To the Editor:

We read with interest the article by Jeffrey et al. on antiviral treatment of chronic HCV infection in injection drug users who had received subcutaneous naltrexone implants.1 The authors are to be commended for their efforts in treating a population which does not always receive such a high level of care for liver diseases.

The authors do not provide information on the magnitude, duration, and specific type of injection drug use in their patients. Also, they do not indicate whether their patients are representative of most injection opiate users seen in Australia. Does the clinic where the study was conducted treat all opiate users or only selected groups? It is possible that the patients in this study had not self-administered opiates long enough to develop the well-documented humoral and cellular immunologic abnormalities seen in more chronic injection drug users.2 This may be a factor in the high rate of sustained virological response (SVR) to antiviral therapy reported by Jeffrey et al. The accompanying editorial3 discusses several additional explanations for the high SVR.

The authors propose that subcutaneous naltrexone implants may have advantages over methadone maintenance in modulating the immune response in former opiate users who will receive antiviral therapy. We and others have reported profound immunologic abnormalities in heroin addicts, and others have reported suppression of specific components of the immune response by the short-acting opiate morphine.2 In chronic maintenance treatment with the long-acting opiate methadone (median duration of treatment: 16 years), we described normalization of several parameters of cellular immunity, including natural killer cell activity.2, 4 Several groups reported satisfactory SVR rates for hepatitis C treatment in former long-term heroin addicts treated with methadone maintenance.3

Addiction is a chronic disease. Methadone maintenance treatment has been in clinical use for more than 40 years,5 has been validated by extensive long-term studies,6 and has been endorsed by a NIH consensus conference.7 The articles cited for addiction treatment outcomes of subcutaneous naltrexone implants describe follow-ups of 2 and 13 months, respectively, for 2 impaired physicians8 and no follow-up of 17 pregnant addicts.9 Long-term studies of subcutaneous naltrexone implants have been initiated in order to determine the role of this medication in the chronic treatment of addiction.

We look forward to further studies by Jeffrey et al. in patients with addictive diseases. We agree with others who have suggested that expertise in both hepatology and the study of chemical dependency will lead to better outcomes in treatment of persons with addiction and chronic hepatitis C.10


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  • 1
    Jeffrey GP, MacQuillan G, Chua F, Galhenage S, Bull J, Young E, et al. Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants. HEPATOLOGY 2007; 45: 111117.
  • 2
    Novick DM, Ochshorn M, Kreek MJ. In vivo and in vitro studies of opiates and cellular immunity in narcotic addicts. In: FriedmanH, SpecterS, KleinTW, eds. Drugs of Abuse, Immunity, and Immunodeficiency. New York: Plenum Press, 1991: 159170.
  • 3
    Dore GJ. Enhancing hepatitis C treatment uptake and outcomes for injection drug users. HEPATOLOGY 2007; 45: 35.
  • 4
    Novick DM, Ochshorn M, Ghali V, Croxson TS, Mercer WD, Chiorazzi N, et al. Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients. J Pharmacol Exp Ther 1989; 250: 606610.
  • 5
    Dole VP, Nyswander ME, Kreek MJ. Narcotic blockade. Arch Intern Med 1966; 118: 304309.
  • 6
    Novick DM, Richman BL, Friedman JM, Friedman JE, Fried C, Wilson JP, et al. The medical status of methadone maintenance patients in treatment for 11-18 years. Drug Alcohol Depend 1993; 33: 235245.
  • 7
    National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction. NIH Consensus Conference: Effective treatment of opiate addiction. JAMA 1998; 280: 19361943.
  • 8
    Hulse GK, O'Neil G, Hatton M, Paech MJ. Use of oral and implantable naltrexone in the management of the opioid impaired physician. Anaesth Intensive Care 2003; 31: 196201.
  • 9
    Hulse GK, O'Neil G, Arnold-Reed DE. Methadone maintenance vs. implantable naltrexone treatment in the pregnant heroin user. Int J Gynaecol Obstet 2004; 85: 170171.
  • 10
    Kresina TF, Seeff LB, Francis H. Hepatitis C infection and injection drug use: the role of hepatologists in evolving treatment efforts. HEPATOLOGY 2004: 40: 516519.

David M. Novick M.D.* † ‡, Mary Jeanne Kreek M.D.*, * The Rockefeller University, New York, NY, † Kettering Medical Center, Kettering, OH, ‡ Wright State University Boonshoft School of Medicine, Dayton, OH.