Research status and hotspots in transjugular intrahepatic portosystemic shunts based on CiteSpace bibliometric analysis

Abstract

BACKGROUND

The transjugular intrahepatic portosystemic shunt (TIPS) is an important technique for treating complications related to portal hypertension in patients with cirrhosis, and the number of publications in the TIPS field continues to rise.

AIM

To facilitate an understanding of the research status and hotspots in the field of TIPS using CiteSpace bibliometric analysis.

METHODS

CiteSpace is a software that depicts the strength of relationships through graphics and connections with diverse functionalities and can be used to analyze the status and hotspots of areas of research. Articles on TIPS in the Web of Science Core Collection were retrieved, and CiteSpace software was used to visualize and analyze the number of publications, journals, countries, institutions, authors, keywords, and citations.

RESULTS

A total of 985 relevant documents were included in the analysis. From January 2013 to December 2022, the number of publications increased annually. The journal, institution, and author with the greatest number of publications in the field of TIPS are the Journal of Vascular and Interventional Radiology, the University of Bonn, and Jonel Trebicka, respectively. The main keywords used in this field are “transjugular intrahepatic portosystemic shunt”, “portal hypertension”, “cirrhosis”, “management”, “stent”, “hepatic encephalopathy”, “refractory ascite”, “survival”, “risk”, and “variceal bleeding”. The greatest obstacle to TIPS placement is currently the occurrence of hepatic encephalopathy. The research hotspots are the mechanism, risk factors, management, and control of hepatic encephalopathy.

CONCLUSION

This bibliometric analysis reported the research status and hotspots of TIPS. Research on postoperative hepatic encephalopathy is the research hotspot in this field.

Key Words: Liver cirrhosis; Transjugular intrahepatic portosystemic shunt; CiteSpace; Visualization; Hotspots

Core Tip: The number of publications in the transjugular intrahepatic portosystemic shunt (TIPS) field continues to rise. This study aims to facilitate an understanding of the research status and hotspots in the TIPS field. CiteSpace software was used to visualize and analyze the number of publications, journals, countries, institutions, authors, keywords, and citations. The greatest obstacle to TIPS placement is currently the occurrence of hepatic encephalopathy, and the research hotspots are the mechanism, risk factors, management, and control of hepatic encephalopathy.

INTRODUCTION

The transjugular intrahepatic portosystemic shunt (TIPS) is an important technique for treating complications related to portal hypertension in patients with cirrhosis, such as gastroesophageal variceal bleeding and refractory ascites, by significantly reducing portal vein pressure by establishing a shunt pathway within the hepatic parenchyma[1]. TIPS was first reported by Richter et al[2] at the University Hospital Freiburg in Germany in 1989, which also marked the international debut of TIPS in the field of portal hypertension treatment. Owing to shunt occlusion and a high incidence of hepatic encephalopathy after TIPS, the procedure has declined in the last few years. However, the widespread use of a new partially PTFE-covered stent has heralded a new era for TIPS since 2004 because of the significantly reduced shunt restenosis rate and the nonsignificant increase in post-TIPS hepatic encephalopathy incidence[3]. Recently, pre-TIPS or early TIPS, has been proven to be an effective and useful treatment for esophageal-gastric varices bleeding, gradually expanding the indications for TIPS. The number of publications in the TIPS field continues to rise, making it necessary to conduct a visualized bibliometric analysis of TIPS-related literature to facilitate an understanding of the research status and hotspots in the field.

Visualized bibliometric analysis is an efficient method for extracting information from a large amount of literature, quantitatively analyzing it, comprehending the main research topics and frontiers, and presenting them visually and intuitively, which cannot be achieved manually. Common visualization tools used in bibliometric analysis include HistCite, VOSviewer, and CiteSpace[4-7]. After evaluating the presentation effects of various software, we chose CiteSpace, a bibliometric analysis software developed by Professor Chen Chao-Mei from Drexel University, which can analyze big data on authors, keywords, research institutions, countries/regions, and cited references in a large number of documents and predict a discipline’s development trend. CiteSpace indicates the strength of relationships through graphics and connections, with diverse functionalities. Its clustering algorithm uses primarily noun phrases to detect research hotspots in various disciplines. This algorithm is adept at identifying pivotal terms in the literature, aiding users in predicting turning points, changes, and future trends in the field[8]. Our objective is to utilize this software to analyze the latest advancements and hotspots associated with TIPS.

MATERIALS AND METHODS

Data sources and search strategy

The Web of Science is an important database platform for accessing global academic information. It has a strict screening mechanism and follows Bradford’s law of bibliometrics. We searched for the subject headings of “portosystemic shunt, transjugular intrahepatic” for TIPS in the Medical Subject Headings. We then selected the Web of Science Core Collection database on the Web of Science platform and searched using the subject heading “TS = (portosystemic shunt, transjugular intrahepatic)” on March 7, 2023, with a 10-year time range from January 1, 2013, to December 31, 2022. We also selected “article” as the document type.

Data analysis

The literature metric analysis software CiteSpace 6.1 was used. The R6 (64-bit) basic version was used to deduplicate the original data[9]. Parameters were set to select all items, including title, abstract, author keywords (DE) and keywords plus (ID), with a selection time frame from January 2013 to December 2022 and a time slice of 1 year. The author, institute, country, keyword and reference nodes were selected for analysis. The g-index and a threshold scale Factor k = 25 were selected, while other values were left as defaults. A TIPS knowledge map was generated to display the research hotspots and trends over the past decade.

RESULTS

Retrieval results and preliminary analysis

A total of 985 relevant documents were retrieved. A simple analysis was conducted on these documents, including yearwise publication volume, author publication volume, institutional publication volume, and journal publication volume. The results revealed that the publication volume related to TIPS increased annually, reaching its peak in 2021 and slightly decreasing in 2022 (Figure 1). The top three authors who published the most on this topic were Professor Jonel Trebicka from Germany, Professor Han Guo-Hong from China, and Professor Carsten Meyer from Germany (Table 1). The top three institutions with the most publications were the University of Bonn, the PLA Air Force Military Medical University, and the University of Barcelona (Table 2). The top three journals that published the most articles were the Journal of Vascular and Interventional Radiology, Cardiovascular and Interventional Radiology, and the European Journal of Gastroenterology Hepatology (Table 3).

Figure 1  Trends of related annual publications.

Table 1 Top 10 authors.

Rank	Author	Quantity	Country
1	Trebicka Jonel	46	Germany
2	Han Guo-Hong	34	China
3	Meyer Carsten	32	Germany
4	Jansen Christian	30	Austria
5	Praktiknjo Michael	29	Germany
6	Gaba Ron C	27	Italy
7	Li Xiao	27	China
8	Liu Fu-Quan	27	China
9	Wang Lei	27	China
10	Fan Dai-Ming	26	China

Table 2 Top 10 productive institutions.

Rank	Institution	Quantity	Country
1	University of Bonn	49	Germany
2	Air Force Military Medical University	40	China
3	University of Barcelona	40	Spain
4	Sichuan University	36	China
5	UDICE French Research Universities	35	France
6	CIBER Centro de Investigacion Biomedica en Red	34	Spain
7	Capital Medical University	31	China
8	Assistance Publique Hopitaux Paris	29	France
9	Goethe University Frankfurt	29	Germany
10	Hospital Clinic de Barcelona	29	Spain

Table 3 Top 10 journals.

Rank	Journal	Quantity	IF (2022)	Publisher
1	Journal of Vascular and Interventional Radiology	64	2.9	Elsevier Science Inc
2	Cardiovascular and Interventional Radiology	57	2.9	Springer
3	European Journal of Gastroenterology Hepatology	51	2.1	Lippincott Williams & Wilkins
4	World Journal of Gastroenterology	33	4.3	Baishideng Publishing Group Inc
5	Digestive Diseases and Sciences	20	3.1	Springer
6	Medicine	20	1.6	Lippincott Williams & Wilkins
7	Liver International	19	6.7	Wiley
8	European Radiology	17	5.9	Springer
9	Scientific Reports	17	4.6	Nature Portfolio
10	Interventional Radiology	17	1.4	Thieme Medical Publ Inc

IF: Impact factor.

Analysis of the country cooperation network

The national collaborative network diagram is drawn on the basis of the cooperation between nations in the published literature. Two authors from different countries appearing in the same article is considered a collaboration. By analyzing the national cooperation network, we can identify the key countries with high numbers of published papers and strong influence in the TIPS field. The top ten countries in terms of the number of published papers on TIPS are the United States, China, Germany, Spain, Italy, France, England, Switzerland, Denmark, and Belgium (Figure 2). Germany ranks third in terms of published papers, with a significant gap with the first-ranked United States and second-ranked China, but publication numbers alone do not truly reflect a country’s influence in this field. Therefore, we focused on extracting information from the national cooperation network map. As shown in Figure 3A, each node represents a country. The size of the node is proportional to the total number of publications. Some nodes have a purple outer circle, indicating higher betweenness centrality (> 0.1); the higher the betweenness centrality, the more important the node is in the network. The lines between countries represent cooperative relationships, and the color of the line represents the first instance of cooperation. The thicker the line is, the closer the cooperation. The United States not only has the most cooperation and published papers but also has the highest betweenness centrality, indicating a strong influence in the TIPS field. Although the number of published papers from Germany, Spain, Italy, and England is not large, they all have relatively high betweenness centrality. The countries ranking from 3^rd to 10^th are all European, with many red lines indicating active cooperation in the TIPS field in 2022 and a high level of influence, which is consistent with the current situation.

Figure 2  Top 10 countries in international cooperation.

Figure 3 Network map. A: Network map of national cooperation. Each node represents a country. The purple outer circle of a node indicates a high degree of betweenness centrality. The color and thickness of the inner circle of a node represent the number of publications in different years. The size of the node is proportional to the total number of publications. The lines between countries represent cooperative relationships, and the color of the line represents the first instance of cooperation. The thicker the line is, the closer the cooperation; B: Network map of institutional cooperation. Each node represents an institution. The purple outer circle of a node indicates a high degree of betweenness centrality. The color and thickness of the inner circle of a node represent the number of publications in different years. The size of the node is proportional to the total number of publications. The lines between institutions represent cooperative relationships, and the color of the line represents the first instance of cooperation. The thicker the line is, the closer the cooperation; C: Network map of authors’ cooperation. Each node represents an author. The purple outer circle of a node indicates a high degree of betweenness centrality. The color and thickness of the inner circle of a node represent the number of publications in different years. The size of the node is proportional to the total number of publications. The lines between authors represent cooperative relationships, and the color of the line represents the first instance of cooperation. The thicker the line is, the closer the cooperation.

Analysis of the institutional cooperation network

The statistics of the number of papers published through institutional cooperation indicate that the top three institutions in terms of publication volume are the Fourth Military Medical University and Sichuan University from China and the University of Bonn from Germany. Among the top ten institutions, five are from China, three are from the United States, and the remaining two are from Germany and Spain (Table 4). According to the institutional cooperation network, the Fourth Military Medical University from China and Northwestern University from the United States have the highest intermediation centrality, and both institutions have a high level of impact on collaborative research in this field (Figure 3B).

Table 4 Top 10 institutions for institutional cooperation.

Rank	Institution	Quantity	Country
1	Fourth Military Medical University	37	China
2	Sichuan University	33	China
3	University of Bonn	31	Germany
4	Capital Medical University	29	China
5	Nanjing University	22	China
6	Univ Illinois Hosp & Hlth Sci Syst	20	United States
7	University of Barcelona	19	Spain
8	Huazhong Univ Sci & Technol	18	China
9	Northwestern University	17	United States
10	Cleveland Clinic	17	United States

Analysis of the author collaboration network

Analyzing the author collaboration network (Figure 3C), we found many teams researching TIPS in various countries, with particularly dense clusters of researchers in Germany, China, and Italy. The four professors in the upper-right corner of the network are all from Germany, including Trebicka Jonel, Meyer Carsten, Praktiknjo Michael, and Jansen Christian. They work closely with other teams. The upper-left corner of the network is dominated by a research team centered on the Chinese academician Fan Dai-Ming and Professor Han Guo-Hong, who have published many important articles in the field of TIPS that have guided clinical work. Notably, a team from Italy led by Professor Gaba Ron C has also performed impressively in the TIPS field. Finally, Professor Xiong Bin’s team from China published many TIPS-related articles in 2022.

Analysis of popular topics and frontiers

The keywords of an article provide a highly summarized representation of its content. By analyzing a large number of articles in the TIPS field via CiteSpace software, we extracted the top ten keywords in articles published between 2013 and 2022, which were “transjugular intrahepatic portosystemic shunt, portal hypertension, cirrhosis, management, stent, hepatic encephalopathy, refractory ascite, survival, risk, and variceal bleeding” (Table 5).

Table 5 Top 10 keywords.

Rank	Keywords	Count
1	Transjugular intrahepatic portosystemic shunt	683
2	Portal hypertension	432
3	Cirrhosis	395
4	Management	328
5	Stent	215
6	Hepatic encephalopathy	140
7	Refractory ascites	136
8	Survival	133
9	Risk	121
10	Variceal bleeding	121

We conducted a burst analysis on keywords, extracted the top 25 keywords with the strongest citation bursts, and sorted them chronologically. Through burst terms, we can understand the frontiers of research, shifts in research focus, and the latest research hotspots, as well as help predict subsequent trends in this field. For example, “sarcopenia” first emerged in 2019 and became a research hotspot from 2019 to 2022 (Figure 4).

Figure 4 Top 25 keywords with the strongest citation bursts. The year indicates the first time the keyword appears. The red bars show when citation bursts start and end and how long they last.

To summarize and categorize the large quantity of keywords, we utilized CiteSpace software to generate a keyword clustering map, which visually presents the categorized keywords (Figure 5). The quality of the map is assessed by two parameters: Modularity (Q value) and silhouette (S value). Typically, Q > 0.3 indicates a significant clustering structure, S > 0.5 indicates reasonable clustering, and S > 0.7 suggests convincing clustering. Our keyword clustering map has a Q value of 0.4078 and an S value of 0.736, indicating good quality. A total of 9 clusters, labeled #0 to #8, were identified, including sarcopenia (#0), portal hypertension (#1), hepatic encephalopathy (#2), budd-chiari syndrome (#3), portal vein puncture (#4), hepatocellular carcinoma (#5), hepatorenal syndrome (#6), accuracy (#7), and mortality in TIPS (#8). Each cluster is represented by a different color block based on publication year, reflecting the research focus for that particular year. For example, in 2013, the keyword cluster was mortality in TIPS, indicating this was a hot research topic that year. Research topics are constantly evolving. In 2019, sarcopenia was first proposed, and after three years, became a prominent representative in related research by 2022. Many researchers have studied the associations between nutritional status and post-TIPS hepatic encephalopathy, with sarcopenia being one of the nutritional indicators[10-13].

Figure 5 Co-occurrence clustering keyword network. Each node represents a keyword, and the connection between keywords represents the co-occurrence relationship. The nodes with different colors in the clustering style represent different clusters. To clearly indicate the scope of a cluster, CiteSpace uses polygons to add shading to the clusters, which shows the boundaries of the clusters.

Analysis of highly cited reference and high betweenness centrality references

The cited reference is an important component of a literature, and when many studies cite the same reference, it indicates that the reference is widely recognized by researchers. Using CiteSpace software, we generated a visualization diagram (Figure 6) of the shared citations of references. The top ten cited publications are distributed from the bottom left to the upper right of the diagram, including five clinical guidelines, four randomized controlled trials, and one review (Table 6).

Figure 6 Co-cited reference network. Each node represents a co-cited reference, and the purple outer circle of the node indicates a high betweenness centrality. The size of the node is proportional to the number of co-citations. The connection between nodes represents the co-citation relationship, and the color of the connection represents the time of the first co-citation. The thicker the connection is, the stronger the link between co-citations.

Table 6 Top 10 cited references.

Rank	Article type	Title	Journal	Author	Citation
1	CPG	Expanding consensus in portal hypertension: Report of the Baveno VI consensus workshop: Stratifying risk and individualizing care for portal hypertension	Journal of Hepatology	deFranchis R	86
2	RCT	Transjugular intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites	Gastroenterology	Bureau C	86
3	CPG	Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases	Hepatology	Garcia-Tsao G	73
4	CPG	EASL clinical practice guidelines for the management of patients with decompensated cirrhosis	Journal of Hepatology	European Assoc Study Liver	62
5	RCT	Early use of TIPS in patients with cirrhosis and variceal bleeding	New England Journal of Medicine	Garcia-Pagan JC	57
6	Review	TIPS: 25 years later	Journal of Hepatology	Rossle M	56
7	CPG	Quality improvement guidelines for transjugular intrahepatic portosystemic shunts	J Vasc Interv Radiol	Dariushnia SR	46
8	RCT	Covered transjugular intrahepatic portosystemic shunt versus endoscopic therapy + β-blocker for prevention of variceal rebleeding	Hepatology	Holster IL	45
9	CPG	The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: Update 2009	Hepatology	Boyer TD	40
10	RCT	Eight millimetre covered TIPS does not compromise shunt function but reduces hepatic encephalopathy in preventing variceal rebleeding	Journal of Hepatology	Wang QH	40

CPG: Clinical practice guideline; RCT: Randomized controlled study; TIPS: Transjugular intrahepatic portosystemic shunt.

Betweenness centrality is an index that measures the importance of a node in a network, and the higher the betweenness centrality is, the greater the node’s importance. CiteSpace uses this index to discover and measure the importance of literature and highlights it with a purple circle. Literature with high betweenness centrality is usually a key turning point connecting two different parts. As shown in Figure 6, we found four nodes with high betweenness centrality in the citation map, representing four articles that have strong influence in the entire network.

DISCUSSION

General information

TIPS placement has developed over the past thirty years, undergoing periods of rapid growth, stagnation, and then growth again[14]. Owing to the widespread use of covered stents, the rate of postoperative stent dysfunction has been reduced to a low level, making TIPS placement once again widely accepted by doctors and patients alike. Through visual analysis via CiteSpace, we found that researchers in this field can be classified into four main groups: Members of the American Association for the Study of Liver Diseases, members of the European Association for the Study of the Liver, Chinese scholars, and researchers from other countries. American scholars publish primarily articles in Hepatology, whereas European scholars prefer to publish in the Journal of Hepatology. Both of these journals are currently reputable in the field of liver disease.

Chinese scholars are highly ranked in terms of publication output, indicating their high activity level in the field. This is related to significant improvements in clinical accumulation and academic awareness among Chinese researchers in recent years. However, research collaboration among Chinese scholars mainly occurs within teams, with less collaboration across different teams. In contrast, Western researchers frequently collaborate across teams.

Through the betweenness centrality index, we have found four articles with strong influence in the field. The first article is “Efficacy of transjugular intrahepatic portosystemic shunts to prevent total portal vein thrombosis in cirrhotic patients waiting for liver transplantation” published by D'Avola et al[15] in 2012, which suggests that TIPS placement can prevent patients with partial portal vein thrombosis from progressing to complete portal vein occlusion and that TIPS does not increase the mortality rate after liver transplantation. This study expanded the indications for TIPS placement and confirmed the clinical benefits of TIPS for patients with portal vein thrombosis. The second article is “Transjugular intrahepatic portosystemic shunt in combination with or without variceal embolization for the prevention of variceal rebleeding: A meta-analysis” published by Qi et al[16] (a member of the team led by Academician Fan Dai-Ming and Professor Han Guo-Hong) in 2014. In the hierarchy of clinical evidence, meta-analysis is at the top of the pyramid of evidence levels. Compared with that in the TIPS-only group, the incidence of variceal rebleeding was significantly lower in the group of TIPS combined with variceal embolization; however, the incidence rates of shunt dysfunction, hepatic encephalopathy, and mortality were similar. It is recommended that combining TIPS with variceal embolization may help decrease the variceal rebleeding rate. The third article is “Covered vs uncovered stents for transjugular intrahepatic portosystemic shunt: A randomized controlled trial” published by Perarnau et al[17] in 2014. This study compared the primary patency of TIPS via covered stents with that of bare stents. The results revealed a 39% reduction in stent dysfunction in covered stents compared with bare stents, without significant differences in hepatic encephalopathy or mortality. This provides strong evidence for the clinical selection of covered stents. The last article is “Emergency TIPS in a Child-Pugh B patient: When does the window of opportunity open and close” published by Trebicka[18] in 2017, which showed that early TIPS may improve patient survival by preventing bacterial translocation and an inflammation response. Moreover, for patients with refractory ascites, it is crucial to perform TIPS placement as early as possible to prevent the progression of acute kidney injury and hepatorenal syndrome caused by complications of portal hypertension. This article discusses the clinical benefits of early TIPS for patients with different indications, providing a reference for clinical practice. These studies promote the application and progression of TIPS for portal hypertension.

Popular topics and frontiers

Analyzing keywords can provide a preliminary understanding of what an article may contain. In clinical publications, articles often cover several keywords, and the co-occurrence of two keywords within an article suggests a certain degree of correlation between them, with the frequency and closeness of their appearance in the article being directly proportional. The top three keywords were the complete expression of TIPS and the most common reason for performing TIPS placement, which is portal hypertension caused by cirrhosis. The remaining keywords include bleeding from varicose veins and refractory ascites in TIPS indications, stents used for channel establishment, hepatic encephalopathy after TIPS, and the risks and management of the entire TIPS placement process.

Through keyword co-occurrence network and clustering diagrams, we found that there is currently a greater emphasis on managing the entire process of TIPS placement, including appropriate patient selection, preoperative evaluation, intraoperative precautions, and postoperative follow-up and the management of related complications. We know that with covered stents, previous comorbid stent dysfunction has been controlled to an extremely low incidence rate. The greatest obstacle to TIPS placement is currently the occurrence of hepatic encephalopathy. Therefore, the research hotspots are the mechanism, risk factors, and management and control of hepatic encephalopathy. With respect to the pathogenesis of hepatic encephalopathy, some studies have shown that the liver must detoxify the nitrogenous compounds from the intestine. However, in patients undergoing TIPS placement, nitrogenous compounds bypass hepatic vessels and enter the systemic circulation through the shunt, eventually entering the central nervous system and interfering with neurotransmission, leading to changes in consciousness and behavior[19]. Moreover, skeletal muscle plays a compensatory role in ammonia metabolism and transport[20], and malnourished patients with sarcopenia are more prone to developing hepatic encephalopathy.

Through the relentless efforts of researchers, various randomized controlled studies with different research objectives or clinical guidelines from liver disease associations have been released, and the etiological classification of portal hypertension patients has become increasingly detailed, with stratification becoming increasingly precise and efficiently managed. The indications for TIPS placement are constantly expanding and include salvage TIPS, pre-TIPS, the prevention of rebleeding, the treatment of refractory ascites, portal vein thrombosis, extrahepatic portal vein obstruction, portal cavernous transformation, and hepatic veno-occlusive disease. As a result, clinical patients have gained more opportunities for treatment. This also explains why current post-TIPS hepatic encephalopathy-related research is on popular topics and frontiers.

Limitations

Although we strictly followed bibliometric research methods, our study has several limitations. First, to ensure the quality of the research, we only obtained data from the Web of Science Core Collection database and selected “articles” for subsequent analysis, which may have led to insufficient retrieval of articles. Second, the number of citations of an article is related not only to its quality but also to when it was published, which introduces inevitable time constraints to this study.

CONCLUSION

This is the first study to conduct a quantitative bibliometric analysis of TIPS and a detailed study of authors, institutions, countries, keywords, and cited literature. It also clarifies the hotpots of future research, including the mechanisms, risk factors, management, and control of hepatic encephalopathy. We believe that with the dedicated research and joint efforts of researchers from various countries, the incidence rate of postoperative hepatic encephalopathy will eventually be reduced to a minimum, and an all-encompassing management process accepted by scholars worldwide will be formed, leading to more people accepting TIPS placement and more benefits for clinical patients.

ACKNOWLEDGEMENTS

We sincerely thank our colleagues who have helped us throughout the research process.