The WHO defines health as ‘a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity’ and quality of life as ‘individuals’ perceptions of their position in life in the context of the culture and value system in which they live and in relation to their goals, standards, and concerns’ 1.
As life expectancy increases, so too do chronic illnesses and their psychological, social, and economic consequences. Liver cirrhosis is one of the most severe chronic diseases in developed countries. Symptoms are highly varied and variable according to the progression of the illness. Without doubt, the impact of these symptoms on patients’ well-being is severe and health-related quality of life (HRQoL) in patients with cirrhosis has been extensively shown to be impaired when compared with the general population 2–5. Patients with cirrhosis often have anxiety because of chronic viral infection 5,6 or emotional problems associated with alcohol 7,8. Furthermore, decompensations of cirrhosis (ascites, gastrointestinal hemorrhage, encephalopathy) and extrahepatic manifestations (cognitive impairment, malnutrition, hyponatremia, sexual problems, sarcopenia, etc.) that are present in the advanced stages of the illness can negatively affect HRQoL in these patients 2–5,9,10.
Patients with cirrhosis frequently present multifactorial cognitive dysfunction. Minimal hepatic encephalopathy (MHE) is defined as cognitive dysfunction attributable to liver failure and portal-systemic shunting, but other factors such as alcohol, comorbidities, psychoactive medications, or sequels of previous overt hepatic encephalopathy may also be involved 11–13. For this reason and considering the characteristics of our patients, here, we use the term ‘cognitive dysfunction’ instead of MHE 13. Cognitive dysfunction has become more relevant in recent years because it has been associated with overt hepatic encephalopathy 14, mortality 15, worsening in HRQoL 4, and deterioration in daily functioning 12.
Cognitive dysfunction in patients with cirrhosis has also been associated with falls 13,16. Falls in these patients can have serious consequences because they have an increased risk of fractures 17 because of a decrease in bone mass 18, and because surgery, if required, can result in complications and mortality 19. In the general population, falls and fractures have been associated with deterioration in HRQoL 20–22. The possible influence of falls on HRQoL in patients with cirrhosis, however, has not yet been evaluated.
The Medical Outcomes Study Short Form health survey (SF-36) has been used widely to evaluate HRQoL in patients with cirrhosis 3,5,23,24. The aim of the study was to evaluate the relationship between falls and HRQoL from a physical and mental perspective in patients with cirrhosis, using the SF-36.
One hundred and eighteen outpatients with cirrhosis visited at two tertiary care hospitals (Hospital de la Santa Creu i Sant Pau and Hospital Vall d’Hebron, Barcelona, Spain) were included in the study from 1 March 2008 until 31 January 2010. Cirrhosis was diagnosed by clinical, analytical, and ultrasonographic findings or by liver biopsy. The exclusion criteria were as follows: hospitalization in the previous month because of decompensation of cirrhosis, advanced hepatocellular carcinoma (according to Milan’s criteria), active alcohol intake (in the previous 3 months), current overt acute or chronic hepatic encephalopathy, cognitive impairment (mini-mental Lobo test <24), neurological disease, inability to perform psychometric tests, marked symptomatic comorbidities (cardiac, pulmonary, renal, untreated active depression), or life expectancy less than 6 months.
We recorded sociodemographic data (age, sex, and educational level) and clinical and analytical data, such as etiology of cirrhosis, previous decompensations, renal function, liver function [Child–Pugh and Model for End-stage Liver Disease (MELD) scores], and pharmacological treatment (diuretics, β-blockers, antibiotics, nonabsorbable disaccharides, and psychoactive drugs).
To define falls, we used the WHO definition: ‘A fall is an event which results in a person coming to rest inadvertently on the ground or floor or other lower level’ 25. We retrospectively recorded the incidence of falls during the previous year and determined the mean number of falls per patient and their consequences.
Previous falls were evaluated by an interview specifically addressed to determine the incidence and characteristics of falls on the basis of a previously described questionnaire 13,16,26,27. Patients’ medical records were revised to check and complete the information provided by the patients and their relatives.
The severity of injuries and the healthcare required for falls were also recorded. Fall injuries were classified as contusion, wound, or fracture 13,16,28. Healthcare required was classified as primary care, emergency room care, or hospitalization 13,16,29. If a patient had more than one fall in the previous year, we considered the severity of the more severe fall.
Quality of life: SF-36
The SF-36 questionnaire was administered to all patients. This test has 36 items that cover eight domains ranging from 0 to 100 4,30,31. Higher scores indicate better HRQoL. The eight domains were grouped into two measures: the Physical Component Score (PCS; including physical functioning, role-limitation physical, bodily pain, and general health) and the Mental Component Score (MCS; vitality, social functioning, role-limitation emotional and mental health) 4. The PCS and MCS are summary scores adjusted for population values (average=50, SD=10) 4. SF-36 has been validated for the Spanish population 30,31. The SF-36 questionnaire was administered by a nurse before the performance of the questionnaire about falls and neuropsychological testing to diagnose cognitive dysfunction.
The Psychometric Hepatic Encephalopathy Score (PHES) was used to evaluate cognitive dysfunction 11,14,32. This test includes a neuropsychological battery composed of five paper and pencil tests: Number Connection Tests A and B, Line Tracing Test, Serial Dotting Test, and Digit Symbol Test. These tests take about 15–20 min to administer and they are easy to interpret. Patients were considered to have cognitive dysfunction when the PHES score was less than −4 points 14,32. To calculate the PHES score, we used the computer program of the Spanish Network of Hepatic Encephalopathy (http://www.redeh.org) 33. PHES was validated for the Spanish population and the results were adjusted for age and educational level 33.
The study was approved by the Ethics Committees of Hospital de la Santa Creu i Sant Pau and Hospital Vall d’Hebron, and all patients provided signed consent to participate.
We analyzed the differences in the SF-36 scores between patients with and without previous falls and patients with and without cognitive dysfunction using Student’s t-test. In addition, we carried out a univariate analysis of factors associated with HRQoL deterioration in the PCS and MCS by Student’s t-test and the Mann–Whitney test for categorical variables and the Pearson coefficient of correlation for the analysis of quantitative variables. Parameters that reached statistical significance in univariate analyses were included in a multivariate analysis by linear regression. Results are expressed as mean±SD or frequencies, and a P value of less than 0.05 was considered statistically significant. Calculations were carried out using the SPSS Statistical Package (version 17.0, 2006; SPSS Inc., Chicago, Illinois, USA).
We included a total of 118 patients. Their characteristics are shown in Table 1. The mean age of the patients was 62.3 years; 66.1% were men and 56.8% had a primary school education. Educational level was higher in men than in women (P=0.001). Alcohol was the most frequent etiology of cirrhosis (61.9%), the mean Child–Pugh score was 6.7, and 40 patients (33.9%) showed cognitive dysfunction assessed by PHES less than −4. Nineteen patients (16.1%) were taking psychoactive drugs, 10 of these being on antidepressant therapy (4/78 men, 5.1% and 6/40 women, 15%, P=0.08).
Of the 118 patients included, 24 (20.3%) had falls in the previous year. The mean number of falls per patient who fell was 1.43±0.89. Injuries because of falls were contusion in eight patients (33.3%), wounds in nine patients (37.5%), and fractures in seven patients (29.1%). The healthcare required because of falls were primary healthcare in six patients (25%) and hospital care in 17 (70.8%) (emergency room care in 12 and hospitalization in five).
The results of the SF-36 according to whether patients presented falls or not are shown in Fig. 1. Patients with falls presented lower scores than patients without falls and the reference population 31. Patients with cognitive dysfunction presented lower scores in all items, except bodily pain, than patients without cognitive dysfunction and the reference population (Fig. 2).
Table 2 shows the univariate analysis of the factors related to PCS of SF-36. The following variables were significantly associated with lower PCS score: presence of diabetes, previous variceal hemorrhage, previous encephalopathy, more advanced Child–Pugh class (A vs. BC), treatment with lactitol or lactulose, the presence of anemia, hyponatremia (serum sodium <130 mmol/l), and lower albumin levels. Lower PHES results, the presence of cognitive dysfunction, and previous falls were also associated with lower PCS scores.
Table 3 shows the univariate analysis of factors related to MCS of SF-36. Adverse results were observed in relation to female sex, alcoholic etiology, antidepressant treatment, presence of cognitive dysfunction, and previous falls. In addition, lower educational level and lower PHES results were associated with worse scores in the MCS.
In the multivariate analysis, the only independent factors that negatively affected the HRQoL in the PCS were cognitive dysfunction, previous variceal hemorrhage, anemia, and hyponatremia (Fig. 3a). On carrying out the multivariate analysis of MCS, the independent factors for worse HRQoL in these domains were female sex and previous falls (Fig. 3b).
This is the first study to show that previous falls affect HRQoL negatively in patients with cirrhosis. In the present study, 20% of patients had at least one fall during the previous year. Moreover, almost one-third of fallers presented fractures and more than 70% of these patients required hospital care because of falls. These data confirm previous studies showing that falls and fractures are frequent in patients with cirrhosis, especially in those with cognitive dysfunction 13,16–18.
We found that previous falls were associated with lower HRQoL in both physical and mental domains of SF-36 in the univariate analysis and in mental domains in the multivariate analysis. The negative impact of falls and fractures on HRQoL has been observed previously in other populations, mainly older individuals 20–22. The physical sequela (functional limitations) and the psychological consequences (e.g. fear of falling) could be the main causes of this deterioration in HRQoL 20–22. It is surprising that in our study falls affected mental domains of HRQoL more than the physical domains. This could be related to the relatively low incidence of fractures, as most falls resulted only in contusions or wounds, which have fewer physical consequences than fractures.
Patients with cirrhosis frequently present subclinical cognitive dysfunction 11,13. In agreement with previous data, in our study, cognitive dysfunction was associated with a negative effect on HRQoL 4,34. Considering the close relationship between falls, cognitive dysfunction, and deterioration in HRQoL 13,16,21,34, it may be difficult to determine whether worsening in HRQoL in patients with falls is related to falls themselves or to coincident cognitive dysfunction. However, the fact that in our study both cognitive dysfunction and falls were independent factors associated with worse HRQoL indicates that the association between falls and impairment in HRQoL is not only because of concomitant cognitive dysfunction.
In addition to previous falls and cognitive dysfunction, in the present study, we found other factors to be associated with lower HRQoL. As in other studies 3,4,6,10, previous decompensation of cirrhosis, such as variceal bleeding or encephalopathy, significantly decreased HRQoL in the physical domains. This type of complication appears in advanced cirrhosis and usually implies significant physical deterioration. Moreover, the side-effects of treatments for patients who present decompensations have been associated with decreased HRQoL, as observed with β-blockers, diuretics, and nonabsorbable disaccharides 3,35. Hyponatremia and anemia are closely related to these complications and in the present study they were independent factors associated with lower scores in the physical domains of HRQoL. Other authors have previously described such associations 3,4,9. Prevention of decompensations and correction of anemia and hyponatremia would help to improve HRQoL in patients with cirrhosis.
It is interesting to point out that in our study, higher Child–Pugh class was associated with lower PCS in the univariate analysis, but the MELD score did not correlate with HRQoL. Other authors have reported similar findings 2,10,23,36. These results can probably be explained by the fact that the only parameters included in the MELD score are analytical – bilirubin, creatinine, and INR – whereas the Child–Pugh index also evaluates other clinical parameters that could have a greater effect on HRQoL, such as the presence of ascites and encephalopathy 2,4,10,35,37. Patients in our study were outpatients and showed a relatively preserved liver function as only 4.2% belonged to Child–Pugh C class. This could explain the lack of statistical significance for the association between HRQoL and the Child–Pugh score in the multivariate analysis.
Lactulose has been shown to improve cognitive function and HRQoL in patients with cirrhosis and cognitive dysfunction 38. In our study, treatment with nonabsorbable disaccharides was associated with lower HRQoL in the physical domains in the univariate analysis. These results are in agreement with those of other authors who observed that nonabsorbable disaccharides can decrease HRQoL, probably because of gastrointestinal side-effects such as bloating, diarrhea, or abdominal pain 35. Another possible explanation for this association is that patients on nonabsorbable disaccharides have usually had previous hepatic encephalopathy, a factor associated with impairment in HRQoL 4,10.
Female sex was associated with lower HRQoL as observed in previous studies, not only in patients with cirrhosis 4 but also in patients with other chronic diseases 39,40 and in the general population 31. Explanations that could account for this difference include emotional factors related to the burden of the caregiving role in women 4 and differences between men and women in self-perception of health 4 and the prevalence of depression 41. It has been shown that depression plays a relevant role in the HRQoL impairment in patients with chronic liver diseases 42. We did not specifically assess depressive symptoms in our study but we observed a trend for antidepressant treatment to be more frequent in women than in men. Moreover, lower educational levels have been related to more impaired HRQoL in other chronic diseases 39,40. As in our study women had lower educational level than men, this could have contributed to the sex differences observed in our study.
The present study has several limitations usually related to the research on HRQoL. First, HRQoL evaluation is subjective. Second, a standardized questionnaire such as SF-36 does not necessarily match the priorities of each specific patient. Moreover, most questionnaires used to evaluate HRQoL provide quantitative results and do not evaluate the qualitative aspects of daily life. Finally, the complex relationships between factors make it difficult to determine the exact influence of each one on HRQoL 5,8,24,37.
Preventive strategies such as multifactorial interventions (including recommendations for daily life) and regular physical exercise have been shown to decrease the incidence of falls in other populations 43. They could therefore be useful to prevent falls and improve HRQoL in patients with cirrhosis. However, to increase patients’ HRQoL it is also necessary to foster interest and knowledge of health professionals in HRQoL and promote the concept of the patient as a whole.
We conclude that previous falls are associated with lower HRQoL in patients with cirrhosis. Strategies addressed to the prevention of falls could be useful to improve HRQoL in these patients.
The authors thank Carolyn Newey for revising the English.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2013 Lippincott Williams & Wilkins, Inc.
cirrhosis; cognitive dysfunction; falls; health-related quality of life