Enhancing Hepatitis C Management: Mortality Trends and Disparities in the US by Sex, Age Group, Race/Ethnicity and Region (1999–2020)
Sophia Ahmed
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorMuhammad Asfandyar Nadir
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorHanzala Ahmed Farooqi
Department of Medicine, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
Search for more papers by this authorHamza Ashraf
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorAli Azlan
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorFariha Hasan
Cooper University Hospital, Camden, New Jersey, USA
Search for more papers by this authorCorresponding Author
Mohammad Ashraf
Wolfson School of Medicine, University of Glasgow, Glasgow, UK
Correspondence:
Mohammad Ashraf ([email protected])
Search for more papers by this authorSophia Ahmed
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorMuhammad Asfandyar Nadir
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorHanzala Ahmed Farooqi
Department of Medicine, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
Search for more papers by this authorHamza Ashraf
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorAli Azlan
Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan
Search for more papers by this authorFariha Hasan
Cooper University Hospital, Camden, New Jersey, USA
Search for more papers by this authorCorresponding Author
Mohammad Ashraf
Wolfson School of Medicine, University of Glasgow, Glasgow, UK
Correspondence:
Mohammad Ashraf ([email protected])
Search for more papers by this authorABSTRACT
Hepatitis C virus (HCV) infection affects approximately 3.9 million people in the United States (U.S.), leading to 8000 to 10,000 deaths annually. Despite advancements in curative treatments since 2014, effective strategies targeting high-risk groups are crucial. This study examines HCV-related mortality trends from 1999 to 2020, focusing on demographic and regional disparities using the CDC WONDER database. A retrospective analysis was conducted using the CDC WONDER database. HCV-related deaths were identified using the International Classification of Diseases, Tenth Revision (ICD-10) codes B17.1 and B18.2. Mortality data were categorised by gender, age, race/ethnicity, region, place of death and urbanisation status. We calculated crude mortality rates (CRs) and age-adjusted mortality rates (AAMRs) per 100,000 population. Joinpoint regression analysis identified significant changes in mortality trends. A total of 324,008 HCV-related deaths were reported. The overall AAMR was 4.27 (95% Confidence Interval [CI]: 4.25 to 4.28). Mortality increased from 1999 to 2014 (1999 to 2007 Annual Percent Change [APC]: 5.00; 2007 to 2014 APC: 1.95) and declined sharply from 2014 to 2020 (APC: −7.11). Males exhibited higher mortality (AAMR: 6.28) than females (AAMR: 2.42). The 55–64 years age group had the highest CR (16.38), while non-Hispanic (NH) American Indians had the highest rate (AAMR: 8.72) among racial groups. Regionally, the South had the highest AAMR (5.80), nearly double that of the West (2.23) and Midwest (2.62). HCV-related mortality trends show significant demographic disparities and regional variations. Targeted interventions are essential to reduce HCV burden, particularly among vulnerable groups.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data analysed in this study were obtained from the CDC WONDER database, which provides access to a wide range of public health datasets. The mortality data used in this analysis are publicly available and can be accessed through the CDC WONDER website at [https://wonder.cdc.gov/]. Any additional datasets generated or analysed during this study are available from the corresponding author upon reasonable request.
Supporting Information
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References
- 1M. M. Denniston, M. R. Klevens, G. M. McQuillan, and R. B. Jiles, “Awareness of Infection, Knowledge of Hepatitis C, and Medical Follow-Up Among Individuals Testing Positive for Hepatitis C: National Health and Nutrition Examination Survey 2001–2008,” Hepatology 55, no. 6 (2012): 1652–1661, https://doi.org/10.1002/hep.25556.
- 2B. D. Smith, R. L. Morgan, G. A. Beckett, et al., “Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945-1965,” MMWR Recommendations and Reports 61, no. RR-4 (2012): 1–32.
- 3I. Williams, “Epidemiology of Hepatitis C in the United States,” American Journal of Medicine 107, no. 6 (1999): 2–9, https://doi.org/10.1016/S0002-9343(99)00373-3.
10.1016/S0002-9343(99)00373-3 Google Scholar
- 4M. G. Hofmeister, Y. Zhong, A. C. Moorman, C. R. Samuel, E. H. Teshale, and P. R. Spradling, “Temporal Trends in Hepatitis C-Related Hospitalizations, United States, 2000-2019,” Clinical Infectious Diseases 77, no. 12 (2023): 1668–1675, https://doi.org/10.1093/cid/ciad425.
- 5H. Bradley, E. W. Hall, E. M. Rosenthal, P. S. Sullivan, A. B. Ryerson, and E. S. Rosenberg, “Hepatitis C Virus Prevalence in 50 U.S. States and D.C. by sex, Birth Cohort, and Race: 2013-2016,” Hepatology Communications 4, no. 3 (2020): 355–370, https://doi.org/10.1002/hep4.1457.
- 6E. von Elm, D. G. Altman, M. Egger, S. J. Pocock, P. C. Gøtzsche, and J. P. Vandenbroucke, “The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies,” Journal of Clinical Epidemiology 61, no. 4 (2008): 344–349, https://doi.org/10.1016/j.jclinepi.2007.11.008.
- 7S. S. Chang, H. Y. Hu, Y. C. Chen, Y. F. Yen, and N. Huang, “Late Hepatitis C Virus Diagnosis Among Patients With Newly Diagnosed Hepatocellular Carcinoma: A Case–Control Study,” BMC Gastroenterology 22, no. 1 (2022): 425, https://doi.org/10.1186/s12876-022-02504-6.
- 8H. Yamana, K. Yamasaki, T. Jo, H. Yatsuhashi, and H. Yasunaga, “A Descriptive Analysis of Acute Viral Hepatitis Using a Database With Electronic Medical Records and Claims Data,” Annals of Clinical Epidemiology 5, no. 4 (2023): 23014, https://doi.org/10.37737/ace.23014.
10.37737/ace.23014 Google Scholar
- 9D. D. Ingram and S. J. Franco, “NCHS Urban-Rural Classification Scheme for Counties,” Vital and Health Statistics 2, no. 154 (2012): 1–65.
- 10R. N. Anderson and H. M. Rosenberg, “Age Standardization of Death Rates: Implementation of the Year 2000 Standard,” National Vital Statistics Reports 47, no. 3 (1998): 1–16.
- 11E. W. Hall, S. Schillie, A. S. Vaughan, et al., “County-Level Variation in Hepatitis C Virus Mortality and Trends in the United States, 2005-2017,” Hepatology 74, no. 2 (2021): 582–590, https://doi.org/10.1002/hep.31756.
- 12D. Kim, P. Konyn, G. Cholankeril, et al., “Decline in Annual Mortality of Hepatitis C Virus–Related Hepatocellular Carcinoma in the United States, From 2009 to 2018,” Gastroenterology 159, no. 4 (2020): 1558–1560, https://doi.org/10.1053/j.gastro.2020.05.007.
- 13A. A. Butt, P. Yan, O. S. Shaikh, V. Lo Re, A. B. Abou-Samra, and K. E. Sherman, “Treatment of HCV Reduces Viral Hepatitis-Associated Liver-Related Mortality in Patients: An ERCHIVES Study,” Journal of Hepatology 73, no. 2 (2020): 277–284, https://doi.org/10.1016/j.jhep.2020.02.022.
- 14V. Calvaruso, S. Petta, I. Cacciola, et al., “Liver and Cardiovascular Mortality After Hepatitis C Virus Eradication by DAA: Data From RESIST-HCV Cohort,” Journal of Viral Hepatitis 28, no. 8 (2021): 1190–1199, https://doi.org/10.1111/jvh.13523.
- 15E. Ogawa, N. Chien, L. Kam, et al., “Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-Term Mortality in Patients With Chronic Hepatitis C,” JAMA Internal Medicine 183, no. 2 (2023): 97, https://doi.org/10.1001/jamainternmed.2022.5699.
- 16N. Z. Janjua, S. Wong, Y. Abdia, et al., “Impact of Direct-Acting Antivirals for HCV on Mortality in a Large Population-Based Cohort Study,” Journal of Hepatology 75, no. 5 (2021): 1049–1057, https://doi.org/10.1016/j.jhep.2021.05.028.
- 17D. Jeong, S. Wong, M. E. Karim, et al., “Treatment of HCV With Direct-Acting Antivirals on Reducing Mortality Related to Extrahepatic Manifestations: A Large Population-Based Study in British Columbia, Canada,” Lancet Regional Health—Americas 29 (2024): 100658, https://doi.org/10.1016/j.lana.2023.100658.
- 18I. Bakr, “Higher Clearance of Hepatitis C Virus Infection in Females Compared With Males,” Gut 55, no. 8 (2005): 1183–1187, https://doi.org/10.1136/gut.2005.078147.
10.1136/gut.2005.078147 Google Scholar
- 19A. White, “Gender Differences in the Epidemiology of Alcohol Use and Related Harms in the United States,” Alcohol Research: Current Reviews 40, no. 2 (2020), https://doi.org/10.35946/arcr.v40.2.01.
- 20B. A. Piasecki, J. D. Lewis, K. R. Reddy, et al., “Influence of Alcohol Use, Race, and Viral Coinfections on Spontaneous HCV Clearance in a US Veteran Population,” Hepatology 40, no. 4 (2004): 892–899, https://doi.org/10.1002/hep.20384.
- 21M. I. Butterfield, H. B. Bosworth, K. G. Meador, et al., “Blood-Borne Infections and Persons With Mental Illness: Gender Differences in Hepatitis C Infection and Risks Among Persons With Severe Mental Illness,” Psychiatric Services 54, no. 6 (2003): 848–853, https://doi.org/10.1176/appi.ps.54.6.848.
- 22R. Baden, J. K. Rockstroh, and M. Buti, “Natural History and Management of Hepatitis C: Does sex Play a Role?,” Journal of Infectious Diseases 209, no. 3 (2014): S81–S85, https://doi.org/10.1093/infdis/jiu057.
- 23S. Lingala and M. G. Ghany, “Natural History of Hepatitis C,” Gastroenterology Clinics of North America 44, no. 4 (2015): 717–734, https://doi.org/10.1016/j.gtc.2015.07.003.
- 24M. J. Alter, D. Kruszon-Moran, O. V. Nainan, et al., “The Prevalence of Hepatitis C Virus Infection in the United States, 1988 Through 1994,” New England Journal of Medicine 341, no. 8 (1999): 556–562, https://doi.org/10.1056/NEJM199908193410802.
- 25C. H. B. S. van den Berg, B. P. X. Grady, J. Schinkel, et al., “Female sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters From a Community-Based Cohort,” PLoS One 6, no. 11 (2011): e27555, https://doi.org/10.1371/journal.pone.0027555.
- 26D. B. Rein, B. D. Smith, J. S. Wittenborn, et al., “The Cost-Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary Care Settings,” Annals of Internal Medicine 156, no. 4 (2012): 263, https://doi.org/10.7326/0003-4819-156-4-201202210-00378.
- 27M. S. Alzahrani, M. K. Maneno, M. N. Daftary, L. T. Wingate, E. B. Ettienne, and C. D. Howell, “Patterns of Hepatitis C-Related Inpatient Mortality in the United States in the Era of Direct-Acting Antivirals,” Journal of Gastroenterology and Hepatology Research 9, no. 3 (2020): 3169–3175.
- 28A. Wasley and M. J. Alter, “Epidemiology of Hepatitis C: Geographic Differences and Temporal Trends,” Seminars in Liver Disease 20, no. 1 (2000): 1–16, https://doi.org/10.1055/s-2000-9506.
- 29M. Reid, J. C. Price, and P. C. Tien, “Hepatitis C Virus Infection in the Older Patient,” Infectious Disease Clinics of North America 31, no. 4 (2017): 827–838, https://doi.org/10.1016/j.idc.2017.07.014.
- 30K. Chan and N. Mangla, “Prevalence and Risk Factors of Hepatitis C Virus Infection in the Rural Northeastern United States,” Annals of Hepatology 27 (2022): 100576, https://doi.org/10.1016/j.aohep.2021.100576.
- 31J. E. Zibbell, K. Iqbal, R. C. Patel, et al., “Increases in Hepatitis C Virus Infection Related to Injection Drug Use Among Persons Aged ≤ 30 Years—Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012,” MMWR. Morbidity and Mortality Weekly Report 64, no. 17 (2015): 453–458.
- 32A. G. Suryaprasad, J. Z. White, F. Xu, et al., “Emerging Epidemic of Hepatitis C Virus Infections Among Young Nonurban Persons Who Inject Drugs in the United States, 2006–2012,” Clinical Infectious Diseases 59, no. 10 (2014): 1411–1419, https://doi.org/10.1093/cid/ciu643.
- 33K. M. Keyes, M. Cerdá, J. E. Brady, J. R. Havens, and S. Galea, “Understanding the Rural–Urban Differences in Nonmedical Prescription Opioid Use and Abuse in the United States,” American Journal of Public Health 104, no. 2 (2014): e52–e59, https://doi.org/10.2105/AJPH.2013.301709.
- 34A. A. Al-Tayyib, S. Koester, and P. Riggs, “Prescription Opioids Prior to Injection Drug Use: Comparisons and Public Health Implications,” Addictive Behaviors 65 (2017): 224–228, https://doi.org/10.1016/j.addbeh.2016.08.016.
- 35S. P. Novak and A. H. Kral, “Comparing Injection and Non-Injection Routes of Administration for Heroin, Methamphetamine, and Cocaine Users in the United States,” Journal of Addictive Diseases 30, no. 3 (2011): 248–257, https://doi.org/10.1080/10550887.2011.581989.
- 36K. A. Ahrens, L. M. Rossen, A. R. Burgess, K. K. Palmsten, and E. C. Ziller, “Rural–Urban Residence and Maternal Hepatitis C Infection, U.S.: 2010–2018,” American Journal of Preventive Medicine 60, no. 6 (2021): 820–830, https://doi.org/10.1016/j.amepre.2020.12.020.
- 37H. L. Cooper, D. H. Cloud, P. R. Freeman, et al., “Buprenorphine Dispensing in an Epicenter of the U.S. Opioid Epidemic: A Case Study of the Rural Risk Environment in Appalachian Kentucky,” International Journal of Drug Policy 85 (2020): 102701, https://doi.org/10.1016/j.drugpo.2020.102701.
- 38S. M. Davis, A. L. Kristjansson, D. Davidov, K. Zullig, A. Baus, and M. Fisher, “Barriers to Using New Needles Encountered by Rural Appalachian People Who Inject Drugs: Implications for Needle Exchange,” Harm Reduction Journal 16, no. 1 (2019): 23, https://doi.org/10.1186/s12954-019-0295-5.
- 39S. M. Walters, D. Frank, M. Felsher, et al., “How the Rural Risk Environment Underpins Hepatitis C Risk: Qualitative Findings From Rural Southern Illinois, United States,” International Journal of Drug Policy 112 (2023): 103930, https://doi.org/10.1016/j.drugpo.2022.103930.
- 40J. N. Laditka, S. B. Laditka, and J. C. Probst, “Health Care Access in Rural Areas: Evidence That Hospitalization for Ambulatory Care-Sensitive Conditions in the United States May Increase With the Level of Rurality,” Health & Place 15, no. 3 (2009): 761–770, https://doi.org/10.1016/j.healthplace.2008.12.007.
- 41M. M. Casey, K. Thiede Call, and J. M. Klingner, “Are Rural Residents Less Likely to Obtain Recommended Preventive Healthcare Services?,” American Journal of Preventive Medicine 21, no. 3 (2001): 182–188, https://doi.org/10.1016/S0749-3797(01)00349-X.
- 42K. N. Ly, A. M. Miniño, S. J. Liu, et al., “Deaths Associated With Hepatitis C Virus Infection Among Residents in 50 States and the District of Columbia, 2016–2017,” Clinical Infectious Diseases 71, no. 5 (2020): 1149–1160, https://doi.org/10.1093/cid/ciz976.
- 43M. L. Castor, M. S. Smyser, M. M. Taualii, A. N. Park, S. A. Lawson, and R. A. Forquera, “A Nationwide Population-Based Study Identifying Health Disparities Between American Indians/Alaska Natives and the General Populations Living in Select Urban Counties,” American Journal of Public Health 96, no. 8 (2006): 1478–1484, https://doi.org/10.2105/AJPH.2004.053942.
- 44M. Landen, J. Roeber, T. Naimi, L. Nielsen, and M. Sewell, “Alcohol-Attributable Mortality Among American Indians and Alaska Natives in the United States, 1999–2009,” American Journal of Public Health 104, no. S3 (2014): S343–S349, https://doi.org/10.2105/AJPH.2013.301648.
- 45D. Ge, J. Fellay, A. J. Thompson, et al., “Genetic Variation in IL28B Predicts Hepatitis C Treatment-Induced Viral Clearance,” Nature 461, no. 7262 (2009): 399–401, https://doi.org/10.1038/nature08309.
- 46Z. A. Sherif, M. Nouraie, R. Begum, et al., “Factors Influencing Treatment Outcome in Hepatitis C Virus Minority Patients at an Inner-City Hospital,” Medicine 99, no. 14 (2020): e19505, https://doi.org/10.1097/MD.0000000000019505.
- 47B. L. Pearlman, “Hepatitis C Virus Infection in African Americans,” Clinical Infectious Diseases 42, no. 1 (2006): 82–91, https://doi.org/10.1086/498512.
- 48C. S. Strahotin and M. Babich, “Hepatitis C Variability, Patterns of Resistance, and Impact on Therapy,” Advances in Virology 2012 (2012): 1–10, https://doi.org/10.1155/2012/267483.
10.1155/2012/267483 Google Scholar
- 49J. Rigg, O. Doyle, N. McDonogh, et al., “Finding Undiagnosed Patients With Hepatitis C Virus: An Application of Machine Learning to US Ambulatory Electronic Medical Records,” BMJ Health & Care Informatics 30, no. 1 (2023): e100651, https://doi.org/10.1136/bmjhci-2022-100651.
- 50O. M. Doyle, N. Leavitt, and J. A. Rigg, “Finding Undiagnosed Patients With Hepatitis C Infection: An Application of Artificial Intelligence to Patient Claims Data,” Scientific Reports 10, no. 1 (2020): 10521, https://doi.org/10.1038/s41598-020-67013-6.
- 51L. Platt, S. Minozzi, J. Reed, et al., “Needle Syringe Programmes and Opioid Substitution Therapy for Preventing Hepatitis C Transmission in People Who Inject Drugs,” Cochrane Database of Systematic Reviews 2017, no. 9 (2017): CD012021, https://doi.org/10.1002/14651858.CD012021.pub2.
10.1002/14651858.CD012021.pub2 Google Scholar
- 52J. Habchi, A. M. Thomas, S. Sprecht-Walsh, et al., “Optimizing Hepatitis C Virus (HCV) Treatment in a US Colocated HCV/Opioid Agonist Therapy Program,” Open Forum Infectious Diseases 7, no. 10 (2020): ofaa310, https://doi.org/10.1093/ofid/ofaa310.
- 53S. R. Bartlett, S. Wong, A. Yu, et al., “The Impact of Current Opioid Agonist Therapy on Hepatitis C Virus Treatment Initiation Among People Who Use Drugs From the Direct-Acting Antiviral (DAA) era: A Population-Based Study,” Clinical Infectious Diseases 74, no. 4 (2022): 575–583, https://doi.org/10.1093/cid/ciab546.
- 54P. Patel, M. T. Wells, E. Wethington, et al., “United States Provider Experiences With Telemedicine for Hepatitis C Treatment: A Nationwide Survey,” Journal of Viral Hepatitis 31, no. 12 (2024): 873–879, https://doi.org/10.1111/jvh.14010.
- 55H. A. Beydoun and J. Tsai, “Screening Rates for Hepatitis B and C Among Low-Income US Veterans: Data From the National Veteran Homeless and Other Poverty Experiences Study,” Journal of Viral Hepatitis 31, no. 10 (2024): 601–613, https://doi.org/10.1111/jvh.13981.
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