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Table of Contents
Year : 2019  |  Volume : 2  |  Issue : 1  |  Page : 41-47

The top 100 articles on hepatitis C

1 Department of Medicine, King Saud University Medical City, Riyadh, Kingdom of Saudi Arabia
2 Department of Medicine, Prince Noura University, Riyadh, Kingdom of Saudi Arabia
3 Department of Medicine, Division of Gastroenterology, University of Rochester, Rochester, NY, USA

Date of Web Publication7-Jan-2019

Correspondence Address:
Othman Tawfiq Almutairi
College of Medicine, King Saud University, Al-Waha, Riyadh
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JNSM.JNSM_27_18

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Background: Hepatitis C infection is considered one of the most common hepatological infections. Many papers have been published, but none have listed the most influential work in the field of hepatitis C. Objectives: The aim of this study is to produce a bibliometric historical review on hepatitis C and its management. Methods: We underwent a title-specific search using Scopus database in 2017; using hepatitis C as our search term. The top 100 most cited articles were obtained and analyzed. Results: The top 100 articles received an average of 1273 citation per paper. The most productive years of publication ranged between 1999 and 2003 which accounted for 33 articles in our list. The top two journals in our list were New England Journal and Hepatology Journal with a contribution to 21 and 20 articles in our list, respectively. Research study category was accounted as the most common study category (60%). The top two specialties of contribution were Medicine (26 articles) and Hepatology (25 articles). Albrecht, J and Mchutchison have produced 9 and 8 articles, respectively, from our 160 authors list. The majority of the papers were created in the United States of America (62%). Conclusions: The identification and clustering of the top 100 most impactful work in hepatitis C serve as an excellent overview of the current trends of publication in the field of hepatitis C to identify areas of research inadequacy and to serves as an efficient guide to achieving evidence-based clinical practice.

Keywords: Bibliometric, citation analysis, hepatitis C virus

How to cite this article:
Aleid M, Almutairi OT, Alfahad L, Jameel M, Almutairi N, Al-Judiabi B. The top 100 articles on hepatitis C. J Nat Sci Med 2019;2:41-7

How to cite this URL:
Aleid M, Almutairi OT, Alfahad L, Jameel M, Almutairi N, Al-Judiabi B. The top 100 articles on hepatitis C. J Nat Sci Med [serial online] 2019 [cited 2023 Mar 23];2:41-7. Available from: https://www.jnsmonline.org/text.asp?2019/2/1/41/242160

  Introduction Top

Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma and liver transplantation worldwide.[1] It is estimated that the prevalence of HCV is 2%–3%, representing 130–180 million infected individuals.[2] HCV patients are at risk of serious complication such as the liver cirrhosis and liver failure.[3]

Several therapies were proposed after the discovery of HCV, including corticosteroids and acyclovir, which proved to be ineffective.[4] Interferon-alpha (IFN-α), which was used as treatment for HBV, had made a tremendous impact in the treatment of HCV at the time and had led to normalization of liver enzymes but on the expense of serious side effects. In the following years, particularly in the 90s, ribavirin was introduced as another effective drug in the treatment of HCV infection. In recent years, however, direct-acting antivirals (DAAs) were introduced to the market which offers much less side effects; and have dramatically developed in few years leading to eventual use of IFN-free regimens.[5]

In 2017, two evolutionary agents in the treatment of hepatitis C were approved by the Food and Drug Administration, which marks the beginning of a new era of non-IFN management of HCV; Vosevi (sofosbuvir/velpatasvir/voxilaprevir by Gilead) and Mavyret (glecaprevir/pibrentasvir by AbbVie). In POLARIS-4 Trial, a 12-week regimen with Vosevi showed a 98% sustained virologic response (SVR) in all 6 HCV genotypes in patients who failed to respond to DAA.[6] AbbVie pharmaceutical company has conducted nine clinical trials in which they have enrolled 2300 HCV-infected patients to receive Mavyret; in 2018, the ENDURANCE-4 trails have shown that the SVR reached at least 93% in noncirrhotic HCV positive patients.[7]

Regarding prevention, HCV vaccine is not yet available despite decades of research.[8] The challenges facing vaccination are many, including the marked heterogeneity of HCV genotypes. Therefore, prevention should focus on treating those who are already infected and should target high-risk populations, such as PWID. The WHO recommends many primary prevention methods, focusing on health-care providers, promoting the safe use and disposal of sharp objects, hand hygiene, and meticulous testing of donated blood.[9]

Due to the significant evolution of HCV therapies and the great number of articles that have been published in HCV management and prevention, a comprehensive literature review was performed to help researchers and readers on identifying the top cited-articles related to HCV that can be used for the educational and scientific purpose.

  Methods Top

Search strategy

We implemented a title-specific search using Scopus Database to distinguish highly cited work on hepatitis C in April 2017 without time restriction.

We used the term “Hepatitis C” as our search key-word without time restriction to publication dates. The query result was arranged from the highest to lowest according to the number of citation count. The top 100 cited articles on hepatitis C were collected and analyzed by the authors.


Pertinent data such as article's title, author (primary author, co-author, and most senior author), first author's specialty, country of origin, journal publication, year of publication, citation count “number of received citation by other papers,” and study category were identified and obtained.[10] Studies were categorized into four categories according to a previously published paper by Azer and Azer.[11] which included the following categories with its definition: articles “reports that represent a great advancement of an important topic and aims to stimulate hypotheses to establish new directions in its given field,” practical guidelines “studies that provide a resource on principals, current evidence, clinical application and regulation,” review studies “studies that performs a critical analysis of the available scientific literature to enhance the current knowledge and to emphasize future direction for further research,” and research papers “a qualitative or quantitative outcome of a research problem that have been approached systemically with a valid and a reliable method.”

Bibliometric parameters

In our analysis, we considered using statistical parameters to quantify the impact of articles, authors, and journals. The following parameters were used; authors H-index “which indicates that the h-number of publication by any given author have received at least h-number of citation by other papers,” SCImago journal rank (SJR) is defined as a parameter that reflects the influence of a given journal according to the number listed citation they received and its source, source-normalized impact per paper (SNIP) which reflects how discipline specific is the journal by the source of citation they receive, and citation per year (CY) is defined as the number of received citation for a given article per year since the year of its publication. The aforementioned bibliometric parameters were obtained from Scopus Database. The authors H-index for the top 5 authors and the journals' SNIP and SJR scores for the top five journals according to their contribution to the top 100 articles on hepatitis C.

  Results Top

Articles analysis

Our research query produced 52,545 articles. The top 100 articles according to the citation count were identified; the following parameters were obtained (citation count, CY “rank,”first author, title, year of publication, and journal of publication are listed in [Supplementary Table 1]. [Additional file 1]The average number of documented citation in the top 100 article is equal to 1273 citations per paper. The top 100 articles were published between 1989 and 2013. Analysis of the publication trends showed that 33 articles were published in the period of 1999–2003. Analysis of study categories showed that research (60%), review (24%) and articles category (16%). General medicine and hepatology specialties contributed to almost 50% of all published articles as shown in [Table 1]. Observation of the top 5 institutes of contribution showed that the highest number of articles were produced by the American pharmaceutical company titled as Merck and Co., incorporation as shown in [Table 2]. Countries of contribution to the top 100 are as follows: USA (62 articles), France (21 articles), Germany (15 articles), Japan (15 articles), UK (13 articles), Italy (11 articles), Spain (9 articles), Switzerland (9 articles), Australia (6 articles), and Canada (6 articles). The most frequently cited article on HCV was by Manns et al. “Peginterferon alfa-2b plus ribavirin compared with IFN-α-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomized trial.” Analysis of the top 10 articles according to their citation count illustrates that the citation count ranged between 5441 and 2178 citations and all published papers were produced after 1996 majorly from the United States [Table 3]. We performed another observation for the top 10 articles of contribution according to their CY count to overcome the bias of time for old articles as shown in [Table 4]. All ten articles were published after the year of 2001 from the United States of America predominantly with a CY range equal to (358–179). Manns et al. and Albrecht et al. were had the most cited two papers according to the citation count and CY with the following titles, respectively.

Table 1: Specialties of contribution to the top 100 articles on hepatitis C

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Table 2: Top 5 institutions of contribution in the top 100 articles on hepatitis C

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Table 3: The top 10 articles on hepatitis C according to the citation count (CC)

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Table 4: The top 10 articles on hepatitis C according to the citation per year

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Authors analysis

A total of 160 authors have contributed to the top 100 articles on hepatitis C with disregard to their authorship position. Analysis of the top 5 most contributing authors according to their number of articles without classifying their authorship status; illustrates that Albrecht et al. contributed to 9 articles from the top 100 articles with an H-index of 49. The highest H-index among the top 5 authors is 109 by Poynard, et al. in which he contributed to 7 articles from the top 100 articles [Table 5].
Table 5: The top 5 authors of contribution to the top 100 articles on hepatitis C

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Journal analysis

Thirty-three journals were involved in publishing the top 100 articles on HCV. We evaluated the top 5 journals of contribution to the 100 articles [Table 6]. The listed top 5 journals were found to account for 60% of articles from the top 100 list. The New England Journal of Medicine produced 21 articles (31848 citations) with a SNIP and SJR score of 14.60 and 14.61, respectively. The second top journal was the Journal of Hepatology, which published 20 articles (21402 citations) with a SNIP and SJR score of 2.43 and 4.75, respectively.
Table 6: The top 5 journals of contribution to the top 100 articles on hepatitis C

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  Discussion Top

Citation analysis aims to evaluate the quality and impact of articles in different medical disciplines such as anesthesiology, critical care, and emergency medicine. The purpose of this study was to highlight the 100 top-cited articles in hepatitis C regarding citation count, CY, first author, title, year of publication, Journal of publication, specialty of contribution, the institution of contribution, and country of contribution. Citation analysis is a fundamental part to measure the scientific influence and productivity.[12]

The 100 top-cited articles in hepatitis C were published from 1989 to 2013 by 33 different journals with an average number of citation of 1273 citations per paper. Apparently, the publication rate has increased dramatically from 1999 to 2003. There was no correlation between the number of authors and the number of citation. For example, 10 authors were involved in the study with the highest citation count which is “Peginterferon alfa-2b plus ribavirin compared with IFN-α-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomized trial” compared to study no. 58 were 46 authors were listed in the article. Furthermore, no association was found between the number of years a paper had since its publication and the number of received citations. In our list, study no. 14 received 1897 citations since it was published in 2011 compared to study no. 24 which received 1453 citation since it was published in 1992.

The study with the highest citation count (5441 citations) and ranked in the 2nd place according to CY with 340 citations was a randomized clinical trial authored by Manns et al. and it was published by Lancet in 2001. The study evaluated different regimens of HCV therapy among 1530 patients with HCV. Subjects were randomized to IFN-α-2b 3 MU subcutaneously three times weekly plus ribavirin for 48 weeks or peginterferon alfa-2b 1.5 μg/kg weekly plus ribavirin for 48 weeks or peginterferon alfa-2b 1.5 μg/kg weekly for 4 weeks then 0.5 μg/kg per week plus ribavirin mg/day for 48 weeks. The study concluded that the combination of peginterferon alfa-2b 1.5 μg/kg per week plus ribavirin has the higher SVR rate in comparison to other treatment regimens.

In addition, Paynard et al. in 1998 evaluated the safety and efficacy of IFN-α-2b plus ribavirin compared to IFN-α-2b alone. The study is one of the top 10 most cited papers, and it concluded that IFN-α-2b plus ribavirin was superior compared to IFN-α-2b in achieving SVR among HCV patients. The article with the highest number of CY (358.46 citations) and second most cited paper (5377 citations) was a randomized clinical trial authored by Fried et al. and it was published in the New England Journal of Medicine in 2002. The study enrolled 1121 patients with chronic hepatitis C who received different therapy regimens for 48 weeks; peginterferon alfa-2a plus ribavirin, IFN-α-2b plus ribavirin or peginterferon alfa-2a plus placebo. The study concluded that patients who received peginterferon alfa-2a plus ribavirin had a higher SVR rate compared to other treatment regimens. Similarly, Hadziyannis et al. found that a higher SVR rate was achieved by peginterferon alfa-2a and a longer treatment duration of ribavirin among HCV genotype 1.[11] The third most cited study was performed by Mchutchison et al.[12] The study compared the efficacy of IFN-α-2b alone or in combination with ribavirin in the treatment of chronic hepatitis C infection. The results confirmed that IFN-α-2b with ribavirin is highly efficacious among HCV patients.

Several studies have shown the significant role of host genotype in predicting treatment response in HCV patients.[13] IL28B was a predictor of clinical response in HCV patients who received IFN-α and ribavirin therapy.[14] The study was cited 178.5/year and its listed in the supplementary table. The study showed that the types of papers which contribute to the 100 top-cited articles were research (60%), review (24%), and articles (16%) as listed in [Table 1]. The top 10 most cited articles were published mainly by medicine and hepatology which confirms that the number of citation is affected by the area of specialty [Table 2]. The top 5 most producing journals to our top 100 articles were as follows: New England Journal of Medicine (21 articles), Hepatology journal (20 articles), Lancet journal (7 articles), Science (7 articles), and Gastroenterology (5 articles). Parametric representation of the journal impact showed that New England Journal of Medicine as the most contributing journal to our list and as the publisher of the top 2nd and 3rd article have the 2nd highest score of SNIP (14.619) and SJR (14.619) which concludes that it is the 2nd most prestigious and field-specific journal of contribution to hepatitis C researches. On the other hand, Lancet journal as the publisher of the top 1 article and the third most contributing journal was found to be the most prestigious and most field-specific journal with its highest SJR (14.63) and SNIP (14.801) score among the top 5 journals [Table 6]. Multiple researchers and institutions had participated in our top 100 articles. Albercht et al. have published 9 articles and was ranked as the most contributing author to our list and as a co-author of the top 100 article with an author's H-index of 49. McHutchison, et al. were ranked as the second most contributing author with 8 articles and an author's H-index of 92. Moreover, he was the author of 1st, 3rd, and 4th articles in our list according to the citation count [Table 5]. The most contributing institution with 9 articles was Merck and Co., incorporation. Then, the National Institute of Diabetes and Digestive and Kidney Diseases, and Centers for Disease Control and Prevention where each contributed to seven articles. In addition, Novartis International AG produced six articles and The Johns Hopkins School of Medicine published 5 articles [Table 3]. The top ten articles which received the highest number of citation were published between 1996 and 2009 mostly by the United States of America with a citation count ranging between (2178-5441 citations.). Their topics were focusing mainly on three aspects concerning hepatitis C; prevalence, natural history, and the management of the disease [Table 5]. Five of the top 10 articles were randomized clinical trials discussing the efficacy of different treatment regimens in HCV patients.[1],[2],[3],[5],[8] IFN-α and ribavirin was the standard of care in managing patients with HCV virus. However, major advances have developed in the field of HCV therapy, and an IFN free regimens have been available in the market since 2014.[15]

A different analysis was performed to the top 10 articles according to the number of citations per year to overcome the bias of citation accumulation over time which shows that top 10 articles were published mainly by the United States of America between 2001 and 2013 with an average CY of 266 citations and their main focus was on the management of HCV [Table 6]. Scopus database is well-known database for bibliometric studies.[16] Informational coverage in Scopus database includes English and nonEnglish articles, articles dating back to 1823 where all the papers published after 1996 have a complete bibliometric representation; currently, Scopus is working on adding full bibliometric coverage on articles published prior 1996. The number of indexed journals in a given database act as an excellent parameter for citation coverage; Scopus database has indexed 20,500 articles with a trackable citation, PubMed database has included 25,000 with untraceable citation and Web of Science (WOS) have indexed 11,000 articles only with the ability to track articles citation. Hypothetically, WOS is considered the best database for citation representation for studies published before in the early 20th century for the bibliometric coverage in that timeline when compared to Scopus; a recent study by Vieira have proved that the usage of Scopus database has provided 20% more citation coverage as compared to WOS database.[17] Furthermore, one of the known limitations to bibliometric studies is the phenomena of authors self-citation which lead to statistical overestimation; in our study, the self-citation accounted for 5% from the total citation count which is considered as nonoverestimating to the overall citation.

  Conclusion Top

The goal of this study is to perform a historical view on hepatitis C and its management by analyzing the top 100 most cited articles throughout history. Highlighting the most influential papers on HCV will help us understand the current multidisciplinary approach in understanding HCV and to explore what are the contemporary factors that need to be identified and worked on in future studies to expand our understanding of hepatitis C and to optimize the disease outcome which will help to reduce the global cost of this pandemic disease. The recent trials of the new non-IFN agents for the management of HCV are expected to have great numbers of citations in the upcoming years and thus will be bibliometrically influential which represent how clinically impactful those trials in the future practice of HCV management.


Our bibliometric analysis has several limitations. First, statistical analysis published before the year of 1996 is not completely available in Scopus database; which makes the statistical analysis for articles published prior that not fully accessible. Second, all bibliometric studies face a bias of analysis toward old papers from the accumulation of citations they have received over the years which underestimate the impactful contemporary papers on hepatitis C and other topics.[18],[19] To overcome such underrepresentation we calculated the citation count per year for all articles to shed the light on the most highly cited articles in the past decade on hepatitis C. To illustrate such a difference, the top 10 articles according to the citation count were published between 1996 and 2009, whereas the top 10 articles according to the CY were published between 2001 and 2013. Third, inherited limitation to citation analysis studies, which includes in-house citation (a group of authors offering authorship as an exchange for an authorship without contribution.), self-citation, omission bias (when authors only cite papers that supports their research objective and omit others)[20],[21] Fourth, the phenomena of citation obliteration by incorporation for classical papers that constitutes the body of knowledge in any topic.[22] Fifth, other limitations that were explored in the literature is the idea of incomplete citation as a strategy to attract readers rather than representing the most impactful articles.[22] Finally, the concept of using the citation count as an accurate reflection of the importance or impact of articles is considered as a limitation.[23]


The authors would like to thank College of Medicine Research Center, Deanship of Scientific Research, King Saud University for supporting our research.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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