As one of the most influential databases for literature, Web of Science (WoS) is widely regarded as the optimal tool for conducting bibliometric analysis, and many researchers have utilized the WoS database to publish bibliometric studies (Thelwall, 2008; Ding and Yang, 2020). Thus, on 8 January 2023, we conducted a search and extracted literature data from the WoSCC database. Using Boolean logical operators, we employed the following search strategy: TS= (“liver graft*” OR “liver transplant*” OR “hepatic transplant*”) AND TS= (“acute rejection” OR “acute graft rejection” OR “acute transplant rejection”). Only literature from the Science Citation Index Expanded (SCI-E) was selected. The retrieval time frame spanned from 1 January 1988, to 31 December 2022, with article types limited to “Article” or “Review” and language limited to English. Ultimately, we analyzed 2,398 articles that met our criteria. A detailed screening process is presented in Figure 1.

We imported the downloaded data from WoS into the Bibliometric Online Analysis Platform (https://bibliometric.com/app), which enabled us to visualize the annual publication trends and collaboration relationships among different countries/regions. VOSviewer is a free bibliometric mapping software that produces various visual maps such as network and density visualization of institutions, journals, authors, and keywords (Van Eck and Waltman, 2010). CiteSpace, a scientific literature visualization software developed by Professor Chaomei Chen, generates a cluster view and timeline view to summarize the knowledge base and research frontiers of the relevant field (Chen, 2006). This can provide insight into potential research hotspots and trends. In this study, we utilized CiteSpace [version 6.1.R3 (64-bit)] as a supplement to VOSviewer. The parameters in CiteSpace were set as follows: Link Retaining Factor (LRF = 3), Look Back Years (LBY = 5), e for Top N (e = 1), Time Span (1988–2022), Years Per Slice (Starzl et al., 1964), Selection Criteria (g-index: k = 25), and Minimum Duration (MD = 1). The integration of these bibliometric software tools can provide a comprehensive analysis and display of literature data, unveiling various characteristics and trends in the studied field.

From 1 January 1988, to 31 December 2022, a total of 2,398 publications related to AR after liver transplantation were identified in the WoSCC database. As shown in Figure 2, there were relatively fewer articles on AR after liver transplantation before the 1990s. However, since the 1990s, publications have increased steadily. It reached its peak in 2005 (n = 126) and then experienced a noticeable decline in 2007. However, in the following 5 years, the number of publications steadily increased. From 2011 to the present, there has been a fluctuating downwards trend in the number of publications, but the annual publication count has remained above 60.

These 2,398 articles were published by 1,965 institutions from 55 countries/regions. As shown in Table 1, the United States (n = 609), China (n = 363), and Germany (n = 236) are the three countries with the highest cumulative publication volumes. Figure 3A displays the annual publication trends of the top 10 countries in terms of total publication count. Notably, although the United States has long dominated the research on AR after liver transplantation, China (n = 19) surpassed the United States (n = 13) in terms of annual publications for the first time in 2013 and has consistently remained ahead in recent years. Figure 3B illustrates the collaboration between different countries. Publications from the United States and European countries have relatively earlier publication dates, whereas articles from Asian countries, including China, South Korea, and India, have predominantly been published in the last decade (Figure 3C). Figure 3D provides a geographical visualization of the countries involved in research related to AR after liver transplantation.

For the institutions, the University of Pittsburgh (n = 66) is the most productive institution, followed by Zhejiang University (n = 54) and the University of California, San Francisco (n = 45) (Table 1). The University of California, San Francisco is the institution with the highest average citations per article among the top ten institutions. Among the top ten institutions, five are from the United States, while three are from China. Figure 4 shows the cooperative relationship between institutions. In contrast to collaboration between countries, there is closer collaboration among domestic institutions.

A total of 456 journals published literature on AR after liver transplantation and cited references from 4,796 journals. Table 2 displays the top 10 journals in terms of publication count and co-cited journals. Transplantation Proceedings ranked highest with 334 articles published. Among the co-cited journals, Transplantation ranked first by a significant margin and was the only journal with over 10,000 citations. Among all the co-cited journals, a density map was generated for the top 1,000 journals with the highest total link strength, providing a clear visualization of highly cited journals in Figure 5.

The dual map overlay feature of CiteSpace was used to display the distribution of journal topics at the disciplinary level, revealing the overall scientific contribution (Chen, 2016). As shown in Figure 6, there are three distinct citation pathways. The two green citation pathways indicate that literature published in Medicine/Medical/Clinical journals primarily cites literature from Molecular/Biology/Genetics and Health/Nursing/Medicine journals. The orange pathway indicates that literature published in Molecular/Biology/Immunology journals primarily cites literature from Molecular/Biology/Genetics journals.

The bibliometric analysis results showed that 12,568 authors participated in research related to liver transplant rejection, citing a total of 29,629 authors’ articles. As shown in Table 3, Neuhaus P (n = 38) ranked first in terms of publication count, followed by Muro M (n = 37), Zheng SS (n = 37), Metselaar HJ (n = 35), and Nashan B (n = 33). In terms of co-cited authors, the top 10 authors were cited more than one hundred times, with Demetris AJ (n = 670) being the most cited author, followed by Starzl TE (n = 530), Wiesner RH (n = 308), Berenguer M (n = 274), and Neuhaus P (n = 219). Additionally, we used VOSviewer to draw a network map based on the collaboration between authors (Figure 7A). Different colors represent different clusters, there is a closer collaboration between authors within the same cluster. Neuhaus P, Samuel D, and Metselaar HJ from different clusters also have good collaborative relationships. Furthermore, there were 1,366 authors with co-cited exceeding 10, a density map was created for the top 1,000 authors with the highest total link strength (Figure 7B), where the levels of yellow and font size clearly indicate highly co-cited authors. It is evident that Demetris AJ is the most frequently cited author in this field.

A total of 5,779 keywords were extracted by using VOSviewer, and we set a threshold of co-occurrence frequency greater than 5 to generate the keyword co-occurrence network after excluding keywords such as “liver transplantation” and “acute rejection”. Table 4 presents the top 20 high-frequency keywords. As shown in Figure 8A, the keywords can be roughly divided into three clusters: Cluster 1 (32 items, red), Cluster 2 (28 items, green), and Cluster 3 (27 items, blue). In CiteSpace, burst detection reveals keywords that have experienced sudden increases in frequency over time, indicating their significance as active research topics (Chen, 2016). We extracted the top 25 keywords with the strongest citation bursts. As exhibited in Figure 8B, keywords such as “antigen,” “monoclonal antibody,” “biopsy,” and “cyclosporine” emerged as bursts in the early stage of research, while the current research bursts are mainly focused on keywords such as “regulatory T cell,” “hepatocellular carcinoma,” “renal function,” “patients receiving everolimus,” and “outcomes."

Co-cited reference analysis is a method used to analyze the shared citation relationships among publications, revealing core literature, knowledge structure, and development directions in a research field. The top ten reference articles, ranked by citation frequency, are presented in Table 5. The article by an international panel in 1997 (Banff schema for grading liver, 1997), titled “Banff schema for grading liver allograft rejection: An international consensus document,” has the highest citation count.

Analysis of the references within the 5 years prior to the publication of the 2,398 articles was conducted to generate clusters that represent research frontiers in different periods. Figure 9A displays a co-cited timeline view clustered using the log-likelihood ratio algorithm. Each node represents a co-cited reference, and the links between nodes indicate that the corresponding references are co-cited within the retrieved set of 2,398 articles. A total of 19 clusters were generated, with the numerical values of the cluster labels negatively correlated with the number of co-cited references in each cluster.

Like keywords, co-cited references can also be analyzed for citation bursts. In this bibliometric analysis, 210 references were found to have citation bursts, and Figure 9B shows the top 25 burst references. It is evident that citation bursts typically occur within 2–3 years after the publication of the referenced papers. From 1995 to 2005, there were multiple papers that experienced citation bursts, and as of 2022, three articles are still in a state of citation bursts.

Using the authoritative literature database, WoSCC, we ultimately extracted 2,398 English papers published in the past 35 years (1988–2022). These papers were authored by 12,568 researchers from 1,965 institutions in 55 countries/regions, published in 456 journals, and cited 48,143 articles published on 4,796 journals by 29,629 authors.

Although the first human liver transplantation was performed as early as 1963, due to the lack of effective immunosuppressive drugs to control AR after surgery, liver transplantation has been controversial (Geissler and Schlitt, 2009). It was not until 1979 that the British scholar Calne RY first applied the immunosuppressive drug cyclosporine to liver transplantation (Williams et al., 1985), that scholars gradually recognized the effectiveness of liver transplantation and promoted the research on AR after liver transplantation. Therefore, as shown in Figure 1, the 1980s was the starting stage of research on AR after liver transplantation. However, with the gradual clinical application of a new type of immunosuppressive drug (such as FK506 and OKT3) in the late 1980s (Millis et al., 1989; Fung et al., 1990), the incidence of postoperative AR greatly reduced, and postoperative survival rate and survival time significantly increased. From the 1990s onwards, research on AR after liver transplantation entered a stage of vigorous development and reached its peak in 2005. However, in the following 2 years, the number of papers published showed a significant decrease, which may be related to new policies for organ transplantation formulated by various countries during this period (Roscam, 2002; Huang, 2007). Since 2011, the number of papers related to AR after liver transplantation has shown a fluctuating downwards trend, but has remained above 60 papers per year, indicating that this field has reached a mature stage.

Both at the national and institutional levels, the United States and its affiliated institutions are the most productive in the field of AR after liver transplantation, and their high average citation count demonstrates their absolute authority in the field (Table 1). The progress made by Asian countries in this field is praiseworthy. However, taking China and its affiliated institutions as an example, although the annual publication volume has increased significantly, the average citation count of articles is relatively low. Although this can be partially explained by the relatively recent publication date of the articles, it is more likely due to concerns about the quality of the papers. This phenomenon is not only limited to this field but is also quite common in other fields. Therefore, for Asian countries such as China to enhance their influence in this field, it is necessary to align with international standards, strengthen cooperation between countries and institutions, and publish more high-quality papers in high-impact journals.

Through subject classification searches in WoS, we found that the articles published in the top ten prolific journals primarily focus on the fields of transplantation and immunology. Analyzing prolific journals allows us to understand the core journals in this field and provides suitable journal choices for researchers to publish their papers. Among the top ten highly cited journals, seven belong to the Q1 zone (Table 2), indicating that high-quality articles published in these journals have significantly contributed to the advancement of the field.

Of the top ten productive authors, nine are from Europe. This finding suggests that European researchers play an important role in the study of AR after liver transplantation. Neuhaus P, as the author with the highest publication volume, mainly conducts clinical research on post-transplant immunosuppressive drugs, particularly calcineurin inhibitors (CNIs), mycophenolate mofetil (MMF), and monoclonal antibodies (Neuhaus et al., 1995; Klupp et al., 1997; Neuhaus et al., 2002). Zheng SS has led multiple studies mainly targeting the prediction of AR after liver transplantation and its influence on prognosis (Wu et al., 2011; Ren et al., 2014; Wei et al., 2018). Muro M’s research mainly focuses on the pathogenesis and risk factors for AR after liver transplantation (Garcia-Alonso et al., 1997; Ontanon et al., 1998; Minguela et al., 2000). Considering co-cited authors, Starzl TE has promoted the clinical application of liver transplantation (Starzl et al., 1964; Starzl et al., 1968). Demetris AJ, Wiesner RH et al. jointly developed histological diagnostic criteria for AR after liver transplantation (Banff schema for grading liver, 1997). The research achievements of these scholars have laid a foundation for the development of AR-related studies after liver transplantation and made significant contributions to the field.

Through clustering analysis and burst detection of keywords and references, we can quickly grasp the hotspots and evolutionary paths in the field of AR after liver transplantation over the past 35 years and explore emerging research directions. The research focus on AR after liver transplantation has shifted from early understanding of its pathogenesis to the development and application of immunosuppressive agents. Currently, the mainly focus is on the diversity of individual immune conditions, the development of novel immunosuppressive agents, and the regulation of immune tolerance. In addition, developing personalized immunotherapy plans to reduce complications caused by immunosuppression and improve long-term outcomes for patients may be one of the important directions for future research in the field of organ transplantation.