Ir Med J. 2008 Nov-Dec;101(10):316-7.

Abstract
Relatively few patients infected with the hepatitis C virus through intravenous drug abuse receive effective antiviral therapy. The aim of this study was to determine if supervised treatment in a drug treatment centre could improve compliance with antiviral therapy. A pilot study of supervised anti-viral treatment in a community non-residential drug treatment facility was conducted. Thirteen patients infected with hepatitis C virus genotype 2 or 3 were identified in a drug treatment clinic. Six patients agreed to treatment. Full treatment course was administered in all 6 with sustained viral response in 5/6. This study demonstrates that effective treatment penetration can be improved for this patient group by shared care with drug treatment services, without the need for significant increases in resources.

Introduction
Approximately 75% of the intravenous drug abusing population in Dublin are infected with the hepatitis C virus and 56% are PCR positive^1,2. Many of these patients have adverse prognostic markers predicting the development of serious liver disease. It is believed that there are in excess of 13,000 previous or current intravenous drug users in Ireland. Using data from other cohorts it can be estimated that approximately 1,200 will develop cirrhosis1. This is a major potential burden on the health service. Effective treatment now exists for hepatitis C and it is possible to eradicate the virus in a significant proportion of cases. For patients with genotype ¹ eradication rates are approximately 40% but rise to 75% - 80% for patients infected with genotype 2 and 3. However, only a minority of patients from the intravenous drug abuse population receive effective antiviral therapy^3,4. Barriers to treatment include poor compliance, continuing alcohol or drug dependence, fear of liver biopsy and psychological or psychiatric factors^4,5. To improve access to treatment we decided to move treatment to the drug treatment clinic where it could be administered in conjunction with methadone maintenance.

Methods
All patients attending the drug treatment clinic in Patrick’s St, Dun Laoghaire were assessed. Details of these patients have been published previously¹. All patients with hepatitis C, RNA positive by PCR, who were infected with genotype 2 or 3 were considered for treatment. If the patients were stable on methadone and had taken no intravenous drugs for 6 months they were referred to the liver unit for further assessment. Mild to moderate alcohol intake, cannabis use or occasional benzodiazepine use were not considered contra-indications to treatment. The assessment in the liver clinic included interviews and examination by a consultant hepatologist and a formalised education process with a hepatitis C hepatology nurse specialist. No liver biopsies were required. A prescription for combination pegylated interferon and ribavirin was then issued. The patients were seen weekly in the drug treatment clinic by a drug treatment specialist. Pegylated interferon was kept in the drug treatment clinic and administered on a weekly basis under the direct supervision of the drug clinic nurse. Weekly blood and urine tests were performed and results forwarded to the liver clinic, as appropriate.

Regular phone consultations with the liver clinic to discuss dose adjustment or management of side effects were encouraged. Appointments at the liver unit included an initial visit, education visit with the HCV nurse, prescription visit and follow up a 1, 3 and 6 months. After the initial patients the 1 month follow-up visit was discontinued. Quantitative hepatitis C PCR was repeated at 3, 6 and 12 and 18 months. This study was approved by the ethics committee St Vincent’s University Hospital.

Results
Thirteen patients with hepatitis C virus genotype 2 or 3 were identified. Six patients received combination antiviral therapy and all completed at least 6 months treatment. The initial patient was treated with non-pegylated interferon 3 million units thrice weekly. All other patients received pegylated interferon (peginterferon alfa-2a). Four patients required dose reduction of interferon because of neutropenia and one of these patients also had ribavirin dose reduced because of anaemia. Two patients required GCSF (neupogen) for treatment of neutropenia. Two patients continued to drink alcohol during treatment. Both females treated had positive urines for opiates during treatment. In one patient this was once only but in the other there were repeated opiate positive urines and one positive for cocaine. Despite this all six had a sustained virological response at 6 months following treatment.

One patient had a clinical and virological relapse at 12 months. Of the patients not treated: 2 declined treatment, 1 was noncompliant with liver unit appointments, 1 was incarcerated in prison and 3 transferred to other drug treatment facilities.

Discussion
Infection with hepatitis C is a major and growing public health problem. We know that it is possible to treat intravenous drug abusers with similar results to the non-using population but in most countries only a minority of potentially eligible actually receive treatment^5,6. In a French study 27 of 404 patients received antiviral therapy and 5 had a sustained virological response⁷. In a British study 50/253 patients attending a hospital based liver clinic received antiviral treatment3. Although not all patients required treatment, drop-outs occurred at all stages of evaluation and treatment in these studies. In a German study 50% of eligible patients started and 40% completed a course of antiviral therapy⁸. These results are very impressive but the treatment was very resource intensive. Patients were admitted to a specialised drug detoxification unit staffed with 2 physicians, trained in addiction medicine and hepatology, 1 psychologist, 6 social workers and 6 nurses. Average length of in-patient stay was 28 days. Such resources are unavailable in many centres. For out patient treatment, non-compliance with clinic appointments or drug therapy is a major problem. In another German study, which included 50 patients on methadone maintenance, 30% discontinued therapy, compared to 12% in a control group⁹.

In our study we aimed to increase compliance by decreasing the number of hospital clinic visits to the minimum and linking antiviral therapy to methadone prescription and dispensing. It had been our experience that patients frequently miss hepatology appointments but rarely miss methadone appointments. We took advantage of this to improve compliance with anti-viral therapy while utilising the existing methadone maintenance programme facilities. Methadone treatment was not in any way contingent on compliance with anti-viral treatment. However the clinic settingprovided continuous medical and social support for patients on anti-viral treatment. As a result complications of anti-viral treatment were addressed promptly and compliance was improved. The impact of anti-viral treatment on illicit drug use could also be addressed without delay.

In this study no additional resources were required. If anything supervision of treatment in the methadone clinic freed up resources in the hospital hepatology clinic. This pilot study suggests this is a workable and cost-effective strategy to improve access to anti-viral therapy which may have widespread applicability. We are currently extending this study to treat patients with genotype 1 hepatitis C virus.

Acknowledgement
This study was supported by a grant from Roche Pharmaceuticals (Ireland) Limited. Roche Pharmaceuticals had no input in the study design or into writing the paper.

Correspondence:
PA McCormick
Liver Unit, St Vincent’s University Hospital, Elm Park, Dublin 4
Email:[email protected]

References

1. Kavanagh P, Moloney J, Quinn C, O’Kelly E, McCormick PA. High morbidity expected from cirrhosis in injecting drug users. Irish Medical Journal 2003; 96:303-305.
2. Cullen W, Bury G, Barry J, O’Kelly FD. Hepatitis C infection among drug users attending general practice. Ir J Med Sci 2003; 172:123- 127.
3. Jowett SL, Agarwal K, Smith BC et al. Managing chronic hepatitis C acquired through intravenous drug use. QJM 2001; 94:153-158.
4. Cullen W, Kelly Y, Stanley J, Langton D, Bury G. Experience of hepatitis C among current or former heroin users attending general practice. Irish Medical Journal 2005; 98:73-74.
5. 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; 29:159-165.
6. Robaeys G, Buntinz F. Treatment of hepatitis C viral infections in substance abusers. Acta Gastroenterol Belg 2005; 68:55-67.
7. Grando-Lemaire V, Goisset P, Sorge F et al. Hepatitis C virus screening in drug users in an addiction out-patient unit. Gastroenterol Clin Biol 2002; 26:1091-1096.
8. Backmund M, Meyer K, Von Zielonka M, Eichenlaub D. Treatment of hepatitis C infection in injection drug users. Hepatology 2001; 34:188-193.
9. 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.