Age of participants.
\r\n\t
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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"79592",title:"Lecturers Awareness, Inclusion and Implementation of Wearable Device as a Means of Enhancing Educational Development in Nigerian Universities",doi:"10.5772/intechopen.101425",slug:"lecturers-awareness-inclusion-and-implementation-of-wearable-device-as-a-means-of-enhancing-educatio",body:'In decades, wearable technology attracted reasonable awareness from educational technology experts. To a layman’s idea, this new concept of wearables offers a new form of technology by using psychomotor level of carrying handheld devices. The smartwatches and health tracking bracelets are the most common, even though many of the characteristics included in these types of device represent additional phases beyond anything that is already available in existing hand-helds and other technology know-how. Given this, the buzz around wearables may seem disappointing; they are nothing more than new and useless electronic toys to those who can afford them. In this perspective, wearables tend to generate initial interest and then quickly fall out of favor (for example, consider the ups and downs of the asymmetrically designed Google Glass wearable camera and head-mounted display system). Not surprisingly, there are staunch skeptics as to whether Wearables and their fans will have much to offer the future of education [1].
Wearable technology refers to computer-based devices that users can wear, examples jewelry, glasses, clothing, shoes or jackets. The advantage of wearable technology is that it can easily incorporate outfits to monitor sleep, association, whereabouts, and social interactions. Using Oculus Rift and other VR headsets, wearables can establish simulated reality. Recently, a new device that integrate seamlessly with the handler’s daily existence and engagements. Smartwatches from Apple and other tech giants already allow handlers to crisscross their email and interact with the interface. Acknowledgments to metered measure, this technology can update movement, actions and time [2].
Eventually, adoption and impression of wearables in training and learning services remains invisible. Nevertheless, the guiding locus is that the most efficient forms and usages of wearable technology for prescribed and familiar learning contexts are under developmental exploration. Technology in Education must realize that wearables are not monumental as a set of technologies that will flourish or nose-dive for enlightening commitments. There is diversity in devices and forms of technology incorporation and in user familiarity. Smartwatches and health trailers are some of what is available and possible. Incorporating educational technologies, the efficiency and worth of wearables will finally depend on many collective and anthropological factors and will fluctuate between environments.
Therefore, this article raises the main argument and future questions educational technologists about wearable technologies should be unequivocal about how wearable technologies are used and how their proposed use supports certain forms of teaching and learning. Despite advances in technological innovation, the education area has been unwilling to admit technology to assist learning, even though the introduction of machines in education, predominantly in the instruction of science, is well dispersed in history. Furthermore, technology usage is primarily restricted to moralistic training and knowledge approaches, where teaching is simplified by using computers and the availability of automated teaching resources. Nevertheless, the usage of digital technology behind wearables is not limited to the use of computers, electronic materials and must be well-matched with a student-focused methodology as an option in augmenting the student knowledge involvement.
To ensure full implementation of the national computer education policy in Nigeria, the state government introduced computer education and literacy in secondary schools in 1997 [3]. The general objectives of the computer literacy program are: to encourage computer literacy in every state of Nigeria; develop the use of computers as teaching tools in all subjects and familiarize students with the use of information technology; to enable the current generation of high school students to appreciate the potential of computers and to be able to use computers in various aspects of life and in subsequent work; and to expose teachers and students to the latest scientific knowledge and skills.
Another major effort to increase the integration of wearables in Nigerian society is the 2001 National Information Technology Policy, labeled “US IT” [4]. As a result of these measures, over the years, the education sector has seen a major increase in the capacity of application of wearables in learning and teaching all aspects of the tutelage system. Conversely, the situation in schools, especially in secondary and primary schools in rural areas, has not been fully addressed over a period of time.
Tella et al. [5] compared the 1987 Nigerian Computer Strategy with current school practices and establish that computer training in Nigeria is restricted towards Centralized Institution and is hardly presented in public schools that cover larger percentage of 80% of Nigerian citadel of learning. Nonetheless, the involvement in the private sector to the education structure has increased the usefulness of wearables in probably all private and public schools, especially in metropolitan areas of Nigeria. For example, in a recent study on computer knowledge levels in private and public secondary school students in metropolitan areas of Nigeria. Pitler [6] found that private high school students had more computer access and use than public high school students.
No significant difference was found in terms of Internet access. Given the situation of schools in urban areas, knowledge about the state of computer literacy in rural areas is still little studied. Do schools in rural areas implement the national education policy in Nigeria? And how are rural schoolchildren responding to this new technology in their environment? In response to the global influence of wearables on education, governments and non-governmental organizations in developing countries are now investing in educational technology to bridge the digital divide and enhance teaching and learning in the new information society. In line with these global developments, the federal government of Nigeria, in its national education policy, recognized the major role of wearables in the modern world and has integrated it into education in Nigeria [7].
For example, in 1987, the federal government, at the 32nd meeting of the Council of Ministers of the National Council of Education, established a national committee for computer education, which is tasked with setting national policy on computer education. The universal objective of the plan is to certify that the community gains the effect of information technology on today’s civilization; and to enable the current age band of schoolchildren at all levels to appreciate the potential of computers and enable them to be able to use computers in many aspects of their later lifetime [8].
The main objective of this study is to find out how lecturers are responding to wearable technology and admission to the Nigerian educational system. The specific objectives of the study are:
Determination of the level of knowledge and acceptance of smart watches by the respondents
Measurement of the most influential factors for the acceptance and use of smart watches by the respondents
Determination of teachers’ perception of the use of the smart watch for teaching and learning.
How do lecturers rate the use of smart watch technology in their work?
The presentation of wearable in education has exaggerated instruction and knowledge in various. Wearable is claimed to possess the possibilities of accomplishment used to satisfy the training needs of individual students, promote equality of instructive opportunities; offer top quality learning resources, increase self-efficacy and independence of learning among students, and improve teachers’ proficient improvement [9]. Its presentation also ensued to modification within the approaches of training and book learning within the new era teaching space. Olakulehin [10] notes that “this shift which has been driven by the excess information and communication devices now gradually reachable to students in class and reception, each of which offers new affordances to teachers and students alike for improving student accomplishment and for meeting the mandate for new era skills.” Related studies have recognized numerous varieties of wearable attainable for training and education.
Agreeing with [11], wearable obtainable in classrooms take account of modest tool-based demonstrations like Microsoft word, wired depositories of methodical data, main ancient brochures, handheld processors, and two-way remoteness knowledge teaching space. In order to efficaciously function within the newly introduced technology learning setting, identifying wearable implements turn out to be indispensable in place of teachers teaching and students learning. Raij et al. [12] reported that notwithstanding the deceptive remunerations of the utilization of wearable for informative persistence, research revealed that, the teaching possibility of wearable is deprived as many teachers and students are still not fully aware of wearable experience.
Profits derived from the utilization of wearable within learning areas can be exploited when impending handlers are capable within the usage of the newest technological innovation. Research revealed there are connections concerning wearable skills and its application for teaching and learning. And this is why [13] posit that an individual without the working knowledge of computers within the modern technological world will not be ready to go far in life as far as his career options are concerned.
Studies have shown that using wearable in education enables students to take a more active role in their learning rather than a passive observer or listener [14]. Given the part awareness of wearable knowledge affects the new information culture; accepting the Nigerian Policy on Education and executing in secondary schools in the rural regions of Nigeria has grown into noteworthy. Common of reports on the state of wearable in the rural areas only recognized inadequate wearable without insight as to how the situation affects students in the rural communities. According to [15] wearable development and application are not well established in rural areas of Nigeria because of poor information infrastructure.
Zheng et al. [16] say that more than 40% of Africa’s population is located in areas not covered by telecommunications services and, as a result, schools located in those areas will have subjectable connectivity issues. However, the full integration of technology into education is far from being achieved. A 2010 study of more than 60,000 classrooms, from elementary to high school in 34 states with various socioeconomic backgrounds and levels, found that 63% of teachers and 73% of students did not use technology [17]. Even as technology advances rapidly, the integration of applications such as those for iOS/Apple products (including the iPad) into education is still in its infancy [18], that is just 2 years ago (Figure 1).
The evolution of wearable.
According to [10] “a previous review of educational technology research found that the ways in which student and teacher use of technology were measured were often limited,” usually measurement using self-report surveys. Few studies measure technology integration through direct observation in the classroom, although observation “can provide a rich source of data to better understand technology use in the classroom” [14]. Although a single case study cannot tell researchers, decision makers and end users all about technology use In schools, it is important to collect as much data as we can to contribute to a general understanding of what is happening in rural schools regarding today’s use of technology. Examining how the types of technology used in schools help educators and the research community grow in understanding the issues and needs associated with successful technology integration to improve teaching and learning, in this particular case, regarding the adoption and allocation of rural school technology/iPad funds for those technologies.
Numerous dynamics stance encounters to effectively incorporating technology into learning. The major factors are support from administrator and wearable awareness quotient. Research revealed that faculty management and backing is necessary in fairly technological skilled improvement enterprises, alongside simple governmental procedures for supervision, misunderstanding, and culpability. With regard to funding, Wearable should provide adequate funding and resources [14] and resources (e.g. computers, iPads, etc.), as teachers report a lack of technology along with major barriers to technology affecting their practice in the classroom [9]. Another obstacle faced by many faculties is the lack of adequate technical support and infrastructure to ensure success with technology [8]. Technical challenges can include the need to carefully plan synchronization logistics and mobile device management as well as to ensure school infrastructure and bandwidth are adequate, powerful enough to support multiple devices directly. These are some of the types of barriers that this study seeks to examine, although administrative support is important for successful technology integration, teacher familiarization with technology is also important. In study [16], respondents classified ignorance with technology as a major barrier impacting teachers’ technology integration. Teachers who wish to learn how to incorporate new technologies into education may let their fears interfere with their effective use and may not be motivated to improve their current practice [6]. Studies show that teachers’ comfort level with technology affects how often and how they use it in their daily lessons [19].
Furthermore, teachers’ confidence in the mastery of new technologies and their perceptions of the usefulness of the latest technologies are important factors in their intention to use them as teaching tools [5]. More important than teacher discipline or level of education is teacher commitment to technology, as teachers typically maintain their students’ use of technology in schools, and better “buying” will translate into greater implementation [5]. Another barrier is the lack of professional development adequate for schools that can be subject to technology integration [1]. Interviewing teachers and managers, [4] they identified one of the main adverse effects to technology having much greater effect on teacher instruction as inadequate CPD that boosts teachers to work in partnership so that they would not feel compelled to understand separately in describing the best way to integrate innovative technology.
Teachers reported inadequate time to discovering newest technological abilities, experimenting, planning in preparing teachings as contests to technology [3, 4, 17]. A comprehensive professional development program must be sustainable, relevant, and connect educators through a supportive community practice which includes modeling, observation and interesting lesson scenarios using technology [18]. Efficient models for professional development are for workers to teach each other about how technology can support education and include peer coaching to improve student achievement [12]. Studies show that without effective and continuous professional development focused on quality education, investment in wearable technology will not have the expected outcome [20].
References [4, 9, 18, 21] have all pointed to the potential of communication technologies for transforming the models and processes of teacher development within the less developed countries (LDCs), as well as for enabling access to quality resources and professional support. Borthwick et al. [1] recommend that wearable agrees that:
Framework tools, which support teachers’ construction and understanding of current professional knowledge;
New learning environments and contexts, enabling teachers to experience new situations, practices and people;
Communication tools, which facilitate structures of social participation between teachers and other educators (eg collaborative assignments);
Metacognitive tools, which allow teachers to reflect on the training process, both individually and in groups (eg conferences; shared products such as electronic self-assessments).
Olakulehin [10] you argue that in this way wearables can make some aspects of teacher pedagogy more efficient, which also has the potential to add to and change the teaching-learning method itself.
Teachers need formal training, but also constant and on-going support from their peers to help them find the best way to integrate technology into their teaching. The use of wearables can enhance teachers’ professional knowledge and skills by enabling new forms of collaboration between teachers. Teachers learn to rework their classrooms from a static environment where there is a one-way flow of data from teacher to student, to a student-centered dynamic environment where students interact with peers as a team, both in their own classrooms and in the classroom.
The proceeding with proficient improvement of educators is basic to the accomplishment of innovation and schooling programs. Exploration concentrates like the Digital Education Enhancement Program (DEEP) report that there is no huge relationship between educators’ earlier information and potentially experience in the utilization of wearables and subsequently the capacity to effectively foster wearable homeroom rehearses [3]. Instructors need formal preparing, yet in addition consistent and continuous help from their companions to assist them with tracking down the most ideal way of coordinating innovation into their educating. The utilization of wearables can upgrade educators’ expert information and abilities by empowering new types of joint effort between instructors. Educators figure out how to improve their homerooms from a static climate where there is a single direction stream of information from instructor to understudy, to an understudy focused unique climate where understudies interface with peers collectively, both in their own study halls and in the virtual classroom.
Obviously, precise abilities cannot be attained without universal talents, and therefore general abilities are not very useful if teachers do not have detailed abilities to relate wearable clothing in their teaching activities. Zheng et al. [16] identifies four main approaches by which the laptop could be adopted for teacher training and professional development.
This last purpose shifts the stress to construing wearable as a result of the medium additionally because the message of teacher education. Oni and Adebisi [11] concludes that it’s potential to support acceptable and property teacher education programme is immense, however that we have got barely began to grapple with these problems effectively. It looks that wearable tools currently gift an opportunity to influence the growing shortage of qualified academics in SSA, and whereas full-time, centre-based teacher education is impractical for in-service provision, a mix of victimization wearable for open and distance learning [8], indicate that alone this could bring its own problems) aboard school-based teacher development offers an attainable and relatively cheap solution (Figure 2).
Portable model in a continuum of portable application approaches for teacher education and development.
There are few empirical studies that examine the employment of wearable technologies in education [6]. Tella et al. [5] tested the utilization of Google glass medical training. The analysis team terminated that wearable devices have the potential to provide distinctive potentialities in role-play-based learning contexts. Another study examined the employment of Google Glass [18] in academic psychology, and so the researchers terminated that this technology fits seamlessly into the teachings, permitting students to need images and video recordings of learning activities.
Certainly, there are several pedagogic possibilities additionally as problems related to the utilization of wearable technologies. However, so as for academics to integrate wearable technologies into their learning styles and to effectively use them among the classroom, they have to 1st perceive the potential areas of use of the devices [20]. Within education there has been analysis examining however wrist-worn devices will support and assist students with intellectual and organic process disabilities in learning [11]. Oni and Adebisi [11] concluded that wearable have promising potential to support students by conducive to their autonomy and reducing the stigma of obtaining a personal assistant who follows and monitors the disabled students’ activities. The potential use of wearable has additionally been studied in regard to e-learning [3, 13, 18, 19], wherever analysis targeted on how the blending of wearable technologies with e-learning systems may support omnipresent learning and collaboration. A study by [6, 17] emphasized moral problems with the employment of wearable in education. Besides the pedagogic opportunities, there are major considerations in terms of privacy, copyright and accessibility There have additionally been studies on using physical activities aboard wearable pursuit technology as a begin line to indicate students regarding acquisition and applied math data. These findings imply a principle for the potential of wearable computers in education, throughout this study; we tend to conceive to understand however wearable computers are used and plan to gain insight into the challenges which can arise in using this kind of technology among the classroom.
This study was conducted in all departments at Tai Solarin University of Education, Nigeria as a pilot study. Thirty (30) Lecturers in different faculties participated in the study. There were two surveys used for this study. The survey consisted of 15 items and the quarterly survey consisted of 10 items. The items used from these surveys were intended to measure general perceptions of and intention to use mobile technology. Specifically, it included perceptions of: education, hindrances to the adoption of technologies, and participants’ intentions to use the device in their own practice. Upon completion of the research they were asked if they would continue the utilization of the Smartwatch in their educational settings.
Tai Solarin University of Education, Nigeria was purposefully selected as the case study for the study. The selection of the school was based on the fact that it is a pioneer University of Education, located in a rural community, and serving educational needs of people living in that rural community and beyond.
Two types of data were collected for this study: responses to online surveys and information from focus groups. The researcher asked participants to fill out a series of surveys at the start of the study and then at 3 months. These surveys were distributed via physical means. The surveys asked about everyday use of the Smartwatch and did not collect any sensitive information. The raw data was put into SPSS for basic statistical analysis, including descriptive statistics and 297/parametric analysis. SPSS was used to analyze archival data of the initial survey as well as the follow-up surveys administered after 3 months. The researcher used quantitative inquiry to investigate educational professionals’ perception and use of Smartwatch devices in curriculum dissemination. We examined whether the participants’ usage rates increased from the start of the of the research study to its completion by applying an Independent Samples t-Test to all responses to the three common questions of the two surveys. We used an Independent Samples t-Test to compare means. In an attempt to examine lecturers’ differences in Smartwatch usage, a one-way ANOVA was used to compare the mean response between lecturers and determine whether the type of exposure may have influenced any part of the results.
The purpose of this study was to identify lecturers’ perceptions about the use of Smartwatch technologies for educational enhancement. The results section provides data analysis results about lecturers’ perceptions to use of mobile technologies, particularly Smartwatch technology.
Initial data was collected from 30 participants; at the end of the study, 5 participants were lost at follow-up (N = 25). The demographic data of age, gender, highest level of education, and gender are shown in the following Tables 1–3.
Age | Percentage (%) | Count |
---|---|---|
18–29 | 27.78 | 5 |
30–39 | 37.04 | 5 |
40–49 | 12.96 | 5 |
50+ | 22.22 | 10 |
Age of participants.
Response | Percentage (%) | Count |
---|---|---|
Bachelor’s degree | 35.5 | 10 |
Post-graduate degree | 64.5 | 15 |
100 | 25 |
Lecturers’ highest level of education.
Response | Percentage (%) | Count |
---|---|---|
Female | 38.89 | 8 |
Male | 61.11 | 17 |
100 | 25 |
Gender of study participants.
Table 1 shows that the most common age range among participants was 30–39 years old (37%). The least common age group was 40–49 years old (13%).
Table 2 reflects the highest levels of education for participants in the study. A total of 15 individuals (65% of participants) had a post-graduate degree. The researcher assumed that individuals in this category were comprised of Professors and Associate Professors. A total of 10 (35%) had a least a Bachelor’s degree; we can confidently assume that these individuals accounted for the lecturers generalization.
Table 3 reflects the gender of participants enrolled in the study. A total of 17 participants (61%) identified as male. Traditional lecturers are male so this level of participation is representative of the population.
Table 4 indicates how many participants were already using wearable technology at the time of enrolment. A total of 17 participants (71.15%) were not currently using wearable technology.
Response | Percentage (%) | Count |
---|---|---|
Yes | 28.85 | 8 |
No | 71.15 | 17 |
100 | 25 |
Current use of wearable technology.
Table 5 indicates lecturers’ perceptions of the value and utility of wearable technology. Mixed reviews on the value of wearable technology for educational enhancement were seen. While perceptions of value of wearable technology at baseline were mostly classified into the “agree” (range: 32–47%) and “strongly agree” (range: 35–47%) category for all of the six questions, there were also some lecturers who answered “neither agree nor disagree” (range: 10–28%). These mixed results may be attributed to the fact that some lecturers were unfamiliar with the use of wearable technology, as noted in Table 4.
Question | Strongly disagree (%) | Disagree (%) | Neither agree nor disagree | Agree (%) | Strongly agree (%) | Total |
---|---|---|---|---|---|---|
Wearable technology devices are valuable educational tools. | 4 | 0 | 12 | 47 | 33 | 17 |
Wearable technology devices are valuable assessment tools. | 2 | 0 | 10 | 45 | 43 | 21 |
Wearable technology makes it easier to communicate with colleagues. | 2 | 2 | 14 | 35 | 47 | 20 |
Wearable technology facilitates increased productivity and efficiency at work. | 2 | 2 | 16 | 45 | 35 | 25 |
Wearable technology can help students achieve better health outcomes. | 2 | 0 | 26 | 36 | 36 | 24 |
Wearable technology can facilitate better students awareness | 2 | 0 | 28 | 32 | 38 | 22 |
Perceptions of value of wearable technology by lecturers.
Researcher used an Independent Samples t-Test to compare the means of the two surveys. For the statement, “My Smartwatch is a valuable education tool,” participants’ perception of value at 1 month (M = 3.49, SD = 1.05; t [96] = 1.29, p value 0.2) was slightly higher than their perception of its value at the end of the 12-month study (M = 3.20, SD = 1.79). There was no significant difference in means. During the one-month follow-up, lecturers’ rates of “agree” and “neither agree nor disagree” responses to this statement were comparable to those at the 3-month follow-up. There was a trend of decreasing perception of the value of the Smartwatch for education at the end of the study (Figure 3). After examined differences in Smartwatch usage. A one-way ANOVA was used to compare the mean response between lecturers and thereby determine whether the type of enhancement may have influenced any part of the results. We found no statistically significant difference between the group means (p > .05). Therefore, we cannot reject the null hypothesis, and we cannot accept the alternative hypothesis.
Graphical trends in wearable technology usage.
The study focuses on the awareness, inclusion and implementation of wearable in enhancing educational development in rural areas. A pilot study was conducted in Tai Solarin University of Education, Nigeria, to authenticate the objectives of the study. It was revealed that even though the utilization of wearable is not required, nevertheless the magnitude of acceptance among the staffs is still low-slung. The challenges to wearable practice among academic personnel arrays commencing from insufficient resources, incapacitated training, inadequate finance by the college management, incapability to acquire personal ICT facilities, inadequate ICT facilities at workstation, poor power supply, inadequate ICT knowledge, deficient time due to capability, inadequate interest in learning.
The use of printing technologies may include learning from electronic books and other computerized support systems. Positive visual learning strategies can include digital storytelling using multimedia software / presentations or story creation websites. By actively participating in digital storytelling and visual support, students have the advantage that they can draw pictures and images in their own words. In terms of high-tech support, there are support materials that would help the reception of the students and materials that would help in the class. There is a wide variety of educational software that is used to improve reading skills. These include The Waterford Early course of study (www.waterford.org), Headsprout Early Reading (www.headsprout.com), PLATO Focus (www.plato.com), Academy of Reading (www.autoskill.com), LeapTrack (www.leapfrogschool.com/), READ 180 (www.hmhco.com/products/read-180), Scholastic (http://www.scholastic.com/home/), Knowledge Box Central (www. knowledgeboxcentral.com/), and Pearson Digital Learning (www.pearsonschool. com).
Recommendations made were that, all employed teachers in Federal, State and personal schools should undertake mandatory training and retraining on ICT programmes in introducing them to new technological trends in enhancing teaching and learning within the 21st Century. This is usually to supply them with sensible and useful information of computer, internet and associated areas of ICT for improved effectiveness and potency. The government ought to develop policies and pointers that may support teachers in their educational work and students in their learning.
Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation (LT) and is a major cause of liver related mortality [1, 2]. Patients transplanted for HCV-related cirrhosis have a worse 5-year survival than those with other indications [3, 4]. HCV eradication prior to LT will likely improve the outcome by eliminating the risk of post-transplant recurrence. Over the last decade, the development of highly effectively DAA agents has allowed for the safe and successful treatment of HCV, shrinking the number of recipients with chronic HCV and improving the post-transplant outcome [5].
Hepatitis C genotype 4 (HCV-G4) is the most prevalent genotype in the Middle East, and Northern Africa [6, 7, 8, 9]. Egypt is the most affected nation by HCV and HCV-G4 accounted for 94. 1% of infections. More than 90% of liver transplants in Egypt are for HCV –G4 [10]. Earlier studies from Saudi Arabia also demonstrated that HCV-G4 is the leading indication for liver transplantation [11]. On the other hand, HCV-G4 is a rare indication for liver transplantation in other parts of the world [12, 13].
The frequency of infection with HCV-G4 is also increasing in European countries, particularly among intravenous drug users and immigrants [14, 15, 16, 17]. HCV-G4 has not been adequately studied in prospective trials evaluating treatment outcomes and remains the least studied variant. However, over the past five years’ data on treatment outcomes of HCV-G4 in the DAA era has been accumulating.
The treatment outcome of HCV-G4 in the interferon era has been reported in multiple studies [18, 19, 20, 21, 22, 23]. A higher rate of spontaneous resolution after acute HCV-G4 infection has been reported [24, 25]. Other studies associated HCV-G4 infection with hepatic steatosis [26, 27]. These observations may have an impact on the natural history and treatment outcomes of HCV-G4.
Direct antiviral agents (DAAs) represent a breakthrough in the management of HCV. First generation DAAs (telaprevir, boceprevir) in post-liver transplant patients resulted in sustained virological response of up to 60% with telaprevir in HCV-G1. However, significant side effects including severe anemia, skin complications and significant drug interactions resulted in major concerns [28]. These agents are currently contraindicated and are not used anymore. Second line direct-acting antiviral DAAs have emerged with better safety and efficacy profiles, leading to dramatic changes in the practice of HCV management [29, 30, 31, 32, 33, 34, 35, 36]. An international, multicenter, long-term follow-up study of 530 patients with chronic HCV infection who received interferon based therapy demonstrated that among patients with advanced hepatic fibrosis, sustained virological response was associated with lower all-cause mortality [37]. The revolutionary discovery of DAAs makes chronic HCV infection a curable disease in patients with advanced liver disease. Liver function may improve after antiviral therapy in patients on the waiting list and could result in patient delisting. Following liver transplantation, DAA treatment is also highly effective so that postponing antiviral treatment to the post-transplant setting may be of benefit for certain patients. The, aim of this Chapter is to examine the natural history and treatment outcomes of HCV-G4 following liver transplantation. This review includes all published studies and abstracts involving HCV-G4 patients.
The introduction of DAAs is a significant therapeutic breakthrough in the management of HCV infection. With a very high cure rate, a large proportion of LT candidates and recipients can be cured of HCV infection by DAA therapies that are safe and well-tolerated. Due to the high efficacy of these drugs, a major decline was observed in the number of LT performed both in patients with decompensated cirrhosis with HCV and in those with hepatocellular carcinoma associated with HCV worldwide [38, 39, 40]. Furthermore, the survival of LT recipients with HCV-related liver disease has clearly improved because of treatment for HCV recurrence. The advent of efficacious DAA therapy to treat HCV recurrence, resulted in an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients with excellent outcome [41].
Re-infection of the graft is universal after liver transplantation regardless of genotype and has a negative impact on medium and long-term outcomes [42]. Western studies evaluating the natural history of HCV- G4 in the pre DAA era suggested a worse outcome compared to other genotypes. Zekry et al. analyzed factors that predicted outcome of HCV-liver transplant recipients in the Australian and New Zealand communities. Among 182 patient transplanted for HCV including 16 patients infected with HCV-G4 and a median follow-up of 4 years. HCV-G4 was associated with an increased risk of re-transplantation and death in univariate and multivariate analyses [43]. Whether this difference in outcomes was related to the pathogenicity of HCV-G4 or to other factors not examined in this study, including donor age, immunosuppression, and compliance with medications, is not clear (Table 1). Furthermore, patients infected with HCV-G4 in this study were older and more likely to have coexisting hepatocellular carcinoma. In a larger study Gane
Factors affecting transplant outcome |
Viral load |
Genotype |
Coinfections |
Alcohol consumption |
Compliance |
Chronic kidney disease |
Sarcopenia |
Steatosis |
Donor Age |
Immunosuppression |
Rejection |
Factors affecting the outcome of HCV-related transplantation
On the other hand, studies from the Middle East show a more favorable outcome. According to reports from Saudi Arabia and Egypt, overall graft and patient survival for HCV-G4 are comparable to rates reported in the international literature. Reports from Saudi Arabia reveal an overall three-year graft and patient survival rates of 90% and 80%, respectively [11, 49, 50, 51, 52, 53]. Similarly, in Egypt, where many active living–related liver transplant programs exist and HCV-G4 represents more than 90% of cases, graft and patient survival rates are approximately 86% [10].
Multiple recent studies from the Middle east evaluated the natural history of HCV-G4 following liver transplantation. A study from Saudi Arabia reported the results of patients who had biopsy-proven recurrent hepatitis C infection and made a comparison between patients with HCV-4 and non-HCV-4 genotype. They clearly demonstrated no significant differences between these two groups in terms of clinical, epidemiological, and histological factors and outcome. They found that in the initial liver biopsy, which was performed after a mean time from transplantation of more than 2 years, there were only four patients who had fibrosis scores greater than stage 3. Two of these patients progressed to cirrhosis on subsequent biopsies [54]. Among many factors included in that analysis, the only factor predictive of an advanced histological score was the HCV RNA level at the time of biopsy.
In studies published from Egypt reporting on living donor related liver (LDLT) transplantation of HCV-G4 patients, similar favorable outcomes were observed. Yosry et al. investigated the outcome of 74 Egyptian patients transplanted for HCV-G4. 31. 1% of patients developed HCV recurrence during a follow up period of 36 months. The majority of patients had mild recurrence, and 91% of the subjects had a fibrosis score of < or = F2. None of the transplanted patients developed cirrhosis or clinical decompensation. Recurrent hepatitis C virus infection was associated with a high pre and post-transplant viral load. The presence of antibodies to hepatitis B core antigen were also associated with disease recurrence [55]. In another study, recurrence was evaluated in 38 Egyptian patients infected with HCV-G4. Patient and graft survivals were 86.6% at the end of the 16 +/− 8.18 months (range, 4-35 months) follow-up period. Clinical HCV recurrence was observed in 10/38 patients (26. 3%). Similar to the previous study, none of the recipients developed cirrhosis or decompensation during the follow-up period [10]. Allam et al. compared the outcomes of Middle Eastern patients who received liver transplantation either in China or locally in Saudi Arabia, respective one- and three-year cumulative survival rates were 81% and 59% in patients transplanted in China compared with 90% and 84% for patients transplanted locally. The incidence of complications was significantly higher especially biliary complications, sepsis, metastasis and acquired HBV infection post-transplant in patients transplanted in China. Patients transplanted in Chine were more likely to undergo postoperative interventions and hospital admissions. This could be explained by the liberal recipient selection criteria, the use of donations after cardiac death, and to the limited post-transplant medical care [56].
HCV-G4 exhibits significant genetic diversity, and there are a number of viral subtypes. The impacts of the various subtypes have been demonstrated in recent studies; for example, HCV G1 subtype 1b patients were more likely to have a better post-transplant outcome compared with subtype 1a [57]. Studies performed in Egypt, where HCV-G4 subtypes 4a and 4b predominate, reveal a better antiviral treatment outcome compared with Saudi Arabia [58, 59, 60]. In a retrospective analysis of HCV-G4 patients, Roulot
More importantly the recent introduction of DAAs have changed the outlook for HCV-infected patients. The use of DAA agents in the liver transplantation setting has eliminated post-transplant HCV recurrence and improved graft and patient survival irrespective of many other factors including viral genotype.
Viral eradication or suppression prior to liver transplantation reduces post-transplant recurrence rates [62]. Interferon-based therapy was the only treatment option for HCV prior to the DAA era, however, interferon was contraindicated in patients with advanced liver cirrhosis. This negatively impacted the HCV outcome in cirrhotic and organ transplant patients [63, 64, 65].
The limited treatment options lead multiple groups to carefully evaluate Interferon based therapy in the pre transplant setting. Everson
Previously treatment options for patients with recurrent HCV after transplantation were limited. IFN based therapy for patients with post-transplant recurrence were the only available option in the past, these regimens are difficult to tolerate and have disappointing efficacy with hard-to-manage drug interactions. Reported SVR rates for PEG-IFN combination therapy following liver transplantation are lower than those in the nontransplant population. Treatment regimens have been hindered by a high incidence of adverse effects, leading to treatment withdrawal.
Dabbous
The treatment of chronic hepatitis C has been revolutionized with the introduction of DAAs. New oral DAAs have emerged with better safety and efficacy profiles, leading to dramatic changes in the practice of HCV management. The goal of HCV treatment is to reduce mortality and liver complications through virologic cure. The end point is sustained virological response (SVR), which is an undetectable viral load at least 12 weeks after completing treatment. The DAAs target various proteins throughout the HCV replication cycle [70]. These choices include sofosbuvir based therapy plus weight-adjusted RBV, ombitasvir/paritaprevir/ritonavir, elbasvir-grazoprevir and glecaprevir/pibrentasvir. The choice between them depends primarily on potential for drug interactions, availability, and cost. Data on the use of these new agents in cirrhotic G4 patients awaiting liver transplantation are limited. Up-to-date studies evaluating the safety and efficacy of these agents in HCV-G4 patients are summarized below.
Sofosbuvir (SOF) is a novel pangenotypic nucleotide analog inhibitor that inhibits HCV RNA replication. SOF is administered orally and inhibits the HCV NS5B polymerase. SOF exerts potent antiviral activity against all HCV genotypes [71, 72, 73, 74, 75].
Curry et al. conducted a trial to determine whether sofosbuvir and RBV treatment before liver transplantation could prevent HCV recurrence afterward. They included 61 patients with child A cirrhosis and HCV of any genotype. All involved patients were on waitlists for liver transplantation for hepatocellular carcinoma and received up to 48 weeks of sofosbuvir (400 mg) and RBV before liver transplantation. Of 46 patients who were transplanted, 43 had HCV-RNA levels of less than 25 IU/ml at the time of transplantation. Of these 43 patients, 30 (70%) exhibited a post-transplantation virological response at 12 weeks [76]. Another study evaluated the efficacy and safety of SOF in combination with RBV in HCV-G4 patients in patients of Egyptian ancestry. 60 patients were included and half of them were treatment-naïve. Patients were treated for 12 weeks (n = 31) or 24 weeks (n = 29). Overall, 23% of patients had cirrhosis. SVR was achieved by 68% of patients in the 12-week group, and by 93% of patients in the 24-week group. Treatment was well tolerated and none of the patients discontinued treatment due to an adverse event [77]. Doss et al. evaluated the efficacy and safety of SOF in combination with ribavirin in HCV-G4 patients in Egypt. 103 patients were included and received a combination of SOF and weight-adjusted RBV. 17% of the study population were cirrhotic. Patients with cirrhosis at baseline had lower rates of SVR (63% at 12 weeks, 78% at 24 weeks) than those without cirrhosis (80% at 12 weeks, 93% at 24 weeks). The most common adverse events were fatigue, headache, insomnia, and anemia. Two patients experienced serious adverse events. No adverse events resulted in treatment discontinuation [78]. In a more recent study, 2400 Egyptian patients with liver cirrhosis due to chronic HCV infection were treated with SOF and RBV for 24 weeks. The majority of included patients were treatment-naive. The overall SVR rate was 71. 2%. The most common adverse events were fatigue, myalgia, headache, insomnia, and anemia. Only 5.6% of patients discontinued treatment due to the appearance of significant complications [79]. In another study 14 409 patients received either dual therapy, SOF/RBV for 6 months (group1) or triple therapy with SOF/peg-IFN-alfa-2a/RBV for 3 months (group 2), in a cohort of patients treated in National Treatment Programme affiliated centres in Egypt. In group 1, the SVR at week 12 was 94% and in group 2 the SVR was 78.7% [80].
The efficacy of this combination following LDLT was also evaluated in Saudi Arabia. Ajlan et al. reported the safety and efficacy data on 36 post liver transplant patients who received SOF and RBV ± peg-IFN. All patients were infected with HCV-G4, mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. The majority of patients had advanced fibrosis. 28 patients were treated with PEG-IFN and RBV in addition to SOF for 12 weeks and the remaining were treated with SOF and RBV only for 24 weeks. By week 4, only four (11. 1%) patients had detectable HCV RNA [81]. In another study 39 Egyptian liver transplant recipients were treated for recurrent HCV-G4 after transplantation with SOF and ribavirin for 6 months. SVR was achieved in 76% of recipients. SVR was significantly higher in treatment-naïve patients and in recipients with a low stage of fibrosis [82]. A prospective multicenter study enrolled 40 patients with compensated recurrent HCV infection of any genotype following liver transplantation. All patients received 24 weeks of SOF 400 mg daily and RBV. Of the 40 patients enrolled and treated, 40% had biopsy proven cirrhosis, and 88% received prior interferon treatment. SVR was achieved by 28 of 40 patients. Relapse accounted for all cases of virological failure, including the only patient with HCV-G4. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported [83]. Forns et al. conducted a post-transplantation study in which SOF and RBV were provided on a compassionate-use basis to patients with severe recurrent HCV, including those with fibrosing cholestatic hepatitis (FCH) and decompensated liver cirrhosis with a life expectancy of less than one year. Patients received SOF and RBV for 24–48 weeks, PEG-IFN was added in some patients. The study population included patients infected with HCV- G4. The overall SVR rate was 59% and was higher (73%) in those with early severe recurrence. 123 serious adverse events occurred in 49 patients (47%). Severe adverse events associated with hepatic decompensation were the most frequent, with 26 adverse events occurring in 19 patients (18%) [84]. However, with the emergence of other treatment options this combination is not considered the best treatment option (Table 2).
Study | Sample size | Genotypes | SVR | Treatment protocol |
---|---|---|---|---|
Ajlan [81] | 36 | 4 | 91.6% | SOF+RBV+PEG-INF for 12 weeks or SOF+RBV for 24 weeks |
Dabbous [82] | 39 | 4 | 76% | SOF+RBV 24 weeks |
Forns [95] | 104 | 1, 2, 3, 4 | 59% | SOF+RBV for 24–48 weeks |
Abaalkhail [93] | 50 | 4 | 86% | LDV-SOF+/-RBV 12-24 weeks |
Mann [94] | 227 | 1,4 (n=27) | 92.5% | SOF+LDV+RBV 12-24 weeks |
Dumortier [108] | 125 | All(11 G4) | 92% | SOF/DCV+/-RBV 12-24 weeks |
Coilly [107] | 137 | All (12 G 4) | 96% | SOF+DAC |
Leroy [102] | 23 (all with FCH) | All (3 G4) | 96% | SOF+DCV for 24 weeks |
Reau [128] | 100 | All (3 G4) | 100% for G4 | Glecaprevir/Pibrentasvir for 12 weeks |
Agarwal [131] | 79 | 1,4 (n=4) | 100% for G4 | SOF/VEL |
Prospective studies that included HCV-G4 patients following liver transplantation.
SVR = sustained virological response, SOF = sofosbuvir, RBV = ribavirin, LDV = ledipsavir, DCV = daclatasvir, SIM = simeprevir, FCH = fibrosing cholestatic hepatitis, Peg-INF = pegylated interferon.
Colombo et al. evalaluated the safety and efficacy of LDV-SOF in kidney transplant recipients with chronic genotype 1 or 4 HCV infection and included patients with cirrhosis. Ten patients in this trial were infected with HCV-G4 and all included patients achieved SVR. Treatment with LDV-SOF for 12 or 24 weeks was well-tolerated and seemed to have an acceptable safety profile among kidney transplant recipients with HCV genotype 4 infection [85]. In a recently published study real-world effectiveness of LDV-SOF was evaluated. 135 patients infected with G4 were included, the overall SVR rate was 89.6% including treatment experienced and cirrhotic patients [86]. Charlton et al. (SOLAR-1) assessed treatment with LDV, SOF, and RBV in patients infected with HCV-G1 or HCV-G4. This study included a cohort of patients with cirrhosis who had not undergone liver transplantation. The SVR rate in the cirrhotic group was 86–89% [87]. Kohli et al. evaluated 12 weeks of combination therapy with LDV and SOV for patients with chronic HCV-G4 infections. 20 (95%) of 21 patients completed 12 weeks of treatment and achieved SVR (95% CI 76-100), including seven patients with cirrhosis. One patient was non-adherent to study drugs and withdrew from the study, but was included in the intention-to-treat analysis. No patients discontinued treatment because of adverse events [88]. Crespo et al. investigated the effectiveness and safety of DAAs in patients with HCV-G4 infection in routine practice. 130 patients with HCV-G4 were treated with LDV/SOV, SVR was achieved in 93. 2% of cirrhotic patients [89]. Abergel et al. also evaluated the efficacy and safety of therapy with LDV and SOF in patients with HCV-G4. Forty-four patients (22 treatments naïve and 22 treatment experienced) received a fixed-dose combination tablet of 90 mg LDV and 400 mg SOV orally once daily for 12 weeks. Ten patients (23%) had compensated cirrhosis. The SVR rate was 93% and was similar in treatment-naïve (95%, 21/22) and treatment-experienced (91%, 20/22) patients. Treatment was well tolerated with no serious adverse events [90]. Sanai et al. assessed real-world safety and efficacy of LDV/SOF with or without RBV in HCV-G4 infected patients with compensated and decompensated cirrhosis. This observational cohort (n = 213) included HCV-G4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600 and 1200 mg daily. Patients with prior DAA failure were excluded from the analysis. Overall, 197 (92.5%) of the patients achieved SVR [91]. The SVR rate was as high as 98% for genotype 4 when using this combination to treat treatment-niave cirrhotic patients for 12 weeks [92]. Abaalkhail et al. evaluated prospectively the safety and efficacy of LDV-SOF for 12 to 24 weeks with or without RBV in treating HCV-4 infected patients with cirrhosis (cohort A) or post-liver transplantation (cohort B). A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were included. SVR was achieved in 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or significant side effects [93].
Cohort B of the SOLAR-1 study enrolled patients who had undergone liver transplantation and included patients with post-transplant liver cirrhosis. Patients were randomly assigned to receive a fixed-dose combination tablet containing LDV and SOF plus RBV for 12 or 24 weeks. The cohort included 108 post-transplant patients. SVR was achieved in 96–98% of patients without cirrhosis or with compensated cirrhosis, in 85%–88% of patients with moderate hepatic impairment, in 60%–75% of patients with severe hepatic impairment, and in all six patients with FCH [87]. Similarly, an open-label study at 34 sites in Europe, Canada, Australia, and New Zealand evaluated treatment outcome in the pre and post-transplant settings. Cohort A included patient with cirrhosis who had not undergone liver transplantation. Cohort B included post-transplantation patients who had either no cirrhosis; CTP-A, CTP-B, or CTP-C cirrhosis; or fibrosing cholestatic hepatitis. Patients in each group were randomly assigned to receive 12 or 24 weeks of LDV (90 mg) and SOF (400 mg) once daily, plus RBV (600–1200 mg daily). The majority of patients were infected with HCV genotype 1 and only 37 were infected with genotype 4. Among all patients with genotype 4 HCV, SVR was achieved by 14 of 18 (78%) patients (12 weeks’ treatment) and 16 of 17 (94%) patients (24 weeks’ treatment) [94]. SOF/LDV combination was also evaluated in the post-transplant setting in a recently published German study that included both genotypes 1, 4. An overall SVR was achieved in 97% of patients [95].
The safety profile of LVD/SOF with RBV was evaluated in a pooled analysis of SOLAR-1 and -2 studies. These two studies included cirrhotic or post–liver transplantation patients infected with genotypes 1 and 4 and were randomized to 12 or 24 weeks of treatment. Treatment in the two trials was well tolerated and safe. RBV-associated anemia was the most common adverse effect, representing over 50% of reported drug-related adverse events [96].
DCV is a pangenotypic NS5A inhibitor with a very low potential for drug interaction and a favorable safety profile. EL-khayat et al. investigated the efficacy and safety of SOF/DCV for treatment of patients with HCV-G4 induced cirrhosis. This was a multicenter study involving 551 patients with HCV-G4 related cirrhosis; 432 naïve patients and 119 treatment-experienced patients. All patients received SOF/DCV/RBV for 12 weeks and when RBV is contraindicated the treatment duration was extended to 24 weeks. SVR rate was 92% in naïve cirrhotic patients and 87% in previous treated patients [97]. In a French study, 176 HCV-G4 patients were treated with SOF and DCV. All the patients enrolled had advanced stages of liver fibrosis. The overall SVR rate was 90%, with the highest rate (97%) reached in cirrhotic patients treated with RBV, a the lowest (88%) in those treated without RBV [98]. In another recently published study involving only HCV-G4 patients, SVR was achieved in 100% of patients who received SOF/DCV with or without RBV. This study included patients with advanced fibrosis and cirrhosis. Adverse events occurred in 32% of patients, but none discontinued treatment [99]. The Phase II, open-label, nonrandomized IMPACT study assessed the efficacy of three DAAs (simeprevir, sofosbuvir, and daclatasvir) in HCV genotype 1/ 4-infected cirrhotic patients with portal hypertension or decompensated liver disease. All patients received simeprevir (SIM) 150 mg, DCV 60 mg, and SOF 400 mg once-daily for 12 weeks. All 40 patients included in the study achieved SVR and the combination was well tolerated [100]. The outcome of SOF/DCV/RBV in non-responders to prior sofosbuvir-based therapy was evaluated in a large Egyptian study that included 1014 patients in which 47% were cirrhotic. Overall SVR was 90.6% with no major side effects [101].
Multiple other studies showed high SVR rates among genotype 4 infected patients [102, 103, 104, 105, 106].
Data on the use of DCV in the post-transplant setting for HCV-G4-infected patients are limited.
In a multicenter prospective study 137 patients with post-transplant HCV recurrence received SOF and DCV. This cohort included 12 patients infected with HCV-G4. The SVR rate after completing treatment was 96% under the intention-to treat analysis. No clinically relevant drug–drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs [107]. A recent prospective multicenter study evaluating SOF based therapy in the post liver transplant setting was conducted and included all genotpes. The main combination regimen was SOF/DCV (73.6%). SVR was 92.8% (on an intent-to-treat basis) [108]. Leroy
SIM is a NS3/4A protease inhibitor with antiviral activity against G1, G2, G4, G5, and G6.
An open-label, multicentre, phase IIa study evaluated the outcome of SIM plus SOF for eight or 12 weeks in HCV-G4 infected patients. This study included 23 cirrhotic patients who received a 12 week course of therapy. Treatment comprised SIM 150 mg and SOF 400 mg daily. All cirrhotic patients achieved SVR and the treatment was well tolerated [110]. In a phase III, open-label, single-arm study the efficacy and safety of 12 weeks of SIM plus SOF in treatment-naïve and experienced HCV-G4 infection, including cirrhotic patients was conducted. All patients achieved SVR including the cirrhotic patients. No serious adverse events were reported and no patients discontinued study treatment [111]. The combination of SIM/SOF in a recently published Egyptian study involving genotype 4 infected patients resulted in a SVR rate of 92% in 100 treated patients [112]. The Phase II IMPACT study was conducted in HCV genotype 1- or 4-infected cirrhotic patients with portal hypertension or decompensated liver disease and assessed the combination of the three direct-acting antivirals SIM, DCV and SOF. All 40 patients achieved SVR [113]. Multiple other studies that included cirrhotic and treatment experienced patients treated with SIM and SOF revealed high SVR rates [114, 115, 116].
The efficacy and safety of SOF-based regimens in the real world among a cohort of Egyptian patients with recurrent HCV post LDLT was evaluated in HCV-G4 infected patients. 190 patients were included. Out of 190, 119 received SOF/RBV, 38 SOF/SIM, 22 SOF/DCV)/ ± RBV, and 11 received SOF/LDV/ ± RBV. SVR rates were as follow: 84.9% in SOF/RBV group, 94.7% in SOF/SIM, 100% in SOF/DCV, and 100% in SOF/LDV. Treatment was well tolerated with no significant drug–drug interactions [117]. The outcome of the combination SIM + SOF ± RBV in a group of liver transplant patients with HCV genotype 4 infection in Spain was evaluated in a real life study. This was a multicenter retrospective study, including 28 HCV genotype 4 patients from 11 liver transplant centers. The SVR was 95.23% including patients with advanced fibrosis and cirrhosis [118].
The combination of ombitasvir, ritonavir and paritaprevir was evaluated in multiple studies involving compensated cirrhotic HCV-G4 patients and revealed high SVR rates reaching 100% in some studies [119, 120, 121, 122, 123, 124]. In a recent meta-analyses, 20 cohorts across 12 countries were identified, totaling 5158 patients infected with G1 and 4. The overall SVR rates were 98.9% for HCV-G4 infected patients [125]. The regimen is contraindicated in Child Pugh classes B and C cirrhosis, therefor its use in the pre transplant setting is limited.
The EXPEDITION-1 trial enrolled 146 patients with compensated cirrhosis, 16 (11%) patients were infected with HCV-G4. Patients in this trial received a fixed dose of glecaprevir (300 mg)/pibrentasvir (120 mg) for 12 weeks. SVR was 100% for patients infected with HCV-G4 [126].
EXPEDITION-8 is a randomized trial that enrolled 343 patients with HCV Genotypes 1–6 and compensated cirrhosis. All patients received an 8-week course of Glecaprevir/Pibrentasvir. Of 343 patients, 13 had HCV-G4. The SVR12 rate in HCV-G4 was 100% [127].
On the other hand, MAGELLAN-2 trial was a phase 3, open-label trial for patients at least 3 months post transplantation. The study enrolled 100 patients of HCV. Three patients with genotype 4 underwent LT. After a 12-week course, all HCV-G4 infected patients achieved SVR 12 [128].
Immunosuppressive therapy should be monitored closely due to the possibility of drug–drug interaction when used with protease inhibitors.
In 2015, ASTRAL-1 evaluated the efficacy and safety of 12-week course of VEL and SOF. Of the 624 patients, 116 (19%) had genotype 4. One fourth of genotype 4 patients had cirrhosis. After a 12-week course of SOV/VEL, all patients (100%) with HCV-G4 achieved SVR [129].
ASTRAL-4 trial enrolled 267 patients with decompensated cirrhosis, CPT B. The study was open label with 3 arms that included: SOF/VEL for 12 weeks, SOF/VEL in addition to RBV for 12 weeks, or SOF/VEL for 24 weeks. In this trial, 8 (3%) patients had genotype 4. Regardless of the assigned arm, all genotype 4 patients (100%) achieved SVR. In this study, 81% of patients with MELD score above 15 had improvement after completion of treatment. This study was one of the earliest trials to evaluate SOV/VEL for decompensated cirrhotic patients [130].
In a recent trial 79 post liver transplant patients with HCV-G 1 and 4 received SOF/VEL daily for 12 weeks. In this trial, 4 patients were infected with HCV-G4. All patients with genotype 4 achieved SVR. There were no deaths or rejection episodes during the study period [131].
POLARIS-1 trial assessed the safety and efficacy of SOF/VEL/VOX taken for 12 weeks vs. placebo. Patients with cirrhosis represented 46% of the study population. All patients with genotype 4 (22) were in the active treatment arm. By the end of the study period, 20 patients (91%) achieved SVR. One cirrhotic patient developed NS5A Y93H resistance-associated substitution and the other one did not receive treatment.
In the POLARIS-4 trial, patients were assigned to either SOF/VEL/VOX or SOF/VEL once daily for 12 weeks. All genotype 4 patients received SOF/VEL/VOX. The SVR rate was 100% for HCV-G4 infected patients [132].
The use of combined SOF/VEL/VOX is not recommended in patients with advanced liver disease CPT C. There are no currently strong data to support SOF/VEL/VOX use post liver transplantation. Case reports showed favorable outcome in the post-transplant setting [133].
A randomized controlled open label trial assessed the effectiveness of EBR/GZR with or without RBV for 12 or 16 weeks. The study population was 420 patients out of whom 36 had HCV-G4. The SVR for HCV-G4 patients was 89% which improved with a longer duration of treatment [134].
Jacobson et al. published the integrated analysis of 6 clinical trials. The analysis included 402 patients who received EBR/GZR once daily +/− RBV, for 12-18 weeks. Twenty-three patients with HCV-G4 were included in the analysis. Six patients were treatment naïve and they all achieved SVR. In the treatment experienced group, 4 patients (100%) achieved SVR after 16-18 week of treatment. However, the success rate was lower in treatment experienced patients with a 12-week course without RBV (66.7%) or with RBV (80%) [135].
Data for this combination in the post-transplant setting is limited.
Despite the high SVR rate associated with DAA in HCV-G4 infected patients, a small percentage of patients do not respond to treatment. In the early era of DAA the most common approach was to add RBV or in some studies PEG-IFN and extend the treatment duration. However, with the emergence of new DAA choices, changing to another DAA became the most common approach. Yousif et al. conducted a prospective cohort study to assess the safety and efficacy of 12 weeks’ retreatment with either combination of SOF/DCV/SMV/RBV (45 patients) or SOF/OBV/PTV/r/RBV (163 patients) in patients who had previously failed NS5A inhibitors-based regimens. The overall SVR rates in the two groups were 98. 1% [136]. In another study, patients who failed SOF/DCV were retreated successfully with other DAAs [137]. In a recently published study quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV-G4 DAAs-experienced patients was successful in eradicating the virus [138]. Multiple other studies revealed similar results [139, 140].
The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically. DAAs have shown to be safe and effective in patients with decompensated cirrhosis with high SVR rates. However, it is still debatable on when to initiate treatment in patients with advanced liver disease. Krassenburg et al. evaluated the impact of SVR in a large international multicenter cohort study, including a large number of patients with HCV-related cirrhosis treated with DAAs. Achievement of SVR was independently associated with a 2. 5-fold lower risk of cirrhosis-related complications or death in patients with compensated cirrhosis. On the other hand, no clinical benefit was apparent with HCV eradication in patients with decompensated liver disease. Among patients with CP-B/C cirrhosis, the event-free survival and LT-free survival did not differ between those with SVR and those without SVR. Furthermore, MELD score improvement did not translate to a beneficial clinical outcome in these subset of patients. Thus, DAA therapy may lower prioritization for LT through MELD score reduction, which is likely to primarily affect those with a more urgent need liver transplantation [141]. Other recently published studies assessed the impact of DAAs on patients awaiting liver transplant. They evaluated whether patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. Treated patient had a significant improvement in the median MELD and Child Pugh score. They concluded that all oral DAAs were able to reverse liver dysfunction and may result in delisting of about 20-30% of patients. Patients with lower MELD scores had higher chances to be delisted. However, the longer term benefits of therapy need to be ascertained [142, 143]. Similarly, Afdahl et al. evaluated the outcome of DAA in compensated and decompensated cirrhotic patients. They also measured the hepatic venous pressure gradient before and after treatment in fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension. They observed a clinically meaningful improvement in portal hypertension in addition to improvements in liver biochemistry, Child–Pugh score and Model for End-Stage Liver Disease scores [144]. The potential benefits of treating patients on the waiting list include potential improvements in overall clinical status that may salvage these patients from liver transplantation; reducing post-transplant recurrence; and avoiding possible post-transplant drug–drug interactions. One concern is that treating these patients may lower their MELD scores and drive them down the transplant list, thus delaying transplantation despite persistent portal hypertensive complications.
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Catarina Guedes and F. Xavier Malcata",authors:[{id:"83136",title:"Prof.",name:"F. Xavier",middleName:null,surname:"Malcata",slug:"f.-xavier-malcata",fullName:"F. 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This chapter will discuss an innovation in seaweed cultivation of the genus Eucheuma, which is the prime marine commodity in the tropical regions of the world. Research conducted during 2015-2017 and 2019 in Southeast Sulawesi Province, Indonesia, provided an overview of the use of floating cage that showed very significant growth results. The research result showed that the growth rates of Eucheuma denticulatum and Kappaphycus alvarezii in floating cage seemed faster and resulted in better thallus morphology. Daily production of E. denticulatum and K. alvarezii that were cultivated in floating cage was higher than daily production of E. denticulatum and K. alvarezii cultivated on longline. Specific growth rate (SGR) of E. denticulatum and K. alvarezii cultivated by using floating cage method was also higher than E. denticulatum and K. alvarezii cultivated by using longline method. Moreover, the cultivation by using floating cages produces good growth rates with no effect of herbivore attacks.",book:{id:"8928",slug:"emerging-technologies-environment-and-research-for-sustainable-aquaculture",title:"Emerging Technologies, Environment and Research for Sustainable Aquaculture",fullTitle:"Emerging Technologies, Environment and Research for Sustainable Aquaculture"},signatures:"Ma’ruf Kasim, Abdul Muis Balubi, Ahmad Mustafa, Rahman Nurdin, Rahmad Sofyan Patadjai and Wardha Jalil",authors:[{id:"309893",title:"Prof.",name:"Maruf",middleName:null,surname:"Kasim",slug:"maruf-kasim",fullName:"Maruf Kasim"},{id:"313040",title:"MSc.",name:"Abdul Muis",middleName:null,surname:"Balubi",slug:"abdul-muis-balubi",fullName:"Abdul Muis Balubi"},{id:"313041",title:"MSc.",name:"Wardha",middleName:null,surname:"Jalil",slug:"wardha-jalil",fullName:"Wardha Jalil"},{id:"313042",title:"MSc.",name:"Ahmad",middleName:null,surname:"Mustafa",slug:"ahmad-mustafa",fullName:"Ahmad Mustafa"},{id:"313043",title:"MSc.",name:"Rahman",middleName:null,surname:"Nurdin",slug:"rahman-nurdin",fullName:"Rahman Nurdin"},{id:"313044",title:"MSc.",name:"Rahmat Sofyan",middleName:null,surname:"Patadjai",slug:"rahmat-sofyan-patadjai",fullName:"Rahmat Sofyan Patadjai"}]},{id:"62842",title:"Integrated Rice and Aquaculture Farming",slug:"integrated-rice-and-aquaculture-farming",totalDownloads:1861,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The burning problems like scarcity of food for ever-growing human population in the present world are addressed by adapting various methods for production of protein, carbohydrate, oils and other food materials. One of the methods to produce high amount of food is integrated farming including rice-aquaculture farming, which produces protein and carbohydrate as major components besides others. Rice-aquaculture farming produces grain (carbohydrate) and animal protein without affecting the quality and quantity of rice yield on the same piece of land and renders additional financial gain besides main crop (rice) like conventional monoculture. The aquatic species grown in the integrated culture are mainly distinct types of fishes, selected crustaceans and other selected species. Profitable rice-aquaculture integrated farming is popular in Asian countries than in Western countries. However, the integrated rice-aquaculture farming has its own limitations. The type of methods, culture species, influencing factors, and pros and cons of rice-aquaculture integrated farming are discussed in the present chapter.",book:{id:"7229",slug:"aquaculture-plants-and-invertebrates",title:"Aquaculture",fullTitle:"Aquaculture - Plants and Invertebrates"},signatures:"Pamuru Ramachandra Reddy and Battina Kishori",authors:[{id:"242524",title:"Dr.",name:"Ramachandra Reddy",middleName:null,surname:"Pamuru",slug:"ramachandra-reddy-pamuru",fullName:"Ramachandra Reddy Pamuru"},{id:"255022",title:"Dr.",name:"Kishori",middleName:null,surname:"Battina",slug:"kishori-battina",fullName:"Kishori Battina"}]},{id:"24074",title:"Embryonic and Larval Development of Freshwater Fish",slug:"embryonic-and-larval-development-of-freshwater-fish",totalDownloads:7428,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"612",slug:"recent-advances-in-fish-farms",title:"Recent Advances in Fish Farms",fullTitle:"Recent Advances in Fish Farms"},signatures:"Faruk Aral, Erdinç Şahınöz and Zafer Doğu",authors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"},{id:"29132",title:"Dr.",name:"Zafer",middleName:null,surname:"Dogu",slug:"zafer-dogu",fullName:"Zafer Dogu"},{id:"39952",title:"Dr.",name:"Erdinc",middleName:null,surname:"Sahinoz",slug:"erdinc-sahinoz",fullName:"Erdinc Sahinoz"}]},{id:"68966",title:"Novel Biofloc Technology (BFT) for Ammonia Assimilation and Reuse in Aquaculture In Situ",slug:"novel-biofloc-technology-bft-for-ammonia-assimilation-and-reuse-in-aquaculture-in-situ",totalDownloads:1907,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Ammonia is one of the most harmful risks for success of fish and shrimp culture. There is no effective solution for harmlessness of ammonia in traditional aquaculture operations except exchanging water, which would bring negative effects on environment, or fixing expensive equipment. Biofloc technology (BFT) that appeared in recent years supplies a novel solution for this issue without exchanging huge water and fixing equipment. This technology could assimilate ammonia almost in real time with many other supplemental benefits. Because of the very high nutritional value for fish and shrimp, bioflocs, the by-product of BFT, could also be reused as a complemented food in situ or a gradient for feedstuff to replace expensive fishmeal or be processed to pellet diet to feed fish and shrimp directly. 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Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). 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Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/79592",hash:"",query:{},params:{id:"79592"},fullPath:"/chapters/79592",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()