Elsevier

Journal of Hepatology

Volume 53, Issue 1, July 2010, Pages 162-169
Journal of Hepatology

Research Article
Demographic, lifestyle, medical and familial factors associated with primary biliary cirrhosis

https://doi.org/10.1016/j.jhep.2010.02.019Get rights and content

Background & Aims

Primary biliary cirrhosis (PBC) is believed to result from the interaction of genetic and environmental factors. The controlled studies aiming to assess risk factors for PBC are still limited. Our aim was to identify risk factors and co-morbidities associated with PBC in a large monocentric cohort.

Methods

We enrolled 222 patients with PBC and 509 controls matched for age, gender, and residential location. Standardized questionnaire data, including more than 200 questions regarding demographic and anthropometric features, lifestyle, individual and familial medical history, and reproductive history, were prospectively collected and examined. Risk factors with odds ratio (OR) and confidence intervals (CI) were determined using conditional logistic regression analyses.

Results

Family history of PBC (OR 6.8, 95% CI 2.8–16.4) or autoimmune thyroid disease (AITD) (OR 7.1, 95% CI 3.5–14.5) in first-degree relatives, and individual history of active or passive smoking (OR 3.1, 95% CI 2.0–5.0), recurrent urinary tract infections (UTI) (OR 2.7; 95% CI 2.0–3.7), AITD (OR 7.7, 95% CI 4.8–12.3), Sjögren syndrome (OR 11.9, 95% CI 5.4–26.3), Raynaud syndrome (OR 7.2, 95% CI 4.3–12.1), pruritus during pregnancy (OR 3.9, 95% CI 2.8–5.3), or abortion (OR 2.0, 95% CI 1.6–2.5) were significantly associated with increased risk of PBC, while use of oral contraceptives (OR 0.6; 95% CI 0.5–0.8) was associated with decreased risk.

Conclusion

This study confirms some of the previously reported risk factors for PBC, namely family history of disease and individual history of smoking, UTI, and autoimmune conditions, and further identifies the use of oral contraceptives as a putative protective factor.

Introduction

Primary biliary cirrhosis (PBC), the main cholestatic liver disease in adulthood, is considered as a model autoimmune disease because of strong association with specific autoantibodies (i.e. antimitochondrial and anti-gp210 antibodies), marked female predominance, and frequent coexistence with other autoimmune conditions. Its pathogenesis remains largely unknown. It is assumed that PBC results from a complex multistep process, in which different combinations of genetic and environmental factors interact [1]. Genetic predisposition is supported by high concordance rate among monozygotic twins [2], high level of PBC aggregates in families [3], and significant associations with some specific gene polymorphisms [4], [5]. Evidence for contribution of environmental factors includes apparent time–space clustering [6], increased prevalence in relation to specific geographical areas [7], [8], and clinical or experimental findings supporting infectious agents or chemical compounds as possible triggering factors [9], [10], [11], [12].

Elucidating the risk factors and co-morbidities associated with PBC is a critical step for understanding its pathophysiology and possibly developing new therapeutic approaches. The data currently available are based on the results of three main studies, two from the US [13], [14] and one from the UK [15]. All of them have pointed out associations with some constitutive and environmental factors, among which family history of PBC, urinary tract infections (UTI), and tobacco exposure were shown to be the most affecting. Beside these factors, a history of gravidity [14], [16], exogenous estrogens [14], and frequent use of cosmetics [14], [15] have been also reported to be associated with an increased risk of the disease.

The main pitfall of case-control studies mostly lies on the risk of selection bias, both for cases and controls. Such biases indeed can affect outcomes and lead to misleading interpretations. It is therefore crucial to confirm prior reported associations among different populations of patients and controls. We report herein the results of a large case-control study on demographic, lifestyle, medical, and familial factors associated with PBC. The study was based on standardized questionnaire data prospectively collected in 222 patients with PBC and 509 unrelated controls matched for age, gender, and residential location.

Section snippets

PBC cases and controls

Three hundred patients with PBC, as identified from the Saint-Antoine hospital database, were pre-screened for the study. All patients were diagnosed on the basis of accepted criteria, including biochemical evidence of prolonged cholestasis, presence of antimitochondrial antibodies (AMA) in the serum and compatible liver histology. Eighty-nine percent were women. The mean age at diagnosis was 51 years. Sixty-five percent were living in Paris area and 87% in the north half of France. Ninety-five

Demographic, anthropometric and socioeconomic features

Demographic, anthropometric, and socioeconomic features of PBC cases and controls are shown in Table 1. Cases and controls were similar with respect to age, gender, and geographical location. The patients showed slightly shorter height (162 ± 8 cm vs. 164 ± 7 cm; p = 0.01), lower weight (64 ± 12 kg vs. 68 ± 15 kg; p = 0.001), and lower BMI (24 ± 4 kg m−2 vs. 25 ± 5 kg m−2; p = 0.02). The distribution of education levels did not differ between the two groups. The proportion of professionally inactive individuals was

Discussion

We report herein the first large case-control study ever performed in France or, and especially in continental Europe, on the risk factors for PBC. Our data confirm the environmental associations previously reported in the US and UK between PBC and smoking, and PBC and recurrent UTIs, as well as the significantly increased rates of reported PBC and AITD in FDRs of patients with PBC [14], [15]. Our results do not support the links previously suggested between PBC and the number of pregnancies

Financial disclosure

The authors report having received a grant from Axcan Pharma® for this study.

Conflicts of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Acknowledgment

The authors thank the Association pour la Lutte contre les maladies Biliaires Inflammatoires (ALBI) for its active participation to the study.

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