45)	0.33 (0.13-0.76)	0.010	-1.44 (0.49)	0.24 (0.90-0.62)	0.003
Pre-frail (n = 97/179)	-0.50 (0.33)	0.61 (0.32-1.17)	0.140	-0.62 (0.35)	0.54 (0.27-1.08)	0.040
Robust (n = 33/50)	Reference	Reference	Reference	Reference	Reference	-
Unplanned hospital admission (yes/total n = 105/266)
Frail (n = 21/37)	1.79 (0.50)	6.00 (2.27-15.79)	< 0.001	1.12 (0.54)	3.07 (1.06-8.90)	0.04
Pre-frail (n = 75/179)	1.19 (0.40)	3.29 (1.51-7.17)	0.003	0.91 (0.42)	2.49 (1.08-5.72)	0.030
Robust (n = 9/50)	Reference	Reference	-	Reference	Reference	-
Early post-transplant complications
Grade ≥ 3 post op complication1,2 (yes/total n = 72/144)
Frail (n = 7/14)	0.43 (0.64)	1.54 (0.44-5.42)	0.500	0.09 (0.70)	1.10 (0.28-4.28)	0.900
Pre-frail (n = 52/97)	0.58 (0.41)	1.78 (0.80-3.97)	0.160	0.33 (0.43)	1.39 (0.60-3.25)	0.400
Robust (n = 13/33)	Reference	Reference	-	Reference	Reference	-
ICU LOS > 4 days3 (yes/total n = 13/142)
Frail (n = 4/14)	1.79 (0.94)	6.00 (0.95-37.86)	0.060	2.24 (1.09)	9.45 (1.11-80.82)	0.040
Pre-frail (n = 7/96)	0.21 (0.80)	1.18 (0.23-5.99)	0.840	0.20 (0.86)	1.22 (0.22-6.65)	0.810
Robust (n = 2/32)	Reference	Reference	-	Reference	Reference	-
LOS > 18 days3 (yes/total n = 28/142)
Frail (n = 5/14)	2.12 (0.92)	8.33 (1.38-50.47)	0.020	1.90 (0.96)	6.66 (1.01-43.80)	0.050
Pre-frail (n = 21/96)	1.44 (0.83)	4.20 (0.93-19.03)	0.060	1.31 (0.79)	3.71 (0.80-17.28)	0.100
Robust (n = 2/32)	Reference	Reference	-	Reference	Reference	-

¹Clavien-Dindo classification (category 3; requirement for re-operation, category 4; requirement for extended intensive care unit stay or ventilation in intensive care unit, category 5; death).

²n = 144 including 2 who died during transplant but have been included in transplant complications.

³n = 1.

The analysis represent 10 points change in the liver frailty index score. P values are reported to three decimal places, with P < 0.001 shown for values below this threshold. Multivariable analysis was adjusted for cofounders of age, sex, presence of hepatocellular carcinoma and model for end-stage liver disease score. LT: Liver transplantation; LOS: Length of stay; ICU: Intensive care unit; OR: Odds ratio; CI: Confidence interval.