Block SJ, Ibrahim Y, Cohen C. Adherence to antiviral treatment among people living with chronic hepatitis B: A global survey. World J Virol 2025; 14(4): 110951 [DOI: 10.5501/wjv.v14.i4.110951]
Corresponding Author of This Article
Suzanne J Block, RN, BSN, MPH, Department of Health, Behavior and Society Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, United States. sblock8@jhmi.edu
Research Domain of This Article
Health Policy & Services
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Observational Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 25, 2025 (publication date) through Dec 25, 2025
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World Journal of Virology
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Block SJ, Ibrahim Y, Cohen C. Adherence to antiviral treatment among people living with chronic hepatitis B: A global survey. World J Virol 2025; 14(4): 110951 [DOI: 10.5501/wjv.v14.i4.110951]
Author contributions: Cohen C and Ibrahim Y conceptualized, administered, and obtained funding for the original study; Block SJ and Ibrahim Y prepared the draft for this manuscript, coded and analyzed the data; Block SJ, Ibrahim Y, and Cohen C reviewed the original draft and interpreted data to provide feedback on the draft manuscript. All authors contributed to the article and approved the final submitted version.
Institutional review board statement: The study that included collecting this data was Institutional Review Board approved by Heartland Institutional Review Board (No. 191221-270). Participation in the survey was voluntary and anonymous.
Informed consent statement: Not applicable. No individual identifying data has been collected. Survey responses were all anonymous.
Conflict-of-interest statement: The Hepatitis B Foundation receives public health program and research grants from Bristol-Myers Squibb Company, GSK plc, Gilead Sciences, Inc., Dynavax Technologies, F. Hoffmann-La Roche Ltd., Vir Biotechnology, Inc., and Precision Biosciences, Inc. Chari Cohen serves on a patient advocacy advisory committee for GSK plc and Gilead Sciences, Inc., with remuneration going directly to the Hepatitis B Foundation. Ibrahim Y serves on a patient/advocacy advisory committee for F. Hoffmann-La Roche Ltd./Genentech, with funds being distributed to the Hepatitis B Foundation. Block S is supported by the training grant T32 CA009314 from the National Cancer Institute, National Institutes of Health. The content of this work is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Please contact the corresponding author for data requests. Data is available upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Suzanne J Block, RN, BSN, MPH, Department of Health, Behavior and Society Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, United States. sblock8@jhmi.edu
Received: June 19, 2025 Revised: September 12, 2025 Accepted: December 2, 2025 Published online: December 25, 2025 Processing time: 189 Days and 17.8 Hours
Abstract
BACKGROUND
Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer. It requires lifelong daily medication, and long-term adherence is often cited as a concern when initiating treatment. Hepatitis B treatment adherence in the context of the patient’s medical and life experiences remains underexplored.
AIM
To evaluate factors associated with adherence to hepatitis B oral antiviral treatment.
METHODS
A global online survey was administered anonymously to adults (aged 18 years or older) living with chronic hepatitis B. A subsample of 614 individuals who reported being on hepatitis B treatment was included in the analysis. Indices for treatment affordability, healthcare service acceptability, and individual physical, psychological, and emotional functioning were constructed (Cronbach’s alpha = 0.71-0.83). Data analysis was conducted using Stata/BE 17.0.
RESULTS
Overall, 81% of respondents reported high adherence to hepatitis B treatment. Lower adherence was observed among individuals who identified as African or African American (P = 0.008). Among participants with low adherence, 60% cited affordability as a challenge (P = 0.068), 53% identified healthcare service acceptability as a challenge (P = 0.04), 79% described physical functioning as a challenge (P = 0.002), and 40.5% reported difficulties with psychological functioning (P = 0.55).
CONCLUSION
Findings demonstrate high treatment adherence, although access to and acceptability of healthcare services, as well as an individual’s physical functioning challenges, appear to be related to low adherence.
Core Tip: As we work towards global hepatitis B elimination, it is essential to understand how individuals’ medical and psychosocial dimensions of care influence treatment adherence. Overall findings from this study demonstrate high treatment adherence among participants living with hepatitis B. However, access to and acceptability of healthcare services, as well as an individual’s physical functioning challenges, appear to be related to low adherence. This study adds new data and can inform future treatment guidelines to better align with patients’ lived experiences and support effective programmatic strategies aimed at optimizing treatment adherence and improving health outcomes for people living with hepatitis B worldwide.
Citation: Block SJ, Ibrahim Y, Cohen C. Adherence to antiviral treatment among people living with chronic hepatitis B: A global survey. World J Virol 2025; 14(4): 110951
Chronic hepatitis B (CHB) remains a global health issue as a major cause of serious liver disease, including cirrhosis and hepatocellular carcinoma, or primary liver cancer[1]. Hepatocellular carcinoma accounts for 80% of all liver cancer cases and ranks as the third most common cause of cancer death worldwide[1]. An estimated 254 million people live with CHB worldwide and are at heightened risk for such complications[1]. The burden of this disease varies by region, with the World Health Organization (WHO) Western Pacific region (97 million) and the African region (65 million) accounting for the majority of people chronically infected[2]. This is followed by the WHO South-East Asian and Eastern Mediterranean Regions, with 61 million and 15 million individuals, respectively. Prevalence is lowest in the WHO European Region and the Region of the Americas, with about 1% of the population living with CHB[1].
Current antiviral treatment can control viral replication and reduce the risk of serious liver disease for people living with hepatitis B (PLWHB)[3]. Without effective treatment, there is a variation in the cumulative risk of developing cirrhosis over five years, ranging from 8% to 20%[3]. However, taking antiviral treatment can be challenging. It is a long-term commitment that can include taking a daily pill for many years or indefinitely[3]. None of these treatments is curative, and most have potential side effects. Side effects range in severity and may include fatigue, decreased mineral bone density, or renal impairment[4]. Under most circumstances, these medications should not be stopped, as discontinuation or non-adherence with antiviral therapy can result in acute hepatitis flares or incomplete viral control[3]. Adherence to antiviral treatments is, therefore, critical for PLWHB.
Adherence is often poor for individuals living with chronic conditions, who tend to require long-term oral antiviral treatment[5,6]. Treatment adherence is defined as the extent of agreement between an individual’s behavior and a healthcare provider’s recommendations[7]. These are health behaviors that extend beyond taking prescribed medication. Adherence is a dynamic process between a patient and provider, who collaboratively create a treatment plan that fits the medical advice from the health provider and the patient’s care preferences, lifestyle, and personal values. For individuals who do not adhere to prescribed medication guidelines, the reasons may be intentional or unintentional, with heterogeneity in the social, economic, healthcare system, and patient- and disease-specific factors that shape their adherence behaviors[6]. In consequence, multiple social-ecological factors can impede adherence globally[6,8].
Ensuring treatment adherence is crucial for PLWHB, given the long-term nature of treatment and potential negative outcomes of prematurely stopping. Common barriers to treatment adherence for PLWHB include the cost of treatments, ease of obtaining medications, including refills, limited knowledge about treatment options, and concerns about side effects[9-11]. In a study of 308 participants with CHB in Wuhan, China, 48.7% reported financial constraints and 45.1% reported unintentional non-adherence, particularly forgetfulness, as barriers to oral antiviral treatment adherence[9]. Another study highlighted the financial burden along with the importance of patient-friendly information[10]. In contrast, concerns about disease progression, positive patient-provider interactions, including easy-to-understand language and time spent with providers, and social support were found to facilitate treatment adherence[9,12,13]. Fear about progressive liver disease has been described as a motivator for adherence to antiviral therapy, alongside the benefits of high-quality clinical encounters with the use of plain language by health providers to ensure clarity and understanding[12]. This reflects the multi-layered barriers that PLWHB face within and outside the healthcare system, which influence whether someone has the capacity to adhere to a treatment regimen.
Examining barriers and enablers, ranging from economic to intrapersonal, can help clarify our understanding of patients’ capacity to adhere to prescribed treatment regimens. This focus on treatment adherence in the context of the multiple dimensions that shape health behaviors remains underexplored for PLWHB. Accordingly, we sought to add to this ongoing and critical discussion by examining treatment adherence and its association with diverse barriers faced by PLWHB. Results can be used to inform discussions about the expansion of CHB treatment and to develop future tools and resources that support long-term treatment adherence among PLWHB.
MATERIALS AND METHODS
Study measures and population
Data for this study were collected through an anonymous global online survey of people living with CHB. The survey tool and recruitment strategies were previously described[14,15]. Eligibility criteria included self-reporting to be 18 years or older and living with CHB. Survey respondents were asked if they were currently taking medication for their hepatitis B. Those who indicated experience with hepatitis B medication were further asked, “How often do you miss taking your hepatitis B medication?” Only respondents who answered that they were currently taking oral antiviral medication (tenofovir disoproxil fumarate, tenofovir alafenamide, or entecavir) for hepatitis B and answered this specific question about medication adherence were included in this analysis (n = 614).
Ethical approval
Institutional Review Board approval was obtained before conducting data collection (No. 191221-270). All survey responses were anonymous, and no personal identifying information was collected.
Data processing
The primary outcome of interest was treatment adherence, captured by participant responses to how often they missed their prescribed hepatitis B antiviral medication. Responses were collapsed into binary outcomes, such that those who answered that they missed their medication every other day or once a week were categorized as reporting low treatment adherence, and those who answered that they missed their medications once a month, a few times a year, or never were categorized as reporting high treatment adherence. The decision to collapse this variable into a binary outcome was informed by expert consultation with virologists and hepatologists based on the potential virological and/or clinical outcomes associated with these various instances of missing medication doses (Email, January 2024).
The primary predictors were assessed via survey questions relevant to the aspects of treatment adherence among PLWHB as described in the literature. Questions related to affordability, acceptability of healthcare services, and individual functioning can be found in Table 1. Additional covariates included age in years (18-30, 31-45, and ≥ 46), gender identity (male/female), ethnicity (White/Other, African/African American, Asian, Asian American, Native Hawaiian, and Pacific Islander), educational attainment (high school or less, technical/vocational/some college, college graduate, postgraduate), and whether one lives in a large city (yes/no).
Table 1 Survey questions on dimensions of treatment adherence.
Q: In order to better understand the medical challenges that you may face as a person living with chronic hepatitis B, please rate the following statements from (not at all challenging, a little bit challenging, somewhat challenging, very challenging, and extremely challenging)
Cost of blood tests and ultrasounds
Cost of doctor visits every 6 months
Cost of medication to control my hepatitis B
Lack of health insurance or a prescription plan
Finding a doctor who knows how to manage my hepatitis B
Going for medical check-ups every 6 months
Q: Please rate the following statements from (not at all challenging, a little bit challenging, somewhat challenging, very challenging, and extremely challenging); because of my chronic hepatitis B diagnosis
I feel less productive
Managing fatigue is a challenge
I worry that my relationships with family and friends are negatively affected
I worry that my ability to do my job is negatively affected
I worry that I will transmit the virus to someone else
I fear that I will face discrimination (for example, lose my job or not get accepted into a school)
I fear that I could develop liver cancer
I fear that I will live a shorter life
I feel shame
I feel like avoiding others
I feel that others avoid me
I feel life is less enjoyable
I feel shame
I feel like avoiding others
I feel that others avoid me
I feel life is less enjoyable
Q: What challenges do you face regarding your hepatitis B medication?
Not wanting to take a pill every day because it reminds me of my chronic condition
Relevant survey items were selected to create the treatment adherence indices on affordability, healthcare service acceptability, and individual physical, psychological, and emotional functioning (Table 2). All survey questions used to compose the indices were 5-point Likert scale items, with response options ranging from 1 to 5, with 1 being not at all challenging to 5 being extremely challenging. Each index was calculated as the average of the 5-point scale scores for the variables included in the index. To facilitate analysis, indices were transformed into binary variables (“challenging” vs “not challenging”) by calculating the sum score of each index and using the mean value of each score as the cutoff value. Values above the mean indicated “challenging” (indicating that affordability, acceptability, or accessibility posed a challenge to healthcare access), while values below the mean were categorized as “not challenging” (indicating no significant challenge regarding healthcare access)[14,16]. Reliability tests were conducted to confirm that the indices were “fit for use”, with all Cronbach’s alpha values exceeding 0.7 (ranging from 0.71 to 0.83)[17]. The specific Cronbach’s alpha values for each index are detailed in Table 2.
Statistical analysis was performed using Stata/BE 17.0 (Stata, no date). χ2 analyses examined the relationship between the covariates of interest, including sociodemographic characteristics, and the index responses. A P-value less than or equal to 0.05 was considered a statistically significant result. The statistical analysis was overseen by Ibrahim Y, who has expertise in biomedical statistics.
RESULTS
The final sample included 614 respondents, with some reporting high treatment adherence (missed their medication once a month/a few times a year/never) (n = 496) and others reporting low treatment adherence (missed their medication once a week/every other day) (n = 118). The sociodemographic characteristics of survey respondents, overall and stratified by treatment adherence, are presented in Table 3. Overall, treatment adherence among survey respondents was considerably high (80.8%). Just under half (47.2%) of all respondents fell within the 31-45 age range, and 78.2% identified as male. Half (52.4%) identified as African or African American and were from the African WHO Region (48.5%). The majority of respondents were also either college graduates (40.7%) or postgraduates (38.4%). Just over half of all respondents (52.6%) reported living in a large city. Lower levels of treatment adherence were reported among respondents who identified as African/African American (P = 0.008). None of the other demographic variables showed statistically significant relationships with treatment adherence. While not significant, respondents aged 18-30 and 31-45, from Western Pacific, Middle Eastern, and African WHO Regions, or those with higher education levels, reported lower adherence to hepatitis B medication.
Table 3 Sociodemographic characteristics of survey respondents based on treatment adherence, n (%)1.
Table 4 shows the relationships between the indices and treatment adherence. Among all survey respondents (n = 614), half (52.7%) said that the affordability of their medical needs, including the cost of blood tests and ultrasounds, doctor visits, and medications, was challenging, and 44.5% said healthcare service acceptability, such as finding a doctor who could manage their diagnosis and going for check-ups biannually, was challenging. For psychological functioning, which pertains to one’s worries and fears surrounding their diagnosis, 38.1% of respondents reported that this aspect was challenging, and two-thirds (67.3%) said physical functioning was challenging. Regarding emotional accessibility, including feeling shame, feeling like others avoided them, feeling like life was less enjoyable, and not wanting to take a daily medication because of the reminder of their diagnosis, 36.7% of all respondents said this was challenging.
Table 4 Survey respondent treatment adherence and healthcare access indices, n (%).
For individuals who reported low treatment adherence to their hepatitis B medication (n = 118), 60.3% said affordability was challenging, compared to 50.9% of those who reported high treatment adherence (n = 496) (P = 0.068). Service acceptability was challenging for just over half (53%) of those who reported low treatment adherence compared to 42.5% of those who reported high treatment adherence (P = 0.04). The psychological functioning index indicates that 40.5% of respondents who reported low treatment adherence found these factors challenging, compared to 37.5% of respondents who reported high treatment adherence (P = 0.55). The majority of respondents who reported low treatment adherence (79.3%) found physical functioning to be challenging, compared to 64.5% of those who reported high treatment adherence (P = 0.002). Lastly, 38.5% of those who reported low treatment adherence reported that emotional functioning was challenging compared to 36.2% of those who reported high treatment adherence (P = 0.65).
DISCUSSION
This study aimed to better understand how well people adhere to hepatitis B antiviral treatment and the diverse barriers that influence treatment adherence among PLWHB. Potential barriers examined included affordability, service acceptability, and an individual’s physical, emotional, and psychological well-being. Despite various treatment challenges identified in this study and previous research[10,11], adherence to daily antiviral treatment was notably high among survey respondents, regardless of age, gender, educational status, or geographic location. This finding aligns with previous studies[18,19].
Affordability of care
Affordability of healthcare is a common concern for people with chronic diseases who must pay for treatments, transportation to appointments, and other related costs. This study found that over half of all respondents found affordability challenging, and it was a reported challenge for a higher percentage (60.3% vs 50.9%) of those who reported low adherence. While these indices were not significantly associated with treatment adherence, the findings demonstrate the continued barrier of treatment costs, a finding consistent with other studies[9].
Service acceptability and the role of the healthcare system
The acceptability of services, including finding a doctor who knows how to manage hepatitis B, and one’s capacity to attend medical check-ups every six months, were significantly associated with treatment adherence in this study. Among survey respondents with low adherence, half reported challenges with service acceptability. This underscores how limited access to providers knowledgeable about hepatitis B or inconsistent medical management may serve as barriers to maintaining a treatment regimen. Finding a health provider who is equipped to manage hepatitis B remains an ongoing issue, with one study based in the United States revealing that 80% of the physicians and medical residents in training surveyed did not feel adequately prepared to care for this patient population[20]. Studies in other countries have shown varying levels of health provider knowledge and awareness regarding hepatitis management, some citing inadequate medical training[21,22]. PLWHB have also expressed that health facilities were unable to meet their needs, including education on their diagnosis, decisions on treatment initiation, and instructions for taking their medications[12,23]. This highlights the role of infrastructural determinants of healthcare, which consists of the healthcare facilities, systems, and health providers and staff who are adequately trained and prepared to care for their patients[24,25]. This infrastructure can shape a patient’s health experience and their preparedness to adhere to a treatment regimen.
The relationship between treatment adherence and physical, psychological, and emotional functioning
Physical functioning, including feelings of exhaustion, unproductivity, and difficulty managing fatigue, was also significantly associated with treatment adherence. While almost 80% of those with lower treatment adherence reported this as a challenge, two-thirds of those with high treatment adherence did, as well. This suggests that the physical burden of CHB is more impactful for PLWHB than is often recognized. Among PLWHB, physical symptoms such as fatigue and muscle pain are commonly reported manifestations of hepatitis B[26]. Given the vast majority of PLWHB reporting physical functioning as a challenge to treatment adherence, we must better understand this as a barrier.
Although patient-reported outcomes are not currently central to treatment initiation decisions for hepatitis B, the observed association between better physical functioning and higher treatment adherence suggests that the potential benefits of early treatment initiation merit further exploration. Notably, physical symptoms may also arise as a side effect of antiviral therapy[4]. Some studies have reported that PLWHB may unintentionally miss doses due to these symptoms[12], while others report that individuals may avoid their medication because of concerns about potential side effects[9]. Distinguishing whether physical symptoms stem from the disease itself or are induced by treatment and understanding the limited evidence on whether antiviral therapy improves physical functioning highlights the complexity of treatment adherence. This must be addressed through open, supportive communication between patients and their healthcare providers to ensure individualized, informed treatment strategies.
Lastly, while over one-third of study participants reported challenges with psychological and emotional functioning due to CHB, these challenges were not significantly related to treatment adherence in this study. Thus, while these challenges may not be directly related to CHB treatment adherence in this study, they are still commonly reported as negatively impacting the quality of life for PLWHB[11,27]. Additionally, in contrast to this study, others have shown that viral suppression due to antiviral medication may improve patient-reported outcomes, including mental health[28,29]. Thus, continued attention to these influences is essential when considering treatment decisions, treatment adherence, and the overall health and well-being of PLWHB.
The role of adherence in the CHB treatment paradigm
The treatment paradigm for CHB has diverged from other chronic conditions that also depend on long-term daily oral treatment, including hypertension, diabetes, and human immunodeficiency virus. For these other conditions, oral medication is widely, if not universally, recommended[30-33]. For CHB, oral medication is recommended only for a subset of the impacted population, based primarily on evidence of liver damage and risk of disease progression[3,4,34,35]. While there is little rigorous data documenting low adherence to antiviral regimens among PLWHB, adherence concerns are widely discussed as a reason to limit treatment eligibility. However, when adherence has been studied, findings often demonstrate relatively high levels of adherence, with some variability[9,18,36,37], and low levels (as low as 1%) of adverse outcomes among people who stop antiviral treatment[38]. Thus, there appears to be a disconnect between perceived and real treatment adherence concerns. Are we problematizing medication adherence for CHB, and can we reframe adherence from serving as a treatment barrier to becoming a treatment enabler?
Looking at human immunodeficiency virus, diabetes, and hypertension as examples, treatment adherence guidelines recognize socioecological factors related to adherence[30-33]. The treatment practice guidelines for these conditions focus heavily on offering provider- and patient-focused guidance for maximizing adherence and promoting interventions that provide patients with resources and support to improve adherence[30-33]. In doing this, they have reframed the focus from nonadherence as a barrier to recommending treatment to optimizing adherence as a key component of treatment. This has fostered broader treatment recommendations and led to the implementation of adherence-focused interventions[39-41]. We can learn from these models to reframe adherence in relation to the CHB treatment paradigm. A better understanding of adherence, as well as the barriers and facilitators, is critical as we continue to work towards global viral hepatitis elimination[42]. This is especially vital at a time when professional treatment guidelines are expanding the pool of PLWHB who are eligible to receive oral antiviral treatment, and as there are growing discussions on whether to further expand hepatitis B treatment more universally[34,43-45].
Study strengths and limitations
This study focuses on a relatively under-researched area - adherence to hepatitis B treatment. This global study of PLWHB incorporates patient-reported experiences and adherence to hepatitis B oral antiviral treatments, providing insights that are often underrepresented in clinical literature. These findings provide valuable contributions to shaping patient-centered approaches for improving hepatitis B care and adherence. Still, study limitations must be acknowledged. Reliance on self-reported data may introduce both recall and social desirability biases. This could affect the accuracy of reported adherence behaviors. Additionally, the voluntary nature of survey participation raises the possibility of self-selection bias, whereby individuals who are more engaged or informed about their condition may be overrepresented in the results. The survey also did not collect information on participant income, and, instead, educational attainment was used as a proxy for socioeconomic status. Although not a perfect substitute, education can offer valuable insights into socioeconomic status and its potential influence on treatment adherence.
The sample was predominantly male, potentially limiting generalizability. This may be partially attributed to disparities in internet access, both in general and particularly among women, in many low- and middle-income countries[46,47]. Structural barriers to healthcare access that disproportionately affect women in these settings may also have influenced the likelihood of being on treatment, thereby impacting the final sample of respondents from low- and middle-income countries who reported receiving antiviral therapy. Finally, the survey was administered only in English, which may have limited participation from individuals who do not speak English. Despite this, the study achieved strong geographic diversity, with responses representing a wide range of countries and regions, enhancing the global relevance of the findings.
CONCLUSION
Treatment adherence is a multifaceted and complex issue that must be understood within the broader context of interactions among patients, providers, and the health system. Despite its critical importance, adherence to hepatitis B oral antiviral treatment remains underexplored. This study found high rates of treatment adherence among study participants and identified affordability, access to acceptable healthcare services, and physical functioning as challenges to adherence. Study results can inform discussions and help develop future tools and resources to support long-term treatment adherence among PLWHB. More research is needed to better understand CHB treatment adherence, including the social-ecological factors associated with low adherence, and how treatment adherence is impacted by co-morbidities, patient preferences, patient-reported outcomes, and patients’ perceived value of treatment. Exploring these constructs will help design interventions and resources for both patients and providers that will support PLWHB and enable treatment adherence. It will also help us better understand the social and economic dimensions of CHB care and treatment access, thereby fostering policy change to break down these barriers.
ACKNOWLEDGEMENTS
We would like to sincerely thank the people living with CHB who offered their valuable insights by voluntarily participating in this survey.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Virology
Country of origin: United States
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade B
Novelty: Grade B, Grade B, Grade B
Creativity or Innovation: Grade B, Grade B, Grade B
Scientific Significance: Grade A, Grade B, Grade B
P-Reviewer: Alshammary RAA, PhD, Iraq; Chen LQ, PhD, Associate Professor, Postdoctoral Fellow, China S-Editor: Bai SR L-Editor: A P-Editor: Xu ZH
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