Cited by 104Hepatitis C virus researchHIV, Drug Use, Sexual RiskLiver Disease Diagnosis and Treatment

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Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis

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Smith, Daniel J., Combellick, Joan, Jordan, Ashly E., Hagan, Holly·2015·International Journal of Drug Policy

DOI 10.1016/j.drugpo.2015.07.004PMC PMC4577462

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Abstract

Background Understanding HCV disease progression rates among people who inject drugs (PWID) is important to setting policy to expand access to detection, diagnosis and treatment, and in forecasting the burden of disease. In this paper we synthesize existing data on the natural history of HCV among PWID, including fibrosis progression rates (FPR) and the incidence of compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC). Methods We conducted electronic and manual searches for published and unpublished literature. Reports were eligible if they (i) included participants who were chronically infected with HCV and reported current or previous injection drug use; (ii) presented original data on disease progression in a study sample comprised of at least 90% PWID; (iii) published between January 1, 1990, and December 31, 2013; and (iv) included data from upper-middle- or high-income countries. Quality ratings were assigned using an adaptation of the Quality In Prognosis Studies (QUIPS) tool. We estimated pooled FPRs using the stage-constant and stage-specific methods, and pooled incidence rates of CC, DC, and HCC. Results Twenty-one reports met the study inclusion criteria. Based on random-effect models, the pooled stage-constant FPR was 0.117 METAVIR units per year (95% CI, 0.099-0.135), and the stage-specific FPRs were F0→F1, 0.128 (95% CI 0.080, 0.176); F1→F2, 0.059 (95% CI 0.035, 0.082); F2→F3, 0.078 (95% CI 0.056, 0.100); and F3→F4, 0.116 (95% CI 0.070, 0.161). The pooled incidence rates of CC, DC, and HCC were 6.6 (95% CI 4.8, 8.4), 1.1 (95% CI 0.8, 1.4), and 0.3 (95% CI -0.1, 0.6) events per 1000 person-years, respectively. Following the stage-constant estimate, average time to cirrhosis is 34 years post-infection, and time to METAVIR stage F3 is 26 years; using the stage-specific estimates, time to cirrhosis is 46 years and time to F3 is 38 years. Conclusion Left untreated, PWID with chronic HCV infection will develop liver sequelae (including HCC) in mid- to late-adulthood. Delaying treatment with the new drug regimens until advanced fibrosis develops prolongs the period of infectiousness to perhaps thirty years. Scaling up of effective HCV prevention and early engagement in care and treatment will facilitate the elimination HCV as a source of serious disease in PWID.

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Vold, J. H., Skurtveit, S. O., Aas, C. F., Johansson, K. A., & Fadnes, L. T. (2020) · BMC Health Services Research · doi:10.1186/s12913-020-05504-y · Cited by 10
Injection Partners, HCV, and HIV Status among Rural Persons Who Inject Drugs in Puerto Rico
Habecker, P., Abadie, R., Welch-Lazoritz, M. L., Reyes, J. C., Khan, B., & Dombrowski, K. (2017) · Substance Use & Misuse · doi:10.1080/10826084.2017.1400562 · Cited by 9
Hepatitis C Management at Federally Qualified Health Centers during the Opioid Epidemic: A Cost-Effectiveness Study
Assoumou, S. A., Nolen, S., Hagan, L. M., Wang, J., Yazdi, G. E., Thompson, W., Mayer, K. H., Puro, J. E., Zhu, L., Salomon, J. A., et al. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2020.05.029 · Cited by 8
“Base case inputs Demographics and hepatitis C epidemiology—Table 2 describes cohort characteristics and hepatitis C epidemiology of the simulated cohort (20-25).”
Background
HCV/HIV coinfection among people who inject drugs and enter opioid substitution treatment in Greece: prevalence and correlates
Fotiou, A., Kanavou, E., Antaraki, A., Richardson, C., Terzidou, M., & Kokkevi, A. (2016) · Hepatology Medicine and Policy · doi:10.1186/s41124-016-0017-5 · Cited by 8
“Median length of injection (years) [Inter-quartile range] 14 [12] 10 [11] 15 [12] 13 [12]”
Cost effectiveness of simplified HCV screening-and-treatment interventions for people who inject drugs in Dar-es-Salaam, Tanzania
Mohamed, Z., Scott, N., Nayagam, S., Rwegasha, J., Mbwambo, J. K. K., Thursz, M. R., Brown, A. S., Hellard, M. E., & Lemoine, M. (2021) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2021.103458 · Cited by 7
Multidisciplinary and Integrated Treatment for Substance Use Disorders and Hepatitis C in an Addiction Treatment Service in India
Ghosh, A., Mahintamani, T., Premkumar, M., Basu, D., Singh, V., Duseja, A. K., Subodh, B. N., Mohindra, R., Sharma, A., & Arora, S. K. (2022) · Indian Journal of Psychological Medicine · doi:10.1177/02537176221086013 · Cited by 7
Chronic hepatitis C infection and liver disease in HIV ‐coinfected patients in Asia
Durier, N., Yunihastuti, E., Ruxrungtham, K., Kính, N. V., Kamarulzaman, A., Boettiger, D. C., Widhani, A., Avihingsanon, A., Huy, B. V., Omar, S. F. S., et al. (2016) · Journal of Viral Hepatitis · doi:10.1111/jvh.12630 · Cited by 7
“As expected, increasing age showed a strong association with advanced liver disease [40,41].”
Hepatitis C services at harm reduction centres in the European Union: a 28-country survey
Pericàs, J. M., Bromberg, D. J., Ocampo, D., Schatz, E., Wawer, I., Wysocki, P. J., Safreed‐Harmon, K., & Lazarus, J. V. (2019) · Harm Reduction Journal · doi:10.1186/s12954-019-0290-x · Cited by 7
“The rate of progression and time to liver fibrosis and related complications are similar among PWID and HIV-uninfected people living with HCV [5].”
Background
Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID
Kim, K., Choi, G. H., Jang, E. S., Kim, Y. S., Lee, Y. J., Kim, I. H., Cho, S. B., Ki, M., Choi, H. Y., Paik, D., et al. (2021) · Epidemiology and Health · doi:10.4178/epih.e2021077 · Cited by 6
“A recent meta-analysis reported that fibrosis progression was faster in PWID than in non-PWID [20]; however, another study showed that the speed of fibrosis progression was not different between PWID without HIV infections and non-PWID [21].”
Result
The Berlin Hepatitis C Manifesto: access to prevention, testing, treatment and care for people who use drugs
Schatz, E., Schiffer, K., Maher, M., Harris, M., Roca, X. M., Matičič, M., & Leicht, A. (2016) · Hepatology Medicine and Policy · doi:10.1186/s41124-016-0021-9 · Cited by 5
Substance use and misuse
Minh, G. L., & SHOPTAW, S. J. (2021) · doi:10.1093/med/9780198816805.003.0079 · Cited by 5
Correlates of anti-hepatitis C positivity and use of harm reduction services among people who inject drugs in two cities in Croatia
Handanagić, S., Šević, S., Barbarić, J., Dominković, Z., Rode, O. Đ., Begovać, J., & Božičević, I. (2016) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2016.11.028 · Cited by 5
Economic Evaluation of Hepatitis C Treatment Extension to Acute Infection and Early-Stage Fibrosis Among Patients Who Inject Drugs in Developing Countries: A Case of China
Liu, Y., Zhang, H., Zhang, L., Zou, X., & Li, L. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17030800 · Cited by 5
Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study
Chang, S., Hu, H., Chen, Y.-C., Yen, Y., & Huang, N. (2022) · BMC Gastroenterology · doi:10.1186/s12876-022-02504-6 · Cited by 4
Health and Economic Impact of Periodic Hepatitis C Virus Testing Among People Who Inject Drugs
Zhu, L., Furukawa, N. W., Thompson, W., Reitsma, M. B., Randall, L. M., Handel, M. M. V., Asher, A. K., Valverde, E. E., Linas, B. P., & Salomon, J. A. (2025) · JAMA Health Forum · doi:10.1001/jamahealthforum.2025.1870 · Cited by 4
Integrating Hepatitis C Care for Opioid Substitution Treatment Patients Attending General Practice: Feasibility, Clinical, and Cost-Effectiveness Analysis
McCombe, G., Swan, D., Lambert, J. S., O’Connor, E., Ward, Z., Vickerman, P. T., Avramovic, G., Crowley, D., Tinago, W., Mafirakureva, N., et al. (2022) · Interactive Journal of Medical Research · doi:10.2196/35300 · Cited by 4
“Other model parameters such as disease transition rates, death rates, health utilities, and health care costs for different HCV disease stages, sustained viral response cure rates for treatment, and disease progression rates after SVR came from the existing literature [34-36,50] (see Supplementary Tables 1 and 2 in Mu…”
Integrated care model and point of care diagnostics facilitate Hepatitis C treatment among patients receiving opioid agonist therapy: a retrospective review of medical records
Häkkinen, M., Tourunen, J., Pitkänen, T., Simojoki, K., & Vuoti, S. (2022) · Substance Abuse Treatment Prevention and Policy · doi:10.1186/s13011-022-00473-3 · Cited by 4
A Microsimulation Study of the Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis Centers
Epstein, R. L., Pramanick, T., Baptiste, D., Buzzee, B., Reese, P. P., Linas, B. P., & Sawinski, D. L. (2022) · Journal of the American Society of Nephrology · doi:10.1681/asn.2022030245 · Cited by 4
Efficacy of a comprehensive strategy for the detection and treatment of hepatitis C infection in a population attending addiction centers
Corona‐Mata, D., Rivero‐Juárez, A., Camacho, Á., Ruiz‐Torres, L., Ruiz-Cáceres, I., Darder, B. D. L. F., Cáceres-Anillo, D., Castro-Granados, M. D. G., Lizaur-Barbudo, M., Cabrera-Gisbert, M. V., et al. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1092960 · Cited by 5
“First, the difficulty in diagnosing and treating HCV infection increases the individual risk of liver disease progression (10).”
Background
Alcohol Use Disorder and Hepatitis C Prevention and Care in People Who Inject Drugs: The State of Play
Marcellin, F., Jaquet, A., Lazarus, J. V., Molina, P. E., & Carrieri, P. (2020) · Seminars in Liver Disease · doi:10.1055/s-0040-1716343 · Cited by 4
The cost of a late-detected outbreak among people who inject drugs. A modeling study
Gountas, I., Hatzakis, A. E., Nikolopoulos, G. K., Touloumi, G., & Souliotis, K. N. (2020) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2020.103032 · Cited by 3
Umsetzung von Testung, Diagnostik und Behandlung der Hepatitis C in Einrichtungen der niedrigschwelligen Drogenhilfe in Deutschland – eine Querschnittsbefragung
Schulte, B., Jacobsen, B., Kuban, M., Kraus, L., Reimer, J., Schmidt, C. S., & Schäffer, D. (2022) · Suchttherapie · doi:10.1055/a-1824-7646 · Cited by 3
“Studien zeigen, dass die Progression von leberassoziierten Folgeerkrankungen bei Menschen mit injizierendem Drogenbrauch mit chronischer HCV-Infektion gegenüber nicht-drogenabhängigen Menschen mit chronischer HCV-Infektion beschleunigt ist [19].”
Background
CHIME - A tailored HCV microelimination project in Viennese people who inject drugs at drug centralized substitution centers
Schwarz, C., Schubert, R., Schwarz, M., Schütz, A., Jenke, A., Bauer, D. J. M., Steinwender, B., Gutic, E., Reiberger, T., Haltmayer, H., et al. (2023) · Journal of Virus Eradication · doi:10.1016/j.jve.2023.100338 · Cited by 3
Recent epidemiological trends in HCV-infection in Ukraine
Шевченко, Т. Н., Shcherbуnina, M. B., Latsinska, S. A., & Дикленко, Т. В. (2017) · Regulatory Mechanisms in Biosystems · doi:10.15421/021733 · Cited by 3
“Ризик зараження HCV серед осіб, які вживають наркотики шляхом внутрішньовенного введення, становить 38–56% випадків (Larsen et al., 2010; Smith et al., 2015).”
Cost-Effectiveness of Point-of-Care Hepatitis C Virus RNA Testing in the US
Rawashdh, N. A., Ferrufino, C. P., Cheng, M. M., Doshi, S., & Kahn, E. B. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.2658 · Cited by 2
Influence of psychiatric disorders and opioid substitution therapy on hepatitis C treatment with direct-acting antivirals in people who inject drugs
Camacho, J. C. F. D. C., Martínez, A. M., Mena, M. A. G., & Planas, J. M. M. (2022) · Gastroenterología y Hepatología (English Edition) · doi:10.1016/j.gastre.2021.09.006 · Cited by 2
Perceived barriers to access to hepatitis C for people who inject drugs in Morocco: A qualitative explorative study
Belrhiti, Z., & Serghini, F. Z. (2023) · Drug Science Policy and Law · doi:10.1177/20503245231199163 · Cited by 2
Randomised controlled trial of active case management to link hepatitis C notifications to treatment in Tasmania, Australia: a study protocol
Marukutira, T., Moore, K. P., Hellard, M. E., Richmond, J., Turner, K., Pedrana, A. E., Melody, S. M., Johnston, F. H., Owen, L., van den Boom, W., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-056120 · Cited by 2
“I want to feel young again”: experiences and perspectives of young people who inject drugs living with hepatitis C in Vancouver, Canada
Jacob, J., Goodyear, T., Coulaud, P.-J., Hoong, P., Ti, L., & Knight, R. (2021) · Canadian Journal of Public Health · doi:10.17269/s41997-021-00535-2 · Cited by 1
Recomendaciones para el manejo de la infección por el virus de la hepatitis C entre usuarios de drogas por vía parenteral
Grebely, J., Robaeys, G., Bruggmann, P., Aghemo, A., Backmund, M., Bruneau, J., Byrne, J., Dalgård, O., Feld, J. J., Hellard, M. E., et al. (2015) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2015.11.011 · Cited by 1
Planning the hepatitis C virus elimination in Cyprus: A modeling study
Gountas, I., Yiasemi, I., Kyprianou, E., Mina, C., Georgiou, C., Katsioloudes, P., Kouroufexi, A., Demetriou, A., Xenofontos, E., & Nikolopoulos, G. K. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i31.5219 · Cited by 1
Blood Borne Viruses (HIV, HBV and HCV) among Participants of a Swedish Needle Exchange Program
Blomé, M. A. (2016) · Lund University Publications (Lund University) · Cited by 1
Hepatitis C in people who inject drugs in the Stockholm needle exchange program : incidence, spontaneous clearance and change in risk behaviour
Kåberg, M. (2019) · Figshare · Cited by 1
Integrating Hepatitis C Care for opioid substitution treatment patients attending general practice: Feasibility, Clinical and Cost Effectiveness (Preprint)Preprint
McCombe, G., Swan, D., Lambert, J. S., O’Connor, E., Ward, Z., Vickerman, P. T., Avramovic, G., Crowley, D., Tinago, W., Mafikureva, N., et al. (2021) · doi:10.2196/preprints.35300 · Cited by 1
Strategies for achieving universal access to hepatitis C virus prevention and care for people who inject drugs
Grebely, J., Bruggmann, P., Treloar, C., Byrne, J., Rhodes, T., & Dore, G. J. (2015) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2015.07.008
Empfehlungen zur Hepatitis Versorgung bei Drogenkonsumierenden
Grebely, J., Robaeys, G., Bruggmann, P., Aghemo, A., Backmund, M., Bruneau, J., Byrne, J., Dalgård, O., Feld, J. J., Hellard, M. E., et al. (2015) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2015.11.010
Epidemiology of Hepatitis C Virus Among People Who Inject Drugs: Protocol for a Systematic Review and Meta-Analysis
Smith, D. J., Neurer, J., Jordan, A. E., & Hagan, H. (2017) · JMIR Research Protocols · doi:10.2196/resprot.7936
“The instrument, which was modified for 2 previous SR/MAs [15-16], evaluates potential sources of bias, such as selection, misclassification, and confounding, in a report; it is also used to evaluate all study designs (eg, cross-sectional, prospective and retrospective cohort, randomized controlled…”
Method
Application of an adapted PRECIS-2 instrument to assess efficacy- and effectiveness-study designs in a systematic review of intervention studies of the hepatitis C virus-care continuum among people who use drugs
Jordan, A. E., Perlman, D. C., Smith, D. J., & Hagan, H. (2018) · Comparative Effectiveness Research · doi:10.2147/cer.s145672
“Hepatitis C virus (HCV) infection causes substantial morbidity and mortality.(11,12) Morbidity and mortality persist in part due to incompletely effective and underimplemented programs to prevent primary infection and reinfection, and to very low rates of implementation of highly efficacious HCV treatment for those ch…”
Opioid use disorder and HCV (hepatitis C virus)
Pericot‐Valverde, I., Ahuja, D., Norton, B. L., & Litwin, A. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-68328-9.00006-0
Substance Use and Co-occurring Infections (Including Immunology)
Magel, T., Wuerth, K. C., & Conway, B. (2020) · Springer eBooks · doi:10.1007/978-3-030-36391-8_82
Estimation of Hepatitis C Prognosis to Inform Treatment Prioritization Decisions
Erman, A. (2020) · TSpace (University of Toronto)
Epidemiology of Hepatitis C Virus: People Who Inject Drugs and Other Key Populations
Wiessing, L. G., Giraudon, I., Duffell, E. F., Veldhuijzen, I. K., Zimmermann, R., & Hope, V. D. (2021) · Springer eBooks · doi:10.1007/978-3-030-64649-3_6
Epidemiology: Modeling of Natural History
Sypsa, V. (2021) · Springer eBooks · doi:10.1007/978-3-030-64649-3_8
Influencia de los trastornos psiquiátricos y la terapia de sustitución con opiáceos en el tratamiento del virus de la hepatitis c con antivirales de acción directa en usuarios de drogas por vía parenteral
Camacho, J. C. F. D. C., Martínez, A. M., Mena, M. A. G., & Planas, J. M. M. (2021) · Gastroenterología y Hepatología · doi:10.1016/j.gastrohep.2021.09.003
Evaluation of the Social Return on Investment (SROI) in Patients with Hepatitis C. The Case of the Mobile Outreach Program (MOP)
Paulo, L., Dutschke, G., Cláudia, P., Elsa, B., Diogo, M., Caldeira, P., Filipa, B., Emília, L., Marinho, R. T., Peixe, P., et al. (2024) · Journal of Addiction Therapy and Research · doi:10.29328/journal.jatr.1001029
HCV Treatment Outcomes in PWID: Impact of Addiction History on SVR12
Milošević, I., Beronja, B., Filipović, A., Mitrović, N., Simić, J., Knežević, N., Ranin, J., Todorović, N., Stevanović, O., Radovanović-Spurnić, A., et al. (2024) · Microorganisms · doi:10.3390/microorganisms12122554
Strategies to Achieve HIV and HCV Infection Incidence Targets Among People Who Inject Drugs: A Stochastic Network-Based Multi-Disease Transmission Modeling StudyPreprint
Reitsma, M. B., Zhu, L., Symum, H., Furukawa, N. W., Broz, D., Delaney, K. P., Ennis, E. R., Estadt, A. T., Handanagić, S., Kanny, D., et al. (2025) · medRxiv · doi:10.1101/2025.05.22.25328020
Additional file 1 of Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study
Chang, S.-S., Hu, H.-Y., Chen, Y.-C., Yen, Y.-F., & Huang, N. (2022) · Figshare · doi:10.6084/m9.figshare.21152846

Authors: Smith, D. J., Combellick, J., Jordan, A. E., & Hagan, H.
Affiliations: New York University (US)
Center for Drug Use and HIV Research (US)
Corresponding author: Smith, Daniel J.
ORCID: Smith, Daniel J.
Combellick, Joan
Jordan, Ashly E.
Hagan, Holly
Venue: International Journal of Drug Policy
Publisher: Elsevier BV
Published: 2015-10
Volume: 26
Issue: 10
Pages: 911-921
ISSN: 0955-3959 (ISSN-L)
DOI: 10.1016/j.drugpo.2015.07.004
PMC: PMC4577462
OpenAlex: W1941992522
Cited by: 104
References: 75
Citations by year: 2026: 3 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 12 · 2018: 13 · 2017: 12 · 2016: 9 · 2015: 6
FWCI: 1.91
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: International Journal of Drug Policy (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (R01DA034637, P30 DA011041)
Topics: Health Sciences › Medicine › Hepatology › Hepatitis C virus research
Health Sciences › Medicine › Epidemiology › HIV, Drug Use, Sexual Risk
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords: hepatitis C virus, people who inject drugs, liver fibrosis progression, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, METAVIR score, incidence rates, harm reduction, harm reduction services, harm reduction funding
MeSH terms: Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, HIV Infections, Substance Abuse, Intravenous, Comorbidity, Incidence, Disease Progression, Hepatitis C, Chronic

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Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis

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