Obstacles to successful HCV treatment in substance addicted patients.

Hepatitis C (HCV) infection in substance addicted patients is common and represents a therapeutically challenging co-morbidity. Alcohol and perhaps other substances of abuse directly influence the natural progression of HCV disease. Concurrent mental health illness, poor socioeconomic status, and unstructured life styles are often incompatible with safe and successful delivery of HCV treatment. These issues and their effect on treatment suitability and outcome are considered in this review. Funding for HCV-addiction research and strong political backing for interventions proven to benefit those struggling with addiction are paramount to increasing access to and uptake of HCV treatment. These interventions include substance cessation programs, safe injection settings to reduce HCV incidence and multidisciplinary teams to facilitate HCV treatment provision.

Evaluation of oral cannabinoid-containing medications for the management of interferon and ribavirin-induced anorexia, nausea and weight loss in patients treated for chronic hepatitis C virus.

OBJECTIVES: The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown. METHODS: All patients who initiated interferon-ribavirin therapy at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between August 2003 and January 2007 were identified using a computerized clinical database. The baseline characteristics of OC recipients were compared with those of nonrecipients. The treatment-related side effect response to OC was assessed by c2 analysis. The key therapeutic outcomes related to weight, interferon dose reduction and treatment outcomes were assessed by Student's t test and c2 analysis. RESULTS: Twenty-five of 191 patients (13%) initiated OC use. Recipients had similar characteristics to nonrecipients, aside from prior marijuana smoking history (24% versus 10%, respectively; P=0.04). The median time to OC initiation was seven weeks. The most common indications for initiation of OC were anorexia (72%) and nausea (32%). Sixty-four per cent of all patients who received OC experienced subjective improvement in symptoms. The median weight loss before OC initiation was 4.5 kg. A trend toward greater median weight loss was noted at week 4 in patients eventually initiating OC use (-1.4 kg), compared with those who did not (-1.0 kg). Weight loss stabilized one month after OC initiation (median 0.5 kg additional loss). Interferon dose reductions were rare and did not differ by OC use (8% of OC recipients versus 5% of nonrecipients). The proportions of patients completing a full course of HCV therapy and achieving a sustained virological response were greater in OC recipients. CONCLUSIONS: The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.

Effect of high-dose vitamin C on hepatic cytochrome P450 3A4 activity.

STUDY OBJECTIVES: To investigate the effect of high-dose vitamin C on cytochrome P450 (CYP) 3A4 activity, and to evaluate possible sex-specific effects on CYP3A4 activity. DESIGN: Single-center longitudinal study. SETTING: Tertiary- and specialty-care teaching hospital. SUBJECTS: Fourteen healthy Caucasian adult volunteers (seven men, seven women). INTERVENTION: Subjects self-administered vitamin C 500 mg twice/day for 14 days. MEASUREMENTS AND MAIN RESULTS: Hepatic CYP3A4 activity was measured by using the erythromycin breath test on days 1 (baseline) and 15. Overall, no significant effect of vitamin C on CYP3A4 activity was observed. Sex and baseline results were significant predictors of changes in CYP3A4 activity. In men, mean activity increased by 21.9% (95% confidence interval -3.88-47.6%). The effect in women was not consistent. CONCLUSION: Sex and baseline CYP3A4 activity appeared to influence the effect of vitamin C on CYP3A4 activity.