Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease [
This meta-analysis was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (
The Medline and Scopus databases were searched for studies with information on either the incidence or prevalence of PBC. The last search was run on 7 July 2020. A literature review was created using the following search terms: (“epidemiology” or “prevalence” or “incidence”) AND (“primary biliary cirrhosis” or “primary biliary cholangitis” or “autoimmune liver disease” or “sclerosing cholangitis” or “biliary liver cirrhosis”). Medical Subject Headings (MESH) were used to increase the precision and efficiency of the search. No language, publication date, or publication status restrictions were imposed. In addition, we expanded the search using the reference lists of relevant review articles identified during the search. Two authors independently screened the literature review using titles and abstracts and assessed full texts where eligible. Disagreements over the inclusion of articles were resolved by discussion with a senior hepatologist.
Studies were included if they met the following criteria: (1) the study was original research; (2) the study reported a prevalence or incidence (or it reported raw data that allowed the calculation of estimates); (3) the study was conducted in Europe; and (4) the study was published in 2000 or later.
Exclusion criteria for the meta-analysis were as follows: (1) the study was a review article; (2) the study was a genome study or an animal study; (3) the study described the epidemiology of PBC among hospitalized patients; and (4) the study did not specifically describe patients with PBC.
Two investigators independently performed the data extraction. We developed a data extraction sheet, pilot-tested it on five included studies, and refined it accordingly. Furthermore, we attempted to acquire any missing information by contacting the corresponding authors of two studies; however, neither one responded to our request. Disagreements over extracted information were resolved by discussion with a senior hepatologist. The following information was extracted from each study: (1) the first author, (2) publication year, (3) country of origin, (4) case-finding methods, (5) methods of diagnosis, (6) raw data (underlying population and number of cases), and estimates of incidence and prevalence together with (7) sex-specific estimates, where available. Age-standardized estimates were preferred to crude estimates. Worth noting is that when multiple annual incidence rates were reported in a specific study, the median value for the period was calculated.
The incidence and prevalence rates were adapted from the original reports. As needed, the underlying population was used to impute the number of cases and vice versa. For sex-specific analyses, the underlying population was divided by two. We used a random-effects model to estimate both the pooled annual incidence rate and the pooled point-prevalence rate (reported per 100,000 inhabitants). The results of meta-analyses are presented graphically using forest plots. We employed the DerSimonian–Laird (DL) approach to estimate the between-study heterogeneity. Two different measures of between-study heterogeneity are reported in this study: (1)
The electronic search yielded 1,373 records (Medline 1,200; Scopus 173). We identified seven more records reviewing the references of PBC-relevant review articles. No unpublished studies were included. After removing duplicates (
Flowchart of studies inclusion.
A total of 16 reports on 18 different studies that were conducted in 13 European countries were included in the analysis. The publication dates of all included studies ranged from April 2007 to June 2020. A total of 17 studies (94.44%) reported local prevalence rates (10–58.2 PBC cases per 100,000 inhabitants) and 13 studies (72.22%) reported local incidence rates (0.79–5.31 new PBC cases per 100,000 inhabitants per year). Seven of these studies (38.89%) reported sex-specific rates. Furthermore, seven studies (38.89%) used at least two case-finding methods and 11 studies (61.11%) reported on specific diagnostic criteria (Table
Reports on PBC incidence and/or prevalence from European countries.
First author | Country | Publication year | Case-finding methods | Diagnostic methods | Population | Prevalence | Female prevalence | Male prevalence | Incidence | Female incidence | Male incidence |
---|---|---|---|---|---|---|---|---|---|---|---|
Rautiainen et al. [ | Finland | 2007 | 1, 2, 5, 6 | 2/3 of a, b, d | 2,972,189 | 18.0 | 29.2 | 5.5 | 1.7 | 2.7 | 0.8 |
Pla et al. [ | Spain | 2007 | 1, 2, 3, 5 | 2/3 of a, b/c, d | 389,758 | 19.5 | 37.02 | — | 1.72 | 2.84 | — |
Eaton et al. [ | Denmark | 2007 | 2 | ICD | 5,472,032 | 12.0 | — | — | — | — | — |
Baldursdottir et al. [ | Iceland | 2012 | 1, 2, 3, 5 | 2/3 of a, b, d | 317,630 | 38.3 | 64.4 | 12.5 | 2.5 | 4.1 | 1.0 |
McNally et al. [ | England | 2014 | 1, 2, 3, 4, 5 | 2/3 of a, b, d | 2,050,000 | — | — | — | 4.509 | 7.668 | 0.949 |
Koulentaki et al. [ | Greece | 2014 | 2 | 2/3 of a, b, d | 600,000 | 36.5 | — | — | 2.088 | — | — |
Boonstra et al. [ | Netherlands | 2014 | 1, 3, 5, 6, 7 | 2/3 of a, b, d | 5,855,630 | 13.2 | — | — | 1.1 | 1.9 | 0.3 |
Heetun et al. [ | Ireland | 2015 | 2 | — | 500,000 | 10.0 | — | — | 1.4 | — | — |
Lleo et al. [ | Italy | 2016 | 2, 7 | — | 9,742,676 | 29.5 | — | — | 1.67 | 2.19 | 1.07 |
Lleo et al. [ | Denmark | 2016 | 2 | — | 5,534,738 | 12.2 | 20.3 | 3.5 | 1.14 | 1.77 | 0.47 |
Gatselis et al. [ | Greece | 2017 | 8 | 2/3 of a, b/c, d | 750,000 | 58.2 | — | — | — | — | — |
Pares et al. [ | Spain | 2018 | 1 (delphi) | 2/3 of a, b, d/US | 46,400,000 | 20.2 | — | — | 2.2 | — | — |
Marzioni et al. [ | Italy | 2019 | 2 | ICD | 1,204,216 | 27.9 | — | — | 5.31 | — | — |
Madir et al. [ | Croatia | 2019 | 2 | 2/3 of a, b, d | 331,288 | 11.5 | — | — | 0.79 | — | — |
Madir et al. [ | Croatia | 2019 | 2 | 2/3 of a, b, d | 296,195 | 12.5 | — | — | 0.89 | — | — |
Marschall et al. [ | Sweden | 2019 | 2, 4, 7 | ICD | 8,065,261 | 34.6 | — | — | 2.6 | — | — |
Drazilova et al. [ | Slovakia | 2020 | 1 | 2/3 of a, b/c, d | 1,600,000 | 14.9 | 28.0 | — | 1.2 | 2.2 | — |
Sebode et al. [ | Germany | 2020 | 7 | ICD | 8,100,000 | 36.9 | 61.2 | 12.4 | — | — | — |
The point-prevalence rate is reported as cases per 100,000 inhabitants. The annual incidence rate is reported as new cases per 100,000 inhabitants. Cases-finding methods: (1) survey of physicians, (2) hospital records, (3) laboratory data on antimitochondrial antibody positivity, (4) death notifications, (5) histology data on liver biopsies, (6) liver transplant records, (7) pharmacy or insurance databases or billing system, and (8) prospectively collected registry. Diagnostic methods: (a) cholestatic liver panel, (b) antimitochondrial antibody positivity, (c) antinuclear (anti-gp210/anti-sp100) antibody positivity, (d) compatible liver histology, ICD: International Classification of Diseases, US: abdominal ultrasound.
In Figure
Choropleth map of PBC point-prevalence rates in Europe.
PBC point-prevalence rates in Europe.
Funnel plot of PBC point-prevalence rates in Europe.
Subgroup analyses of PBC point-prevalence rates. (a) Diagnostic criteria. (b) Case-finding methods. (c) Underlying population. (d) Former Eastern/Western Bloc.
(a) Female PBC point-prevalence rates in Europe. (b) Male PBC point-prevalence rates in Europe.
In Figure
Choropleth map of annual PBC incidence rates in Europe.
Annual PBC incidence rates in Europe.
Funnel plot of annual PBC incidence rates in Europe.
Subgroup analyses of annual PBC incidence rates. (a) Diagnostic criteria. (b) Case-finding methods. (c) Underlying population. (d) Former Eastern/Western Bloc.
(a) Annual female PBC incidence rates in Europe. (b) Annual male PBC incidence rates in Europe.
This study aimed to map the incidence and prevalence rate of PBC in Europe. The pooled point-prevalence rate was 22.27 cases per 100,000 inhabitants (95% CI: 17.98–27.01), and the pooled annual incidence rate was 1.87 new cases per 100,000 inhabitants (95% CI: 1.46–2.34). PBC, similarly to other autoimmune disorders, is a female-predominant disease [
The employment of different case-finding methods may result in different reported rates. We found that both the prevalence (24.54, 95% CI: 16.98–33.49) and the incidence rate (2.15, 95% CI: 1.48–2.94) were higher in studies that reported at least two case-finding methods when compared to studies that did not report any case-finding method or reported only one (prevalence rate: 21.07, 95% CI: 15.66–27.27; incidence rate: 1.63, 95% CI: 1.17–2.16). However, this subgroup analysis did not explain the presence of heterogeneity.
The incidence was relatively stable during the last couple of years. The prevalence, on the other hand, steadily increased [
Few studies reported a north-south, north-west, or south-east prevalence gradient [
The European Union, the United Kingdom, Switzerland, and Norway altogether have approximately 527 million inhabitants. When extrapolating from the pooled prevalence rate, roughly 115,000 patients should be diagnosed with PBC in these countries. However, the true number of cases would be significantly higher because a substantial portion of PBC patients, specifically patients with the asymptomatic clinical course, remains undiagnosed. According to one report, approximately one in 1,000 women could be suffering from PBC [
We describe the incidence and prevalence of PBC in European countries. The true prevalence is probably higher than the reported prevalence, because asymptomatic patients are frequently undiagnosed. Improving awareness of PBC among physicians will catalyse a more effective diagnostic process and will thus result in a higher prevalence of PBC in the European population.
The data (in an excel file) used to support the findings of this study are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.
The research did not receive specific funding but was performed as part of the employment of the authors at Pavol Jozef Safarik University in Kosice.