Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs.

BACKGROUND: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. METHODS: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. DISCUSSION: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy.

OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied. METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01). CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.