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Enhancing hepatitis C treatment uptake and outcomes for injection drug users EDITORIAL
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Hepatology Jan 2007
Gregory J. Dore, B.Sc., MBBS, FRACP, M.P.H., Ph.D. 1 2 *
1Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales Sydney, Australia
2Infectious Diseases Physician, HIV/Immunology/Infectious Diseases Clinical Services Unit, St. Vincent's Hospital, Darlinghurst, Australia
"....Low rates of HCV treatment among current IDU and the heterogeneity of the IDU population indicate that further HCV treatment research and development of IDU-specific strategies are required. In this issue of HEPATOLOGY, Jeffrey and colleagues present extremely encouraging HCV treatment outcomes among an IDU population in Perth, Australia.[16] An intention-to-treat based SVR rate of 62% was recorded among 50 patients....Key features of the study population and HCV treatment program were the predominant use of naltrexone implants for opiate dependency treatment, high frequency of injection drug use prior to opiate dependency treatment but limited injection drug use during and following HCV treatment, and the delivery of HCV treatment within a multidisciplinary clinic established at a community-based drug treatment center....
....a multidisciplinary approach with expertise in clinical hepatology or infectious diseases, addiction medicine and psychiatry appears to be a common feature of successful programs. Other components of some successful programs have been peer-based education,[7] specific psychotherapy sessions,[8] and regular patient review.....Strategies to improve HCV treatment outcomes among current IDUs should include education and training for addiction medicine physicians and an improved understanding of addiction medicine among HCV treatment physicians...."
Article Text
The majority of people with hepatitis C virus (HCV) in North America, Europe and Australia have acquired infection through injection drug use.[1][2] HCV prevalence ranges from 30% to 90% among former and current injection drug users (IDUs).[1][3] Prior to 2002 current IDUs were not generally evaluated for HCV treatment, despite considerable heterogeneity in patterns of drug use. In 1997, a National Institutes of Health (NIH) consensus statement on management of HCV recommended that IDUs should have a period of illicit drug use abstinence for 6-12 months prior to HCV treatment.[4] In 2002, NIH consensus panel recommendations shifted stating that individuals with active injection drug use could be considered for HCV treatment.[5] These recommendations were reinforced through American Association for the Study of Liver Disease (AASLD) practice guidelines for diagnosis, management, and treatment of HCV.[6]
These changes in recommendations resulted from advances in HCV treatment, preliminary evidence of successful treatment programs for current IDUs and persons receiving drug dependency treatment in the United States[7] and Europe,[8] and concerted advocacy.[9] Although there is ongoing debate as to the appropriateness of HCV treatment for current IDUs,[9][10] several groups have now reported treatment outcomes among both current IDU and drug dependency treatment populations,[7][8][11-14] with sustained virological response (SVR) rates of 29% to 50%. These studies were conducted prior to availability of pegylated interferons and some included interferon monotherapy regimens. In two studies that used non-IDU based controls matched for other baseline demographic and clinical characteristics including HCV genotype, SVR rates were 42% (cases) versus 56% (controls),[13] and 33% (cases) versus 37% (controls).[11] Despite the relatively small sample size of these studies, considerable heterogeneity in IDU populations across studies, and the apparent 5% to 15% lower SVR rates than among non-IDU populations, several important findings have emerged. First, it is possible to successfully and safely use interferon and ribavirin in current and recovering IDUs including within opiate detoxification programs or opiate dependency maintenance programs.[7][8][12][13] Second, HCV treatment can be successful even for persons who continue to inject illicit drugs, although more frequent use is correlated with less success.[7][14] Third, HCV treatment does not have a major impact on drug dependency treatment requirements or increase injection drug use.[7][11][13]
Revised HCV treatment recommendations for current and recovering IDUs, and encouraging HCV treatment outcomes in preliminary studies have provided impetus for IDU treatment programs, but a small minority of current IDUs receive treatment. An Australian survey of approximately 2,500 current IDUs attending Needle Syringe Programs in 2003 found prior and current HCV treatment rates among participants with HCV of 4% and 0.6%, respectively.[15] The explanation for low rates of HCV treatment among IDUs is probably multifactorial. Barriers to HCV treatment access may relate to lack of understanding and low prioritisation among patients, lack of treatment consideration or active discrimination by clinicians, and limited HCV treatment infrastructure, particularly in settings of drug dependency treatment.
Low rates of HCV treatment among current IDU and the heterogeneity of the IDU population indicate that further HCV treatment research and development of IDU-specific strategies are required. In this issue of HEPATOLOGY, Jeffrey and colleagues present extremely encouraging HCV treatment outcomes among an IDU population in Perth, Australia.[16] An intention-to-treat based SVR rate of 62% was recorded among 50 patients (49 with chronic HCV infection) commenced on interferon and ribavirin therapy, a figure higher than previous studies within IDU populations and consistent with non-IDU clinical trial-based outcomes. Key features of the study population and HCV treatment program were the predominant use of naltrexone implants for opiate dependency treatment, high frequency of injection drug use prior to opiate dependency treatment but limited injection drug use during and following HCV treatment, and the delivery of HCV treatment within a multidisciplinary clinic established at a community-based drug treatment center.
The authors speculate about the potential enhanced role of naltrexone (opiate antagonist) versus the more widely used methadone (opiate replacement) in terms of HCV treatment outcomes. They cite studies demonstrating that opiates inhibit endogenous interferon production[17] and impair innate immune responses to infectious agents,[18] and suggest the absence of these effects may partly explain the improved HCV treatment outcomes compared to previous studies within methadone maintenance therapy programs. However, there are several alternate explanations for the encouraging and improved outcomes in their study. First, previous studies often included patients treated prior to combination therapy and there is limited data available on outcomes with pegylated interferon and ribavirin therapy, the major therapy used in their study. Second, favourable treatment factors included a majority of genotype 2 and 3 patients (although genotype 1 SVR was 53%) and a small proportion of bridging fibrosis/cirrhosis patients. Third, the relative stability of their patient population with infrequent injection drug use during HCV treatment should have assisted HCV treatment outcomes; commencement of HCV treatment a median of 6 months following opiate detoxification and some possible selection of more stable patients may have been important factors. Some studies of HCV treatment outcomes in current IDU populations have been conducted within weeks of commencement of opiate detoxification. Fourth, inclusion of a clinical psychologist within their multidisciplinary clinic and ready access to other psychiatric services may have reduced HCV treatment neuropsychiatric morbidity and contributed to the high level of adherence; almost half of their patients received antidepressant therapy during HCV treatment.
The potential improved HCV treatment outcomes using naltrexone implants over other forms of drug dependency treatment should be investigated, preferably in a randomized controlled trial. Such a study would require randomisation of current IDU with HCV to different forms of drug dependency treatment with a period of stabilisation (3-6 months) prior to HCV treatment. Outcomes could cover both drug use patterns and HCV treatment outcomes (including numbers commenced and successful treatment achieved).
Irrespective of whether naltrexone has provided an independent benefit within the setting of HCV treatment in their study, Jeffrey and colleagues have provided further optimism for enhancing HCV treatment uptake and outcomes among current IDU populations. Although various drug treatment and HCV treatment delivery models have been utilized, a multidisciplinary approach with expertise in clinical hepatology or infectious diseases, addiction medicine and psychiatry appears to be a common feature of successful programs. Other components of some successful programs have been peer-based education,[7] specific psychotherapy sessions,[8] and regular patient review.
Strategies to improve HCV treatment outcomes among current IDUs should include education and training for addiction medicine physicians and an improved understanding of addiction medicine among HCV treatment physicians. Recent recommendations to hepatologists involved in HCV clinical management include the need for education on substance use including aspects of risk reduction, certification in treating opioid dependency and participation in multidisciplinary teams providing HCV care to IDUs.[19] Drug dependency treatment settings should play an integral role in expanded access to HCV treatment. In the United States, more than 200,000 people are receiving opioid replacement therapy, of whom an estimated 90% have HCV infection.[20] Strategies to enhance primary care involvement in both drug dependency treatment and HCV treatment should also be introduced to broaden the practitioner base for care of current and recovering IDUs. Case managers are often utilized in the drug dependency treatment setting, therefore the incorporation of aspects of HCV treatment into their role could improve adherence among current and recovering IDUs. Finally, reduction of stigma and discrimination related to both HCV and injection drug use is required to provide the foundation upon which programs to enhance HCV treatment uptake and outcomes among current IDUs should be built.
References
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12 Schaefer M, Schmidt F, Folwaczny C, Lorenz R, Martin G, Schindlbeck N, et al. Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. HEPATOLOGY 2003; 37: 443-451. Links
13 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: 120-124. Links
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16 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: 111-117. Links
17 Geber WF, Lefkowitz SS, Hung CY. Effect of morphine, hydromorphone, methadone, mescaline, trypan blue, vitamin A, sodium salicylate, and caffeine on the serum interferon level in response to viral infection. Arch Int Pharmacodyn Ther 1975; 214: 322-327. Links
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20 Krantz MJ, Mehler PS. Treating opioid dependence. Growing implications for primary care. Arch Intern Med 2004; 164: 277-288. Links
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