Exploring the landscape of viral hepatitis: A comprehensive retrospective analysis of mortality trends and disparities in the United States (1999–2020)

Abstract

Viral hepatitis (VH) remains a leading cause of preventable mortality in the United States (US). Despite advancements in antiviral therapies, disparities in VH-related mortality persist across demographic, racial, and geographic groups. This study analyzes trends in VH-related mortality among US adults between 1999 and 2020 to identify high-risk subgroups and inform public health interventions. This retrospective cohort study analyzed VH-related deaths among US adults (≥25 years). Data were obtained from the CDC WONDER database, with cases identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes B15–B19. Age-adjusted mortality rates (AAMRs) were calculated per 1,00,000 individuals and stratified by age, gender, race and geographical location. Temporal trends in mortality were analyzed by estimating annual percentage changes (APCs) in the AAMRs using the joinpoint regression model. A total of 3,59,035 VH-related deaths were recorded among US adults during 1999 to 2020 with a cumulative overall AAMR of 7.36 (95% CI: 7.33–7.38). Overall, the AAMRs increased significantly from 1999 to 2013 (APC: +3.21; P < .01), followed by a significant decline until 2020 (APC: −5.61; P < .01). Men exhibited higher AAMRs than women, with middle-aged adults (45–64 years) most affected compared to young (25–44 years) and older adults (65 to 85+ years). Non-Hispanic (NH) American Indians/Alaska experienced the highest AAMRs followed by NH Blacks/African Americans, Hispanics, NH Asians/Pacific Islanders and NH Whites populations. Geographically, mortality rates were higher in urban areas than in rural areas, in the Western region relative to other regions and in the District of Columbia compared to other states. Significant disparities in VH-related mortality persist across demographic and geographic subgroups, with particularly higher rates among men, NH American Indian/Alaska Native population, middle-aged adults, and residents of urban and Western US regions. Targeted public health strategies are essential to address these inequities and improve outcomes.

1. Introduction

Viral hepatitis (VH) is a silent yet significant global health challenge, responsible for more than 1.3 million deaths annually, making it the second leading cause of infectious disease-related mortality worldwide.^[1] It remains a leading cause of liver-related illnesses and preventable deaths in the United States (US) claiming thousands of lives each year.^[2] From 2017 to 2020, the US recorded 6,40,000 cases of hepatitis B (HBV) and 4 million cases of hepatitis C (HCV) infections.^[3,4] The CDC (Centers for Disease Control and Prevention) VH Surveillance Report for 2022 reported 118 hepatitis A (HAV), 1797 HBV and 12,717 HCV-related deaths.^[2] From 2010 to 2018 HCV infections accounted for 0.4 million hospitalizations.^[5] A hypothetical US study projected 3,24,000 preventable deaths nationwide, from HBV alone between 2020 and 2050.^[6]

The epidemiology of VH varies widely, with clinical outcomes influenced by demographics, risk factors, and the type of virus.^[7,8] HBV and C are particularly fatal being linked to liver cirrhosis and cancer while hepatitis E and HAV are less fatal and disproportionately impact vulnerable populations, including older adults and pregnant women in low-resource settings.^[2,9] Key demographic factors like gender, age, ethnicity, geographical location and socioeconomic status are closely linked to VH prognosis.^[10] The recent COVID-19 pandemic disrupted testing and treatment, further exacerbating the differences in clinical outcomes. The literature examining such disparities is limited within the US context. In particular, there remains a significant gap in comprehensive analyses of VH-related mortality stratified by demographic and geographic factors in the United State. Such stratified data is crucial for identifying disparities in mortality across various populations and for guiding targeted public health interventions.^[11,12]

This study aims to address this gap by examining the trends in cumulative nationwide VH-related mortality over the past 2 decades, focusing on age, gender, race, and geography. By providing a deeper understanding of these trends, this research seeks to inform public health strategies and policy decisions that can mitigate the impact of VH and reduce health disparities.

2. Materials and methods

2.1. Study settings and patient screening

In this retrospective cohort study, the VH-related mortality data was sourced from the wide-ranging online data for epidemiologic research (WONDER) database, managed and regulated by the CDC.^[13] The data originates from US residents’ death certificates and is collected and organized by the National Vital Statistics System and the National Center for Health Statistics.^[14] The death certificates provide information about the cause of death and the demographics of the decedents. The cause of death is grouped as underlying, contributing, and multiple while demographics comprise age group, gender, race, and geographic location. All the death certificate data where VH was listed as the underlying or contributing cause of death from the multiple cause of death record publicly available in the CDC WONDER online database.^[15] For the identification and screening of diseases, the mortality causes in the CDC WONDER database are classified according to the International Classification of Diseases 10th Revision Clinical Modification (ICD-10-CM). For the present study, the VH-related deaths were identified by using ICD-10-CM codes B15 (acute HAV), B16 (acute HBV), B17 (other acute VH), B18 (chronic VH) and B19 (unspecified viral infections).^[16] Our study adhered to the STROBE guidelines.^[17] However, no institutional review board approval was sought as the study solely relied on publicly available deidentified data.^[15]

2.2. Data compilation and organization

The VH-associated mortality data encompassing nationwide fatalities in US adults aged 25 and above from January 1999 to December 2020 was compiled. The mortality statistics were described by demographics and geographical location within the US. The demographics comprised gender (male, female), age (young adults [25–44], middle-aged adults [45–64] and older adults [65 and above]) and race or ethnicity (Hispanics, non-Hispanic [NH] White, NH Black/African American, non-Hispanic Asian/Pacific Islander, non-Hispanic American Indian/Native American). These demographics align with previously published studies based on CDC WONDER data.^[18] Geographically, the mortality data was stratified by states and US Census Bureau’s defined regions that is Northeast, Midwest, South, and West.^[19] Additionally, the National Center for Health Statistics’ (NCHS) Urban–Rural Classification Scheme based on the US 2013 census, was utilized to stratify the population into metropolitan (large metropolitan areas [population ≥ 1 million] and medium/small metropolitan areas [population between 50,000 and 9,99,999]), and nonmetropolitan (population ≤ 50,000) areas.^[20] In addition, a comparative analysis of chronic HBV- and HCV-related mortality was performed over the study period.

2.3. Data preparation and statistical analysis

The raw VH mortality data was analyzed and described in terms of age-adjusted mortality rates (AAMR) and annual percentage changes (APCs). The VH-related deaths were standardized to the year 2000 US population to calculate AAMRs per 1,00,000 individuals with corresponding 95% CIs.^[20] AAMRs were calculated per million (10,00,000) for comparison between chronic HBV and HCV-related mortality to better detect changes over time. AAMRs were further stratified into demographic variables like year, gender, race-ethnicity, census region, and urban-rural classification. The log-linear Joinpoint regression model was applied to determine mortality trends over time by calculating annual percent changes (APC) in AAMRs and corresponding 95% confidence intervals (CIs). In our analysis of 22 years, the joint point regression software was calibrated to identify joinpoints between 0 and 4 whenever it encountered significant temporal variations in mortality patterns. The software also recommends the optimal number of inflection points, which are lower than the maximum number. This is particularly useful if the variation in trend is greatest with fewer inflection points. The APCs, along with 95% CI, were calculated through a combined application of the parametric method, permutation test, and grid search method (2, 2, 0). Positive APC indicates an increase in mortality rates and vice versa. The statistical significance of APCs was assessed using 2-tailed t tests. A P-value <.05 and CIs without 0 reflect statistically significant findings. All the analysis was made through the Joint Point Regression Program (version 5.2.0; National Cancer Institute).^[21]

3. Results

A total of 3,59,035 VH-related deaths were reported among US adults (≥25 years), between 1999 and 2020 with an overall AAMR of 7.36 (95% CI: 7.33–7.38). The death count doubled over the study period rising from 9527 in 1999 to 16,948 in 2020, representing a 42% increase. Data about the place of death was provided for 3,41,659 mortalities. Maximum deaths took place in medical facilities (56.2%) followed by decedents’ homes (27.3%), nursing homes or long-term care facilities (9.4%) and hospice facilities (7.1%) respectively. In terms of etiology, information was available for 3,11,506 deaths, of which the highest mortalities were attributed to chronic VH (88.8%) followed by acute HBV (10.2%) and acute HAV (0.9%) respectively (Tables S1 and S2, Supplemental Digital Content, https://links.lww.com/MD/Q592).

3.1. Annual trends in VH-related AAMR

The AAMR for VH-related deaths among US adults was 5.37 per 1,00,000 in 1999. It significantly increased to 8.53 by 2013 (APC: 3.21; 95% CI: 2.67–3.76; P < .01), followed by a significant decrease to 6.1 by 2020 (APC: −5.61; 95% CI: −6.9 to −4.32; P < .01; Fig. 1, Tables S1 and S3, Supplemental Digital Content, https://links.lww.com/MD/Q592).

Figure 1.

Sex-stratified and overall viral hepatitis-related age-adjusted mortality rates per 1,00,000 among US adults from 1999 to 2020.

3.2. VH-related AAMR stratified by sex

Men consistently exhibited higher AAMRs than women throughout the study period. The AAMR for men nearly doubled from 1999 to 2013 (APC: 3.37; 95% CI: 2.83–3.90; P < .01) followed by a significant decline through 2020 (APC: −5.5; 95% CI: −6.67 to −4.3; P < .01). Similarly, women experienced a significant increase in AAMR from 1999 to 2014 (APC: 2.38; 95% CI: 1.86–2.89; P < .01) after which the rate significantly declined through 2020 (APC: −6.7; 95% CI: −8.5 to −4.9; P < .01; Fig. 1, Tables S3 and S4, Supplemental Digital Content, https://links.lww.com/MD/Q592).

3.3. VH-related AAMR stratified by age

The highest AAMR was observed in middle-aged adults (45–64 years) followed by older adults (≥65 years) and young adults (25–44 years). The AAMR for middle-aged increased sharply from 1999 to 2007 (APC: 7.8; 95% CI: 6.42–9.16; P < .01) followed by a gradual increase through 2014 (APC: 1.78; 95% CI: 0.29–3.22; P = .02). Thereafter the rate significantly declined until 2020 (APC: −10.9; 95% CI: −12.3 to −9.3; P < .01).

In older adults, the AAMR remained stable from 1999 to 2004 (APC: −2.02; 95% CI: −5.24 to 1.31; P = .211), later increased significantly from 2004 to 2015 (APC: 4.09; 95% CI: 3.06–5.12; P < .01), and remained stable afterwards until 2020 (APC: 0.60; 95% CI: −1.54 to 2.78; P = .56).

For young adults the AAMR remained almost constant from 1999 to 2002 (APC: −1.4; 95% CI: −5.5 to 2.87; P = .485), later significantly declined through 2012 (APC: −6.7; 95% CI: −7.64 to −5.75; P < .01) with a further decline until 2020 (APC: −1.44; 95% CI; −2.95 to 0.08; P = .06; Fig. 2, Tables S3 and S5, Supplemental Digital Content, https://links.lww.com/MD/Q592).

Figure 2.

Viral hepatitis-related age-adjusted mortality rates per 1,00,000 stratified by age groups among US adults from 1999 to 2020.

3.4. VH-related AAMR stratified by race/ethnicity

Analysis of VH-related mortality data by race/ethnicity showed the highest overall AAMR in the NH American Indians/Alaska Natives, followed by NH Blacks/African Americans, Hispanics, NH Asians/Pacific Islanders and NH Whites.

The AAMRs for NH American Indians/Alaskan natives significantly increased between 1999 and 2013 (APC: 5.59; 95% CI: 4.21–6.99; P < .01), later declined until 2020 (APC: −1.9; 95% CI: −4.5 to 0.72; P = .142).

For the NH Blacks/African Americans, the AAMR rose significantly from 1999 to 2014 (APC: 2.24; 95% CI: 1.77–2.70; P < .01), followed by a significant steep decline until 2020 (APC: −6.62; 95% CI: 8.09 to −5.11; P < .01).

The AAMR for Hispanics remained stable between 1999 and 2004 (APC: −0.75; 95% CI: −3.90 to 2.51; P = .61), increased until 2007 (APC: 6.30; 95% CI: −6.26 to 20.54; P = .30), and stabilized afterwards until 2014 (APC: 0.78; 95% CI: −2.55 to 1.0; P = .35). The rate then significantly declined until 2020 (APC: −9.16; 95% CI: −10.81 to −7.46; P < .01).

Among NH Asians/Pacific Islanders no significant change occurred in AAMR between 1999 and 2012 (APC: 0.05; 95% CI: −1.23 to 1.13; P = .91). Thereafter the rate declined sharply until 2020 (APC: −6.09; 95% CI: −8.05 to −4.10; P < .01).

For the NH White population, the AAMR increased significantly from 1999 to 2013 (APC: 3.66; 95% CI: 3.11–4.20; P < .001), then declined until 2020 (APC: −5.00; 95% CI: −6.34 to −3.65; P < .01; Fig. 3, Tables S3 and S6, Supplemental Digital Content, https://links.lww.com/MD/Q592).

Figure 3.

Viral hepatitis-related age-adjusted mortality rates per 1,00,000 stratified by race and ethnicity among US adults from 1999 to 2020.

3.5. VH-related AAMR stratified by geographical area/location

3.5.1. States

Among states, the District of Columbia exhibited the highest AAMR (18.77) followed by Oklahoma (14.53) while Wisconsin demonstrated the lowest AAMR (3.51). States within the top 90th percentile of AAMR included the District of Columbia, Oklahoma, Louisiana, New Mexico, Oregon, Alaska, California, Washington, Texas and Tennessee. Conversely, Wisconsin, Utah, South Dakota, North Dakota, Illinois, Wisconsin, Minnesota, New Hampshire, and Connecticut fell in the 10th percentile (Fig. 4, Table S7, Supplemental Digital Content, https://links.lww.com/MD/Q592).

Figure 4.

Viral hepatitis-related age-adjusted mortality rates per 1,00,000 stratified by states among US adults from 1999 to 2020.

3.5.2. Census regions

Regional classification of mortality data revealed the highest AAMR in the Western region followed by the Southern, Northeastern, and Midwestern region. Except for the Southern region The AAMR for all other regions initially increased from 1999 to 2014 followed by a significant decline until 2020.

For the Southern region, the AAMR initially increased from 1999 to 2006 (APC: 3.9; 95% CI: 2.63–5.18; P < .01), followed by a further significant increase until 2015 (APC: 1.73; 95% CI: 0.91–2.55; P < .01). This was succeeded by a significant decline through 2020 (APC: −5.6; 95% CI: −7.04 to −4.13; P < .01; Fig. 5, Tables S3 and S8, Supplemental Digital Content, https://links.lww.com/MD/Q592).

Figure 5.

Viral hepatitis-related age-adjusted mortality rates per 1,00,000 stratified by census region among US adults from 1999 to 2020.

3.6. Rural-urban areas

Metropolitan areas exhibited higher overall AAMR (7.5) than nonmetropolitan areas (6.7). In Metropolitan areas, the AAMR significantly increased from 1999 to 2008 (APC: 3.46; 95% CI: 2.48–4.45; P < .01), followed by a further increase through 2014 (APC: 1.41; 95% CI: −0.47 to 3.34; P = .13) and significant decline afterwards until 2020 (APC: −6.81; 95% CI: −8.41 to −5.19; P < .01).

The AAMR for nonmetropolitan areas significantly increased from 1999 to 2013 (APC: 4.7; 95% CI: 3.96–5.45; P < .01), followed by a significant decline through 2020 (APC: −2.80; 95% CI: −4.39 to −1.18; P < .01; Fig. 6, Tables S3 and S9, Supplemental Digital Content, https://links.lww.com/MD/Q592).

Figure 6.

Viral hepatitis-related age-adjusted mortality rates per 1,00,000 stratified by urbanization status among US adults from 1999 to 2020.

3.7. Comparison of chronic hepatitis B virus and hepatitis C virus infection-related mortality

The overall AAMR for chronic HBV-related mortality was 1.4 per million, compared to 54.3 per million for chronic HCV-related mortality.

The AAMR for chronic HBV decreased significantly from 1999 to 2004 (APC: −4.96; 95% CI: −10.05 to −2.31; P = .01), followed by a significant increase from 2004 to 2009 (APC: 6.20; 95% CI: 2.77–12.42; P = .02). This was followed by a significant decline from 2009 to 2018 (APC: −1.40; 95% CI: −6.12 to −0.50; P = .02), and a steep significant increase from 2018 to 2020 (APC: 8.81; 95% CI: 1.06–15.31; P = .02; Fig. 7A).

Figure 7.

(A) Chronic hepatitis B virus-related age-adjusted mortality rates per 1,000,000 stratified by urbanization status among US adults from 1999 to 2020, (B) chronic hepatitis C virus-related age-adjusted mortality rates per 1,000,000 stratified by urbanization status among US adults from 1999 to 2020.

The AAMR for chronic HCV remained stable from 1999 to 2002 (APC: −21.22; 95% CI: −67.44 to 52.24; P = .18), followed by a steep significant increase from 2002 to 2005 (APC: 168.56; 95% CI: 72.50–283.93; P = .02). This was followed by another significant increase from 2005 to 2014 (APC: 2.89; 95% CI: 0.11–7.72; P = .04) and a significant decline from 2014 to 2020 (APC: −7.55; 95% CI: −15.68 to −3.82; P = .02; Fig. 7B).

4. Discussion

The primary finding of our analysis indicates a notable increase in VH-related mortality rates from 1999 to 2014, followed by a gradual decline extending to 2020. Men’s AAMR was double to that of women’s. AAMRs were slightly higher in middle-aged adults compared to older adults and were 13 times greater than those in young adults. Non-Hispanic American Indians/Alaska Natives were the most affected racial group. Regionally, the District of Columbia and the Western region reported the highest mortality rates. Metropolitan areas also exhibited higher AAMRs, underscoring significant inequities across populations.

Age-stratified data revealed that middle-aged adults bear the highest burden of VH mortality, followed by older and young adults. This pattern mirrors the natural progression of chronic HBV and HCV infections, where prolonged exposure escalates the risk of liver complications such as cirrhosis, hepatocellular carcinoma, and liver failure.^[22] For middle-aged adults, the initial increase in AAMR during 1999 to 2007, followed by a significant decline post-2014 coincides with the advent and widespread use of direct-acting antivirals for HCV, enhancing treatment efficacy.^[23] Notably, HCV has disproportionately affected individuals born between 1945 and 1965 – the “baby boomer” cohort – resulting in elevated mortality rates in earlier years. Studies indicate that 3.3% of baby boomers are HCV antibody-positive, accounting for up to 75% of all HCV infections in the US.^[24] For older adults, the rise in AAMR during 2004 to 2015 followed by a decline reflects the complex interplay of aging, the cumulative burden of untreated chronic hepatitis, and advancements in antiviral therapies. Chronic HBV and HCV infections often progress more rapidly to severe liver disease in this age group, contributing to higher mortality.^[25] However, improved treatments and expanded screening have likely tempered mortality rates post-2015. With heightened awareness and access to treatment, the number of individuals initiating HCV treatment increased from approximately 0.5 million in 2014 to over 2 million in 2017, significantly reducing mortality in older populations.^[26] The steady decline in the AAMR among young adults from 1999 to 2020 reflects the impact of various targeted efforts. Harm reduction strategies, including needle exchange programs and opioid substitution therapy, have been instrumental in reducing new HCV infections within this demographic.^[27,28] The HBV vaccine, which has greatly cut down on new HBV infections and helped lower the overall death rate from VH in younger people, is another important factor in this trend.^[29]

The higher AAMR in men compared to women may be attributed to biological, behavioral, and healthcare access factors. Men are more prone to severe liver diseases, with studies showing lower viral clearance rates for HCV in males (33.7%) compared to females (44.6%).^[30,31] Co-infections with HIV and other infections are more common in males, often complicating management and worsening health outcomes.^[32] Lastly, the higher use of alcohol, and tobacco smoking among males is associated with the higher occurrence of HBV-related liver diseases. The lower mortality rates in women are explained by slower disease progression, immune differences, and hormonal factors.^[33] Furthermore, the prevalence of hepatitis E virus is significantly lower in the US population compared to developing countries, where it is a major contributor to maternal mortality.^[34] The improvements in antiviral therapies have benefited both genders, leading to the observed decline in mortality rates after 2013.

Despite recent improvements in healthcare access, significant disparities were noted in racial analysis of mortality data. The higher AAMR in American Indians/Alaska Natives and Blacks/African Americans may be driven by fewer economic opportunities, low education, social segregation, higher exposure to risk factors and limited healthcare access including fewer referrals for VH treatment and surgical procedures for end-stage liver disease compared to other races.^[35–37] Additionally, the higher prevalence of other co-morbidities including cardiovascular disorders and alcohol-related diseases can potentially exacerbate liver damage and worsen the outcomes. Poor response to antiviral therapy can also be a potential explanation for higher death rates in Blacks/African Americans.^[38] Unlike other races, the AAMRs for Hispanic or Latino populations showed varied trends, with a slight decline until 2004, a brief increase in 2007, and inconsistent decreases thereafter. Studies have shown that Hispanics have lower rates of HCV diagnosis and treatment uptake compared to non-Hispanic Whites, they also had the lowest rates of outpatient follow-up after an initial positive HBsAg or HBV DNA test.^[39,40]

In region-based analysis, the highest AAMR was recorded in the Western region. This may be attributed to increased injectable drug use, a greater percentage of patients with chronic HCV or B, and perhaps delayed treatment accessibility in the region.^[41] Moreover, disparities in state-level public health infrastructure, healthcare accessibility, and economic status likely account for these regional discrepancies.^[41,42] Higher rates in the South are a consequence of increasing incidence of HCV infections during the opioid epidemic, gaps in healthcare access and structural imbalances spanning obstacles associated with poverty, insurance coverage, and healthcare infrastructure.^[41,43] Conversely, the Northeast and Midwest areas saw comparatively lower AAMRs, both observing substantial decreases after 2013. These locations may have benefited from the earlier and more extensive introduction of VH screening programs, especially among baby boomers, as discussed earlier.^[8]

Metropolitan regions regularly exhibited elevated AAMRs in comparison to nonmetropolitan locations. The increased rates may indicate higher population density and a greater incidence of high-risk behaviors, including the previously discussed injectable drug use.^[41,44] Furthermore, urban places frequently function as central locations for diagnostic and reporting services, which may result in more precise mortality documentation. These results were similar to the study by Ming et al which examined the impact of urbanization on HAV morbidity in China from 2005 to 2018, finding a 79.4% decline in annual cases, from 5.64 to 1.16 per 1,00,000 people.^[45] Higher GDP per capita and more hospital beds per 1000 people were associated with reduced morbidity, while higher illiteracy rates were linked to increased morbidity. Notably, nonmetropolitan regions had a more pronounced rise in AAMR during the initial study phase, reaching its peak in 2013. This tendency could reflect the delayed implementation of hepatitis screening and treatment programs in remote regions, exacerbated by systemic healthcare access barriers.^[46] Rural communities frequently encounter substantial challenges, such as a scarcity of healthcare practitioners, lengthy travel distances to medical facilities, and restricted public health funding, which can impede timely diagnosis and treatment.^[44] The slower decline indicates the need for more robust interventions tailored to rural communities. These could include mobile health units to bring screening and treatment to underserved areas, telemedicine programs to overcome geographic barriers, and increased investment in rural healthcare infrastructure. Education campaigns targeting rural populations to reduce stigma and improve awareness about VH prevention and treatment are also essential.

5. Limitation

This study has several limitations to consider. First, the data comes from the National vital statistics system, which relies on death certificates to report causes of death. This may lead to underreporting if VH is not listed as the main cause of death. Second, the study does not include important details such as disease stage, comorbidities, history of antiviral treatment, alcohol use, or intravenous drug use, which are crucial for understanding what drives mortality. Third, while public health interventions for VH are mentioned, their implementation, coverage, or impact on reducing deaths was not analyzed. Fourth, the study does not address challenges in accessing or affording hepatitis treatments, which can limit their effectiveness. Fifth, it does not account for factors like income, healthcare access, or systemic inequalities, which likely contribute to differences in mortality rates.

Lastly, because this study is observational, it cannot prove that specific interventions caused the changes in mortality trends. Further research should include individual-level data, examine barriers to treatment, and assess the impact of public health programs to better guide efforts to eliminate VH.

6. Conclusion

The VH-attributed mortality rate increased until 2014 followed by a slow steady decline. The AAMR exhibited numerous disparities with elderly men, American Indian/Alaska Native, and African American populations in urban West and South regions affected the most. The study highlights the positive impact of vaccination and screening programs in mitigating mortality. To sustain this progress, targeted public health strategies including expansion of vaccination access, subsidizing antiviral therapies, enhancing blood screening, and raising awareness are crucial. Equitable resource distribution and investments in health infrastructure are essential to address disparities and achieve sustained declines in mortality.

Author contributions

Conceptualization: Usama Idrees, Humza Saeed, Abdullah Imtiaz, Ali Ahmed, Muhammad Husnain Ahmad.

Data curation: Usama Idrees, Safa Nasir, Aafeen Mujeeb, Iqra Shahid, Ayesha Sehar, Abdullah Imtiaz, Muhammad Awais Alam.

Formal analysis: Usama Idrees, Safa Nasir, Mohammad Dheyaa Marsool, Humza Saeed, Zainab Fatima, Khansha Saeed, Iqra Shahid, Syed Muhammad Ali Najafi, Ayesha Sehar, Muhammad Husnain Ahmad.

Investigation: Usama Idrees, Humza Saeed, Aafeen Mujeeb, Syed Muhammad Ali Najafi, Ayesha Sehar, Muhammad Awais Alam.

Methodology: Usama Idrees, Safa Nasir, Mohammad Dheyaa Marsool, Humza Saeed, Zainab Fatima, Aafeen Mujeeb, Khansha Saeed, Iqra Shahid, Ayesha Sehar, Muhammad Awais Alam.

Project administration: Mohammad Dheyaa Marsool, Syed Muhammad Ali Najafi, Ayesha Sehar, Abdullah Imtiaz, Muhammad Husnain Ahmad.

Software: Safa Nasir, Mohammad Dheyaa Marsool, Humza Saeed, Zainab Fatima, Aafeen Mujeeb, Ali Ahmed, Muhammad Husnain Ahmad.

Supervision: Usama Idrees, Safa Nasir, Mohammad Dheyaa Marsool, Humza Saeed, Zainab Fatima, Aafeen Mujeeb, Abdullah Imtiaz, Muhammad Awais Alam, Ali Ahmed, Muhammad Husnain Ahmad.

Validation: Usama Idrees, Safa Nasir, Khansha Saeed, Abdullah Imtiaz, Muhammad Awais Alam, Ali Ahmed, Muhammad Husnain Ahmad.

Visualization: Usama Idrees, Zainab Fatima, Aafeen Mujeeb, Iqra Shahid, Syed Muhammad Ali Najafi, Ayesha Sehar, Abdullah Imtiaz, Ali Ahmed, Muhammad Husnain Ahmad.

Writing – original draft: Usama Idrees, Safa Nasir, Mohammad Dheyaa Marsool, Humza Saeed, Aafeen Mujeeb, Khansha Saeed, Iqra Shahid, Syed Muhammad Ali Najafi, Ayesha Sehar, Abdullah Imtiaz, Muhammad Awais Alam, Muhammad Husnain Ahmad.

Writing – review & editing: Usama Idrees, Safa Nasir, Mohammad Dheyaa Marsool, Humza Saeed, Zainab Fatima, Aafeen Mujeeb, Khansha Saeed, Iqra Shahid, Syed Muhammad Ali Najafi, Ayesha Sehar, Abdullah Imtiaz, Muhammad Awais Alam, Ali Ahmed, Muhammad Husnain Ahmad.