Literature review
Electronic and manual searches identified a total of 1,724 English citations. After review of the titles and abstracts, 1,695 citations were excluded according to the eligibility and ineligibility criteria. The remaining 29 studies were selected for full article review. After careful examination of the full texts, five studies were excluded because of duplicate reports for the same subjects, reports unrelated to prevalence of PBC, and no data on prevalence or incidence for PBC. Twenty-four studies were thus included in this systematic review[5–7,9–27,30], which comprises 22 studies based on cases and 2 based on general population (Figure 1). Among 327 studies published in Chinese (searched in Chinese database), 4 based on general population were selected and no papers based on cases were found[28,29,31,32]. There was full concordance between the two independent reviewers with respect to the final inclusion and exclusion of the studies reviewed.
Characteristics of included studies based on cases
As shown in Table 1, among the 22 studies included in this review, 12 studies were from Europe, 4 from Asia, 5 from North-America and 1 from Oceania. Although all of them were published since 2008, the period of the studies spanned from 1980 to 2015. Studies varied in size from 10 to 8680 PBC patients which were 37,302 in total and covered over 112.62 million inhabitants. Median age at diagnosis ranged from 51 to 65, and the ratio of male/female from 1:2.3 to 1:18.8 which was 1:4.1 in total. Eight studies described the race distribution of patients. The cases were searched and found from hospital medical record system, population-based administrative database, commercial laboratories, and /or personal registry physicians among others. All of them were diagnosed on the basis of PBC guidelines in accordance with or similar to those made by American Association for the Study of Liver Diseases or European Association for the Study of the Liver[33–35].
Global prevalence of PBC and its factors shown in cases-based studies
The included studies on prevalence of PBC showed significant variation in association with gender, age, region and race (Table 2). The lowest and highest prevalence rates of the disease were found in Brunei Darussalam and Crete, Greece, 2.6 and 58.2 per 100,000 age- and sex matched inhabitants, respectively[6,10].
It is well known that women are susceptible to PBC. In present analysis, the mean proportion of female patients was 80.2% (69.8–100%) in total. The disease prevalence rates in women and men ranged from 8.3 to 64.4 per 100,000 inhabitants and 2.1 to 15.4 per 100,000 inhabitants, respectively. The impact of age on PBC prevalence was analyzed in six studies[5,9,13,15,18,21]. Most of them demonstrated that prevalence of the disease increased along with age, and was significantly higher in patients aged ≥40 than those aged < 40, with the highest prevalence rate occurring in patients aged 60–79 years. The impact of race on PBC prevalence was analyzed in five studies[5,10,12,13,21]. The prevalence was 11.5 to 46.0, 30.8, and 2.3 to 5.6 per 100,000 inhabitants in White race, Black race (mainly African American), Yellow and Brown races (mainly Asian), respectively. It was noteworthy that the disease prevalence was 44.7 per 100,000 inhabitants in Asian American[5]. Additionally, prevalence of 22.7 to 39.2, 11.1 to 58.2, and 2.6 to 25.5 (2.6 to 5.6 excepting Israel) per 100,000 inhabitants were reported in America, Europe, and Asia-Pacific regions, respectively (Figure 2).
Global incidence of PBC and its factors shown in cases-based studies
As shown in Table 2, data from different countries reported a wide difference in the disease frequency, ranging from an incidence of 0.8 to 5.3 per 100,000 inhabitants per year. The lowest and highest incidence rates were found in New Zealand and Italy, respectively[12,19].
Part of studies analyzed the impact of gender, age, race and region on PBC incidence. There were year incidence rates of 1.4 to 11.3 per 100,000 inhabitants, and 0.04 to 2.3 per 100,000 inhabitants in women and men, respectively. Similarly to the impact of age on prevalence, incidence of the disease was significantly higher in patients aged ≥40 than those aged < 40, with the highest incidence rate occurring during 60–79 years old. The impact of race on PBC incidence was analyzed in only two studies, in which incidence rates were 8.2, 4.0, 4.4 and 1.4 per 100,000 inhabitants in Asian American, Black/African American, White race and native Israelis population, respectively[5,13]. Additionally, annual incidence of 1.5 to 4.9, 1.0 to 5.3, and 0.8 to 2.0 (0.8 to 0.9 excepting Israel) per 100,000 inhabitants were reported in America, Europe, and Asia-Pacific region, respectively (Figure 2).
Epidemiology of positive AMA-M2 and PBC in general population-based studies
From the Medline, Embase and Cochrane databases, we found 2 studies based on general population, and from Chinese databases, we found 4 studies. All of the 6 studies were originated from Chinese individuals who undergoing health check-ups (Tables 3 and 4)[27–32]. AMA-M2 was detected by ELISA or immunoblotting, and cases were ascertained on the basis of 2009 guidelines[34,35]. The studies were performed after 2005 and varied in size from 6,658 to 36,459 individuals with 107,490 (female/male: 53,818/53,672) in total.
Out of 107,490 individuals, 1034 were positive for AMA-M2 and 150 were diagnosed as PBC, and total prevalence rates of positive AMA-M2 and PBC were 961.9 (ranging from 430.7 to 1,456.9) and 139.5 (49.2 to 276.6) per 100,000 individuals, respectively. When combing all of the six studies, prevalence rates of positive AMA-M2 were 609.5 (303.3 to 1,144.3) and 1315.4 (515.7 to 1,884.1) per 100,000 individuals in men and women, and the prevalence ratio of male/female were 1:2.2. Prevalence rates of PBC were 41.6 (23.5 to 53.5) and 171.1 (77.4 to 214.9) per 100,000 individuals in men and women, respectively, and the prevalence ratio of male/female were 1:4.1. Five study described the association of age and prevalence, and showed that prevalence rates of both positive AMA-M2 and PBC increased with age, and were significantly higher in individuals aged ≥40 than those < 40, and the peaks occurred over 55 years old[27,29–32].