The bibliometric analysis identifies the most influential articles in the field during the past several decades, highlights contributions that have led to significant advances, and reveals current trends in the field (16). We ranked these articles by the total number of citations according to the WoSCC database and analyzed the T100 articles in this field. Through the analysis of the most frequently cited articles, we discovered the research hotspots of PBC in recent decades. In addition, we can identify potential future research directions.
From the 1970s to the early 2000s, the number of studies on PBC grew slowly. Over the last 20 years, the amount of research in this field has experienced explosive growth. The number of citations of an article depends partly on when the article was published, as citations accumulate over time (16). Thus, more than half of the articles in our study were published between 2010 and 2015. These findings are consistent with those of other recent bibliometric analyses. However,several articles with high citation density published in recent five years, which made them accumulate relatively low total citations due to less time, such as Nevens, F et al. (17) (2016), and Corpechot, C et al. (18) (2018). The high interest of these researches suggested the promising academic influence in the foreseeable future.
Some bibliometric studies have reported that journals with high impact factors, such as NEJM or Nature, were the leading journals within their respective fields (19). However, we found that Hepatology and Journal of Hepatology were the most productive journals, despite their relatively low impact factors. Indeed, they published 28 and 8 articles in the T100 articles, respectively. This result highlights a growing trend in which highly influential articles are published in specialized journals, and are not limited to the most well-known general medical journals (16).
One-third of the T100 articles were basic science (n = 29), showing the significant role of basic science to PBC in the last decade. The main body of basic science is to explore pathogenesis and optimize the treatment (20). Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic (13). In 29 basic studies, a total of 14 articles studied the susceptibility sites of PBC. The genome-wide association studies (GWAS) have identified multiple genes influencing the susceptibility to PBC in HLA and non-HLA loci (21). Among them, IL-7, 13q14, and IL-12 are star loci (22–24). Multiple of these PBC risk loci were also shared risk loci in other autoimmune diseases (25). The existence of shared autoimmunity susceptibility loci could contribute to the frequent appearance of additional autoimmune diseases in individuals with PBC and their families (26). Therefore, whether it is now or in the future, the exploration of new autoimmunity susceptibility loci has always been the focus of mechanism research of PBC.
In recent years, the role of therapy in the management of PBC has considerably increased. In 100 records, an analysis of the research focuses revealed that 20% were related to therapy. Among the T100 articles, therapy was the hot topic (n=20). UDCA is currently the only FDA-approved medical treatment for PBC (27). However, about a third of patients are not sufficiently controlled with UDCA monotherapy, which drives the search for additional therapeutic approaches (28). Of the 20 articles on treatment, 15 described second-line treatment for PBC. Two RCTs, one on obeticholic acid (OCA) (17) and the other on bezafibrate (18) were published in top journals (NEJM) and generated high citation rates. National Institute for Health and Care Excellence (NICE) has appraised OCA and recommended OCA within its marketing authorization as an option for treating PBC in combination with UDCA for people whose disease has responded inadequately to UDCA or as monotherapy for those who cannot tolerate UDCA (4). In addition, Corpechot C et al. (18) found that in patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid, add-on therapy with bezafibrate for 24 months resulted in a higher rate of complete biochemical response than ursodeoxycholic acid therapy plus placebo. Rituximab, an anti-CD20 monoclonal antibody, selective B-cell depletion with rituximab was safe and associated with a significant decrease in autoantibody production, but had limited biochemical efficacy in PBC patients with an incomplete response to UDCA (29), it can even worsen the severity of IBD patients (30).
PBC is primarily a biliary disease, so when signs of failure of hepatocyte function develop, such as coagulopathy or jaundice, these usually indicate advanced and typically irreversible disease (4). Therefore, all PBC patients should receive lifelong follow-up and need to make risk predictions. If necessary, they also need to add second-line treatment. In the T100 articles, many studies (n=10) have assessed the prognostic significance of biochemical data collected following UDCA treatment. More risk scores and prognosis models for predicting the prognosis of PBC patients have been developed (31, 32). Survival of those with advanced PBC with biochemical response to UDCA is significantly better than for nonresponders. Prognostic information, based on bilirubin and albumin levels, is superior to that provided by alkaline phosphatase (ALP) levels (33). Early-stage patients who show ALP and aspartate transaminase (AST) ≤ 1.5× upper limit of normal, and normal bilirubin level after 1 year of treatment appear to be at very low or no risk of liver failure or progression to cirrhosis (34).
In conclusion, this report presents major advances and changes in research regarding PBC. The single treatment method entered a bottleneck period, and combined treatment with immunosuppressant, local therapy, and surgery will become the next research focus to identify possible beneficial treatment combinations.