Multidimensional Frailty Assessment and Post-Transplant Outcomes in Liver Transplant Candidates

Frailty will be assessed using the Liver Frailty Index (LFI), which is calculated from three standardized physical performance tests: grip strength (kg, average of three trials), chair stands (seconds to complete five repetitions), and balance test (seconds, up to 10 seconds in three positions). LFI score will be calculated according to the standard LFI formula. Frailty severity will be categorized as:

≥4.5: Severe frailty 3.2-4.4: Moderate frailty <3.2: Not frail Unit of Measure: LFI score (continuous) Direction: Higher scores indicate greater frailty (worse outcome).

The 6-minute walk test (6MWT) will be conducted according to European Respiratory Society and American Thoracic Society guidelines along a 30-meter corridor. Participants will be instructed to walk as far as possible in six minutes. Distance walked will be recorded in meters and rounded to the nearest meter. Oxygen saturation, heart rate, blood pressure, and fatigue (Modified Borg Scale) will be recorded before and after the test, with continuous SpO₂ and heart rate monitoring during the walk. Frailty classification will be based on the following thresholds: <250 m (severe frailty), 250-350 m (moderate frailty), >350 m (not frail).

Unit of Measure: Meters (continuous) Direction: Higher walking distance indicates lower frailty (better outcome).

The Karnofsky Performance Status (KPS) is a subjective measure of frailty, originally developed for oncology and subsequently applied in cirrhosis. The scale ranges from 0% (death) to 100% (normal; no complaints; no evidence of disease), scored in 10-point increments. Applicable to both hospitalized and ambulatory patients. Frailty classification will be based on the following thresholds:

0-40% = Severe frailty 50-70% = Moderate frailty

≥80% = Not frail Unit of Measure: Percentage (%) Direction: Higher KPS score indicates lower frailty (better outcome).

The Activities of Daily Living (ADL) scale is a subjective measure of frailty, developed to assess functional status in aging populations. It evaluates six functions: bathing, dressing, toileting, continence, transferring, and feeding. The scale is self-reported and scored from 0 (dependent) to 6 (independent). Frailty classification will be based on the following thresholds: ≥2 difficulties (severe frailty), 1 difficulty (moderate frailty), and 0 difficulties (not frail).

Unit of Measure: Score (0-6) Direction: Higher scores indicate lower frailty (better outcome).

Nutritional status will be assessed using the Nutritional Risk Index (NRI). The NRI score will be calculated using serum albumin level (g/dL), current body weight (kg), and usual body weight (kg) according to the following formula:

NRI = (15.19 × serum albumin [g/dL]) + (41.7 × current weight / usual weight)

Nutritional status will be categorized as follows:

NRI ≥ 100: No malnutrition 97.5 ≤ NRI < 100: Mild malnutrition 83.5 ≤ NRI < 97.5: Moderate malnutrition NRI < 83.5: Severe malnutrition Unit of Measure: NRI score Direction: Higher NRI values indicate better nutritional status.

Phase angle will be measured using bioelectrical impedance analysis (BIA) as an indicator of cellular integrity and nutritional status. Measurements will be performed according to standard BIA procedures at the time of hospital admission.

Phase angle values will be categorized according to predefined study criteria as follows:

<4.4 degrees: Abnormal 4.4-5.4 degrees: Borderline

≥5.4 degrees: Normal Unit of Measure: Degrees Direction: Higher phase angle values indicate better cellular health and nutritional status.

Sarcopenia will be assessed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Evaluation will include assessment of muscle strength, muscle mass, and physical performance using standardized measurement procedures at hospital admission.

Sarcopenia will be classified as:

Probable sarcopenia: Low muscle strength Sarcopenia: Low muscle strength and low muscle mass Severe sarcopenia: Low muscle strength, low muscle mass, and low physical performance Unit of Measure: Categorical classification (probable sarcopenia, sarcopenia, severe sarcopenia) Direction: Lower sarcopenia severity indicates better muscle status.

Handgrip strength will be measured using a hand dynamometer in the dominant hand following a standardized protocol (patient seated, elbow at 90 degrees, three trials, best value recorded). Low muscle strength will be defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria as <27 kg for men and <16 kg for women.

Unit of Measure: Kilograms (kg) Direction: Higher handgrip strength indicates better muscle strength and physical status.

Skeletal Muscle Index (SMI) will be assessed using bioelectrical impedance analysis (BIA). Appendicular skeletal muscle mass (ASM) will be calculated as the sum of muscle mass of the upper and lower extremities. SMI will be derived by dividing ASM (kg) by height squared (m²), according to the formula:

SMI = ASM / height² Low muscle mass will be defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria as SMI <7.0 kg/m² for men and <5.5 kg/m² for women.

Unit of Measure: kg/m² Direction: Higher SMI values indicate better skeletal muscle mass and physical status.

Gait speed will be measured using the 4-meter walk test. Participants will be instructed to walk at their usual pace over a 4-meter course, and time will be recorded with a stopwatch. Gait speed will be calculated as distance (4 m) divided by time (seconds) and expressed in m/s. Low physical performance will be defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria as gait speed ≤0.8 m/s.

Unit of Measure: Meters per second (m/s) Direction: Higher gait speed indicates better physical performance.

Anxiety symptoms will be assessed using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A), which consists of 7 items. Each item is scored from 0 to 3, producing a total score ranging from 0 to 21. Higher scores indicate greater anxiety symptoms. A score of ≥10 will be considered indicative of clinically significant anxiety, based on the validated Turkish version of the scale.

Unit of Measure: HADS-A score (0-21) Direction: Higher scores indicate higher anxiety symptoms (worse outcome).

Depressive symptoms will be assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), which consists of 7 items. Each item is scored from 0 to 3, producing a total score ranging from 0 to 21. Higher scores indicate greater depressive symptoms. A score of ≥7 will be considered indicative of clinically significant depression, based on the validated Turkish version of the scale.

Unit of Measure: HADS-D score (0-21) Direction: Higher scores indicate higher depressive symptoms (worse outcome).

Psychological distress will be assessed using the Hospital Anxiety and Depression Scale (HADS), a 14-item self-report questionnaire. Each item is scored from 0 to 3, producing a total score ranging from 0 to 42. The total score is calculated as the sum of all items (HADS Total = HADS-A + HADS-D). No validated universal cut-off exists for the total score; therefore, it will be analyzed as a continuous variable.

Unit of Measure: Total HADS score (0-42) Direction: Higher scores indicate greater psychological distress (worse outcome).

Comorbidity burden will be assessed using the Charlson Comorbidity Index modified for orthotopic liver transplant candidates (CCI-OLT). The index includes five comorbidities with the following weights: COPD (3 points), coronary artery disease (2 points), connective tissue disease (2 points), renal insufficiency (2 points), and diabetes mellitus (1 point). Renal insufficiency is defined as serum creatinine >1.5 mg/dL in the most recent preoperative test. The total CCI-OLT score will be calculated as the sum of the weighted comorbidities.

Unit of Measure: CCI-OLT score (continuous) Direction: Higher scores indicate greater comorbidity burden (worse outcome).

Length of stay in the intensive care unit (ICU) after orthotopic liver transplantation will be recorded. ICU stay duration will be calculated in days from the day of transplantation until discharge from the ICU.

Unit of Measure: Days Direction: Shorter ICU stay indicates better outcome.

Length of hospital stay after orthotopic liver transplantation will be recorded. Hospital stay duration will be calculated in days from the day of transplantation until hospital discharge.

Unit of Measure: Days Direction: Shorter hospital stay indicates better outcome.

Requirement for postoperative invasive mechanical ventilation after orthotopic liver transplantation will be recorded. Prolonged mechanical ventilation is defined as ventilation lasting ≥24 hours.

Unit of Measure: Categorical (prolonged ventilation ≥24 hours vs <24 hours) Direction: Less prolonged mechanical ventilation indicates better outcome.

Incidence of early postoperative complications within 30 days after orthotopic liver transplantation will be recorded. Complications include infection, bleeding, biliary complications, and graft dysfunction. Complications will be reported as present or absent and categorized by type.

Unit of Measure: Categorical (present/absent; type-specific) Direction: Fewer complications indicate better outcome.

Mortality status within 30 days after orthotopic liver transplantation will be recorded.

Unit of Measure: Binary (alive vs deceased) Direction: Lower mortality indicates better outcome.