BIBLIOMETRIC ANALYSIS OF PUBLICATIONS ON HEPATITIS D VIRUS PUBLISHED IN 1984–2022

Background: Hepatitis D virus research has advanced in recent decades. In this study, we aim to quantitatively analyze the scientific data in the field of "hepatitis D virus" by using bibliometric analysis. Methods: Research documents published in the Web of Science database between 1984 and 2022 were included in the study. The search keywords were "hepatitis D" or "hepatitis-D" or "HDV" or "hepatitis virus D." The full record and cited references of documents extracted were converted to a " bibtex " file as well. The R-Studio software's Bibliometrix package and Biblioshinny application are used to perform the bibliometric analysis. Results: A total of 1530 publications written by 6042 authors were identified. Most of the publications were articles (62.81%). The number of published articles increased gradually, especially after 2008. The articles of the authors were mostly published in the United States, Germany, and China. The affiliation where the most studies were conducted was Hannover Medical School (8.82%). Also, the United States and Germany were found to be the main countries in the collaboration network. Mario Rizzetto was the author of the most published articles on HDV. The most frequently used words in the articles were "infection," "prevalence," and "b-virus." Conclusion: Clinical and epidemiological studies on HDV were given more focus, while studies on treatment were less numerous. It can also be predicted that potent treatment options will increase more in the coming years, and the frequency of studies on this will increase.


INTRODUCTION
Hepatitis, defined as inflammation of the liver tissue, can lead to chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Inflammation of the liver can be caused by several different factors: autoimmune disease, fatty liver disease, certain drugs, alcohol consumption, and viral infection [1]. The etiologic agents of viral hepatitis have only been identified in the last few decades. Almost all viral hepatitis is caused by five main viruses. These are the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Viral hepatitis infects millions of people each year; some of them could lead to HCC, liver cirrhosis, and death over many years [2][3][4]. The most common causes of liver cirrhosis, liver cancer, and death-related viral hepatitis are HBV and HCV. It is estimated that approximately 354 million people worldwide are infected with HBV or HCV [2].
The HDV was discovered after the discovery of a new nuclear antigen in patients with a severe form of chronic hepatitis B in the mid-1970s. In the report first published in 1977, this antigen, called the "delta antigen," was believed to be the hepatitis B antigen [5,6]. Three years later, experiments in chimpanzees demonstrated that hepatitis delta antigen (HDAg) is a structural component of an infectious pathogen that requires HBV for its life cycle [7]. HDV is recognized as a defective human ribonucleic acid (RNA) virus that requires the presence of hepatitis B surface antigen (HBsAg) for persistence and transmission [8,9]. Acute HDV infection occurs after the simultaneous ingestion of HDV and HBV (coinfection) or when carriers of HBsAg are superposed (superinfection) with HDV [8][9][10]. HDV is highly pathogenic. While only 2% of coinfection cases become chronic, it results in chronicity in more than 90% of superinfection cases. Particularly in HDV superinfection, pre-existing liver damage is exacerbated, leading to faster progression to cirrhosis in 70% to 80% of cases [11]. The number of HDV infections seems to have decreased since the 1980s, due to the successful worldwide HBV vaccination program [12].
Bibliometric analysis plays an active role in identifying articles and authors who have contributed to many scientific and medical fields [13]. Research on viral hepatitis has increased over the years. Bibliometric analysis can be used as a tool to analyze trends in these studies and help us identify gaps that can be addressed to prevent and control viral hepatitis. 14 In our literature review (Google Scholar, Pubmed), we did not find any bibliometric analysis on HDV. In this study, we aim to quantitatively analyze the scientific data in the field of HDV by using bibliometric analysis.

MATERIALS AND METHODS
In the first step, documents published on HDV were extracted from the Web of Science (WOS) database (Clarivate Analytics, Philadelphia, PA, USA) which is one of the most popular platforms used for searching the scientific literature. The second step was to conduct the bibliometric analysis using the Bibliometrix package and Biblioshiny application included in the R-Studio software. The Bibliometrix application contains the following sections: overview, sources, authors, documents, clustering, conceptual structure, and intellectual structure.
The following search strategy was used. Document types: All (Article, meeting abstract, review, letter, editorial material, proceeding papers, and other type publications). Timespan: 1984-2022. Indexes: The data used in this study were retrieved from the WOS Core Collection database (all indexes) on October 5, 2022. Editions: All Data source: The keywords '"hepatitis D" or "hepatitis-D" or "HDV" or "hepatitis virus D" were used in our search. On October 5, 2022, all electronic searches were completed. English was used for search. Data collection: The WOS database was used for evaluating the bibliographic records. Authors, publication years, published journals, institution, country, frequency of citation, words, and collaboration networks were all retrieved for each publication. These were used to investigate the worldwide knowledge domain HDV research development patterns. As a measure of publishing impact, the Hirsch (H) index was used.

Descriptive analysis
Summary statistics of the data retrieved from the WOS database are given in Table 1. A total of 1530 publications have been conducted by 6042 authors between 1984 and 2022. The number of documents with a single author was 120 (7.84%). The publications have been published in 453 different sources (journals, books, etc.). Moreover, the annual growth rate was found to be 12.03 percent.

Most influential sources
The top 10 relevant and locally cited sources were given in Table 2. The two most important journals in the field of HDV were determined to be the Journal of Hepatology    Figure 4 denotes the most frequent words by the number of occurrences and percentage. A total of 2070 of the most frequent words were found in the field of HDV. The most frequent word in the articles was found to be "infection," with 270 occurrences and a 3% frequency. This was respectively followed by the "prevalence" (186, 2.067%) and the "b-virus" (157, 1.744%). The occurrence of the "delta virus" was 146 (1.622%). Figure 5 shows the co-occurrence network of the words. According to Figure 5, articles are grouped into three clusters according to the co-occurrences of the words. Keywords with the same color belong to the same subject clusters in studies with hepatitis D. In Cluster 1; it was observed that the keywords related to epidemiological studies such as 'infection', 'prevalence', 'b-virus', and 'epidemiology' were mostly repeated. In Cluster 2; the keywords related to virology studies such as 'delta-virus', 'replication', 'antigen', 'liver', and 'RNA' were mostly repeated. In Cluster 3; the keywords related to hepatitis D treatment studies, such as 'therapy', 'chronic delta hepatitis', 'interferon', 'efficacy', and "lamivudine mostly occurred keywords. Figure 6 shows the connections between the authors and countries publishing the articles on the HDV.

DISCUSSION
The evaluation of research output has grown in importance for the scientific research community throughout time, and bibliometric analysis is now a widely utilized tool in the field of medicine. Despite not being designed for this purpose, bibliometric methods are routinely used to assess the work of specific researchers and to establish academic ranking, advancement, remuneration, and research funding. The data obtained as a result of bibliometric analyses can provide the following scientific outputs to the researchers. 'What are the most important keywords, on which topics have articles been published and not published, and which publications of which countries/institutions/authors have been mostly cited?
What are the most popular topics with the most citations? Which journals have published the most publications on this subject?, etc.' [15][16][17][18][19][20]. For this reasons, since our study is the first bibliometric analysis study published on HDV, it can give ideas to the relevant field researchers For quantitative scientometrics and bibliometrics research, one option is to utilize Bibliometrix, the comprehensive science mapping analysis tool. It offers a number of functions for importing bibliographic data from databases such as Scopus, Clarivate Analytics Web of Science, Digital Science Dimensions, Cochrane Library, Lens, and PubMed, performing bibliometric analysis, and creating networks for co-citation, coupling, scientific collaboration, and keyword analysis [21,22]. Despite the fact that many HDV studies have been conducted, we found no bibliometric analysis in our review of the literature. We aimed to conduct a bibliometric analysis that will contribute to the scientific world by creating a general perspective on HDV. In this study, published literature on HDV between 1984 and 2022 was extracted from the WOS database, and overviews, sources, authors, documents, clustering, conceptual structure, and intellectual structure were examined. In this period, a total of 1530 publications written by 6042 authors were identified. 120 of the studies (7.84%) had a single author. It was observed that the publications were published by 453 different sources. Most of the publications were articles (62.81%) and meeting abstracts (13.07%). It was determined that the majority of the publications were published in English (93.3%). The number of published articles increased gradually, especially after 2008, and almost 50% of the articles were published after 2013. HBV and HCV infections are getting more attention due to their high global prevalence and wider and more effective treatment modalities. Although HDV is seen less frequently than the other two viral hepatitis, studies have accelerated in recent years, and it is expected to increase more in the future due to the fact that the treatment is limited to interferon and the comorbidity and mortality associated with the disease are high. It can be foreseen that there will be more studies to be done, especially on the treatment of HDV, in the future.
Hepatitis D is a major health problem worldwide. Although the prevalence of HDV infection on a global scale is not fully known, recent meta-analyses show that approximately 15-60 million people worldwide are exposed to HDV, and its prevalence varies in different geographic regions [12,[23][24][25]. HDV epidemiology has changed continuously over the past decade after the advent of hepatitis B vaccination [26]. In Europe, HDV remains endemic in Moldova and Romania [26][27][28]. In the USA, HDV infection is not perceived as a major problem. In the NHANES study covering the years 1999-2012, only 0.02% had a positive anti-HD value [26,29]. HDV is declining in Saudi Arabia, Northern Africa, the Caucasus, and Israel. In Turkey and Iran, which have historically been endemic for HDV, the prevalence of the infection has decreased. In Asia, the rate of HDV is high in the central part of the continent, especially in Mongolia, Uzbekistan, Tajikistan, and Kyrgyzstan [26]. HDV appears to play a minor role in China, India, and Indonesia, although these countries bear a large part of the global HBV burden [26]. The authors' geographical locations can provide information about disease distribution [29]. According to our analysis, it was determined that the articles of the authors were mostly published in the USA, Germany, China, and Italy.  [30]. In a bibliometric analysis of HAV, the most attractive journals were Vaccine, Hepatology, and the Journal of Medical Virology [31]. Another bibliometric analysis associated with HEV conducted by T. Ahmad et al [32] reported that the Journal of General Virology, Emerging Infectious Diseases, and Journal of Clinical Microbiology were the leading journals.
The most frequently used words in the articles were "infection," "prevalence," and "b-virus." It shows that the studies are mostly carried out on clinical and epidemiological grounds related to HDV. The low frequency of keywords related to treatment is an important finding. Chronic hepatitis D is a difficult disease to treat. Long-term administration of standard interferon-a (IFNa) is the only approved treatment option in many countries [6]. Studies continue on new treatment options that can be used in the treatment of chronic HDV, such as nucleic acid polymers (REP 2139-Ca), farnesyltransferase inhibitors (Lonafarnib), and bulevertide (formerly Myrcludex B) [33]. It can be foreseen that more studies will be published in the near future, especially on treatment modalities.

CONCLUSION
In conclusion, this study takes a bibliometric perspective on scope, trends, publication styles, and the contributions of countries and authors' studies on hepatitis D since 1984. It is seen that there has been a significant increase in the number of published articles, especially since 2008. Especially considering the occurrence and percentage of keywords, it can be predicted that clinical and epidemiological studies on hepatitis D will receive more focus, and studies on treatment will receive less. Also, it can be said that the authors' articles are mostly published in the USA, Germany, China, and Italy, but since many studies are carried out in international cooperation, they may not give a clear idea about the distribution of the disease in that region. Considering the potential negative effects of HDV, it can be predicted that potent treatment options will increase more in the coming years, and the frequency of studies on this will increase.

LIMITATIONS and ADVANTAGES
The data extraction method has limitations on the scope of the current work. Due to the use of the terms bibliometrics, informetrics, and scientometrics, we specifically target publications where the authors acknowledge that their work is a component of bibliometric research. As a result, the development of our data collection technique was guided by our goal of capturing the academic landscape of the use of those keywords across all branches of research. We do not want to imply that the bibliometrics field is defined by these three words. It might be difficult to describe an academic field in a search query. These techniques depend on having a ground truth dataset to compare their results to and on choosing a precision/recall tradeoff. We used a single database by searching selected keywords and used only one scientometric technique, which can lead to bias.