Pegylated Interferon and Ribavirin in Hepatitis C Patients on Opioid Pharmacotherapy
Pegylated Interferon and Ribavirin in Hepatitis C Patients on Opioid Pharmacotherapy
The purpose of this study is to see if treatment of chronic hepatitis C in people who are on
 opiate replacement therapy such as methadone or buprenorphine (including patient who still
 inject drugs) is safe and effective.
It is estimated that in excess of 170 million people worldwide are infected with the
 hepatitis C virus (HCV) resulting in 1.4 million deaths annually. In developed countries HCV
 is most commonly transmitted through injecting drug use (IDU) with estimates suggesting up to
 80-90% of incident cases are due to unsafe injecting practices. Infection results in chronic
 infection in around 75% of cases and it is these patients who subsequently develop the
 life-threatening complications of liver failure and hepatocellular carcinoma due to
 progressive fibrosis.

 Current standard of care consists of a combination of pegylated interferon and ribavirin
 which results in sustained virological response rates (SVR, defined as undetectable HCV RNA
 24 weeks post treatment) in 54-63% of patients. This is strongly dependent on viral genotype
 with genotype 1 patients achieving lower SVR rates compared to genotype 2 and 3. These
 therapies are however associated with significant side effects, most notably psychiatric.
 Depression, anxiety and irritability are common and of concern is the attendant risk of
 suicidality in patients with a chronic illness in which depression is particularly common.
 Mood disorders have been reported to occur in up to 50% patients on therapy and can result in
 dose reductions and discontinuation in 40% and 20% patients respectively.

 While more effective therapies have become available for the treatment of chronic HCV, they
 have not been largely utilised in patients actively injecting. This is due to concerns about
 potential poor adherence to treatment regimens, reinfection due to ongoing IDU, increased
 incidence of concomitant alcohol abuse, potential for increased side effects (especially
 psychiatric), concerns about pregnancy with ribavirin use due to non-adherence to
 contraception as well as active discrimination by practitioners. There are however
 considerable potential advantages including: improvement in the health of the infected
 individual, potential for decreasing the burden of disease to the community with its
 attendant costs as well as the potential for impact on transmission and its inherent
 potential public health benefits.

 This multicentre study was conducted to determine the response rates as well as the AE
 profile and the psychiatric impact of therapy in a population with chronic hepatitis C (CHC)
 who were receiving opiate pharmacotherapy, many of who were still injecting.
Inclusion Criteria:

 1. 18 years of age or older

 2. on opioid substitution therapy (methadone or buprenorphine)

 3. serologic evidence of chronic hepatitis C infection determined by a detectable
 anti-HCV antibody for 6 months or greater with evidence of detectable HCV RNA

 4. elevated ALT on at least two occasions at least one month apart within the past 6
 months, with at least one during the screening period preceding the initiation of
 study drug dosing.

 5. HCV treatment-naïve

 6. Liver biopsy findings consistent with the diagnosis of chronic hepatitis C infection
 (unless contraindicated due to a bleeding disorder)

 7. Compensated liver disease (Child-Pugh Grade A clinical classification).

 8. All fertile males and females receiving ribavirin were required to be using two forms
 of effective contraception during treatment and during the 6 months after treatment

 9. Women of child bearing potential were required to have a negative urine or blood
 pregnancy test documented within the 24-hour period prior to the first dose of study
 drug

 Exclusion Criteria:

 1. Women who were pregnant, breastfeeding or planning a pregnancy

 2. Male partners of women who were pregnant

 3. Patients who had previously received therapy with any systemic anti-neoplastic or
 immunomodulatory treatment (including supraphysiologic doses of steroids and
 radiation) 6 months prior to the first dose of study drug

 4. Recipients of any investigational drug 4 weeks or 5 half lives, whichever was longer,
 prior to the first dose of study drug

 5. A positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab

 6. A history or other evidence of a medical condition associated with chronic liver
 disease other than HCV

 7. Haemoglobin <12 g/dL in women or <13 g/dL in men, a neutrophil count <1500 cells/mm3
 or platelet count <90,000 cells/mm3 at screening and serum creatinine level >1.5 times
 the upper limit of normal at screening.)

 8. A history of a severe seizure disorder or current anticonvulsant use

 9. Patients with a history of immunologically-mediated disease, chronic pulmonary disease
 associated with functional limitation, severe cardiac disease, coronary artery
 disease, cerebrovascular disease, major organ transplantation or other evidence of
 severe illness, malignancy, or any other conditions which would make the patient, in
 the opinion of the investigator, unsuitable for the study

 10. Patients with a history of thyroid disease which is poorly controlled on prescribed
 medications

 11. Evidence of severe retinopathy

 12. Evidence of excessive substance abuse as judged by the investigator

 13. Patients with an increased baseline risk for anaemia (e.g. thalassaemia,
 spherocytosis, history of gastrointestinal bleeding, etc) or for whom anemia would be
 medically problematic.

 14. Patients with a history of severe psychiatric disease (defined as acute phase of
 schizophrenia or bipolar disorder manic, mixed or depressive phase, severe anorexia,
 history of severe multiple episodes of self harm, currently screening as high or
 moderate suicide risk, current major depressive episode or current psychosis of any
 cause at screening)