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Keywords:

  • liver disease;
  • quality of life;
  • questionnaire;
  • validity

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Objective:  To assess the reliability and validity of a Spanish version of the LDQOL 1.0 (Liver Disease Quality of Life questionnaire).

Methods:  Observational, cross-sectional study in Spanish patients awaiting liver transplantation (LT). Feasibility was assessed by analyzing administration times and missing responses. Ceiling and floor effects were calculated and reliability was tested by examining internal consistency (Cronbach's alpha). Convergent validity was tested by examining correlations between LDQOL disease-specific and Short Form health survey with 36 questions (SF-36) dimensions. Known groups' validity was tested by examining the LDQOL's capacity to discriminate between groups defined by etiology and Child–Turcotte–Pugh (CTP) scores.

Results:  A total of 200 patients were included for analysis. Mean age (SD) was 52.6 (9.8) years and 73% of the sample were male. The most common indication for LT was liver cancer (34%). Mean (SD) time to complete the questionnaire was 35.8 minutes (21.2 minutes). Missing responses were highest on the dimensions of sexual functioning and symptoms of liver disease. Ceiling effects were over 20% on 7 of the LDQOL's 12 disease-specific scales. Cronbach's alpha coefficients were over 0.70 on all but 2 dimensions. Correlations between SF-36 and LDQOL disease-specific dimensions generally fulfilled the hypotheses, with 35 of the 40 highest and lowest correlations (87.5%) being in the expected direction. The LDQOL discriminated well between patients in CTP class A and C, and as hypothesized, hepatocarcinoma and alcoholic cirrhosis patients scored better on most dimensions than patients with hepatitis C virus or other etiologies.

Conclusions:  The Spanish version of the LDQOL 1.0 has shown satisfactory reliability and validity.


Introduction

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Advanced liver disease impacts both patient survival and quality of life (QOL) [1], although several treatments, including liver transplants, have been shown to lead to substantial improvements on both of these outcomes [2–4]. The standardized measurement of patients' health-related QOL (HRQOL) therefore has an important role to play in the assessment and management of liver disease patients [5,6]. For that reason, several questionnaires have been developed to measure the impact of liver disease and its treatment on patients' HRQOL [7–9]; one of the most complete of the currently available instruments is the Liver Disease QOL Questionnaire (LDQOL 1.0) [7].

The LDQOL 1.0 was designed to be a disease-specific, self-report measure for patients with advanced, chronic liver disease [7]. It includes the generic SF-36 health survey as well as 75 disease-specific items that measure HRQOL in 12 dimensions. Testing of the original US English version of the questionnaire showed the instrument to be reliable and valid for use in pretransplant liver disease patients and patients submitted for liver transplant evaluation. A short version of the LDQOL developed more recently has also proven to be responsive to changes over time as well as predicting mortality in patients with advanced liver disease [10,11].

A preliminary validation of an adapted Spanish version of the LDQOL was performed in posttransplant patients [12], but it has not been validated for use in pretransplant patients, which was the original target group for the instrument. It is important to validate instruments in different populations because the specific characteristics of those groups may affect psychometric performance. Likewise, when HRQOL questionnaires are adapted for use in different languages and cultural contexts, the new language version will require revalidation to ensure that adaptation has not affected instrument performance [13,14].

Earlier studies with the LDQOL found that there was only a low to moderate correlation between LDQOL 1.0 scores and clinician-derived indices of severity such as the Child–Turcotte–Pugh (CTP) and Model for End Stage Liver Disease (MELD) scores [15]. Fewer studies have examined in detail the relationship between LDQOL scores and demographic and clinical variables such as age, gender, and etiology. More detailed knowledge of the influence of these variables on LDQOL scores would be helpful in designing future studies and in interpreting results.

The objectives of the present study are therefore to validate the Spanish version of the LDQOL 1.0 questionnaire in pretransplant liver disease patients and to analyze the impact of a range of clinical and sociodemographic variables on LDQOL 1.0 scores.

Methods

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Study Design

This was a prospective, observational, cross-sectional study designed to validate the Spanish version of the LDQOL 1.0 in pretransplant patients and explore the association between clinical and sociodemographic variables and HRQOL in those patients. The study was performed in the Liver Transplant Unit of University Hospital of Bellvitge, a large teaching hospital in Barcelona with a well-established liver transplant program. The patients were recruited from May 2002 to June 2006. The study was approved by the hospital's ethics committee and all the patients provided informed consent to participate.

Study Population

The patients invited to participate in the study were Spanish-speaking adults over the age of 18 with chronic liver disease who had been accepted as candidates for liver transplantation in the center's Liver Transplant Unit. The patients were all outpatients who were recruited consecutively into the study over the four-year inclusion period. The patients with fulminant hepatic failure or who were unable to respond to the questionnaire because of language problems were excluded from the study.

Outcomes Measurement

The LDQOL is a disease-specific instrument designed to measure HRQOL in patients with chronic liver disease and in liver transplant candidates [7]. It consists of a 36-item generic core (the SF-36) and 12 disease-specific scales with a further 75 items. The SF-36 measures health status in 8 dimensions of health: physical functioning (10 items), role limitations because of physical problems (4 items), bodily pain (2 items), general health (5 items), energy/vitality (4 items), social functioning (2 items), role limitations caused by emotional problems (3 items), and mental health/emotional well-being (5 items). As well as scores for the individual dimensions, the SF-36 generates two summary measures, the Physical Component Summary (PCS) scale and the Mental Component Summary scale (MCS) [16]. The SF-36 has been used in a number of studies in liver transplantation [6].

The 12 disease-specific scales included in the LDQOL are liver disease-related symptoms (17 items), liver disease-related effects on activities of daily living (10 items), concentration (7 items), memory (6 items), sexual functioning (3 items), sexual problems (3 items), sleep (5 items), loneliness (5 items), hopelessness (4 items), quality of social interaction (5 items), health distress (4 items), and self-perceived stigma of liver disease (6 items). An additional item about the use of drugs to treat insomnia was added to the sleep dimension in the Spanish version of the instrument because it was considered relevant by local investigators [17]. The Spanish version of the disease-specific scales was produced using the recommended methodology of forward and back translation and patient testing [18], although with input from a US Spanish version of the instrument provided by the original authors. The SF-36 has previously been adapted and validated for use in Spanish [19] and was incorporated directly into the Spanish version of the LDQOL.

Disease-specific LDQOL items are answered on scales with between four and six response options. The raw scores by dimension are recoded on a 0 to 100 scale, with higher scores indicating better HRQOL, and dimension scores are obtained using simple arithmetic sums. The instrument does not generate an overall score. In most of the questions in the LDQOL, patients are asked to think about the impact of their liver disease over the last 4 weeks, the same recall period as used in the SF-36. Although the LDQOL 1.0 was originally designed to be self-administered, it was administered by interview in the present study because patients preferred this mode of administration.

When calculating LDQOL scores, we did not impute values for missing responses, and dimension scores were therefore only calculated for individual patients with no missing response in a particular dimension.

Other Variables

Data collected from clinical records included age, sex, educational level, CTP class, MELD score, and etiology, which included chronic hepatitis C (HCV), liver cirrhosis (LC) because of alcohol liver cirrhosis (ALC), hepatocellular carcinoma (HCC), chronic hepatitis B, primary biliary cirrhosis/primary sclerosing cholangitis, familial amyloid polyneuropathy, Budd Chiari syndrome, cryptogenic cirrhosis, and autoimmune hepatitis. The HCC patients also all had cirrhosis attributable to another LD etiology.

The CTP score is used to assess the prognosis of chronic liver disease, particularly cirrhosis, based on five clinical measures of liver disease (bilirubin, serum albumin, INR, ascites, hepatic encephalopathy). Each measure is scored from 1 to 3, with 3 indicating most severe derangement. The score is classified into CTP class A to C by adding scores on all measures and indicating increasingly poor prognosis [20]. Another means of classifying liver disease patients is the MELD score, which uses serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. The scores range from 6 to 40. In the present study, we used the Mayo scoring algorithm and it was analyzed as a continuous score [21].

Sample Size

A sample size of 200 was chosen to approximate the number (n = 221) included in the original validation study and because it was considered the maximum number that could be feasibly included over the available four-year inclusion period.

Statistical Analysis

The sample's sociodemographic and clinical characteristics were analyzed using descriptive statistics. The feasibility of the Spanish version of the LDQOL 1.0 was tested by analyzing the time taken to administer the questionnaire and the percentage of missing responses by dimension.

Score distributions were evaluated by calculating the observed range of scores and the proportion of patients with the worst and best possible scores (floor and ceiling effects) on each dimension as an indicator of the extent to which scales capture the range of the underlying dimension. The reliability of the Spanish version was tested by examining the internal consistency of each of the dimensions [22].

Validity was tested in several ways. Convergent validity was tested by examining the extent to which scores on LDQOL disease-specific dimensions demonstrated logical relationships with the SF-36 based on a series of predefined a priori hypotheses [22]. We expected disease-specific scales that measure primarily physical aspects of health (symptoms of liver disease, effects of liver disease) to correlate more highly with the PCS and the SF-36 scales of physical functioning, role physical, bodily pain, and general health while the LDQOL scales of concentration, memory, quality of social interaction, health distress, loneliness, hopelessness, and stigma of liver disease were expected to correlate more strongly with the MCS and the SF-36 scales of vitality, social functioning, role emotional and mental health/emotional well-being. We also examined correlations between the LDQOL 1.0 and MELD scores. In this case, we expected correlations to be low to moderate (0.1–0.5) because the LDQOL is designed to measure a different concept to this type of clinical measure, although some degree of correlation is expected.

Known groups' validity was tested by determining whether the instrument could discriminate between groups in which differences in HRQOL would be expected to occur [22]. In particular, we examined whether the instrument could discriminate between the patients according to CTP class and hypothesized that the patients in CTP class A would report better HRQOL than those in class B or C. We also examined the instrument's ability to discriminate between patients with different etiologies. For this analysis, we divided the sample into four groups (HCC, HCV, CH ALC, and others). The “others” group included all the patients not included in the first three groups, particularly chronic hepatitis B, primary biliary cirrhosis/primary sclerosing cholangitis, familial amyloid polyneuropathy, and Budd Chiari syndrome. We hypothesized that the patients with HCC would generally have better scores on the LDQOL than either the HCV or CH ALC patients because liver function is often only minimally impaired in the patients with HCC, while the patients with cirrhosis have generally poorer liver functioning and overall health [23].

Finally, and in the nature of an exploratory analysis, we investigated the relationship between age and gender and scores on the LDQOL.

Statistical Methods

The internal consistency of LDQOL dimensions was assessed using Cronbach's alpha coefficient [22]. We also calculated 95% confidence intervals (CI) for the alpha coefficients using a bootstrap technique to facilitate statistical comparisons across studies [24]. Hypotheses for convergent validity were tested using the multitrait multimethod matrix method [25] with Pearson's correlation coefficient (r) for normally distributed continuous variables. Pearson's correlation coefficient was also used to investigate association between LDQOL 1.0 scores and the MELD score and age. Spearman's correlation coefficient was used to test for association between LDQOL scores and gender, while analysis of variance (ANOVA) and t tests were used to test for differences between groups according to CTP category and etiology. The level of statistical significance was set at 0.05, and all tests were two-sided. No adjustments were made for multiple comparisons. All analyses were performed in version 13.0 of SPSS (SPSS Inc., Chicago, IL).

Results

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Sample Characteristics

A total of 210 patients who were candidates for liver transplant were initially approached to participate in the study, the majority with advanced chronic liver disease. Four patients were excluded because they had fulminant hepatitis or encephalopathy and four because of language difficulties. One patient refused to participate. Of those who met the inclusion criteria who agreed to participate, one failed to complete the study interview, leaving a total of 200 patients for analysis.

The mean age (SD) of the patients was 52.6 (9.8) years and 73% of the sample were men (see Table 1). The most common indication for liver transplant was HCC (34%), and 48% of the sample had a combined etiology. All of the patients with liver cancer also had cirrhosis: 41 because of HCV, 15 because of alcohol, 3 because of HBV, and 9 because of other causes. For the overall sample, the mean (SD) MELD score was 15.0 (4.9) and 69.5% were in CTP class B or C.

Table 1.  Sample demographic and clinical characteristics (n = 200)
 N, SD (%)
  1. CBP, primary biliary cirrhosis; FAP, familial amyloidotic polyneuropathy; MELD, Model for End Stage Disease.

Sex N (%) 
 Male146 (73.0)
Age mean years (SD)52.6, 9.8
Educational level N (%) 
 Primary education93 (58.1)
 Secondary education44 (27.5)
 University education15 (9.4)
Etiology (indication liver transplant) 
 Tumor68 (34.0)
 Cirrhosis (alcohol)46 (23.0)
 Hepatitis C43 (21.5)
 Other (hepatitis B, PBC/colangitis; Ch cryptogenic, FAP, Budd Chiari, Peliosis, autoimmune hepatitis)43 (21.5)
Child–Turcotte–Pugh class N (%)8.1, 2.1
 Not applicable20 (10.0)
 A41 (20.5)
 B86 (43.0)
 C53 (26.5)
MELD mean (SD)15.0 (4.9)

Feasibility

Mean (SD) time to complete the LDQOL 1.0 was 35.8 minutes (21.2 minutes). The dimension of sexual functioning had the largest number of missing responses (62.5% of patients with a missing response on at least one item). This was followed by the dimension on symptoms of liver disease (16.5% of the patients with at least one missing response). None of the remaining dimensions had over 7% of the patients with a missing response.

Ceiling and Floor Effects and Reliability

As shown in Table 2, ceiling effects were observed on several of the SF-36 scales (three out of the eight scales with over 20% of the sample scoring at the ceiling) and on the disease-specific scales (8 of the 13 scales with over 20% of the sample scoring at the ceiling). There were no significant floor effects on any of the dimensions or summary scores. The patients scored across the full theoretical range of scores on most of the dimensions. The internal consistency of the disease-specific dimensions of the LDQOL was generally satisfactory, with all but two dimensions having a Cronbach's alpha value of 0.70 or greater. The lowest value was for the dimension of sexual problems in women (α = 0.64).

Table 2.  Distribution characteristics and reliability of Liver Disease Quality of Life Questionnaire (LDQOL) dimensions
LDQOL 1.0 scaleNumber of itemsMean scoreStandard deviationMinimum scoreMaximum score% Scoring the floor% Scoring the ceilingCronbach's α (95% CI)
  • *

    3 for men and 3 for women.

  • It was not possible to calculate 95% CI for this value, presumably because of the low number of respondents.

SF-36        
 Physical functioning1057.426.60.0100.03.64.10.89 (0.87–0.91)
 Role limitations-physical429.237.60.0100.052.815.00.85 (0.80–0.89)
 Role limitations-emotional356.344.30.0100.031.845.30.87 (0.83–0.91)
 Social functioning265.831.60.0100.04.033.20.78 (0.69–0.84)
 Bodily pain258.031.40.0100.03.524.00.89 (0.85–0.92)
 Energy/fatigue444.028.10.0100.07.72.60.84 (0.78–0.88)
 Emotional well-being561.926.40.0100.02.69.30.86 (0.82–0.89)
 General health540.019.90.0100.01.00.50.68 (0.65–0.75)
  Physical component summary 36.910.414.264.7   
  Mental component summary 43.115.68.2769.5   
Disease-targeted scales        
 Symptoms of liver disease1769.417.90.0100.00.50.50.76 (0.70–0.81)
 Effects of liver disease1055.022.90.0100.01.06.00.81 (0.77–0.84)
 Concentration774.924.10.0100.01.022.10.91 (0.88–0.93)
 Memory678.821.30.0100.00.522.10.88 (0.85–0.91)
 Quality of social interaction584.216.220.0100.00.033.20.71 (0.63–0.77)
 Health distress456.129.30.0100.05.58.00.87 (0.83–0.90)
 Sleep668.320.516.7100.00.06.00.63 (0.54–0.70)
 Loneliness592.612.920.0100.00.061.30.67 (0.50–0.76)
 Hopelessness470.322.16.3100.00.014.60.71 (0.63–0.78)
 Stigma of liver disease687.418.312.5100.00.045.70.78 (0.69–0.84)
 Sexual functioning363.933.10.0100.08.625.80.85 (0.77–0.90)
 Sexual problems*3 (m)63.834.60.0100.07.133.90.82 (0.70–0.90)
3 (f)87.020.833.3100.00.056.50.64 (–)

Convergent and Discriminant Validity

Our initial hypotheses regarding correlations between SF`36 summary scores and the disease-specific dimensions of the SF-36 were generally confirmed (Table 3). The LDQOL dimensions that measured liver disease symptoms and the effects of liver disease correlated most strongly with the PCS (r = 0.57 and r = 0.48, respectively), while the MCS correlated strongly with scales that measured health distress (r = 0.66, P < 0.01), concentration (r = 0.45, P < 0.01), and hopelessness (r = 0.42, P < 0.01). Taking the two highest and two lowest correlations for the first 10 disease-specific dimensions, a total of 35 of the 40 correlations observed (87.5%) were in the expected direction. For example, in the case of the health distress dimension, the two highest correlations were with the MCS and the emotional well-being dimension as expected, while the two lowest correlations were with the PCS and physical functioning dimensions, also as expected. In 5 of the 40 cases, the correlations were not as expected. For example, the highest correlation for the symptoms scale was with the SF-36 vitality dimension, whereas we had hypothesized that the strongest correlations would be seen with the physical dimensions. We had not made a prior hypothesis regarding the sexual functioning dimensions as we were unsure which direction the correlations would take.

Table 3.  Correlation coefficients between Liver Disease Quality of Life Questionnaire (LDQOL) disease-specific dimensions and SF-36 summary scales and dimensions
LDQOL scalesSF-36 scales
Disease-specific dimensionsPCSMCSPFRPBPGHVSFREEW
  • *

    Correlation statistically significant at P < 0.05.

  • Correlation statistically significant at P < 0.01.

  • Coefficients marked in bold are the two highest for each LDQOL dimension. Cells marked in pale grey are the two lowest coefficients for each dimension.

  • BP, bodily pain; C, concentration; ELD, effects of liver disease; EW, mental health/emotional well-being; GH, general health; HD, health distress; Hop, hopelessness; M, memory; MCS, Mental component summary scale; PCS, Physical component summary scale; PF, physical functioning; QSI, quality of social interaction; RE, role limitations caused by emotional problems; RP, role limitations because of physical problems; SF, social functioning; Sfu, sexual functioning; SLD, stigma of liver disease; Sle, sleep; Spro (f), sexual problems (female); Spro (m), sexual problems (male); SxD, symptoms of liver disease; V, energy/vitality.

SxD0.570.440.540.520.560.580.640.530.370.48
ELD0.480.380.490.480.400.560.510.500.260.48
C0.260.450.360.390.250.410.490.460.330.48
M0.220.290.240.290.200.300.370.330.220.29
QSI0.17*0.400.180.260.280.300.360.400.250.44
HD0.210.660.340.430.370.520.530.540.480.74
Sle0.320.380.370.370.280.360.460.480.240.41
Lon0.020.290.020.15*0.15*0.18*0.18*0.230.220.26
Hop0.240.420.320.280.290.440.430.380.320.46
SLD0.17*0.350.260.250.210.250.330.400.250.33
Sfu0.260.220.240.330.16*0.270.320.280.140.23
Spro (m)0.31*0.35*0.36*0.410.150.380.400.360.260.28*
Spro (f)0.220.400.54*0.250.130.360.580.560.260.45*

Statistically significant correlations with the MELD score were seen on a number of the SF-36 dimensions, with the strongest correlations being with the physical functioning summary score (r = 0.25, P < 0.001) and the role limitation-physical dimension (0.27, P < 0.01). Only three of the disease-specific LDQOL dimensions showed statistically significant correlations with the MELD, those being the symptoms of liver disease, effects of liver disease, and concentration dimensions, with correlations of 0.29, 0.15, and 0.15, respectively (all P values 0.05 or greater).

Known Groups' Validity

Differences in LDQOL scores by disease-specific dimensions according to CTP class are shown in Figure 1. The patients in CTP class A scored better than the patients in classes B and C in almost all dimensions except loneliness. The largest differences between the patients in class A and classes B and C were on the symptoms dimension (mean scores of 77.8, 67.1, and 63.9, respectively; P < 0.001 for difference between CTP-A and CTP-C), effects of liver disease (means scores 65.9, 49.9, and 55.9, respectively; P < 0.05 for difference between CTP-A and CTP-B), and sexual functioning dimensions (mean scores 75.4, 63.7, and 57.0, respectively; P < 0.005 for CTP-A and CTP-C).

image

Figure 1. Differences in LDQOL scoring by disease-specific dimensions according to CTP class. Shapes: square Child class A; triangle Child class B; circle Child class C. LDQOL dimensions: SxD, symptoms of liver disease; ELD, effects of liver disease; C, concentration; M, memory; QSI, quality of social interaction; HD, health distress; Sle, sleep; Hop, Hopelessness; SLD, stigma of liver disease; Sfu, sexual functioning; Spro (m), sexual problems (male); Spro (f), sexual problems (female).

Download figure to PowerPoint

Table 4 shows the mean scores on all LDQOL disease-specific dimensions according to etiology. The dimensions of symptoms, effects of liver disease, concentration, and sleep all showed statistically significant differences between the HCC group and the hepatitis C group. The symptoms dimension also discriminated between the HCC and the others group. Although results in the other dimensions were not statistically significant according to the 95% CI, there was a clear tendency toward higher levels of QOL in patients with HCC compared with those with HCV or the group of Other pathologies. Patients in the CH ALC group also had relatively high scores on most of the dimensions, though with notably poorer scores in the dimension of sexual functioning.

Table 4.  Mean scores and 95% confidence intervals (CI) on LDQOL disease-specific dimensions by indication for liver transplant
LDQOL (95% CI)
Indication for liver transplantSxDELDConc.Mem.QSIHDSleLonHopSLDSfuSP (men)SP (women)
  1. Conc, concentration; ELD, effects of liver disease; HCC, hepatocellular carcinoma; HCV, chronic hepatitis C; HD, health distress; Hop, hopelessness; LC ALC, liver cirrhosis due to alcohol; Lon, loneliness; Mem, memory; QSI, quality of social interaction; Sfu, sexual functioning; SLD, stigma; Sle, sleep; Spro, sexual problems; SxD, symptoms of liver disease; Dimensions where statistically significant differences occur between groups are marked in pale grey.

HCC75.9 (71.9–79.8)63.2 (57.5–68.8)81.7 (77.5–85.8)82.4 (78.2–86.5)86.4 (82.8–89.9)61.7 (54.8–68.5)73.5 (69.1–77.9)94.1 (91.7–96.4)74.3 (69.4–79.1)91.6 (88.1–95.0)68.5 (60.9–76.0)70.9 (57.4–84.3)90.3 (70.7–100)
LC ALC67.6 (61.9–73.2)54.1 (47.8–60.3)75.5 (67.4–83.5)81.9 (75.9–87.8)87.4 (82.5–92.9)61.5 (52.2–70.4)71.9 (65.5–78.2)95.9 (93.3–98.4)70.8 (63.4–78.1)87.8 (83.0–95.5)56.8 (47.0–66.5)61.9 (20–100)66.7 (39.1–94.2)
HCV64.1 (59.4–68.7)47.1 (40.7–53.4)68.4 (61.5–75.2)71.8 (64.3–79.2)80.0 (75.3–84.6)51.2 (42.5–60.1)59.8 (53.7–65.8)87.8 (82.1–93.4)69.5 (62.8–76.1)83.9 (77.9–89.8)64.5 (53.9–75.0)62.2 (40.9–83.4)93.3 (85.7–100)
OTHERS66.1 (60.2–71.9)50.9 (43.9–57.8)70.1 (62.4–77.7)76.8 (69.3–84.2)81.5 (75.8–87.1)46.6 (37.9–55.2)64.7 (58.1–71.2)91.6 (87.5–95.6)64.1 (57.0–71.1)83.7 (76.3–91.0)63.6 (52.7–74.7)53.2 (32.1–74.3)87.3 (63.9–100)

Effect of Age and Gender

As shown in Table 5, age was only weakly correlated with HRQOL on two of the SF-36 dimensions (bodily pain, r = 0.156, P < 0.05 and social functioning, r = 0.160, P < 0.05) and on 3 of the disease-specific scales (quality of social interaction, r = 0.295, P < 0.01; loneliness, r = 0.161, P < 0.05; and stigma of liver disease r = 0.274, P < 0.01), with the older respondents scoring slightly better on those five dimensions. There were statistically significant differences between the men and the women on three of the disease-specific dimensions (symptoms, quality of social interaction, and sexual functioning), with the men scoring higher on the symptoms dimension (mean scores of 71.1 and 64.7 for the men and women, respectively; P < 0.05) but lower on the quality of social interaction (mean scores of 90.2 and 81.9, for the women and men, respectively; P < 0.01) and sexual functioning (mean scores of 79.6 and 58.2, for the women and men, respectively; P < 0.01) dimensions. There was a tendency toward lower scores in the women in most of the SF-36 dimensions though differences were not statistically significant.

Table 5.  Effect of age and gender on LDQOL scores
LDQOL scalesAgeGender
NrP valueMenWomenP value
NMean (SD)NMean (SD)
  • *

    Correlation significant at 0.05 (2-tailed).

  • Correlation significant at 0.01 (2-tailed).

  • r, Pearson's correlation coefficient.

SF-36 scales        
 Physical functioning197−0.065NS14458.6 (26.3)5354.1 (27.4)NS
 Role limitation-physical1930.119NS14129.7 (37.4)5227.9 (38.6)NS
 Bodily pain2000.156*<0.0514660.4 (31.5)5451.4 (30.5)NS
 General Health perceptions1950.084NS14240.9 (19.5)5339.4 (21.1)NS
 Mental Health1930.104NS14064.0 (25.7)5356.2 (27.7)NS
 Role limitation-emotional1920.101NS14158.4 (44.4)5150.3 (43.9)NS
 Social functioning1990.160*<0.0514668.2 (31.1)5359.2 (32.3)NS
 Vitality/energy/fatigue1950.085NS14145.7 (27.6)5439.6 (29.4)NS
 Physical summary score1860.059NS13637.0 (9.8)5036.6 (11.8)NS
 Mental summary score1860.136NS13644.2 (15.3)5040.1 (16.3)NS
Liver disease targeted scales        
 Symptoms of liver disease2000.046NS14671.1 (17.6)5464.7 (17.9)<0.05
 Effects of liver disease2000.059NS14655.2 (23.2)5454.4 (22.1)NS
 Concentration1990.075NS14575.0 (24.1)5474.6 (24.1)NS
 Memory1990.051NS14577.7 (21.7)5481.7 (20.1)NS
 Quality of social interaction1990.295<0.0114581.9 (16.7)5490.2 (12.9)<0.001
 Health distress1990.128NS14557.8 (29.4)5451.7 (28.9)NS
 Sleep1990.102NS14567.6 (20.3)5470.1 (21.0)NS
 Loneliness1990.161*<0.0514591.8 (13.7)5494.6 (10.3)NS
 Hopelessness1990.056NS14569.7 (22.2)5471.6 (22.1)NS
 Stigma of liver disease1990.274<0.0114586.8 (19.5)5488.8 (14.6)NS
 Sexual functioning1980.097NS14558.2 (33.7)5379.6 (25.8)<0.001
 Sexual problems (m)560.063NS
 Sexual problems (f)23−0.263NS

Discussion

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

This study has shown the Spanish version of the LDQOL to be a reliable and valid instrument for use in Spanish patients with advanced chronic liver disease awaiting transplant. In an earlier study, we had examined the properties of the Spanish version in post-transplant patients and found that the questionnaire was also generally reliable in this group of patients [12]. This instrument adds to disease-specific instruments already adapted for use in Spain, such as the Chronic Liver Disease Questionnaire [26].

Although the LDQOL is a relatively long questionnaire, the rate of missing responses was generally low, presumably at least in part because the questionnaire was interview-administered. The main exception was the dimension of sexual problems, which had a high rate of missing responses primarily because a relatively high proportion of the patients reported that they had not had sexual relations in the past 4 weeks. Some of the patients were also reluctant to respond to items in this dimension in the presence of an interviewer. The questionnaire also took a considerable time to administer (mean of 35.8 minutes), although it is a very complete instrument covering a wide range of relevant dimensions for liver disease and transplanted patients. It also incorporates the generic SF-36, a fact which should be borne in mind in studies where both generic and disease-specific measures of HRQOL are required. The short version of the LDQOL developed recently might provide a useful alternative where the long version is impractical [10].

The LDQOL showed substantial ceiling effects on a number of the disease-specific scales. This is likely because in a substantial proportion of the sample, the primary indication for transplant was HCC, and these patients have been shown to score relatively well on generic HRQOL measures [23]. High ceiling effects on the loneliness and quality of social interaction dimensions could stem from a cultural effect because of the presence of strong social and family networks in Spain. Comments from the patients during cognitive debriefing also indicated that the stigma dimension may not be wholly relevant for the Spanish patients because many found the idea of being embarrassed or self-conscious about the disease unusual and alien. The dimensions of loneliness, hopelessness, stigma, sexual functioning, and sexual problems also showed the highest ceiling effects in the original version (18.7%, 12.3%, 18.2%, 24.3%, and 24.1% [7]), suggesting that the items included may not adequately capture the full range of effects and/or that the dimensions may not be as relevant to patients as some others. Such effects are important as they may affect the instrument's ability to reflect improvement over time.

With regard to the high ceiling effect seen on the sexual problems (women) scale, this may have been due to a reluctance to acknowledge problems in this area of their lives with an interviewer present. It is also possible that scale items were not relevant for the entire sample for the time period covered (4 weeks) because frequency of sexual intercourse has been shown to decrease in women with nonalcoholic liver disease [27]. However, we were not able to ascertain whether this was the case in our sample, although this is certainly an aspect of using the LDQOL that would warrant further research.

In terms of reliability, the Spanish version of the LDQOL was generally satisfactory in the present study. The Cronbach's alpha values were over the recommended 0.70 threshold [28] for 8 of the 12 disease-specific dimensions, and close to 0.70 on the remaining dimensions. On the SF-36, the 0.70 threshold was met on all but one of the eight dimensions. This means the LDQOL is suitable for use at the group level; very few of the dimensions, however, had an alpha value of 0.90 or over so they would not be suitable for use with patients at an individual level. Interestingly, the four dimensions that showed the poorest results on Cronbach's alpha in the present study also had some of the lowest alphas on the original version, although they were all over the threshold of 0.70 except for quality of social interaction [7]. Further work may be required to bolster reliability in these scales.

In the development of the original LDQOL, factor analysis was used to investigate the scale structure of that version [7]. In the present study, as our aim was to determine whether the Spanish instrument would be sufficiently reliable and valid for use in research settings, we preferred to investigate whether the LDQOL dimensions formed coherent scales through the calculation of Cronbach's alpha. As all of the alphas for the disease-specific dimensions were very close to or above 0.70, which is the generally recommended threshold for use of this type of instrument at group level [28], we considered that to be a sufficient indication of reliability to suggest that the instrument could be used in research settings in Spain.

Likewise, it should be noted that all of the interviews were carried out by the same psychologist who was involved in the study from the outset (LJC), so interrater reliability was not an issue here. However, this would be an aspect that would warrant research in future studies.

With regard to convergent validity, we found that the LDQOL disease-specific dimensions correlated as expected with individual SF-36 dimensions and summary scores. Correlations were particularly strong between LDQOL 1.0 disease-specific dimensions and the MCS and SF-36 dimensions that measure psychological and social functioning, indicating the considerable focus on psychological and emotional aspects of the illness in the LDQOL 1.0. Only a small number of the hypotheses regarding the likely pattern of correlations were not met, and the deviations from the hypotheses were generally minor, suggesting good convergent validity for the Spanish measure.

On the other hand, correlations with the MELD score were generally low to moderate, although strongest with the physical functioning dimensions of the SF-36. This likely reflects the aspects measured by the MELD and is similar to findings observed with the original version of the instrument [15]. Likewise, we found that the dimensions that best discriminated between groups defined by the CTP category were symptoms of liver disease, effects of liver disease, and sexual functioning, which also showed some of the strongest correlations with the CTP score in the original validation study [7], although correlations between clinician-derived measures and HRQOL have generally been found to be weak [15,29]. The fact that sexual problems did not discriminate well between the groups in our study may be due to the high number of missing responses.

Our analysis of the known groups' validity suggests that a number of dimensions on the LDQOL Spanish version distinguished adequately between the patients defined by clinical categories. In particular, the instrument was successful at discriminating between the patients defined by CTP class (see Fig. 1), although we also found that HCV was associated with considerably worse HRQOL on most of the LDQOL disease-specific dimensions than either HCC or LC ALC. Although these differences were only statistically significant on four dimensions (symptoms, effects of liver disease, concentration, and sleep), they are nevertheless in line with results from similar studies that showed that patients with HCV tend to have worse HRQOL than patients with other etiologies [30,31]. The present results also complement those found in previous studies that found differences between cirrhotic and noncirrhotic patients [32].

On the other hand, our analysis of the effect of sociodemographic variables showed that age and gender generally had only a small effect on LDQOL 1.0 scores. The poorer score on the social interaction dimension in men may be due to the disease leading to greater restrictions on social activities or a tendency to be more withdrawn, perhaps because of a greater impact on self-image though this has been little explored in the literature. The poorer score in men on the sexual functioning dimension does receive some support in the literature, which suggests that men with CTP grades B and C have significant sexual dysfunction and significant reduction of both total and free testosterone levels [33]. This contrasts with findings in women that suggest that liver disease does not have a significant impact on sexual satisfaction or desire [27,34].

In general, the results of validity testing support the use of the instrument in future studies in Spain, although further testing is still required in larger, more heterogeneous samples, and in longitudinal studies to test the instrument's sensitivity to change. Likewise, additional information, such as the magnitude of a minimal clinically relevant difference on the different dimensions would help to improve interpretability [35].

The study had some limitations. Firstly, although the sample was relatively large, the study was performed in only one center and the sample included a high proportion of HCC and male patients. Both of these characteristics limit the generalizability of the results. The inclusion of a large number of HCC cases reflects the case mix on the waiting list at this center [36]. It should also be noted that at least some of the impact on HRQOL is likely to be due to the underlying cirrhosis rather than the tumor itself, which tends to be asymptomatic. The questionnaire was administered by interview and the results might differ if the questionnaire was self-administered. Future studies should examine whether there are systematic differences in the scores using the two different modes of administration. Finally, we were not able to examine the instrument's sensitivity to change as these are results from a cross-sectional study. Analysis of this aspect is currently ongoing for the Spanish version of the LDQOL. Finally, we did not impute values for missing responses as the proportion of missing responses was low in most of the scales, and they were not concentrated in particular items within the scales. In the present study, the relatively small proportion of missing responses would not have overly biased results. However, if higher proportions of missing responses are observed or if they are more systematic, then other methods of imputing scores should be considered, such as simple mean imputation, or more sophisticated techniques such as regression imputation [37].

In conclusion, the Spanish version of the LDQOL 1.0 provides a reliable and valid means of measuring outcomes in patients with liver disease awaiting transplant. The fact that it is a very complete instrument means that administration time is considerable and the new, shorter version may prove more practical for much clinical research or clinical practice. The considerable ceiling effects on a number of dimensions also suggest its performance in longitudinal studies should be carefully evaluated.

Source of financial support: The study was supported by grants from the Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain (FIS 03-0079) and from the Red Temática de Investigación en Trasplante RETIC FIS C 03/03.

References

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References