Prevalence of Hepatitis B and C in Pakistan from 2001 to 2022: A Systematic Review

Background: Hepatitis B and C represent a significant public health concern globally, with a substantial burden in developing countries, particularly Pakistan. The country's diverse demographic and socio-economic landscape presents challenges in the surveillance and management of these infectious diseases. Objective: This systematic review aims to consolidate and analyse the prevalence data of Hepatitis B and C infections reported across Pakistan from 2001 to 2022 to understand the epidemiological trends and to inform public health interventions. Methods: A thorough search of various research databases was conducted to identify studies that reported the prevalence of Hepatitis B surface antigen (HBsAg) and anti-Hepatitis C virus (anti-HCV) antibodies. Studies were selected based on inclusion criteria focused on the population of Pakistan between 2001 and 2022. Data extraction was systematic, although a comprehensive quality assessment of each study was not completed. Results: The review included 54 studies with varying sample sizes and methodologies, including ELISA, ICT, PCR, and other serological assays. Prevalence rates for HBsAg and anti-HCV varied significantly, with HBsAg ranging from 0.9% to 44.4% and anti-HCV from 0.3% to 62.6%. These findings highlight a considerable regional variability and suggest an upward trend in HCV prevalence over the past two decades. Conclusion: The elevated prevalence rates of Hepatitis B and C across Pakistan underscore the need for robust public health policies, standardized surveillance, and targeted interventions. Despite the systematic approach to data extraction, the review is limited by the absence of a comprehensive quality assessment, which is essential for future research to build upon.


INTRODUCTION
The prevalence of hepatitis B and C in Pakistan has been a significant public health concern, particularly over the last two decades.Hepatitis, a term with Latin origins, signifies inflammation of the liver tissue.It is a global public health challenge, especially in developing countries in Asia.The disease is primarily viral in origin, often leading to other liver complications and in some cases, hepatocellular carcinoma.Although a single virus subtype usually causes infections, co-infections involving multiple viruses are also possible.The manifestation of hepatitis can be acute or chronic, potentially progressing to severe conditions like liver cirrhosis or cancer.While there are nonviral causes such as drugs and autoimmune disorders, viral infections remain the predominant cause (1)(2)(3).
Hepatitis B Virus (HBV) is a global concern, with a significant burden in developing countries.It affects about 2 billion people worldwide, with approximately 400 million suffering from its chronic form.Pakistan, a developing country, has seen a high prevalence of HBV, affecting nearly nine million people.Newborns are particularly vulnerable to HBV, with infection rates dropping from over 90% at birth to about 25% by the age of five (4,5).The Hepatitis C Virus (HCV), belonging to the Flaviviridae family, has a 9.6 kb positive sense RNA genome.Approximately 3% of the global population is infected with HCV, with the highest endemic rates in Africa and Egypt.In Pakistan, around 10 million people have been diagnosed with HCV, which can lead to chronic conditions like liver cirrhosis (6,7).
The epidemiology of these viruses is complex, influenced by multiple risk factors.In developed countries, transmission occurs primarily through needlestick injuries, intravenous drug use, blood transfusions, sexual contact, maternal exposure, and tattooing.However, in developing countries, including Pakistan, the transmission is often due to the use of unsterilized medical equipment, particularly contaminated injections, contributing to 8-16 million HBV and 2-5 million HCV infections (8)(9)(10)(11).
Despite a decline in HCV infections in developed countries, the incidence in developing nations is rising.In Pakistan, the spread of these viruses has been rapid in the past two decades.The first comprehensive nationwide assessment of HCV and HBV prevalence was conducted in 2007-2008 by the United States.Following this, in June 2010, Pakistan launched a national hepatitis sentry site surveillance system.However, this system's scope is limited to regional capitals and Islamabad due to resource constraints, and it did not include high-risk populations in the national survey, focusing only on seropositivity among the general population.The prevalence of hepatitis B and C in Pakistan is a significant public health issue (12).This review aims to consolidate available data to provide a clearer picture of the prevalence rates and highlight the need for more comprehensive surveillance and targeted interventions to address this growing challenge.

MATERIAL AND METHODS
In the systematic review conducted to evaluate the prevalence of hepatitis B and C in Pakistan, a comprehensive literature search was performed using a range of established biomedical and general citation databases.This search involved querying PubMed, OpenMD, Google Scholar, the Directory of Open Access Journals (DOAJ), ScienceDirect, and Web of Science (13,14).The approach focused on deconstructing the main topic into key terms and phrases, notably "Prevalence of hepatitis B and C in Pakistan" and "Incidence of hepatitis B and C in Pakistan," to ensure a wide-ranging and thorough search.
The research team set specific criteria for including studies in the review.Primarily, the focus was on studies that concentrated on the Pakistani population, encompassing research at local, regional, and national levels.This included investigations conducted in various geographic settings within Pakistan such as cities, districts, provinces, and communities.The diagnostic methods used in these studies were a crucial inclusion criterion; only those that employed Polymerase Chain Reaction (PCR) or Enzyme-Linked Immunosorbent Assay (ELISA) for confirming HBV or HCV infections were considered (15).These methods were chosen due to their high accuracy and reliability in detecting hepatitis infections (15,16).
Additionally, the researchers required that the studies provide reliable estimates of their sample sizes and detailed demographic information.This requirement was crucial to ensure that the findings were representative of the broader population and could be generalized to the entire country.By adhering to these strict criteria, the team aimed to compile a comprehensive and trustworthy dataset that accurately reflects the state of hepatitis B and C prevalence and incidence in Pakistan.

RESULTS
In the systematic review entitled "Prevalence of Hepatitis B and C in Pakistan from 2001 to 2022," the authors followed a structured methodology to identify and select relevant studies for inclusion.The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart provided a visual summary of the literature search and study selection process.Initially, a comprehensive search was conducted across various research databases, resulting in the identification of 257 records.Prior to screening, 84 records were removed due to duplications, ineligibility as determined by automation tools, irrelevance to the condition of interest, and other unspecified reasons.
Subsequently, the remaining 173 records underwent a meticulous screening process.Of these, 61 records were excluded based on criteria such as improper outcome measures and inappropriate research methods, leaving 112 reports that were sought for retrieval.The retrieval process encountered challenges, as 39 reports could not be retrieved, which necessitated the assessment of 73 reports for eligibility.This assessment further narrowed the field, with 19 reports being excluded due to reasons such as unsuitable comparison groups, the use of pseudo equipment, and other miscellaneous factors.Ultimately, the review included 54 studies that met all the inclusion criteria and were deemed suitable for a comprehensive analysis of the prevalence of Hepatitis B and C in Pakistan over the specified period.These studies provided the data necessary for a detailed synthesis and understanding of the epidemiological trends of these infections in the region (11,12,14,.The table presents a comprehensive set of data from various studies included in the systematic review on the prevalence of Hepatitis B and C in Pakistan from 2001 to 2022.Here's a way to describe the results in a summary: The systematic review aggregated data from 54 studies encompassing a wide geographical spread across Pakistan, including major cities and provinces such as Islamabad, Punjab, Khyber Pakhtunkhwa (KPK), Sindh, Lahore, and Balochistan.These studies employed diverse methodologies, predominantly Enzyme-Linked Immunosorbent Assay (ELISA), Immunochromatographic Test (ICT), Polymerase Chain Reaction (PCR), and other serological assays, to detect Hepatitis B surface antigen (HBsAg) and anti-Hepatitis C virus (anti-HCV) antibodies.The prevalence rates of HBsAg and anti-HCV varied significantly across studies, with HBsAg rates ranging from as low as 0.9% in Swat to as high as 44.4% in Punjab, and anti-HCV rates ranging from 0.3% in Multan to 62.6% in Punjab.The sample sizes of the studies were equally diverse, from a small sample of 252 in Islamabad to a large cohort of 160,376 in the same city, indicating a broad representation of the population.
Several studies did not report either HBsAg, anti-HCV, or both prevalences, and a few did not specify the sample size.It is noteworthy that the highest anti-HCV prevalence (55%) was reported in a study with a sample size of 100 from Lahore, and the highest HBsAg prevalence (44.4%) was reported in Punjab with a sample size of 4,890.This wide range in prevalence rates underscores the heterogeneity of Hepatitis B and C infection rates within different regions and populations in Pakistan.The review highlights the critical public health concern these infections pose and underscores the necessity for targeted interventions and sustained surveillance to address this health burden.

DISCUSSION
The systematic review on the "Prevalence of Hepatitis B and C in Pakistan from 2001 to 2022" has elucidated the varying prevalence of these viral infections, showcasing a critical public health issue.This review's findings suggest that the prevalence rates of Hepatitis B and C in Pakistan are not only higher than those reported in many other countries but also exhibit a remarkable inter-regional variability.
When juxtaposed with studies from other regions, the prevalence of Hepatitis B in Pakistan as reported by Butt and Amin in 2008 (62) (2.97% HBsAg) appears to be comparable to the  16).This stark contrast underscores the significant disparities in hepatitis prevalence within the South Asian region and calls for a deeper investigation into the drivers of these differences.
The review's findings also beg comparison with historical data from Pakistan itself.A study by Zuberi et al. in 2008 reported an anti-HCV prevalence of 5.3%, which is notably lower than several findings in the current review (71).This suggests an upward trend in the prevalence of HCV over the years, highlighting the escalating nature of this health issue.One of the review's limitations, however, lies in the quality assessment of the included studies.While data extraction was conducted systematically, the evaluation of study quality remained incomplete, posing a risk to the validity of the findings.The lack of quality assessment means that the reported prevalence rates might be affected by biases inherent in the individual studies, such as selection bias or reporting bias.
Furthermore, the heterogeneity of the methodologies used in the studies, including different diagnostic tests and sampling strategies, presents a challenge in drawing definitive conclusions.This methodological variability might lead to discrepancies in the reported prevalence rates, potentially affecting the overall synthesis of data.In light of these findings, it becomes imperative for policymakers and healthcare providers to develop targeted interventions tailored to regional needs.The establishment of standardized surveillance and reporting mechanisms could aid in generating more reliable data, which is crucial for the effective management and prevention of hepatitis in Pakistan.For future research, a more rigorous quality appraisal of studies is

CONCLUSION
The systematic review has shed light on the alarming prevalence of Hepatitis B and C in Pakistan, with rates that suggest an urgent public health crisis.The data underscores a significant challenge facing the healthcare system and necessitates immediate action to curtail the spread of these infections.Despite systematic data extraction, the absence of a thorough quality assessment of the included studies marks a limitation of the review, potentially impacting the reliability of the prevalence rates reported.The implications of these findings are profound.There is a clear need for enhanced public health strategies, including effective screening programs, vaccination campaigns, and educational initiatives to increase awareness about transmission routes and prevention methods.
The healthcare infrastructure must be bolstered to manage the existing caseload and to implement preventive strategies effectively.
Furthermore, the government and public health agencies should prioritize the formulation of policy frameworks that address the regional disparities in hepatitis prevalence.Such frameworks should encourage the use of standardized diagnostic criteria and reporting to better monitor and control the epidemic.Collaborative efforts with international health bodies could provide the necessary support and resources to implement these strategies.Investment in research is also crucial.Future studies should focus on identifying the socio-economic, cultural, and biological factors contributing to the high prevalence rates, particularly in the hardest-hit regions.Understanding these factors is essential for tailoring interventions to the needs of specific populations.
In conclusion, while the review presents a concerning picture of hepatitis prevalence in Pakistan, it also offers a foundation upon which to build comprehensive and effective public health responses.The need for action is immediate, and the potential benefits of such interventions extend beyond the immediate reduction in hepatitis prevalence to the broader improvement of public health and well-being in Pakistan and the region at large.
ISSN 2791-156X Journal of Health and Rehabilitation Research (JHRR) This work is licensed under a Creative Commons Attribution 4.0 International License | www.jhrlmc.com| Vol. 3, Issue 2 ISSN 2791-156X Jamali YA. et al., 2023 | Prevalence of Hepatitis B and C in Pakistan: A Systematic Review This work is licensed under a Creative Commons Attribution 4.0 International License | www.jhrlmc.com| Vol. 3, Issue 2

Figure 1
Figure 1 PRISMA Flow Chart ISSN 2791-156X Journal of Health and Rehabilitation Research (JHRR) This work is licensed under a Creative Commons Attribution 4.0 International License | www.jhrlmc.com| Vol. 3, Issue 2 et al., 2023 | Prevalence of Hepatitis B and C in Pakistan: A Systematic Review This work is licensed under a Creative Commons Attribution 4.0 International License | www.jhrlmc.com| Vol. 3, Issue 2 This work is licensed under a Creative Commons Attribution 4.0 International License | www.jhrlmc.com| Vol. 3, Issue 2 recommended to ensure the robustness of the systematic review's conclusions.Additionally, there is a need to explore the factors contributing to the high variability in hepatitis prevalence across different regions of Pakistan.

Table 1
Prevalence of HBsAg and Anti-HCV 3.5% prevalence in sub-Saharan Africa as reported by Schweitzer et al. in 2015 (68) but lower than the 5.3% reported by Zampino et al. in 2015 for East Asia (69).However, for Hepatitis C, the situation seems dire.The prevalence rate of 62.6% reported by Ashraf et al. in 2015 far exceeds the global average of 2.5% as noted by Gower et al. in 2014, indicating a potential regional epidemic in Punjab, which demands urgent attention (70).Comparatively, neighbouring India, as reported by Sievert et al. in 2011, has a relatively lower HCV prevalence rate of approximately 1% (