Abstract
Primary biliary cirrhosis (PBC) is generally a slowly progressive disease that may lead to cirrhosis and liver failure. However, patients with PBC often suffer from a variety of symptoms long before the development of cirrhosis that include issues of daily living that have an impact on their work environment and their individual quality of life. We therefore examined multiple parameters by taking advantage of the database of our cohort of 1032 patients with PBC and 1041 matched controls. The data were obtained from patients from 23 tertiary referral centers throughout the United States and from rigorously matched controls by age, sex, ethnicity, and random-digit dialing. The data showed that patients with PBC were more likely than controls to have significant articular symptoms, a reduced ability to perform household chores, and the need for help with routine activities. Patients with PBC rated their overall activity similar or superior to that of controls; however, more of them reported limitations in their ability to carry out activities at work or at home and difficulties in everyday activities. PBC cases also more frequently reported limitations in participating in certain sports or exercises and pursuing various hobbies; however, they did not report significant limitations in social activities. In a multivariable analysis, household income, a diagnosis of systemic lupus erythematosus, limitations in work activities, a reduction in work secondary to disability, and church attendance were independently increased in PBC cases with respect to controls.
Conclusion
Our data indicate that the quality of life of patients with PBC in the United States is generally well preserved. Nevertheless, patients with PBC suffer significantly more than controls from a variety of symptoms that are beyond the immediate impact of liver failure and affect their lifestyle, personal relationships, and work activities.
Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease that affects predominantly middle-aged women.1 A current hypothesis of PBC pathogenesis is that environmental factors trigger autoimmunity in subjects with a susceptible genetic background.2 The importance of genetics in the disease etiology is strongly supported by the concordance rates observed in monozygotic twins.3 A role for environmental factors as triggers is also suggested by experimental data regarding infectious agents and xenobiotics, epidemiological studies demonstrating a geoepidemiological pattern of disease, and the presence of specific risk factors.
Common symptoms of early-stage PBC (that is, before the appearance of liver cirrhosis and its complications) are classically described as fatigue and pruritus. Thus, the negative impact of PBC on affected subjects’ well-being may be far more significant than that resulting only from advanced liver disease. Several studies have investigated this issue, primarily using questionnaires for fatigue or health-related quality of life (QoL) in European patients enrolled through tertiary referral centers of patient foundations4–7 with limited data from the United States.8 The impaired QoL in patients with PBC has been found to be independent of the severity or stage of the disease while being significantly associated with fatigue and, to a lesser extent, pruritus.5–7 However, the impact of PBC on daily work and leisure activities has not been assessed in a controlled study.
We recently conducted the largest case-control study to date of environmental, familial, and medical factors associated with PBC; the study was based on structured, standardized telephone interviews of patients with PBC and controls. Initially, on the basis of data obtained in that study, we reported on the risk factors and comorbidities in PBC.9 In this report, we describe the QoL of patients with PBC in our large epidemiological study, including the impact of having the disease on everyday work and leisure activities.
Patients and Methods
Study Participants
All data were obtained from the USA PBC Epidemiology Study concluded in 2005.9 This case-control study was conducted with 1032 patients and 1041 matched controls with a modified US National Health and Nutrition Examination Study III (NHANES III) questionnaire. Briefly, between November 1999 and June 2004, 1090 patients with PBC were referred from 23 tertiary referral centers for liver diseases throughout the United States. Patients were eligible for inclusion if the diagnosis of PBC had been made between 1996 and 2004 and was based on predetermined criteria. To assess accuracy, the diagnosis of PBC was re-evaluated blindly in a subgroup of 100 patients and confirmed in all cases. Controls were selected by random-digit dialing. For each enrolled case, one control individual was selected through matching for sex, 5-year age group, race, and geographical area. All cases and controls were administered the questionnaire developed from questions on the NHANES III during a telephone interview by trained personnel. The case-finding and control-matching methods and details of the techniques of questionnaire administration were described previously in our report on risk factors for PBC.9 The present analysis focused on questions referring to 4 major areas: (1) articular symptoms (12 questions), (2) activity limitations (in both household and job-related activities; 30 questions), (3) hobbies and leisure activities (28 questions), and (4) social life (13 questions). Most items had multiple interrelated subquestions. The response rates were 99%–100% for all questions in both groups, with the exception of a few items inquiring about social life, as illustrated later.
Statistical Analysis
Descriptive statistics were first used to compare characteristics and measures of QoL in PBC cases and matched controls. The unadjusted analyses of differences between cases and controls for QoL factors were performed with the Wilcoxon test for continuous variables and Fisher’s exact test for categorical variables.
We next developed a multivariable model using conditional multiple logistic regression analysis. The backward elimination model selection strategy was used to ensure that the models were relatively parsimonious, with a criterion of P < 0.05 for the inclusion of variables. Race, sex, geographical location, income group, and age were included in the model as candidate explanatory variables because they were used as matching criteria in the surveys. In addition, annual household income was also included as a candidate variable. In the multivariable analysis, 116 observations were lost because of missing values of some variables. All statistical comparisons were made with SAS software (SAS Institute, Inc., Cary, NC) and were two-sided. P values < 0.05 were considered statistically significant, and no correction for multiple comparisons was made to reduce the risk of type II errors.10 Continuous variables are expressed as means ± the standard deviation throughout this article.
Results
Sociodemographic Characteristics
Details about the sociodemographic characteristics of the study population can be found in our previous publication.9 Briefly, a total of 1032 patients (95% of those contacted) and 1041 matched controls (80% of those contacted) were enrolled in the study. Among cases, the mean age at diagnosis of PBC was 51 ± 10 years. Cases were included from every state in the United States, except Delaware and Hawaii. No significant differences were observed between cases and controls with respect to sex, age, education level, and ethnicity. However, the reported annual household income was significantly higher in patients with PBC versus controls.
Articular Symptoms and Signs
We investigated articular symptoms in subjects with PBC because of their potential to impact QoL and the previously reported prevalence rates of systemic lupus erythematosus (SLE) and rheumatoid arthritis.9 The frequency of pain, stiffness, and swelling at major body joints in patients with PBC and matched controls is presented in Table 1. Overall, a greater proportion of patients with PBC versus controls reported joint pain and stiffness, although statistical significance was reached only for hip pain (26% of patients with PBC versus 20% of controls; P = 0.004). Despite a similar prevalence of knee pain in PBC cases and controls, patients experienced bilateral knee pain and stiffness significantly more frequently. In fact, bilateral knee pain occurred in 71% of patients with PBC versus 60% of controls (P = 0.002), and stiffness occurred in 86% of patients with PBC versus 70% of controls (P < 0.001). Wrist stiffness was also significantly more common among PBC cases than controls (31% of patients with PBC versus 25% of controls; P = 0.002) with similar duration of the reported episodes.
Table 1.
Prevalence of Reported Symptoms and Signs Related to the Major Joints in Patients with PBC and Controls
| Symptom | Cases (%) | Controls (%) | P | |
|---|---|---|---|---|
| Knee | Pain | 356/1032 (35%) | 320/1041 (31%) | 0.075 |
| Bilateral | 253/356 (71%) | 192/319 (60%) | 0.002 | |
| At rest and upon movement | 188/354 (53%) | 198/319 (62%) | 0.019 | |
| Stiffness | 260/1030 (25%) | 234/1040 (23%) | 0.149 | |
| Bilateral | 22/259 (86%) | 163/234 (70%) | <0.001 | |
| Duration > 30 minutes | 140/260 (54%) | 131/264 (56%) | NS | |
| Swelling | 101/1032 (10%) | 113/1041 (11%) | NS | |
| Wrist | Stiffness | 316/1032 (31%) | 256/1041 (25%) | 0.002 |
| Duration > 30 minutes | 159/316 (50%) | 141/256 (55%) | NS | |
| Hip | Pain | 265/1031 (26%) | 212/1041 (20%) | 0.004 |
| Bilateral | 129/264 (49%) | 91/212 (43%) | 0.018 | |
| Comorbidities | Rheumatoid arthritis | 103/1032 (10%) | 83/1041 (8%) | 0.129 |
| SLE | 27/1032 (3%) | 5/1041 (0.5%) | <0.001 |
NS indicates not significant.
Activity Limitations
All patients with PBC and controls were asked about difficulties with daily activities and their needs for special assistance or devices in the performance of everyday activities (Table 2). A significantly larger proportion of patients with PBC reported the need for help with routine aspects of daily living than controls (13% of PBC cases versus 10% of controls; P = 0.008). Difficulty in performing household chores was reported significantly more frequently by patients with PBC than matched controls (28% of patients with PBC versus 21% of controls; P = 0.039). Notably, no differences between PBC cases and controls were observed for walking endurance or the ability to carry weights (plausibly associated with fatigue) or for impaired mental acuity during money management.
Table 2.
Reported Characteristics of Daily Activities in Patients with PBC and Matched Controls
| Capability | Cases (n = 1032) | Controls (n = 1041) | P | |
|---|---|---|---|---|
| Difficulty in | Walking a quarter of mile | 230 (22%) | 227 (22%) | NS |
| Walking up 10 steps | 215 (20%) | 204 (20%) | NS | |
| Stooping, crouching, or kneeling | 471 (46%) | 468 (45%) | NS | |
| Lifting or carrying 10 pounds | 245 (24%) | 218 (21%) | NS | |
| Doing chores around house | 294 (28%) | 223 (21%) | 0.039 | |
| Preparing own meals | 100 (10%) | 77 (7%) | 0.06 | |
| Managing money | 87 (8%) | 74 (7%) | 0.058 | |
| Walking room to room on the same level | 66 (6%) | 66 (6%) | NS | |
| Standing up from an armless straight chair | 227 (22%) | 200 (19%) | 0.2 | |
| Getting in or out of bed | 172 (17%) | 169(16%) | NS | |
| Eating, cutting, and drinking | 52 (5%) | 52 (5%) | NS | |
| Dressing self | 123 (12%) | 113 (11%) | NS | |
| Need | Help with personal care | 29 (3%) | 37 (4%) | NS |
| Help with routine needs | 139 (13%) | 101 (10%) | 0.008 | |
| Special device to deambulate | 53 (5%) | 66 (6%) | NS | |
| Special device to eat | 1 (0.1%) | 5 (0.48%) | NS | |
| Special device to dress | 8 (0.78%) | 13 (1%) | NS |
NS indicates not significant.
The self-assessment of overall activity showed that comparable proportions of PBC cases and controls reported feeling less active than they had 12 months previously (Table 3). Quite surprisingly, a significantly greater proportion of controls than patients with PBC described themselves as being less active overall than people of their same age (36% of patients with PBC versus 40% of controls, P < 0.001) and less active than they had been 10 years previously (23% of PBC cases versus 31% of controls, P < 0.001). Conversely, a significantly greater proportion of patients with PBC than controls reported having limitations in the type of professional work that they could perform (36% of PBC cases versus 22% of controls; P < 0.001). Patients with PBC also reported having had to change jobs because of health-related causes more frequently than controls (39% of patients with PBC versus 26% of controls; P < 0.001). Similarly, PBC cases more frequently reported limitations in the performance of housework (31% of PBC cases versus 19% of controls; P < 0.001) and accomplishment of everyday activities (41% of PBC cases versus 30% of controls; P < 0.001).
Table 3.
Self-Assessment of Overall Activity and Work-Related History in Patients with PBC and Matched Controls
| Cases (n = 1032) | Controls (n = 1041) | P | ||
|---|---|---|---|---|
| Overall activity | Same as 12 months ago | 513 (49%) | 512 (49%) | NS |
| More than 12 months ago | 191 (18%) | 175 (17%) | ||
| Less than 12 months ago | 346 (33%) | 354 (34%) | ||
| Same as same-age people | 373 (36%) | 415 (40%) | <0.001 | |
| More than same-age people | 337 (33%) | 390 (38%) | ||
| Less than same-age people | 327 (32%) | 234 (23%) | ||
| About the same as 10 years ago | 237 (23%) | 323 (31%) | <0.001 | |
| More than 10 years ago | 149 (14%) | 166 (16%) | ||
| Less than 10 years ago | 664 (63%) | 552 (53%) | ||
| Work activity | Limits in job type/effort | 376 (36%) | 234 (22%) | <0.001 |
| Disease-related job change | 402 (39%) | 273 (26%) | <0.001 | |
| Limits in housework | 330 (31%) | 200 (19%) | <0.001 | |
| Limits in everyday activities | 426 (41%) | 313 (30%) | <0.001 |
NS indicates not significant.
Hobbies and Leisure Activities
There were significant differences between PBC cases and controls with respect to participation in sports, physical exercise, and hobbies (Table 4). Patients with PBC reported engaging in many aerobic activities less frequently than controls and were also significantly less likely than controls to participate in a variety of hobbies. Of note, PBC cases were either no more or less likely than controls to have hobbies in which chemicals were involved, including gardening with pesticides, oil painting, and glass blowing.
Table 4.
Hobbies and Sports/Exercise in Patients with PBC and Controls
| Cases (n = 1032) | Controls (n = 1041) | P | ||
|---|---|---|---|---|
| Sports/exercise* | Jogging or running | 64 (6%) | 90 (9%) | 0.03 |
| Riding a bike | 211 (20%) | 232 (22%) | NS | |
| Swimming | 125 (12%) | 155 (15%) | 0.072 | |
| Aerobics | 107 (10%) | 140 (13%) | 0.035 | |
| Dancing | 113 (11%) | 116 (11%) | 0.889 | |
| Calisthenics | 343 (33%) | 331 (32%) | NS | |
| Weightlifting | 219 (21%) | 188 (18%) | 0.077 | |
| Other exercises | 387 (37%) | 339 (33%) | 0.019 | |
| Hobbies | Gardening | 204 (32%) | 244 (33%) | NS |
| With pesticides | 308 (29%) | 402 (39%) | <0.001 | |
| Jewelry making | 26 (2%) | 75 (7%) | <0.001 | |
| Oil painting | 25 (2%) | 84 (8%) | <0.001 | |
| Watercolor painting | 43 (4%) | 72 (7%) | 0.007 | |
| Glass blowing | 1 (0.1%) | 5 (0.5%) | 0.218 | |
| Stained-glass making | 11 (1%) | 29 (3%) | 0.006 | |
| Making ceramics | 24 (2%) | 126 (12%) | <0.001 | |
| Charcoal drawing | 20 (2%) | 46 (4%) | 0.002 | |
| Pastel drawing | 20 (2%) | 39 (4%) | 0.017 | |
| Photography | 114 (11%) | 206 (20%) | <0.001 | |
| Playing a musical instrument | 103 (10%) | 230 (22%) | <0.001 | |
| Other art-related hobby | 224 (22%) | 319 (31%) | <0.001 |
NS indicates not significant.
“Sports/exercise” refers to the 30 days prior to the interview.
Social Life
We evaluated factors generally regarded as contributing to one’s social life in patients with PBC and controls (Table 5). Such factors included contacts with relatives, friends, and neighbors and participation in social settings such as club meetings and religious services. Patients with PBC reported meeting with relatives or friends more often than controls (P = 0.004). However, there were no significant differences between patients with PBC and controls in the other investigated factors related to social life, and we should note that response rates were significantly reduced for some of these questions in both populations.
Table 5.
Social Life in Patients with PBC and Matched Controls
| Social Activity | Cases | Controls | P |
|---|---|---|---|
| Talking on the telephone with relatives, friends, or neighbors (times per week) | 4.7 ± 2.1 (n = 425) | 4.5 ± 2.1 (n = 489) | 0.109 |
| Getting together with friends or relatives (times per month) | 8.3 ± 7.4 (n = 1018) | 7.5 ± 7 (n = 989) | 0.004 |
| Visiting neighbors (times per month) | 5.2 ± 7.6 (n = 665) | 6.1 ± 9.7 (n = 667) | NS |
| Attending church or religious services | 691/1032 (66%) | 737/1041 (70%) | 0.067 |
| Belonging to a club (times per month) | 4.2 ± 4.4 (n = 735) | 4.2 ± 4.1 (n = 690) | NS |
NS indicates not significant.
Multivariable Analysis
To further assess QoL-related factors in PBC, we developed a multivariable model using conditional multiple logistic regression analysis (Table 6). In this model, variables referring to articular symptoms of knee stiffness in the past 6 weeks, the location of knee stiffness, and SLE were significantly associated with PBC. With respect to activities and the self-assessment of activities, limits in job type/effort or housework were also associated with PBC. To our surprise, yet in accordance with the univariate analyses, feeling more active than 10 years before was also associated with PBC. Various hobbies (weightlifting, gardening, pesticide use, jewelry making, oil painting, ceramic work, photography, and playing music) and social activities (church attendance) were also significantly associated with PBC. Variables that tended to have higher prevalence in PBC were a diagnosis of SLE, limitations in housework, limitations in work, disability-caused reduction in housework, weightlifting, and church attendance. Age and household income were the only significant confounders in this analysis.
Table 6.
Results of a Multiple Logistic Regression Model (Backward Elimination)
| β | OR | 95% CI | P | |
|---|---|---|---|---|
| Confounders | ||||
| Age | 0.0130 | 1.013 | 1.002, 1.024 | 0.017 |
| Income | 0.1786 | 1.196 | 1.142, 1.251 | <0.001 |
| Articular symptoms/related diseases | ||||
| Knee stiffness in the last 6 weeks | 1.6179 | –† | <0.001 | |
| Location of knee stiffness | 0.6150 | –† | <0.001 | |
| SLE comorbidity | 0.8534 | 5.511 | 1.813, 16.752 | 0.003 |
| Overall and work-related activity | ||||
| Having difficulty walking a quarter of a mile | –* | 0.021 | ||
| Having trouble stooping | –* | 0.048 | ||
| Needing help with personal care | −0.3245 | 0.523 | 0.287, 0.951 | 0.033 |
| Less active than 10 years before | 0.2558 | 1.710 | 1.336, 2.190 | <0.001 |
| More active than 10 years before | 0.0252 | 1.358 | 0.985, 1.873 | |
| Limits in work | 0.2724 | 1.724 | 1.245, 2.387 | 0.001 |
| Limits in kind of housework | 0.2469 | 1.639 | 1.133, 2.369 | 0.009 |
| Having to reduce housework | 0.2125 | 1.530 | 1.108, 2.111 | 0.01 |
| Hobbies and sports | ||||
| Weightlifting | 0.1461 | 1.339 | 1.028, 1.745 | 0.030 |
| Gardening the previous month | 3.8228 | –† | 0.843 | |
| Gardening with pesticides | –* | –† | 0.037 | |
| Regular jewelry making | −0.4317 | 0.422 | 0.242, 0.734 | 0.002 |
| Regular oil painting | −0.4452 | 0.411 | 0.243, 0.694 | <0.001 |
| Regular ceramic making | −0.6973 | 0.248 | 0.149, 0.413 | <0.001 |
| Photography | −0.2312 | 0.630 | 0.470, 0.843 | 0.002 |
| Music | −0.4755 | 0.386 | 0.288, 0.518 | <0.001 |
| Other art-related hobby | −0.2143 | 0.651 | 0.513, 0.827 | <0.001 |
| Social life | ||||
| Going to church (no versus yes) | −0.1589 | 0.728 | 0.584, 0.908 | 0.005 |
One model was created, and the variables are presented here as subdivided in the text and in the previous tables. β indicates the probability of type II error; CI, confidence interval; and OR, odds ratio.
The number of levels prohibits presentation in the table.
Terms involved in interactions do not have meaningful ORs.
Discussion
We have obtained diverse QoL-related information from the largest population of patients with PBC reported to date. The study was designed to evaluate risk factors for PBC and comorbidities9 and QoL by comparing the answers of 1032 patients with PBC and 1041 matched controls in the United States with a modified NHANES III questionnaire. The results suggest that having PBC leads to various limitations in activities and social life, ultimately impacting QoL, although possibly to a lesser extent than that observed in other countries.
Fatigue has been regarded as the cardinal symptom of patients with PBC, regardless of the disease stage, and, combined with other features, appears to be the primary contributor to an impaired QoL in affected individuals,4 as supported by data obtained with validated questionnaires.11 However, the evaluation of the prevalence and severity of fatigue is a complex issue because these are influenced by several social and possibly geographical factors and the contribution of abnormalities of the musculoskeletal and neurological function is difficult to assess. A PBC-specific questionnaire has been validated only recently in patients from the United Kingdom, and its use demonstrated a significant impairment in the QoL due to fatigue and, to a lesser extent, pruritus in affected individuals.11 Because most studies of PBC have been conducted with British patients, it is unclear if social, economic, or geographical issues unique to Northern Europe share the potential to influence the results. Thus, the applicability of the results to PBC in other countries or parts of the world is currently unclear. Furthermore, none of the studies has assessed the impact of medical care on patients’ perception of disease, as has been reported for patients with chronic hepatitis C.12
To overcome these limitations of earlier studies, we compared relevant information obtained from our interview-based study of patients with PBC in the United States and carefully matched controls. Although we are aware of the fact that our modified NHANES III questionnaire has not been independently validated in patients with PBC, as in the case of the PBC-40,11 answers to the questions are accurate, as confirmed by the nearly uniform consistency obtained when the questionnaire was readministered in a subset of patients.9 Several differences exist between the validated PBC-40 questionnaire and the tool used herein, including the fact that the NHANES III was not designed to investigate QoL only. However, the NHANES III questionnaire has provided important information regarding risk factors for nonalcoholic fatty liver disease,13,14 and this indicates that it is suitable for use in patients with chronic liver disease. It is also of note that we cannot currently conclude whether the self-reported data regarding the QoL can be accurate estimates of QoL-related symptoms,15 whereas our multivariable analysis is the first attempt to discriminate the potential confounding effect of comorbidities associated with fatigue and impaired QoL.
The results of the present study show that only a minority of the American patients with PBC experienced significantly more difficulties with household chores (among 12 activities of everyday life) in comparison with matched controls. In addition, patients with PBC more frequently required help with routine needs than controls did. Surprisingly, the same percentage of patients with PBC and controls described their overall activity as being less than it had been 12 months ago. In contrast, significantly more controls than PBC cases described their level of overall activity as being lower than people of their same age or compared with what it had been 10 years before. The latter comparison led also to a significant independent association in the multivariate analysis. In all cases, it is of note that the activity data from controls were similar to those of earlier NHANES III reports.16 A significantly greater proportion of patients with PBC reported compromised work activities, which ranged from limitations in the types of jobs that they held to their capacities for work-related effort. Indeed, a greater percentage of patients with PBC had changed jobs as a result of their disease. Similarly, greater proportions of patients with PBC than controls reported limitations in their ability to perform housework and to participate in daily activities. These observations were independent of the presence of potentially invalidating comorbidities such as SLE or rheumatoid arthritis.
What causes the apparent discrepancies between our data and previous studies from the United Kingdom11 and France4 remains to be determined. We can only hypothesize multiple factors. First, the clinical features of enrolled subjects might play a role, and we could not stratify our PBC cases according to disease severity. However, it is of note that the follow-up duration (that is, the time between diagnosis and participation in the study) in our PBC series had to be less than 5 years for enrollment criteria,9 whereas previous studies reported a significant impact of fatigue in patients with a disease duration of 7 ± 4 years.6 Second, we cannot overlook the possibility that ethnic, geographical, or genetic factors might also influence the degree of QoL impairment cited by patients and controls from different countries. Third, the enrollment criteria are not expected to play a role in the observed discrepancies because our series was obtained from tertiary referral centers and the diagnosis was independently confirmed; this was similar to what was done in previous consistent studies.4,6
One possible confounding factor that could underlie differences between patients with PBC and controls in response to QoL questions is the discrepancy between the socioeconomic status of the patients and controls.9 For example, the significantly higher household income of patients with PBC versus controls might facilitate employment in fields with fewer physical challenges, the ability to hire help for household chores, and less need for perseverance in retaining employment or performing housework. Such higher socioeconomic status among PBC cases may also contribute to their significantly higher assessment of the overall activity status in comparison with same-age individuals or themselves 10 years before. Also, patients with PBC may receive superior health care. However, our multivariable analysis controlled for the effects of higher income in PBC cases and still suggested that QoL was somewhat impaired in PBC in comparison with controls. Furthermore, the self-referral of diagnoses such as SLE might lead to an incorrect estimate of their prevalence rates, although we submit that data from our previous work9 were consistent with other studies. In this regard, we are also aware that the proposed impact of SLE in patients with PBC might also be read as secondary to the perception of the condition rather than the actual multiorgan disease. Lastly, we note that additional confounding factors might result from the use of tertiary referral centers for patient enrollment and the limited clinical information on all included PBC cases. These two issues might lead to the overrepresentation of more severe stages of PBC and to the lack of a subanalysis related to the disease stage or PBC-related symptoms, respectively. However, we note that the mean duration of follow-up in our series was less than 5 years,9 thus possibly minimizing the former possible flaw.
Our study results also provide some information related to theories regarding the pathogenesis of PBC in light of the most recent evidence.17–20 In particular and on the basis of the proposed role for xenobiotics in the generation of T and B cell responses to conserved epitopes expressed in the E2 subunit of the pyruvate dehydrogenase complex, the PBC-specific autoantigen,21,22 it is noteworthy that patients with PBC did not identify excessive exposure to chemicals, such as gardening with pesticides. In fact, certain exposures were generally more common in controls. Although controversial,23,24 some studies have claimed that a retrovirus infection may be a factor in triggering PBC and that swimming pools may be one source of such an infection. However, our data show that comparable minorities of patients with PBC and controls engaged in swimming. Clearly, on the basis of studies of humans with PBC, intensive studies of the genetics of other autoimmune diseases, and the multiple effector pathways identified in both human and animal models with PBC, the etiology of this disease has a genetic and environmental influence, which has been called a combination of bad luck and bad genes.25–28
In conclusion, the results of our study indicate that the QoL of patients with PBC in the United States is generally well preserved. Despite limitations in work activities and a greater likelihood of job changes secondary to having the disease, patients with PBC rate their overall activity as comparable or superior to that of controls. They engage less frequently in jogging, running, or aerobics than controls but are as likely to participate in other sports and exercises that require exertion, such as cycling, swimming, dance calisthenics, and weightlifting. However, PBC cases engage in significantly fewer hobbies than controls. These data in some ways conflict with reports from other geographical areas. Therefore, studies of patients with PBC from different parts of the world using standardized and validated questionnaires should be performed.
Acknowledgment
The authors are grateful to Mr. Reiner Bruggrabber and Ms. Kaman Sit for assistance in tracking and confirming the collection of data and to a unique group of patients, the PBCers, for their meritorious effort in helping patients and research to achieve further knowledge and a cure for PBC and without whose help this study would not have been possible.
Supported by National Institutes of Health grant DK56839.
Abbreviations
- β
probability of type II error
- CI
confidence interval
- NHANES III
National Health and Nutrition Examination Study III
- NS
not significant
- OR
odds ratio
- PBC
primary biliary cirrhosis
- QoL
quality of life
- SLE
systemic lupus erythematosus
Appendix
The members of the USA PBC Epidemiology Group are as follows (in alphabetical order): Fred Askari, University of Michigan, Ann Arbor, MI; Nancy Bach, Mt. Sinai School of Medicine, New York, NY; Nathan Bass, University of California, San Francisco, CA; Gordon D. Benson, UMDNJ-Robert Wood Johnson Medical School, Camden, NJ; Andres Blei, Northwestern University, Chicago, IL; Andrea D. Branch, Mt. Sinai Medical School, New York, NY; Thomas Capozza, Scripps Clinic, La Jolla, CA; David J. Clain, Beth Israel Medical Center, New York, NY; Robert Gish, California Pacific Medical Center, San Francisco, CA; Richard Green, Northwestern University, Chicago, IL; M. Edwyn Harrison, Mayo Clinic, Scottsdale, AZ; Steven Herrine, Thomas Jefferson University, Philadelphia, PA; Emmet B. Keeffe, Stanford University, Palo Alto, CA; Natasha Khazai, University of Michigan, Ann Arbor, MI; Kris V. Kowdley, University of Washington, Seattle, WA; Edward L. Krawitt, University of Vermont, Burlington, VT; John Lake, University of Minnesota, Minneapolis, MN; Douglas LaBrecque, University of Iowa, Iowa City, IA; Velimir Luketic, Medical College of Virginia, Richmond, VA; Andrew Mason, Ochsner Clinic, New Orleans, LA; Marlyn J. Mayo, University of Texas at Southwestern, Dallas, TX; Timothy McCashland, University of Nebraska, Omaha, NE; Santiago Munoz, Albert Einstein Medical Center, Philadelphia, PA; Paul Pockros, Scripps Clinic, La Jolla, CA; Don Rockey, Duke University, Durham, NC; and Alastair D. Smith, Duke University, Durham, NC.
Footnotes
Potential conflict of interest: Nothing to report.
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