Injection Drug Users: The Overlooked Core of the Hepatitis C Epidemic
Brian R. Edlin and Michael R. Carden
Center for the Study of Hepatitis C, Weill Medical College of Cornell University and Center for the Study of Hepatitis C, Weill Medical College of Cornell University, New York, New York
Reprints or correspondence: Dr. Brian R. Edlin, Weill Medical College of Cornell University, 411 E. 69th St., Rm. KB-218, New York, NY 10021 (Email: bre2002@med.cornell.edu ).
The publisher's final edited version of this article is available at Clin Infect Dis
See other articles in PMC that cite the published article.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1611492/?tool=pmcentrez

 

Injection drug users (IDUs) constitute the core of the hepatitis C epidemic in the developed world. Four times more prevalent than HIV infection, hepatitis C virus (HCV) has been acquired by at least 5 million Americans and an estimated 170 million people worldwide. In developed countries, people who use illegal drugs by injection are the largest group of persons with HCV infection and the group among whom most new infections occur. Viral transmission is uncontrolled among IDUs, with incidence rates ranging from 16%–42% per year [1–4], and yet, our efforts to control this pandemic have largely ignored the population in whom its biology and epidemiology are being played out with the most devastating effects.
Disease control depends on epidemiology, basic science, treatment, and prevention. In each of these spheres, work on HCV has focused on convenient populations—patients who come to our clinics and offices of their own accord—rather than the more challenged and stigmatized populations in whom the epidemic continues to rage out of control. The ubiquitously quoted estimate of the number of Americans infected with HCV—4 million—was derived from the National Health and Nutrition Examination Survey, a study of the housed, noninstitutionalized, civilian population of the United States [5]. But the populations most severely affected by HCV are poorly captured by this study. Disproportionately low response rates can be expected in government surveys from persons engaged in illegal activities, disclosure of which could result in incarceration or deportation. In addition, the National Health and Nutrition Examination Survey sampling frame, by design, explicitly excluded several large groups known to have high prevalences of injection drug use and HCV infection: people who are homeless, incarcerated, hospitalized, or institutionalized. Available estimates of the sizes and HCV prevalences of these populations suggest that at least a million more Americans have been infected with HCV than estimated by the National Health and Nutrition Examination Survey data [6].
New HCV infections in persons who inject illicit drugs are probably not well-represented in official estimates of HCV incidence in the United States, either. National estimates of the number of new HCV infections—about 30,000 per year—are based on data from cases of acute HCV infection reported to health departments in the 4 US counties (recently expanded to 6) participating in the Sentinel Counties Study of Acute Viral Hepatitis [7]. The calculations rely on the estimate that 1 in 6 new infections come to medical attention. HCV infections in IDUs, however, are rarely symptomatic, and probably<1% come to medical attention and are diagnosed [8, 9]. Thus, the true incidence of HCV infection among IDUs may be even less accurately ascertained by our surveillance system than the prevalence. The official estimates of these numbers tell us about infections in those of us who are stably housed, have nothing to fear from the criminal justice system, and go to the doctor when sick, but tell us little about those at the core of the epidemic.
If epidemiologists overlook IDUs when studying HCV, it is little wonder that basic scientists and treatment researchers do the same. Critical lessons about effective human immune responses to HCV infection can be learned from persons who clear the virus during the acute phase of infection. But although tens of thousands of IDUs in the United States become infected every year, most of our insights about the biology of acute HCV infection have come from less representative but more accessible sources—rare cases of symptomatic acute HCV infection that come to medical attention and occupationally exposed health care workers [10, 11]. And even as considerable progress has been achieved in developing new effective antiviral regimens for HCV infection, persons who inject illegal drugs, even former IDUs receiving methadone maintenance treatment, are routinely excluded from clinical trials of new HCV therapies.
Because, even by official estimates, most HCV transmission in developed countries occurs through the use of contaminated injection equipment during illicit drug injection, one might expect that prevention efforts would, of necessity, focus on stopping transmission among IDUs, even if other clinical or scientific efforts focused on more accessible populations. Most official publications on the prevention and control of HCV infection [12–14], however, have avoided directly recommending the central strategies for preventing blood-borne disease transmission among IDUs: accessible substance abuse treatment, syringe exchange programs, removal of the legal barriers to syringe access and possession, community-based outreach, and HCV testing and treatment programs for IDUs and incarcerated persons [15]. Prisons offer an unparalleled opportunity for HCV prevention and treatment [16], because an estimated 29%–43% of HCV-infected persons in the United States pass through the corrections system annually [17], but the opportunity is almost universally squandered [18]. Despite their centrality in the epidemic, IDUs all too often seem invisible to epidemiologists, basic scientists, clinicians, and public health authorities alike.
One official document that illuminated this blind spot was the 2002 National Institutes of Health consensus statement on the management of HCV [19]. Departing from previous guidelines, this document recommended that drug users be considered for HCV treatment on a case-by-case basis, just like other patients, and that drug use in and of itself not be considered a contraindication. This change was based on the recognition that data did not exist to support the previous recommendation, made in 1997 [20], that drug users not be treated for HCV infection until they had abstained from all illicit drug use for at least 6 months [21]. Nonetheless, few data exist to guide physicians considering treating active drug users for HCV infection outside of special targeted programs [22–38], and most hepatologists still adhere to the old guidelines on this matter. As a consequence, despite the new guidelines, very few drug users have access to treatment for HCV infection [39].
Current treatment regimens for HCV infection appear to eradicate the virus from 50% of patients [40], averting the risk of liver failure or liver cancer [41]. When restrictive criteria are applied to substance users with HCV infection, however, the proportion that remains eligible for antiviral therapy quickly evaporates, as reported by Hagan and her colleagues in this issue of Clinical Infectious Diseases [42]. Four-hundred four IDUs were drawn from the more than 1 million active IDUs in the United States with HCV infection. Of these 404, only 4% would be offered treatment if those with problem drinking, moderate-to-severe depression, or recent injection drug use are considered ineligible. If this is the best we can do—if the “incredible shrinking” pool of patients depicted in their figure is all we can hope to treat—we will forever remain consigned to treating patients at the peripheries of the epidemic, and the burden of liver disease will continue to rise.
But can patients with these problems be treated for HCV infection? A growing number of studies suggest that they can. Reports from Munich [22–24], Oakland [25], Chicago [26], Rhode Island [27], New York [28], Vancouver [29], England [30], France [31], Italy [32], Belgium [33], Dusseldorf [34], Switzerland [35], Austria [36], Norway [37], and Australia [38], reviewed elsewhere [43–45], have suggested that drug users treated for HCV infection can achieve sustained virologic response rates similar to those in other populations, even if they have psychiatric comorbidity, and even if they continue to use drugs while receiving treatment, although more frequent drug use may be associated with less success [25]. Many of these studies, however, reported on small, diverse groups of sometimes highly selected patients recruited and treated in different settings with differing strategies. Data are sparse on the characteristics that distinguish those who can be successfully treated and the programmatic elements that are critical for success. Larger studies that carefully characterize patient and program characteristics and outcomes are needed to provide this information. The need for such research is urgent, in view of the overwhelming prevalence of HCV infection in this population [46, 47], the increasing morbidity and mortality of the disease [48], and the limited access that IDUs have to liver transplantation [49]. In the meantime, these same considerations demand that we use what we know already to expand and replicate existing programs that have been successful [50].
Cultural and behavioral barriers encumber work with IDUs, whether in research, clinical care, disease prevention, or public health. Nonetheless, until these barriers are overcome, the HCV epidemic will continue to spread unabated, and morbidity and mortality from liver disease will continue to rise. Fortunately, experience working effectively with IDUs is available from a relatively large community of professionals serving substance-using populations, including those working in substance abuse treatment, HIV prevention, harm reduction, HIV care, primary medical care, social services, and other areas. Knowledge and experience with HCV infection and its treatment, however, are needed in these circles. Dialogue and collaboration between experts in HCV treatment and practitioners who have experience with IDUs will be needed to bring the unseen core of the HCV epidemic into view, so that progress can be made toward effective prevention of infection and effective treatment and care of those with HCV infection at the core of the epidemic. The Ryan White CARE Act has provided resources for productive collaboration among providers serving patients with HIV infection. Advocacy for the needs of persons with HCV infection may be required to get needed resources allocated to support similar work on HCV. The all-too-frequently overlooked core of the epidemic is the battleground on which efforts to control HCV infection in the developed world will be won or lost.
Acknowledgments
Financial support. National Institutes of Health (grants R01-DA-09532, R01-DA-13245, and R01-DA-16159).
Potential conflicts of interest. B.R.E. and M.R.C.: no conflicts.
o ReferencesReferences
1. Garfein RS, Doherty MC, Monterroso ER, Thomas DL, Nelson KE, Vlahov D. Prevalence and incidence of hepatitis C virus infection among young adult injection drug users. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;18(Suppl 1):S11–9. [PubMed]
2. Hagan H, Thiede H, Weiss NS, Hopkins SG, Duchin JS, Alexander ER. Sharing of drug preparation equipment as a risk factor for hepatitis C. Am J Public Health. 2001;91:42–6. [PMC free article] [PubMed]
3. Hahn JA, Page-Shafer K, Lum PJ, et al. Hepatitis C virus seroconversion among young injection drug users: relationships and risks. J Infect Dis. 2002;186:1558–64. [PubMed]
4. Judd A, Hickman M, Jones S, et al. Incidence of hepatitis C virus and HIV among new injecting drug users in London: prospective cohort study. BMJ. 2005;330:24–5. [PMC free article] [PubMed]
5. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556–62. [PubMed]
6. Edlin BR. Five million Americans infected with the hepatitis C virus: a corrected estimate [abstract #44]. Oral presentation at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (Boston) 2005 Hepatology. 2005;42(4 Suppl 1):213A.
7. Centers for Disease Control and Prevention (CDC) Atlanta: CDC; 2005. [Accessed 26 October 2005.]. Disease burden from hepatitis A, B, and C in the United States. http://www.cdc.gov/ncidod/diseases/hepatitis/resource/dz_burden02.htm.
8. Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology. 1999;29:908–14. [PubMed]
9. Hagan H, Snyder N, Hough E, et al. Case-reporting of acute hepatitis B and C among injection drug users. J Urban Health. 2002;79:579–85. [PubMed]
10. Lechner F, Wong DK, Dunbar PR, et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med. 2000;191:1499–512. [PMC free article] [PubMed]
11. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 2001;194:1395–406. [PMC free article] [PubMed]
12. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR Recomm Rep. 1998;47(RR19):1–39.
13. Centers for Disease Control and Prevention (CDC) Atlanta: CDC; 2001. [Accessed 26 October 2005]. National hepatitis C prevention strategy. http://www.cdc.gov/ncidod/diseases/hepatitis/c/plan/index.htm.
14. Alter MJ. Prevention of spread of hepatitis C. Hepatology. 2002;36(5 Suppl 1):S93–8. [PubMed]
15. Edlin BR. Prevention and treatment of hepatitis C in injection drug users. Hepatology. 2002;36(5 Suppl 1):S210–9. [PMC free article] [PubMed]
16. Allen SA, Spaulding AC, Osei AM, Taylor LE, Cabral AM, Rich JD. Treatment of chronic hepatitis C in a state correctional facility. Ann Intern Med. 2003;138:187–90. [PubMed]
17. Hammett TM, Harmon MP, Rhodes W. The burden of infectious disease among inmates of and releasees from US correctional facilities, 1997. Am J Public Health. 2002;92:1789–94. [PMC free article] [PubMed]
18. Boutwell AE, Allen SA, Rich JD. Opportunities to address the hepatitis C epidemic in the correctional setting. Clin Infect Dis. 2005;40(Suppl 5):S367–72. [PubMed]
19. National Institutes of Health (NIH) Management of hepatitis C: 2002. NIH Consensus State-of-the-Science Statement. 2002 19:1–46. [Accessed 26 October 2005.]; http://consensus.nih.gov/2002/2002HepatitisC2002116html.htm.
20. National Institutes of Health (NIH) Management of hepatitis C. NIH Consensus Statement . 1997 15:1–41. [Accessed 26 October 2005.]; http://consensus.nih.gov/1997/1997HepatitisC105html.htm.
21. Edlin BR, Seal KH, Lorvick J, et al. Is it justifiable to withhold treatment for hepatitis C from illicit-drug users? N Engl J Med. 2001;345:211–4. [PMC free article] [PubMed]
22. Backmund M, Meyer K, Von Zielonka M, Eichenlaub D. Treatment of hepatitis C infection in injection drug users. Hepatology. 2001;34:188–93. [PubMed]
23. Schaefer M, Schmidt F, Folwaczny C, et al. Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. Hepatology. 2003;37:443–51. [PubMed]
24. Backmund M, Reimer J, Meyer K, Gerlach JT, Zachoval R. Hepatitis C virus infection and injection drug users: prevention, risk factors, and treatment. Clin Infect Dis. 2005;40(Suppl 5):S330–5. [PubMed]
25. Sylvestre DL, Litwin AH, Clements BJ, Gourevitch MN. The impact of barriers to hepatitis C virus treatment in recovering heroin users maintained on methadone. J Subst Abuse Treat. 2005;29:159–65. [PubMed]
26. Van Thiel DH, Anantharaju A, Creech S. Response to treatment of hepatitis C in individuals with a recent history of intravenous drug abuse. Am J Gastroenterol. 2003;98:2281–8. [PubMed]
27. Taylor LE. Delivering care to injection drug users coinfected with HIV and hepatitis C virus. Clin Infect Dis. 2005;40(Suppl 5):S355–61. [PubMed]
28. Litwin AH, Soloway I, Gourevitch MN. Integrating services for injection drug users infected with hepatitis C virus with methadone maintenance treatment: challenges and opportunities. Clin Infect Dis. 2005;40(Suppl 5):S339–45. [PubMed]
29. Conway B, Grebely J, Tossonian H, Lefebvre D, de Vlaming S. A systematic approach to the treatment of HIV and hepatitis C virus infection in the inner city: a Canadian perspective. Clin Infect Dis. 2005;41(Suppl 1):S73–8. [PubMed]
30. Jowett SL, Agarwal K, Smith BC, et al. Managing chronic hepatitis C acquired through intravenous drug use. QJM. 2001;94:153–8. [PubMed]
31. Cournot M, Glibert A, Castel F, et al. Management of hepatitis C in active drugs users: experience of an addiction care hepatology unit. Gastroenterol Clin Biol. 2004;28:533–9. [PubMed]
32. Neri S, Bruno CM, Abate G, et al. Controlled clinical trial to assess the response of recent heroin abusers with chronic hepatitis C virus infection to treatment with interferon alpha-n2b. Clin Ther. 2002;24:1627–35. [PubMed]
33. Robaeys G, Van Vlierberghe H, Mathei C, Van Ranst M, Bruckers L, Buntinx F. Simialr compliance and effect of treatment for chronic hepatitis C resulting from intravenous drug use in comparison with other infection causes. Eur Gastroenterol Hepatol. 2006;18:159–66.
34. Mauss S, Berger F, Goelz J, Jacob B, Schmutz G. A prospective controlled study of interferon-based therapy of chronic hepatitis C in patients on methadone maintenance. Hepatology. 2004;40:120–4. [PubMed]
35. Huber M, Weber R, Oppliger R, et al. Interferon alpha-2a plus ribavirin 1000/1200 mg versus interferon alpha-2a plus ribavirin 600 mg for chronic hepatitis C infection in patients on opiate maintenance treatment: an open-label randomized multicenter trial. Infection. 2005;33:25–9. [PubMed]
36. Baewert A, Ebner N, Thau K, Fischer G. Treatment of hepatitis C/subtype 2 or 3 with pegylated interferon in combination with ribavirin in a population of opioid-dependent patients [abstract 35].. Program and abstracts of the 67th Annual Scientific Meeting of the College on Problems of Drug Dependence (Orlando, FL); Philadelphia. College on Problems of Drug Dependence; 2005. p. 9.
37. Dalgard O. Follow-up studies of treatment for hepatitis C virus infection among injection drug users. Clin Infect Dis. 2005;40(Suppl 5):S336–8. [PubMed]
38. Matthews G, Kronborg IJ, Dore GJ. Treatment for hepatitis C virus infection among current injection drug users in Australia. Clin Infect Dis. 2005;40(Suppl 5):S325–9. [PubMed]
39. Seal KH, Kral AH, Lorvick J, Gee L, Tsui JI, Edlin BR. Among injection drug users, interest is high, but access low to HCV antiviral therapy. J Gen Intern Med. 2005;20(suppl 1):171.
40. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–65. [PubMed]
41. Coverdale SA, Khan MH, Byth K, et al. Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study. Am J Gastroenterol. 2004;99:636–44. [PubMed]
42. Hagan H, Latka MH, Campbell JV, et al. Eligibility for treatment of hepatitis C virus infection among young injection drug users in 3 US cities. Clin Infect Dis . 2006;42:669–72. (in this issue) [PubMed]
43. Robaeys G, Buntinx F. Treatment of hepatitis C viral infections in substance abusers. Acta Gastroenterol Belg. 2005;68:55–67. [PubMed]
44. Dore GJ, Thomas DL. Management and treatment of injection drug users with hepatitis C virus (HCV) infection and HCV/human immunodeficiency virus coinfection. Semin Liver Dis. 2005;25:18–32. [PubMed]
45. Geppert CM, Arora S. Ethical issues in the treatment of hepatitis C. Clin Gastroenterol Hepatol. 2005;3:937–44. [PubMed]
46. Thomas DL, Vlahov D, Solomon L, et al. Correlates of hepatitis C virus infections among injection drug users. Medicine (Baltimore) 1995;74:212–20. [PubMed]
47. Lorvick J, Kral AH, Seal K, Gee L, Edlin BR. Prevalence and duration of hepatitis C among injection drug users in San Francisco, Calif. Am J Public Health. 2001;91:46–7. [PMC free article] [PubMed]
48. Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000;31:777–82. [PubMed]
49. Koch M, Banys P. Liver transplantation and opioid dependence. JAMA. 2001;285:1056–8. [PubMed]
50. Edlin BR, Kresina TF, Raymond DB, et al. Overcoming barriers to prevention, care, and treatment of hepatitis C in illicit drug users. Clin Infect Dis. 2005;40(Suppl 5):S276–85. [PMC free article] [PubMed]